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in the following the present invention will now be described in more detail hereinafter with reference to the accompanying figures , in which non - limiting examples of the invention are illustrated . however , the present invention may be embodied in different forms and should not be construed as limited to the embodiments set forth herein . rather , these examples are provided so that this disclosure will be thorough and will convey the scope of the invention to persons skilled in the art . fig1 illustrates a plug connector 100 that represents a typical srs connector design with a top housing 110 and a bottom housing 120 that are mounted upon each other to form the connector housing 130 . both top housing 110 and the bottom housing 120 , are usually composed of an electrically insulative material , such as plastic . the connector housing 130 protects the electrical conducting components inside the connector housing 130 from environmental influences such as moisture or physical damage and allows a mechanical and electrical connection to a corresponding counter connector , i . e . a socket . the bottom housing 120 comprises bottom housing latches 122 at the mounting end 160 . when the plug connector 100 is mated with a counter connector 150 at the mounting end 160 , the provided bottom housing latches 122 flexible engage corresponding latches or grooves of the counter connector 150 , thereby locking the two connectors with each other . a connector position assurance ( cpa ) member 140 , respectively a secondary locking device , is located on the upper side of the connector housing 130 . the cpa member 140 comprises two cpa arms 142 that are interconnected by an integral web 144 . after full mating of the plug connector 100 with the counter connector 150 , the cpa member 140 can be pushed downwardly in fig1 , so that the cpa arms 142 slide downwards along the mating direction 600 . this has the effect that the cpa arms 142 block a further movement of the bottom housing latches 122 and hence lock them . this prevents from any unwanted decoupling of the bottom housing latches 122 and the and hence a decoupling of the plug connector 100 from the counter connector 150 . the bottom housing 120 also comprises cavities 124 . those cavities 124 often comprise a cylindrical shape with a circular cross section as shown , and are divided along mating direction 600 into a top or first cavity portion 126 and a bottom or second cavity portion 128 , as seen towards the mounting end 160 . two female terminals 132 are fitted into the cavities 124 , which are composed from an electrically conducting material . the female terminals 132 are designed to engage with a male counterpart ( e . g . a pin 152 ) of the counter connector 150 and thus establish an electrical connection . the female terminals 132 can also be distinguished , similarly to the cavities , into a top or first terminal portion 134 , which fits in the first cavity portion 126 and a bottom or second terminal portion 136 which fits in the second cavity portion 128 . notably , the quality of fixation of the female terminal 132 is dependent on the “ guiding length ”, which is the length where the outer surface of the first terminal portion 134 is in contact with the inner surface of the first cavity portion 126 . the second terminal portion 136 comprises spring arms 138 for grabbing a corresponding male pin 152 , which enters the second cavity portion 128 during the mating process , at the mounting end 160 , against the mating direction 600 , and for guiding it inside the cavity . the second terminal portion 136 is not in contact with the inner walls of the second cavity portion 128 . a mechanical fixation of the female terminals 132 is thus only effected by the respective first terminal portions 134 inside the first cavity portion 126 . in fig1 , the cavities 124 have a cylindrical shape with the same circular cross - section along the lengths of the cavities . the position of the female terminals 132 along mating direction 600 may thus vary since no other means for safeguarding the terminal &# 39 ; s position are provided when the female terminals 132 are brought inside the cavities 124 during the assembly of the plug connector 100 . also no additional stabilization in mating direction 600 is granted when pulling forces occur in mating direction 600 , for example during unmating of the plug connector 100 from the counter connector 150 . as depicted in fig1 , the “ guiding length ” of the first terminal portion 134 exhibits around the same length as the spring arms 138 of the second terminal portion 136 . a sufficient “ guiding length ” is needed to ensure a proper stabilization of the female terminals 132 inside the cavities 124 in this prior art design . therefore , the overall size of the plug connector 100 is relatively large . fig2 depicts in a preferred embodiment of the invention a sectional view of a bottom housing 200 in un - mounted condition . the bottom housing 200 can be identical to the bottom housing 120 of fig1 except for the shape of the cavities . thus , also the bottom housing 200 may comprise locking arms and it can be mounted with the same top housing 110 as shown in fig1 . naturally , the connector housing 130 may also be a single piece or it can be composed of more than two parts . the cavity 210 inside the housing is designed in a way to house a fitting female terminal 300 ( as it is shown in fig3 ). the cavity 210 can be designed in a cylindrical manner , in particular with a circular cross section . as can be seen in fig2 , the cavity 210 divides into two portions : a first cavity portion 212 and a second cavity portion 214 which are adjacent to each other . a cavity step 218 is provided between the first 212 and second cavity portions 214 at the position where the two portions merge with each other . at the mounting end 220 an opening is provided , where the male terminal counterpart ( e . g . a pin 232 ) of a corresponding counter connector 230 can enter the cavity 210 . for the purpose of pre - alignment of the pins 232 , corresponding means 240 are located at the mounting end 220 to pre - determine the angles under which a male pin 232 is able to enter the second cavity portion 214 . the design of the terminal allows grabbing and aligning a corresponding male pin 232 of a counter connector 230 . at the inner walls of the first cavity portion 212 , protruding ribs 216 are provided . those ribs are integrally formed with the inner walls of the cavity 210 and extend coaxially from the top of the first cavity portion 212 to the cavity step 218 , provided at the bottom of the first cavity portion 212 , where the first cavity portion 212 merges with the second cavity portion 214 . thus , the ribs extend for about 100 % of the length of the first cavity portion 212 in mating direction 600 . in fig2 , the diameter d 1 of the first cavity portion 212 is larger than the diameter d 2 of the second cavity portion 214 and the cavity step 218 is provided where the two cylindrical portions merge with each other . the cavity step 218 serves as a stop member for the female terminal 132 as one can take from e . g . fig4 . accordingly , the protruding ribs 216 do not extend into the second cavity portion 214 since they would possibly interfere with any parts of a corresponding female terminal 300 that is housed in the cavity 210 . a circular cross section may be of advantage for a facilitated production ( molding ) process . since the bottom housing 200 is usually produced in a one - piece design using the same material , comparable material parameters ( e . g . rigidity , resistivity ) apply for all locations along the inner surface of the cavity , allowing a facilitated estimation of the behavior of the connector . fig3 depicts the corresponding female terminal 300 , designed to fit in the cavity 210 . it comprises a first terminal portion 310 and a second terminal portion 320 . both terminal portions are aligned along the mating direction 600 and a terminal step 330 is provided or formed at the position where the two portions merge with each other . the first terminal portion 310 has a cylindrical cross section and a length along mating direction 600 that is small compared to the length of the second terminal portion 320 . the second terminal portion 136 comprises two spring arms 322 extending in mating direction 600 for engagement with a corresponding male terminal . additionally , locations 312 are marked , where the protruding ribs 216 engage the female terminal 300 in mounted condition ( see fig4 ). hence , the lengths of the protruding ribs 216 and the first cavity portion 212 correspond to the “ guiding length ”, that is the length of the first terminal portion 310 which is in contact with the inner walls of the first cavity portion 212 . the two spring arms 322 narrow from the terminal step 330 towards their distal ends , i . e . towards the mounting end 220 . further , each of the two spring arms 322 is flexibly attached to the terminal step 330 , so that it is able to bend outwards up to a certain degree in a reversible manner . at the distal end , the two spring arms 322 comprise a tulip - shaped mating end 324 , which allow to grab and align entering pins 152 even under bad conditions , e . g . in a very inclined way . opposite to the tulip - shaped mating end 324 , there is an electrical collector 340 attached on the top of the first terminal portion 310 . the electrical collector 340 serves for electrical connection of the female terminal 132 with a signal wire . fig4 depicts a sectional view of the bottom housing 200 comprising the cavity 210 in mounted condition . the female terminal 300 is located inside the cavity 210 , such that the cavity step 218 and terminal step 330 of the cavity 210 and the female terminal 300 engage each other . protruding ribs 216 are depicted which extend from the cavity step 218 parallel to the mating direction 600 to the top side of the first cavity portion 212 . the ribs are designed in a way that they do not come into contact with the edge of the terminal step 330 during the assembly of the female terminal 300 within the cavity 210 . since the female terminal 300 is inserted from the top side ( as seen from the orientation shown in fig4 ), the edge of the terminal step 330 could possibly damage the protruding ribs 216 when brought downwards in mating direction 600 . accordingly , the protruding ribs 216 have to be dimensioned and located in a way that they are not damaged during assembly . the first terminal portion 310 is located in the first cavity portion 212 and comprises a cylindrical shape with a circular cross section . the respective dimensions of first terminal portion 310 and first cavity portion 126 are chosen such that the first terminal portion 310 is snugly held in the first cavity portion 212 . the length of the first terminal portion 310 corresponds to a “ guiding length ” that is smaller , compared the length of the second terminal portion 320 . the reduction of guiding length is possible due to the increased stability , caused by the engagement of the steps of the female terminal 300 and cavity 210 and the additional clamping of the female terminal 300 by the protruding ribs 216 . the two spring arms 322 of the second terminal portion 320 are housed in the second cavity portion 214 , which comprises a smaller diameter d 2 than the first cavity portion 126 . on top of the first terminal portion 310 , an electrical collector 340 is attached for tapping the electric current from the female terminal 300 , and for transferring it by means of a wire or cable further through and out of the connector . as can be seen in fig4 , the electrical collector 340 is mechanically stabilized by guiding means , which are integrally formed on the upper side of the bottom housing 200 . this leads to additional mechanical stabilization of the female terminal 300 preventing the terminal from any unwanted movements during cable pull or during the mating / unmating of the connector . fig5 depicts a top view of the bottom housing 200 . one can see the two cavities 210 , whereby on the left - hand side no terminal is yet mounted and on the right - hand side a female terminal 300 is mounted . the two cavities 210 are cylindrical and reveal a circular cross section . in the un - mounted condition , the first cavity portion 212 is depicted with a total of four protruding ribs 216 , integrally formed with the inner walls of the first cavity portion 212 . all protruding ribs 216 are equally distributed along the circumference of the inner wall of the first cavity portion 212 . in mounted condition the protruding ribs 216 additionally clamp and thus fix the female terminal 300 inside the cavity 210 , as indicated on the right - hand side . due to the equal distribution , the ribs at the same time provide an accurate centering of the terminal inside the cavity . as can be seen in this top view , also the first terminal portion 310 comprises circular cross section . while this invention has been described in terms of the preferred embodiments thereof , it is not intended to be so limited , but rather only to the extent set forth in the claims that follow . moreover , the use of the terms first , second , primary secondary , etc . does not denote any order of importance , but rather the terms first , second , etc . are used to distinguish one element from another . furthermore , the use of the terms a , an , etc . do not denote a limitation of quantity , but rather denote the presence of at least one of the referenced items . | 7 |
although the present invention , to be described hereinafter , is intended to be used in any environment wherein a circuit is needed to activate a relay , it works well in a telecommunication system and as such will be described in this environment . however , this should not be construed as a limitation on the scope of the present invention since it is within the skill of the art to make minor changes , if any , to the described invention and extend said invention to other fields . fig1 shows a telecommunication system in which the present invention finds use . the telecommunication system is comprised of a communication link identified by numeral 10 . the communication link transmits data from a remote location into the wire concentrator identified by numeral 12 . data from wire concentrator ( wc ) 12 is transmitted over conductor 14 to a remote location . the wire concentrator 12 is connected over conductors 16 and 18 respectively , to a station 20 . in the preferred embodiment of this invention conductors 16 and 18 are twisted wire pairs . the function of wire concentrator 12 is to switch station 20 into the network so that data which is transmitted on conductor 10 is conveyed to the station and data which is to be transmitted from station 20 is transmitted out on conductor 14 . to this end wire concentrator 12 includes switching relays , whose contacts are identified by a1 , a2 , b1 and b2 , and a pair of transformers 22 and 24 . the transformers are interconnected to said contacts . the relay coil and control circuit which drive the coil are embedded in the circuit means identified by numeral 26 . circuit means 26 is connected through a pair of choke coils to transformers 22 and 24 respectively . station 20 includes a business machine ( not shown ) which is to be coupled at terminals 28 and 30 respectively to conductors 16 and 18 . the business machine ( not shown ) is interconnected by transformers 32 , 34 , choke coil 36 and adapter control circuit 38 to terminals 28 and 30 respectively . usually the wire concentrator 12 has no electrical power of its own . therefore , the electrical power for activating the relay is supplied from adapter control circuit 38 . usually a dc relay current of approximately 150 milliamperes is required to pick these relays . the telecommunication configuration of fig1 poses several problems . for example , the adapter control circuit cards which drive the relay are usually populated with lsi ( large scale integrated ) circuitry which cannot directly drive the relays because lsi circuitries are generally low voltage , low current devices . if one wants to use lsi circuitries to drive the relays , high current discrete transistors and current limiting resistors must be provided on these cards . also , the distance between the adapter control circuit and the wire concentrator must be relatively short in order to minimize the voltage drops in the interconnecting transmission wires 16 and 18 , respectively . because a relay usually requires a relatively large amount of current , in order for this configuration to work , the adapter control circuit 38 of the using machine ( not shown ) must supply a relatively large amount of current through the adapter card to power the relays . this dictates that the host machine must be designed with a significant amount of power for driving the relay at a remote distance . fig2 shows one embodiment of the present invention which eliminates the above recited limitations of the arrangement of fig1 . the circuit in fig2 is implemented in relay coil and control circuit means 26 ( fig1 ). terminals 40 and 42 of the circuit are connected to the choke coil 37 ( fig1 ). terminal 42 represents the ground potential ( that is negative terminal ) of the circuit ; while terminal 40 represents the positive terminal . the excitation coil of the relay includes a reset coil and a set coil ( fig2 ). one end of the reset coil is connected to negative terminal 42 and the positive end of the reset coil is connected to cathode ( c ) of a programmable unijunction transistor ( put - 1 ). as will be explained hereinafter , the function of put - 1 is to sense the incoming signal from the adapter control circuit 38 ( fig1 ) and to discharge capacitor c1 through the reset coil when said signal falls below the signal on capacitor c1 . still referring to fig2 the gate electrode of put - 1 is coupled through resistor r1 to positive terminal 40 . likewise , diode d1 interconnects the gate electrode and the anode electrode of put - 1 . a capacitor c1 is coupled across terminals 40 and 42 respectively . the size of capacitor c1 is such that the charge stored thereon is sufficient to activate the set coil and reset coil of the relay consecutively . capacitor c2 connects the positive plate of capacitor c1 to the positive terminal of the set coil and the negative terminal of the set coil is coupled to the anode electrode of silicon control rectifier ( scr1 ). the cathode ( c ) of scr1 is connected to negative terminal 42 while the gate electrode of scr1 is connected through zener diode d3 and resistor r2 to the positive plates of capacitors c1 and c2 respectively . as will be explained hereinafter , the function of scr1 is to discharge a portion of the charge in c1 through the set coil of the latching relay when the voltage in c1 exceeds that of the reference voltage of d3 . a diode d2 is connected across negative terminal 42 and positive terminal 40 . in operation , when a voltage , say greater than 5 volts , is applied between terminals 40 and 42 respectively , a relatively low volume current , say within the submilliamp range , flow through r1 and d1 and charges c1 . ideally , no current will flow through the other path of the circuit until the charge and voltage accumulated in c1 equals the voltage of d3 . when this occurs , the zener diode conducts and current flows into the gate of scr1 . scr1 in turn conducts and discharges c1 through c2 into the set coil of the relay . with current flowing through the set coil , the relay contacts ( fig1 ) move into the closed position . the current flow from c1 to c2 decreases exponentially to zero . with c2 charge the current drain of c1 is halted . as long as the applied voltage between 40 and 42 is present , c1 remains charged and the only current through r1 and d1 is a small trickle current through r2 and d3 and the gate of scr1 . should the input voltage fall either intentionally or via a wire break , current stops flowing through d1 . put - 1 or some other equivalent sensing means sees its gate lead now at a lower potential than its anode lead . ( the anode voltage of the put is at the voltage potential of c1 .) it is worthwhile noting that a put is a very high impedance device when the gate electrode voltage is less than the anode electrode voltage . however , when the conditions are reversed , that is , the anode voltage is higher than the gate voltage , the put becomes a low resistance device . both c1 and c2 discharge through put - 1 via the path through d2 . the current which flows through the put enters the reset coil of the latching relay to place the relay in the second or reset condition . fig3 shows an alternative embodiment of the present invention . in this embodiment the enabling voltage which is applied to terminals 40 and 42 respectively may be less than five volts , say 3 . 5 volts . in order to simplify this discussion , elements which are common in fig2 and 3 are identified by the same numeral . as with fig2 terminals 40 and 42 ( fig3 ) are connected to the choke coil 37 of fig1 . terminals 42 represents the negative terminal of the circuit while terminal 40 represents the positive terminal . the function of the circuit in fig3 is to accept a relatively low voltage , low current signal at terminals 40 and 42 , respectively and to generate an adequate current which when passed through the set coil forces the contact of the relay ( fig1 ) into a first state , say the set state . in the event that the signal at terminals 40 and 42 is discontinued , the circuit provides a current through the reset coil to force the contact of the latching relay ( fig1 ) into the second state , say the reset state . to this end , a put - 1 is coupled through diode d2 to the base emitter of a switching means t1 . in the preferred embodiment of this invention , switching means t1 is a transistor . the negative terminal of the set coil is connected to the base of transistor t1 while the emitter of transistor t1 is connected to the negative terminal 42 . resistor r4 interconnects the cathode of put - 1 to negative terminal 42 . the positive terminal of the set coil is connected to positive terminal 40 . a diode d3 is placed in parallel with the set coil and interconnects the negative terminal of the set coil to the positive terminal 40 of the circuit . the gate electrode of put - 1 is connected to a node identified by numeral 44 . node 44 interconnects resistors r5 and r6 respectively . resistors r5 and r6 are a voltage divider network and provide a reference voltage level at node 44 . the resistors are connected across positive terminals 40 and 42 , respectively , as will be explained subsequently , when the voltage on capacitor c1 is greater than the reference voltage generated at node 44 , the put conducts and turns t1 on . this forces c2 to discharge current through the set coil . still referring to fig3 the anode electrode of put - 1 is coupled through r1 and r2 to provide terminal 40 . a storage capacitor c1 interconnects the anode electrode of put - 1 to negative terminal 42 . the positive plate of capacitor c1 is connected through transistor t2 to negative terminal 42 and the positive terminal of the reset coil . in order to place the latching relay in its second ( that is the reset state ) the positive terminal of the reset coil is connected to a switching means identified as put - 2 . the negative terminal of the reset coil is connected to negative terminal 42 . put - 2 is comprised of a cathode electrode which is connected to the positive terminal of the reset coil , a gate electrode which is connected to positive terminal 40 and an anode electrode which is connected to the positive plate of capacitor c2 . a diode d1 interconnects the gate electrode of put - 2 to its anode electrode . the negative 42 . as will be is connected to the negative terminal 42 . as will be described hereinafter , c2 formed a storage means which stores sufficient current to energize both the set coil and the reset coil of the relay . although it is within the skill of the art to select values for the various electrical components of fig3 . table i gives a set of values which works satisfactorily . however , these values should not be construed as a limitation on the scope of the present invention since it is fully recognized that one of ordinary skill can change these values without departing from the scope of the present invention . table 1______________________________________schematicreference description______________________________________r1 24 . 9k 1 % 1 / 8 watt resistorr2 511 1 % 1 / 8 watt resistorr3 1k 1 % 1 / 8 watt resistorr4 3 . 32k 1 % 1 / 8 watt resistorr5 698k 1 % 1 / 8 watt resistorr6 432k 1 % 1 / 8 watt resistorc1 33 microfarad 10 v . tantalum capacitorc2 1k microfarad 10 v . tantalum capacitorc3 8 microfarad 10 v . tantalum capacitort1 , t2 2n3252 transistor or equivalent . put1 , put2 ge d13t2 programmable uni - junction transistor or equiv . d1 1n60 or equiv . germanium dioded2 , d3 1n4150 or equiv . silicon diode______________________________________ still referring to fig3 in operation a relatively low voltage , say greater than 3 . 6 volts , is applied to terminals 40 and 42 , respectively . c1 and c2 begin to charge . simultaneously , voltage dividers r5 and r6 establish a reference potential at node 44 which is transmitted to the gate electrode of put - 1 . when c1 charges to a value greater than the reference voltage at g , put - 1 switches on and discharges c1 into r4 . during this discharge , as long as the voltage across r4 is greater than say 2 diode drops ( v d2 + t1 vbe ) current flows into the base of t1 , turning it on . t1 turning on causes c2 to discharge through the set coil . this current transfers the relay contacts into the first state ( say the set state ). preferably , the value of c2 is chosen such that approximately 70 % of its initial charge is left after t1 stops conducting . this ensures that enough energy is in the system to reset the relay immediately after a relay set should the source voltage drop for any reason . it ought to be noted that this is a precaution against the relay being left in an undesirable set condition after a station stops transmitting signals . also , r1 - r6 resistors are chosen to keep the put - 1 current above its valley point or &# 34 ; holding current &# 34 ; after the initial discharge of c1 . if allowed to turn off , the circuit would recycle to initiate another c1 charge and put - 1 turn - on pulse . this is a relaxation oscillator behavior and would be undesirable . the holding current , however , is too low to produce a voltage drop across r4 greater than two diode drops . still referring to fig3 put - 2 forms the switching device which initiates the rest cycle of the relay . as long as the required voltage is applied to terminals 40 and 42 , a microamp bias current flows in the put - 1 circuitry and through d1 . put - 2 with its gate and anode electrodes connected across d1 sees a more positive voltage on the gate electrode than the anode . in this configuration put - 2 is a high impedance device and does not conduct . if the source voltage on terminals 40 and 42 drops , the anode electrode of put - 2 is left at the voltage of c2 which is the most positive in the circuit . simultaneously , the signal on terminal g drops . when g falls below ( say 0 . 6 volt ) the voltage of the anode ( a ) electrode , put - 2 conducts and discharges c2 into the reset coil . this in turn transfers the relay contact to its original or reset condition . the c2 discharge continues until the valley current is reached and put - 2 is turned off . the circuit is now reset awaiting another application of the source voltage for another cycle . this concludes the detailed description of the present invention . it should be noted that the put function is a comparator in the above - described circuit arrangement . it is within the skill of the art to replace the put . therefore , it is within the skill of the art to replace the put by an equivalent circuitry without departing from the scope of the present invention . several benefits inure to one who uses the above invention . among the benefits are the following : the power needed to control the excitation coil of the relay is provided from lsi circuitry . no external high power circuitry is needed to drive the relay . the drive distance from the business machine at station 20 ( fig1 ) to wire concentrator 12 is essentially unlimited . this is possible because the current which is supplied from adapter control circuit 38 is small . therefore , the voltage losses in the drive lines represent a minor voltage drop at the relay . in fact , the peak circuitry input may contain a large resistor to control the charging time of the integrating capacitor c1 ( fig2 ) or c2 ( fig3 ). because the circuit utilizes the gate of a very fast turnon put to sense the condition ( i . e . the absence or presence ) of the input signal , the relay is reset within a relatively short time interval . finally , because the energy needed to activate the relay is derived from a small current over a period of time ( integrated ), the host power requirement can be decreased by orders of magnitude to the point of being negligible compared to conventional relay driver circuits . although the invention has been particularly shown and described with reference to a preferred embodiment thereof , it will be understood by those skilled in the art that various changes in from and details may be made therein without departing from the spirit and scope of the invention . | 7 |
the dynamic power management device implements a dynamic power management strategy having several different elements in order to achieve significant power savings . dynamic power management is applied not only to solid state memories but also to the dynamic power management device itself . the basic element of the power conservation strategy is to essentially turn off all functions not required at any particular time . the dynamic power management device may be used in conjunction with non - volatile semiconductor memories , for example , in which case power to the memories may be substantially or completely turned off except during access . the dynamic power management device may be used to greatest advantage in conjunction with drams , however , because of the requirement of drams for a continuous supply of power . when used in conjunction with drams , the dynamic power management device supplies power to the memory sufficient to maintain memory information during periods of no data access activity and sufficient to exchange memory information with the memory during periods of data access activity . hence , during periods of no data access activity , a minimal voltage is supplied to memory . during periods of data access activity , a greater operational voltage is supplied to memory . during transitional periods from non - activity to activity , the voltage is ramped up and then ramped back down . for drams , data access activity includes both memory refresh and memory access . furthermore , inputs to memory chips are &# 34 ; driven softly &# 34 ; to conserve power . for capacitive loads , the power consumed is proportional to the time rate of change of voltage , dv / dt . the time rate of change of voltage is also referred to as the slew rate . the dynamic power management device uses slew rate controllers , driver circuits designed to have voltage rise and fall times prolonged in comparison to those of usual driver circuits , in order to reduce the slew rate and hence power consumption . furthermore , address inputs are encoded using gray code such that only one address input changes at a time . finally , in order to minimize the power consumed by multiple chips , data is stored into and read out of the chips serially with tens or even hundreds of consecutive bytes being stored on a single chip , such that only one chip needs to be active at any given time , thus reducing power consumption . referring now to fig1 the dynamic power management device 10 may be interposed between a host device provided with an intelligent interface , such as an at / ide , esdi or scsi interface , and the solid state memory 13 . intelligent interfaces such as the ide , esdi and scsi interfaces are typically attached between a host computer and a rotating memory device . the host merely requests blocks of data information in 512 - byte increments . the data is then intelligently managed between the rotating memory device and the host system . an error recovery system causes operations resulting in errors to be retried . in this manner , the intelligent interface provides a data path from the mass storage device to the host system without apparent data failure . the power management device may be used in a solid state disk that in comparison to conventional hard disks offers greatly improved performance but looks to the computer exactly like a conventional hard disk . as seen in fig1 the dynamic power management device 10 provides all of the data , address and control inputs for the solid state memory 13 . the dynamic power management device also provides an operating voltage vcc to the solid state memory 13 . the voltage vcc is dynamically varied , or &# 34 ; cycled &# 34 ; according to different modes of operation of the solid state memory 13 . the data output of the solid state memory 13 is received by the dynamic power management device 10 . preferably , the power management device 10 is realized predominantly as a single integrated circuit . in fig1 blocks to the left of the dashed vertical line are preferably realized on a single chip . the slew rates of all of the digital inputs to the solid state memory 13 are minimized using slew rate controllers 15 , 17 and 19 to conserve power . as previously mentioned , the slew rate controllers may be input drivers designed to have prolonged rise times and fall times in comparison to conventional input drivers . further power conservation is achieved by gray coding address inputs to the solid state memory 13 . a binary address generator 21 generates binary addresses in response to a request from the host or in response to a refresh timer block 23 . the refresh timer block 23 implements two different refresh timers , one for regular refresh and one for extended refresh , to take advantage of the extended refresh capabilities of some solid state memories . extended refresh is much slower , typically ten times slower , than conventional refresh and therefore consumes less power . binary addresses generated by the address generator 21 are gray coded by an encoder 25 before being input to the slew rate controller 17 and to the solid state memory 13 . power to the solid state memory is controlled using pulse width modulation ( pwm ) by a pwm rate controller 27 . power is supplied by either a main battery bat1 or a backup battery bat2 selected between by a power director 29 . voltages from the main and backup batteries , a select signal from the power director 29 and a pulse width modulation signal from the pwm rate controller 27 are all input to an external low pass filter 31 . in an exemplary embodiment , the low pass filter 31 may be a conventional rlc filter and may additionally include a selection circuit and a fet power driver . the selection circuit selects either the main battery , the backup battery , or possibly some other power source to supply power to the fet power driver . the pulse width modulation signal from the pwm rate controller 27 is filtered in the low pass filter and input to the fet power driver , which produces the voltage vcc . the voltage vcc is used to power the solid state memory 13 and is also input to the power director 29 . closed - loop power monitoring is performed by the power director 29 , an a / d converter 33 and a power feedback block 35 under the control of a timing sequencer and arbitor 37 . the power director 29 receives voltages from each of the power sources in addition to the controlled voltage vcc . preferably the power director 29 also produces an internal reference voltage for calibration purposes . the foregoing voltages are input to an analog multiplexer or other analog switch and are selected in turn by the timing sequencer and arbitor 37 to be sampled using the a / d converter 33 . the digital representation of the selected voltage is input to the power feedback block 35 , which compares the voltage value with a voltage value required by the solid state memory 13 in a particular mode of operation . the power feedback block 35 notifies the timing sequencer and arbitor 37 whether or not the selected voltage is sufficient for the desired operation . if not , the pulse width duty cycle may be increased or another source may be selected . closed - loop monitoring ensures that an adequate voltage is applied to the solid state memory 13 . the timing sequencer and arbitor generates all the necessary control signals for the solid state memory 13 including ras , cas and we signals . when power is insufficient , the control signals that initiate an operation are delayed until adequate power has been confirmed . the timing sequencer and arbitor 37 also arbitrates between memory access by the host and memory refresh . data is input to and output from the solid state memory 13 across a data path including an error correction block 39 and a serializer / deserializer 41 . error detection and correction is performed using a well - known polynomial cyclic redundancy code ( crc ). incoming data is therefore error correction coded , serialized in the serializer / deserializer 41 and input to the solid state memory 13 through the slew rate controller 17 . data output from the solid state memory 13 are deserialized in the serializer / deserializer 41 and input to the error correction block 39 for error detection and correction . error - free data is then transferred to the host on a parallel data bus 43 . data path control is provided by a dma controller 45 in cooperation with a data sequencer 47 connected to the timing sequencer and arbitor 37 . the dma controller 45 performs data transfer handshaking with the host . the dma controller 45 is also provided with byte count registers to keep track of the number of data bytes remaining to be transferred . the data sequencer 47 signals the dma controller 45 when a data byte is ready to be transferred , whereupon the dma controller 45 issues a dma request ( drq ) to the host . upon acknowledgement of the request from the host by means of a dma acknowledge signal ( dack ), the byte is transferred on the parallel data bus 43 . when all bytes have been transferred , the dma controller 45 raises a transfer done signal , signaling the host that the requested number of data bytes , for example 512 , have been transferred . the data sequencer 47 controls all timing internal to the dynamic power management device 10 . the data sequencer 47 therefore controls conversion of data between serial and parallel . the data sequencer also controls operation of the error correction block , 39 supervises direct memory access , and times out the memory control signals ras , cas and we . the dynamic power management device is also provided with a daisy chain controller 49 allowing multiple dynamic power management devices each associated with one or more solid state memories to be connected together to realize a single high - capacity solid - state memory . the daisy chain controller 49 is provided with a serial input si and a serial output signal so for communication with a daisy chain controller in another dynamic power management device . when data is required to be read from or written to a solid state memory associated with a dynamic power management device ( slave ) other than the dynamic power management device in communication with the host ( master ), the data sequencer 47 causes a command to be daisy chained to the appropriate dynamic power management device . data provided from another power management device is transferred in serial form from the daisy chain controller 49 to the serializer / deserializer 41 where it is converted to parallel form for transfer to the host . data from the host to be provided to another dynamic power management device is serialized in the serializer / deserializer 41 and transferred to the daisy chain controller 49 to be passed down the chain to the appropriate dynamic power management device . operation of the dynamic power management device 10 to cycle power to the solid state memory 13 in accordance with different modes of operation of the solid state memory may be appreciated from fig2 a - 2d . during a standby period of operation shown in fig2 b , the operational voltage supplied to the solid state memory 13 , shown in fig2 a , cycles between approximately 1 . 5 volts and 2 volts . during this period , the pulse width modulation signal is set to a minimum duty cycle sufficient to maintain data in the solid state memory 13 . with each pulse , the voltage rises to approximately 2 volts ; between pulses , the low pass filter 31 causes the voltage to be sustained at about 1 . 5 volts . in preparation for a refresh cycle during a prepare refresh period shown in fig2 b , the duty cycle of the pulse width modulation signal is increased , causing the voltage to ramp up from about 1 . 5 volts to about 3 volts . when the voltage has reached about 3 volts , sufficient to perform a refresh operation , the power feedback block 35 of fig1 signals the timing sequence and arbiter 37 that it may proceed with a ras cycle , initiating refresh . during a refresh period shown in fig2 b , the ras signal generated by the timing sequencer and arbiter 37 drops low from a nominal value of about 2 . 7 volts . current flow increases correspondingly from a quiescent current of about 100 microamps to about 1000 microamps . when refresh has been completed , the ras signal is again raised , causing the current to drop to the quiescent level . the voltage supplied to the solid state memory is thereafter ramped down during a prepare standby period , after which the dynamic power management device 10 resumes standby operation . referring now to fig3 expansion of the solid state memory from a single solid state memory device to any number of solid state memory devices may be achieved in two different ways . using the daisy chain capability described in relation to fig1 multiple dynamic power modules may be daisy chained together , each constituting a memory node . in addition , the dynamic power module may be modified to provide multiple ports , and a string of multiple memory devices may be connected to each port . in fig3 four ports are provided and four memory devices are connected to each port such that a total of 16 memory devices are controlled by each dynamic power module . connection of the memory devices to the dynamic power modules has been illustrated in simplified form . each of the illustrated busses in practice includes data , address and control signals as well as an analog power bus . the voltage across one of the strings of four memory devices during operation of the dynamic power modules is shown in fig4 . during refresh , the voltage rises to about 3 . 3 volts . in between refresh intervals , the voltage pulsates between about 1 . 5 and 2 . 5 volts . the corresponding plot of power consumption is shown in fig5 . in between refresh intervals , power consumption remains well below 2 milliwatts . slight power &# 34 ; bumps &# 34 ; occur at approximately 1 microsecond intervals , corresponding to the pulse width modulation rate . during refresh , power consumption spikes up sharply to about 13 milliwatts for a period of time on the order of 100 nanoseconds . power consumption then subsides and resumes the previous pattern . a corresponding plot of total battery power consumed over time is shown in fig6 . the amount of power consumed increases at a rate of about 3 milliwatts per microsecond up until refresh , at which time a step increase in power consumption of about 20 milliwatts occurs , followed again by power consumption at the 3 milliwatt per microsecond rate . fig7 shows the expected life of a 15 milliamp - hour hot standby battery powering 8 drams as a function of time as power is cycled to the drams . during standby , expected battery life varies from a maximum of just less than 60 days to a minimum of slightly more than 20 days . during access , expected battery life drops precipitously to just several days . on the average , using dynamic power management , the battery may be expected to last more than 30 days , ample time under any normal circumstance . when coupled with the dynamic power management device of the present invention , drams therefore provide a high - performance , high - reliability and cost - competitive alternative to small form factor hard disk assemblies . the dynamic power management device , besides dynamically managing power consumption of the solid state memory , may also be designed to dynamically manage its own power consumption . typically , the solid - state memory is accessed only about 10 % of the time and operates in refresh and standby modes 90 % of the time . the dynamic power management device may therefore sleep 90 % of the time during refresh and standby modes . during refresh mode , only a simple counter is required to remain running to preserve refresh activity . the dynamic power management device wakes up upon access by the host . the dynamic power management device sleeps by : turning off all unnecessary logic ; stopping all unnecessary clocking ; reducing the clock frequency by a factor of 10 ; shutting off all unnecessary driver transistors to the outside world ; waking up when accessed by an external interface request ; and automatically readjusting clocks and active circuits . by managing its own power consumption in addition to the power consumption of memory , the dynamic power management device minimizes overall power consumption . the foregoing has described the principles , preferred embodiments and modes of operation of the present invention . however , the invention should not be construed as limited to the particular embodiments discussed . instead , the above - described embodiments should be regarded as illustrative rather than restrictive , and it should be appreciated that variations may be made in those embodiments by workers skilled in the art without departing from the scope of the present invention as defined by the following claims . | 8 |
in an exemplary embodiment of the present invention , as illustrated in fig1 there is provided a television signal scrambler 10 for use in a television system , such as a cable tv system . the scrambler 10 includes a visual channel 12 and an audio channel 14 which are combined at a summing network and amplifier 16 . the output from network 16 is applied to a mixer 18 together with a carrier signal from an oscillator 20 having an output frequency selected to produce a television signal on mixer output 22 for a preselected channel frequency . a scrambling circuit 24 is provided , operative on the visual channel 12 , to generate a scrambled picture carrier on output line 26 . the audio channel 14 is unscrambled and provides an audio modulated carrier on an output 28 for combination with the scrambled picture carrier on line 26 by the summing network 16 . the audio channel 14 includes a conventional source 30 of audio signals , such as a microphone and preamplifier ( not shown ). the audio signal from the source 30 frequency modulates ( fm ) the output signal from a 4 . 5 mhz sound carrier oscillator 32 for appropriate placement of the sound signal in a standard television channel . the fm modulated sound signal in turn amplitude modulates an intermediate frequency ( if ) carrier on input 34 of a modulator 36 . the sound modulated if carrier is passed through a filter 38 to remove the upper sideband and 45 . 75 mhz carrier and provide the desired if sound carrier on line 28 . the visual channel 12 includes a conventional source 40 of video signals , such as from a tape recorder or video camera ( not shown ). the video signals on line 42 are applied to an if carrier modulator 44 provided with the same if carrier on input 46 as applied to input 34 of the if carrier modulator 36 in the sound channel 14 . the output from modulator 44 is passed through a filter 48 which provides a vestigial sideband signal on filter output 50 for combination in a coupler 53 with a scrambling if carrier on line 52 from scrambling network 24 . the scrambler network 24 operates by altering the characteristics of the carrier employed in the transmission of the television signal . the carrier used originates at an output 54 of the voltage controlled oscillator 56 which normally operates at an intermediate frequency ( if ) of 45 . 75 mhz . the carrier on line 54 is applied through a directional coupler 58 to a signal splitter 60 which provides the inputs 34 and 46 for the modulators 36 and 44 , respectively , with the same if carrier signal . another output of coupler 58 is applied to a phase shift network 62 which in the exemplary embodiment provides about 180 ° overall phase shift to the if carrier appearing at the output of directional coupler 26 . the phase shifted if carrier on line 64 is applied to a phase change switch 66 whose output 68 is applied through an adjustable attenuator 70 to provide a scrambled if carrier on the output 52 . the switch 66 is a device that either blocks or passes the phase shifted carrier depending upon the logic level state of a signal at a control input 72 . any conventionally known pin diode electronic switch may be used for the phase change switch 66 in fig1 . a low frequency or coding source 74 produces a coding signal at an output 76 . the coding signal source may be an oscillator , or a specially coded low frequency signal which can convey useful information to a subscriber location . coding may be obtained with pulse modulation by , for example , turning a coding oscillator on for different time periods respectively interpreted as different information . the coding signal source 74 provides a coding signal having a pair of alternating signal levels . this signal at output 76 becomes the control input 72 for the phase change switch 66 and a control input for the voltage controlled oscillator 56 . during the first signal level intervals , such as the logic &# 34 ; 0 &# 34 ; s , the switch 66 is closed and therefore passes the phase shifted carrier at the output 64 to the attenuator 70 . during the second signal level intervals , such as the logic &# 34 ; 1 &# 34 ; s , the switch 66 is open and does not pass the phase shifted carrier to the atlernator 70 . since the if carrier phase change sequence is to be removed at the receiver , a pilot signal representative of the coding signal is transmitted . this pilot signal is generated by fm modulating the if carrier a predetermined amount simultaneously with the phase changed sequence of the carrier . the coding signal output 76 is thus coupled to the if variable oscillator 56 to provide the latter with a small amount of frequency deviation , i . e . about ± 15 khz at the low coding signal rate of up to 500 hz . the deviation and modulation frequency of the if carrier is kept small to avoid measurable television picture signal interference which would be objectionable to a subscriber at the receiver end . preferably , the coding signal source 74 is keyed by the vertical sync pulses on an output 78 from the video signal source 40 , as shown in the illustrative embodiment of fig1 . thus , the carrier phase may be altered as often as every picture frame if desired . the advantage of keying the coding signal transitions to the vertical sync pulses is that the rapid phase transition is performed during vertical retrace time which allows the decoder sufficient time to correct the decoder phase before the beginning of the next frame . structurally , the source 74 could merely be a counter which counts the vertical sync pulses , and the coding signal is merely the output of one or more of the stages of the counter . preferably , more than 50 % of the frames are transmitted with a phase changed carrier to insure that a sufficient level of scrambling is obtained . a typical coding signal format meeting this preferred feature is illustrated in fig2 a and 2b . in fig2 a , first signal level intervals ( i . e . phase change intervals ) are the logic &# 34 ; 0 &# 34 ; s and the second signal level intervals ( i . e . normal carrier intervals ) are the logic &# 34 ; 1 &# 34 ; s . thus , for the total time interval for nine picture frames , four frames are with normal carriers and five frames are with phase changed carriers . since carrier switching is preferably performed during vertical retrace time , the maximum rate of phase change is 60 per second . the program code ( i . e . the useful digital information forming the coding signal ) can serve a variety of functions in a pay tv system . for a simple subscription system , the transmitted code must match a &# 34 ; wired - in &# 34 ; or &# 34 ; code - of - the - month &# 34 ; that is resident in the converter in order to operate the decode function . alternatively , the code might represent a multiplicity of subscription packages that can be purchased , i . e ., sports events , drama , and allows operation of the proper converter . preferably , the phase change of the carrier is substantially 180 ° ( i . e . a phase inversion ) since this provides more effective scrambling without additional circuitry . the amplitude of the scrambling carrier on line 52 is adjusted by the attenuator 70 to be sufficient to completely replace the normal carrier in the vestigial sideband signal on line 50 . preferably , the inverted carrier amplitude is 110 % of the peak amplitude of normal carrier signal on line 50 . since the peak amplitude of the normal signal is the sync pulse , the sync pulse for the phase inverted frame is at 10 % of peak amplitude . as a result , the white level of one field has the same level as sync in an alternate field . referring now to fig3 a decoder 80 is illustrated in block diagram form whereby the received television signal on a cable television input line 82 corresponds to the television signal generated in a scrambled form on the output line 22 in the scrambler 10 illustrated in fig1 . the decoder 80 includes a converter circuit 81 for converting the carrier of the scrambled television signal to a desired intermediate frequency ( if ). the television signal is applied to a first mixer 84 which is supplied by a local oscillator via an input 85 frequency from a voltage controlled oscillator ( vco ) 86 tunable over a wide range with a channel selector 88 in the form of a potentiometer . the frequency of the vco 86 is selected so that an output 90 of the first mixer 84 is an if signal of 330 mhz which , in turn , is passed through an if amplifier 92 . an output 93 of the if amplifier 92 is applied to a second mixer 94 which , in turn , is supplied with a local oscillator signal from a source 96 having a frequency selected to provide a predetermined normally unused television channel signal at an output 97 . in many localities such unused channel is channel 3 , as shown in fig3 so that the frequency of the oscillator 96 is 391 . 25 mhz to provide a television signal carrier at a frequency of 61 . 25 mhz ( channel 3 ) on the output 97 of the second mixer 94 . an if filter 98 removes other frequencies and provides only the channel 3 signal on a converter output 100 . the decoder 80 includes the capability for regenerating the coding signal and for removing the frequency modulation from the scrambled television signal . these features are accomplished in the exemplary embodiment by a phase lock network , represented generally by the numeral 101 , which is used to control the input to the voltage control oscillator 86 of the converter . the phase lock network 101 includes a reference signal oscillator 102 which provides a signal on an output line 104 to an automatic phase control ( apc ) detector 106 . the frequency of this signal is the same as the normal if frequency output of the converter , which in the example is 61 . 25 mhz . the ( apc ) detector 106 compares the phase of the oscillator if signal with the phase of the if converted , scrambled television signal present on an input line 104 for the phase lock network . the if converted , scrambled television signal at the output 100 of the converter 81 is amplified by a gain control amplifier 110 and then amplitude limited by a limiter 112 . the function of the detector 106 is to generate an output 116 which is a function of the instantaneous phase difference between the reference if signal oscillator output 104 and the if converted , scrambled television signal . the detector output 116 is in turn applied to an automatic phase control amplifier 120 which suitably amplifies the signal so that it may control the frequency of the voltage controlled oscillator 126 in the converter 81 . the output signal 121 of the apc amplifier 120 is directly related to the coding signal since the output is a function of the frequency modulation of the carrier of the television signal . thus , in operation , the vco 86 has its frequency varied such that the output 100 from the converter is a constant 61 . 25 mhz . in this manner , the frequency modulation is removed and the coding signal is regenerated at output 121 of the phase lock network 101 . the decoder 80 also includes apparatus responsive to the regenerated coding signal for replacing the scrambling carrier with a regenerated normal carrier during the time intervals in which the carrier phase was altered ( i . e . inverted in the preferred embodiment ). this is accomplished by directing the regenerated coding signal at the amplifier output 121 to a decode logic 122 . the purpose of the decode logic 122 is to reshape the waveform of the output 121 so as to be compatible with the circuitry being driven by the decode logic . for example , in the exemplary embodiment , the output 121 is a low level ( 2mv p - p ) signal , and the decode logic includes multistage high - gain operational amplifier circuitry for generating an output signal of about 5 volts on an output line 126 . the regenerated coding signal on output 126 is sent to a data processing logic 128 which in turn utilizes the information contained or coded onto the regenerated coding signal . in an important aspect of the present invention , the decoder 80 includes means for automatically controlling the gain of the unscrambled television signal . the purpose of this automatic gain control system is to maintain a fixed sync signal level at the decoding summing point since proper decoding depends on the decoding carrier being 180 ° out of phase and 110 % of the signal amplitude . slight errors between the two levels result in a noticeable 30 hz flicker on the decoded signal . as shown in fig3 a decode on - off agc circuit 135 provides an output on line 137 which is combined at a hybrid combiner 138 with the output on line 104 from the gain controlled amplifier 110 . the output 140 of the hybrid combiner 138 is directed at 143 to the tv receiver ( not shown ). the combiner output 140 is also directed to an agc amplifier - detector circuit 142 having an output 144 ranging between 1 to 2 volts depending upon the peak input signal level . this circuit provides an output which is directly related to the peak voltage ( sync amplitude ) during the normal , non - inverted fields . the output 144 of the detector is then applied to an agc sample - hold switch 132 which applies this voltage on an output 146 to the gain control amplifier 110 during normal carrier intervals in response to the logic level signal on line 126 . the logic level on the line 126 which is representative of inverted frames directs the agc detector output 144 through the sample and hold switch 132 onto line 134 to the decode on - off and agc 135 . this signal from detector 142 in turn determines the level of the reference oscillator signal on line 117 that is applied via line 137 to the combiner 138 . the following , together with fig4 describes the operation of a preferred embodiment of the agc sample - hold switch 132 and the decode on - off and agc circuit 135 shown in the block diagram of fig3 . a switch sw2 such as a siliconix type dg181 spdt cmos switch , is used to charge either of pair of capacitors , c1 and c2 , to the peak agc voltage , depending on the logic level derived from the regenerated coding signal on the output 126 of the decode logic 122 . when a &# 34 ; normal &# 34 ; field is being received , the upper switch section is closed and the capacitor c1 charges to the agc voltage which is present on the output 144 from the detector . the time constant of the capacitor c1 and the load resistance of the agc detector ( 120 kω ) ( not shown ) is long enough to completely remove any video components from the output . the agc voltage is buffered by an operational amplifier unity gain follower a1 which has extremely high input impedance . the output of the amplifier a1 is applied via the output 146 to the gain control amplifier 110 ( not shown in fig4 ) and to the inverting input of a high gain differential amplifier a2 . during reception of fields having an inverted carrier , the peak signal level is dependent on modulation level , and cannot be used for developing an agc voltage . however , at the beginning of each inverted field , the regenerated coding signal generates a logic voltage to reverse the switch sw2 . thus , the capacitor c1 is disconnected from the agc detector 142 and its voltage is retained because of the high input impedance of the follower a1 . amplifier a1 continues to apply the &# 34 ; stored &# 34 ; agc voltage to gain control amplifier 110 and to the differential amplifier a2 . the logic closes the lower switch section , connecting the capacitor c2 and the noninverting input of amplifier a2 to the agc detector . the logic also turns off a transistor q2 , and allows a decode level control , resistor r1 , to adjust the amplifier a2 output voltage to some slight negative value . ( during &# 34 ; normal &# 34 ; field reception , the transistor q2 is &# 34 ; on &# 34 ; and a negative input voltage is applied to the amplifier a2 , driving it to positive saturation of nearly + 15 v output . this positive voltage reverse biases the pin diodes in the decode switch sw1 , disconnecting the decode carrier from the combiner 138 . however , the negative output from the amplifier a2 , as set by the resistor r1 , slightly forward biases the pin diodes which are now a current controlled attenuator , and passes the decode carrier from the line 117 to the combiner 138 via the line 137 . the detector 142 now sees a decoded signal with sync at maximum level , and the agc detector charges c2 to the peak signal level . the amplifier a2 wll continue to increase the pin diode forward current and the decode carrier level until the voltage on the capacitor c2 equals the stored voltage across the capacitor cl . thus , the decoded signal is automatically adjusted to equal normal signal levels . should the signal strength vary , the capacitor c1 voltage will change during normal fields , and the differential amplifier a2 will adjust the decode carrier level so c2 voltage again equals the new agc voltage . the following table identifies the various components used in the circuit of fig4 . ______________________________________r1 5 kω r8 56 kω r15 39 kω c5 . 01 μfr2 39 kω r9 10 kω r16 47 kω c6 100 μfr3 47 kω r10 8 . 2 kω r17 1 kω q1 2n3904r4 10 kω r11 330 kω c1 10 μf q2 2n3904r5 10 kω r12 100 ω c2 10 μf a1 1 / 21747r6 100 kω r13 5 . 6 kω c3 100 μf a2 1 / 21747r7 8 . 2 kω r14 5 . 6 kω c4 . 01 μf______________________________________ the embodiments of the present invention are intended to be merely exemplary and those skilled in the art shall be able to make numerous and various modifications of them without departing from the spirit of the present invention . all such modifications and variations are intended to be within the scope of the present invention as defined by the appended claims . | 7 |
fig1 is a block diagram illustrating the outline configuration of a network system 1 of the first example . this network system 1 has a configuration in which a printer 2 - 1 , printer 2 - 2 , printer 2 - 3 ( hereinafter collectively referred to as a “ printer 2 ”), and a personal computer ( hereinafter referred to as a “ pc ”), which serves as a host computer , 3 - 1 , pc 3 - 2 , pc 3 - 3 ( hereinafter collectively referred to as a “ pc 3 ”) are connected to a lan 4 . fig2 is a block diagram illustrating the electrical connection configuration of the printer 2 . this printer 2 embodies the image formation apparatus of the present invention . in this printer 2 , a cpu 11 that carries out various types of calculation , and collectively controls the respective parts , an rom 12 that stores various types of control program to be implemented by the cpu 11 and fixed data , and an ram 13 that provides a working area for the cpu 11 are connected through a bus 14 . to this bus 14 , a printer engine 15 that carries out printing on a sheet , such as a paper , or the like , by a prescribed printing method through a prescribed interface as appropriate , a communication control apparatus 16 that carries out communication to another printer 2 or a pc 3 through the lan 4 providing a network , an operation panel 17 with which a user carries out various types of operation , a liquid crystal display 18 that displays various types of message , and a nonvolatile memory 19 are connected . as the printing method for the printer engine 15 , various printing methods such as the electrophotography method , the ink jet method , and the like , can be applied . hereinbelow , as a unit which embodies the image formation apparatus of the present invention , the printer is used as an example for description . however , the image formation apparatus of the present invention may be adapted to be a digital copying machine , or the like , for embodiment . fig3 is a block diagram illustrating the electrical connection configuration of the pc 3 . in the pc 3 , a cpu 21 which carries out various types of calculation and collectively controls the respective parts , and a memory 22 made up of various types of rom and ram are connected through a bus 23 . to this bus 23 , a magnetic storage apparatus 24 , a communication control apparatus 25 which carries out communication with a printer 2 or another pc 3 through the lan 4 , an input apparatus 26 including a mouse and a keyboard , a display 27 , such as an lcd , or the like , are connected through a prescribed interface as appropriate . in the magnetic storage apparatus 24 , a printer driver 28 , which is an application program being run on a prescribed os , is set up . with the printer driver 28 , the pc 3 is capable of outputting a printing job to the printer 2 , carrying out various types of setting of the printer 2 , and in addition , receiving various commands from the printer 2 . fig4 is a figure illustrating a network address table stored in a nonvolatile memory 19 in the printer 2 , and therein , network addresses for identifying the printer 2 as the communication destination existing on the network are registered . as the network address , for example , the ip ( internet protocol ) address and the mac ( media access control ) address are available . and in fig4 , examples of mac address are given . the network address table as shown in fig4 gives an example of table stored in the nonvolatile memory 19 in the printer 2 - 3 as shown in fig1 , indicating that the mac address of the printer 2 - 1 , printer 2 - 2 existing on the lan 4 is “ xx : xx : xx : xx : xx : 0a ”, “ xx : xx : xx : xx : xx : 0b ”, respectively . thereby , the printer 2 - 3 recognizes the printer 2 - 1 and the printer 2 - 2 existing on the same network . the outline of the processing implemented by the printer 2 will be described next . the printer 2 includes a user registration table as shown in fig5 . fig5 shows restriction information indicating , for each particular user id identifying the user , functions of the printer engine 15 in which the utilization is restricted . herein , the “ restriction information ” specifies the function that the particular user can utilize and the function that the particular user cannot utilize . as such functions , there are “ color printing / black and white printing ”, “ one - sided printing / two - sided printing ”, “ type of pick - up cassette ( in other words , restriction for usable and unusable paper sizes , and paper type )”, and the like . for example , by registering the color printing for a specific user as the restriction information in the user registration table , the specific user is allowed or forbidden to perform the color printing . accordingly , upon receiving the printing job from a user whose user id is registered ( since the user id is incorporated in the printing job by the printer driver 28 , the user can be identified . ), the printer 2 refers to the user registration table and causes the printer engine 15 to perform the printing job within the limitation for the user in the restriction information . for example , the printing job requesting the color printing from a user who is allowed to perform the color printing is allowed to be performed , but the printing job requesting the color printing from a user who is not allow to perform the color printing is cancelled . and , when the printer 2 receives restriction information update data for updating the restriction information from a specific transmission destination , for example , an operational panel 17 , which is a user interface of the printer 2 , or a user having a administrator privilege , the printer 2 refers to a network address table and sends such restriction information update data to other printer 2 . on the other hand , when the printer 2 receives such restriction information updating data from another printer 2 , such restriction information updating data is used to update the user registration table . furthermore , considering that the limitation for usable functions varies depending on the user , the printer 2 refers to the restriction information for each of the users in the user registration table , and sends an image indicating the usable function , in this example , information ( command ) instructing to display an icon to the pc 3 that a user is currently utilizing ( for example , the pc 3 that the user is currently using can be identified , if a network address of the pc 3 that the user with a user id is currently using is registered to the user registration table in association with the user id while the user registration table is updated as necessary ). the printer driver 28 of the pc 3 then displays on the display 27 the icon visually showing the usable functions for each of the printers 2 that the user of the pc 3 can utilize . for example , in fig1 , example icons with a shape of printer are shown , each illustrating , from left to right , that full color printing is possible , that only the gray printing is permitted , and that the plus 1 color printing is permitted . additionally , the icon may visually show the printing cost for processing the printing job for each particular function to be utilized . fig1 provides an example where the printing cost is visually shown by the size of the icons in descending order , from the full color printing , the plus 1 color printing to the gray color printing . as another processing example , when the limitation for the number of printing sheet is included in the restriction information , more specifically , when the number of the printing sheet is limited for each of the users , the following processing is performed . in this case , in the user registration table ( which will be described later in detail with reference to fig5 ), a prescribed function that can be utilized in printing by the printer engine 15 , for example , “ restriction information ”, which is an upper limit for the usable number of the printing sheet , is stored for each of the user id , which is an identifier of each user a , b and c . additionally , in the user register table , a “ user information ”, which is the current value of number of the printing sheets for each of the users , is stored in association with the user id . then , upon receiving a printing job from the user ( since the user id is incorporated in the printing job by the printer driver 28 , the user can be identified ), the printer 2 refers to the user registration table , and causes the printer engine 15 to perform the printing job within the upper limit for such user provided in the “ restriction information ”. in other words , in an example where the number of the printing sheet is limited for each of the users , when the total number in which the number of the printing sheet requested by the printing job is added to the number of the printing sheet in the user information exceeds the upper limit for the restriction information , the printer cancels the printing job . on the other hand , when the total number does not exceeds the upper limit , the printer 2 performs the printing process . when the printer 2 processes the printing job , the user information in the user registration table is updated in accordance with the process of the printing job . for example , in an example where the number of the printing sheet is limited , the user information is updated so as to add the number of the sheet printed by the printing job . then , as is the case with the above description , upon receiving the restriction information update data that updates the restriction information from a prescribed transmission destination , for example , the operation panel 17 , which functions as the user interface of the printer 2 , or the user having the administrator privilege , the printer 2 refers to the network address table ( fig4 ), and sends such restriction information update data to other printer 2 . additionally , when the printer 2 receives such restriction information update data from the other printer 2 , the user registration table is updated based on such restriction information update data . furthermore , when the printer 2 causes the printer engine 15 to perform the printing job , the printer 2 refers to the network address table ( fig4 ), and sends to the other printer 2 the user information update data in which the user information is updated in accordance with the process for such printing job . for example , in an example where the number of printing sheet is limited for each of the users , when the printer prints out five sheets through processing of the printing job , the printer 2 sends that information to the other printer 2 . and , upon receiving the user information update data from the other printer 2 , the printer 2 updates the user registration table on the basis of such user information update data . for example , in an example where the number of the printing sheet is limited for each of the users , when the printer receives the information that five sheets are printed for a specific user , five sheets are added to the user information for the specific user in the user registration table . additionally , the printer 2 refers to the upper limit number of the restriction information and the current number of the user information in the user registration table , and sends an image visually indicating the current number in accordance with the upper limit number , for example , information ( command ) instructing to display an icon , to a pc 3 that is currently used by the user ( for example , if the network address of the pc 3 that the user is currently using is registered to the user registration table in association with the user id while the network address is updated as appropriate , pc 3 that is currently used by the user can be identified .). the printer driver 28 of the pc 3 then displays on the display 27 the icon visually showing the current number in accordance with the upper limit for each of the printers 2 to the user of such pc 3 . the purpose of this display is to indicate the degree of closeness of the current number to the limit number . specifically , the color of the icon becomes gradually lighter as the current number approaches the upper limit number ( fig1 a ). and , the size of the icon becomes gradually smaller as the current number approaches the upper limit number ( fig1 b ), etc . next , more specific examples of processing will be described with reference to flowcharts . the present example of processing is an example in which plural printers 2 ( in this example three printers 2 ) as a whole are enabled to unifiedly limit the number of printing sheets for each particular user . therefore , in the nonvolatile memory 19 in the printer 2 , the user registration table as shown in fig5 that manages the limitation of printing for each of the users is registered . in the user registration table , the “ upper limit value of number of printing sheets ”, which is the “ restriction information ”, and the “ current number of printing sheets ”, which is the “ user information ”, are registered for each particular user id in association with the user id . the “ upper limit value of number of printing sheets ” is the upper limit value of number of sheets in which such user may print out using the respective printers 2 over the time period of one month , for example . and in this example , 50 sheets , 150 sheets , 100 sheets are set for the users a , b , and c , respectively . the “ current number of printing sheets ” is the total number of sheets in which such user prints out using the printers 2 from , for example , the beginning of this month up to now . next , the processing performed by the printer 2 will be described . fig6 is a flowchart illustrating the processing that the printer 2 performs upon reception of a printing job from a user . first , upon receiving a printing job from some user ( yes in step s 1 ), the printer 2 ( the cpu 11 thereof ) acquires the information ( the current job information ) included in that printing job ( the current job ) ( step s 2 ); acquires the current value of number of printing sheets , which is the user information for the user who performs this printing job , from the user registration table as shown in fig5 ( step s 3 ); and re - calculates the user information ( step s 4 ). for example , when the user a performs a printing job requesting for printing of one sheet , the printer 2 extracts the current job information of this one sheet ; acquires the user information , which is the current number of printing sheets of 40 sheets in the example as shown in fig5 ; and re - calculates to obtain the user information with 41 sheets by adding newly requested one sheet to the 40 sheets . as described later , when receiving the updated information of the user information to be registered in the user information table from other printer 2 , the printer 2 stores this updated information . and , the printer 2 determines whether the other printer 2 updates the similar user information ( such updated information is stored in the ram 13 ) ( step s 5 ). when the other printer 2 updates the similar user information ( yes in step s 5 ), the printer 2 again re - calculates the user information ( step s 4 ). for example , in a case where the user information is updated through the printing job performed by the user a and the updated information is stored in the ram 13 in the other printer 2 , when the other printer 2 processes the printing job of five sheets , this five sheets are added to the 41 sheets obtained as a result of the re - calculation in step s 4 described above to obtain the 46 sheets . in this way , when the user information is again re - calculated ( step s 4 ) because the user information is updated ( yes in step s 5 ), or the user information is not updated ( no in step s 5 ), it is determined whether the current job is within the restriction range of the upper limit value of number of printing sheets in the restriction information ( step s 6 ). for example , when , by processing the current job through steps s 4 and s 5 , the number of printing sheets for the user a becomes 46 sheets as described above , since the upper limit value of the number of printing sheets for the user a is 50 sheets , the current job is within the restriction range . when this current job is not within the restriction range of the upper limit value of number of printing sheets ( no in step s 6 ), the user uses up the number of printing sheets approved therefor , the current job is cancelled ( step s 7 ). since , when the current job is within the restriction range of the upper limit value of number of printing sheets ( yes in step s 6 ), the number of printing sheets for the user is within the range approved therefor , the current job may be permitted . then , the user information is updated ( step s 8 ); the user information after the updating is sent to the other printers 2 ( step s 9 ); and the printing processing on the current job is implemented ( step s 10 ). for example , in the example described above , when processing the current job changes the number of printing sheets for the user a into 46 sheets , the current number of printing sheets for the user a in the user registration table is updated to 46 sheets , and the user information that the current number of printing sheets for the user a is 46 sheets is sent to the other printers 2 . when a certain printer 2 updates the user information ( step s 8 ) and sends the user information after the updating to other printer 2 ( step s 9 ), the other printer 2 receiving the data on which the information is updated performs a process . fig7 is a flowchart for the processing performed by this other printer 2 . first , when the printer 2 receives user information updating data ( yes in step s 11 ), it is determined whether the printer 2 is processing the printing job and the user information is not updated ( step s 12 ). in other words , for example , when the printer 2 receives a printing job for printing one sheet from the user a , and it is being processed , the step s 12 gives a determination of yes . in this case , the user information is re - calculated ( step s 13 ). for example , in such a case when the user a has a current number of printing sheets of 40 sheets , and sends a printing job for printing one sheet , and this job is being processed , the printer 2 re - calculates by adding one sheet to the current number of printing sheets of 40 sheets . in this way , when the printer 2 is processing the printing job , and the user information is not updated ( yes in step s 12 ), the user information is re - calculated ( step s 13 ), and otherwise ( no in step s 12 ), the user information is updated without re - calculating the user information ( step s 14 ). specifically , in such a case when the user a has a current number of printing sheets of 40 sheets and sends a printing job for printing one sheet , and this job is being processed , the printer 2 re - calculates by adding one sheet to the current number of printing sheets of 40 sheets . then , if the user information updating data indicates that the user a performs printing of five sheets with other printer 2 , the current number of printing sheets for the user a in the user registration table is updated with 46 sheets by adding five sheets to 41 sheets . and , when the user information is re - calculated ( step s 13 , yes in step s 15 ), the user information is sent to the other printers 2 ( step s 16 ). this process is for informing the other printers 2 that the user information is changed as a result of the printing job being processed by the printer 2 . for example , in the example described above , when the printer 2 receives a printing job for printing one sheet from the user a and this job is processed , the user a sends the user information indicating that printing of one sheet is executed . this user information is stored in the ram 13 in the printer 2 as the sending destination , and whether that user information exists or not is determined at the above - described step s 5 . fig8 is a flowchart of a process in a case when the printer 2 acquires restriction information updating data for updating the upper limit value of number of printing sheets in the restriction information . when the printer 2 acquires the restriction information updating data ( yes in step s 21 ), this restriction information updating data is used to update the restriction information ( step s 22 ). for example , when the upper limit value of number of printing sheets for the user a is 50 sheets in the user registration table , and the printer 2 receives the restriction information updating data for changing it into 60 sheets , the upper limit value of number of printing sheets for the user a in the user registration table is updated to 60 sheets . and , in a case where the restriction information updating data is inputted from the operation panel 17 , which provides the user interface for the printer 2 ( yes in step s 23 ), or in a case where it is inputted by a user having an administrative privilege ( yes in step s 24 ), the restriction information updating data is also sent to the other printers 2 ( step s 25 ). accordingly , the printer 2 that receives the transmission also updates the restriction information ( step s 22 ). when the restriction information updating data is data that is sent from another printer 2 ( no in step s 23 , no in step 24 ), there is no need for notification to the other printers 2 , thus the processing in step s 25 will not be implemented . fig9 is a flowchart of a process that is implemented by the printer 2 when the user information is re - calculated ( step s 4 ) in the above - stated processing in fig6 . in other words , when the user information is re - calculated ( step s 4 ) in the processing in fig6 ( yes in step s 31 ) and the result of the re - calculation is under the upper limit value of number of printing sheets in the restriction information ( yes in step s 32 ), a command is sent to the pc 3 currently utilized by the user who outputs the printing job , for instructing it to display the numerical value as a result of the re - calculation , in other words , an image ( in this example , an icon ) that varies depending upon the current number of printing sheets to the upper limit value of number of printing sheets ( step s 33 ). thereby , the pc 3 displays the icon as specified on the display 27 on the basis of the printer driver 28 . fig1 a shows an example of the icon in this case , which can inform the user that the upper limit value of number of printing sheets is being approached , by gradually thinning the color thereof as the current number of printing sheets approaches the upper limit value of number of printing sheets . in addition , fig1 b illustrates an icon of which size is gradually decreased as the current number of printing sheets approaches the upper limit value of number of printing sheets . besides these , various techniques which visually inform the user that the upper limit value of number of printing sheets is being approached can be considered . the second example is an example for limiting the number of printing sheet for each of the users . in this example , in a case where a user tries to print exceeding its own limit number of printing sheets , and there is a margin in other users for the number of printing sheets to be printed , the printing requested by the user can be performed using the margin while the entire limit number for the group including plural users is maintained . in the second example , the hardware configuration and so on of the network system 1 are the same as those in the first example of the invention , thus the same signs and numerals will be used while a detailed description is omitted . additionally , the network address table is the same as that in fig4 , thus a detailed description is also omitted . fig1 is an explanatory drawing of the user registration table stored in the nonvolatile memory 19 in the second example . in this user registration table , an upper limit value of number of printing sheets , which is restriction information , and a current number of printing sheets , which is user information , are registered for each user id of a user . in the second example , users a , b , c form a group . and in addition to the upper limit value of number of printing sheets for each of the users , a “ total restriction value ”, which is an total upper limit value of printing sheets for all of the users a , b , c , is also registered . the total restriction value is equal to the total value of the upper limit values of number of printing sheets for each of the users a , b , c . additionally , each of the upper limit value of number of printing sheets , which is the restriction information , and the current value of number of printing sheets , which is the user information , is , for example , restriction value for a specific one month . in the printer 2 , a “ user history ” indicating an average value of printing performed in each month in the recent one year , which is obtained from a log of a printing job , for example , in the recent one year for each of the users , is registered in the user registration table . in the example shown in fig1 , the upper limit value of number of printing sheets for the user a is 50 sheets , the current value of number of printing sheets for the same is 45 sheets , and the user history for the same is 50 sheets . and , the total restriction value for the users a , b , and c as a whole is 300 sheets . fig1 and fig1 are flowcharts illustrating the processing which is implemented by the printer 2 upon reception of a printing job from a user . first , when the printing job is acquired from the user ( yes in step s 41 ), the information ( the current job information ) included in the printing job ( the current job ) is acquired ( step s 42 ); the current number of printing sheets , which is the user information for the user who performs the printing job , is acquired from the user registration table as shown in fig1 ( step s 43 ); and it is determined from the user history whether , after execution of the current job , it can be estimated to attain the upper limit value of number of printing sheets in the restriction information within a prescribed period of time can be estimated ( step s 44 ). for example , assuming that the user a requests the printer 2 to execute a printing job of three sheets on the 15th day of a certain month when the current value of number of printing sheets therefor is 45 sheets , “ 48 * 30 / 15 = 96 & gt ; 50 ” is given . and from this trend , the upper limit value of number of printing sheets of 50 sheets will be exceeded up to the end of the month . thus , it can be estimated from the user history information that , after the execution of the current job , the upper limit value in the restriction information is attained within a prescribed period of time ( yes in step s 44 ). in this way , when it can be estimated from the user history information that , after the execution of the current job , the upper limit value in the restriction information is attained within a prescribed period of time ( yes in step s 44 ), a command is sent to the pc 3 which is currently utilized by the user , for causing the display 27 to show a warning display ( step s 45 ). this is for causing the user to refrain from excessive printing . then , the current job information is re - calculated ( step s 46 ). when the current job is within the restriction range of the upper limit value of number of printing sheets , which is the restriction information for the user ( yes in step s 47 ), the current value of number of printing sheets , which is the user information for the user , is updated in the user registration table ( step s 48 ). additionally , in the user registration table , the user history for the user is also updated ( step s 49 ). such updating of the user history is carried out , because processing of the printing job received in step s 41 causes the average value of the actual results of printing for each of the months in the last one year to be changed . when the value of the current job exceeds the restriction range of the upper limit value of number of printing sheets , which is the restriction information for the user ( no in step s 47 ), it is determined whether the result of adding the number of sheets for the current job at this time to the total actual result based on the user history for the grouped users a , b , and c as a whole exceeds the total restriction value ( step s 50 ). for example , in the example in fig1 , from the user history for the users a , b , and c as a whole , the trend is such that printing of 270 sheets per month is executed by three persons in total . even if , to this , the printing job of 5 sheets at this time is added , the value of 300 sheets will not be exceeded , thus the step s 50 gives a determination of no . when a determination of yes is given at the step s 50 , it means that the total restriction value for the grouped users as a whole is exceeded , thus a command is sent to the pc 3 which is being currently utilized by the user , for causing the display 27 to indicate the excess ( step s 51 ). and , the execution of the current job is cancelled ( step s 52 ). when the step s 50 gives a determination of no , it means that , if the current job is processed , the total restriction value for the grouped users as a whole will not be exceeded , thus on the basis of the user history of each of the users , the restriction information for each of the users is re - allocated . first , based on the user history of other users , the number of printing sheets available to print is obtained from the number of printing sheets in which each of the other users can print out ( step s 53 ). for example , when the user a requests the printing job of five sheets under the condition where the upper limit value of number of printing sheets for the user a is 50 sheets and the current value of number of printing sheets for the user a is 48 sheets , three sheets are exceeded from the upper limit value of number of printing sheets for the user a . assuming that the upper limit values of number of printing sheets for the other users b and c are 150 sheets with the user history of 130 sheets and 100 sheets with the user history of 90 sheets , respectively , the margins for the users b and c , which are estimated based on the past trend of the users b and c , are 20 sheets and 10 sheets , respectively . since the ratio is 2 : 1 , it is considered that the exceeded three sheets can be supplied two sheets from the user b , and one sheet from the user c . otherwise , considering “ 1 - 130 / 150 : 1 - 90 / 100 ≈ 13 : 10 ”, the exceeded three sheets can be supplied two sheets from the user b and one sheet from the user c . in this way , after the numbers of printing sheets to be allotted to the other users are determined ( step s 53 ), the user information for the current user is re - calculated ( step s 54 ). in this example , the current value of number of printing sheets for the user a is 48 sheets , and 5 sheets are to be printed , thus the result of the re - calculation will be 53 sheets . additionally , the user information and the restriction information for the current user are updated ( step s 55 ). in this example , the user information and the restriction information for the user a in the user registration table will be updated to 53 sheets , respectively . in this case , the original upper limit value of number of printing sheets for the user is exceeded . thus , the time period for displaying the above - described warning display ( step s 45 ) is altered ( step s 56 ). this makes it possible for the user to more carefully consider whether the subsequent printing is to be executed or not . and , the printing job at this time is reflected to the user history for the current user ( step s 57 ). and , it is determined whether the printing for the current user in the future ( during this month ) is permitted ( step s 58 ). such determination can be made based on the trend of the actual result of the user on the number of printing sheets in the past ; for example , when the re - allocation as described above is successively carried out for the user over three months , permission is not given , and otherwise , it is given . when the printing for the current user is rejected ( no in step s 58 ), a flag indicating that the subsequent printing job for the current user is rejected is erected ( step s 59 ). thereby , a command indicating that the subsequent printing job for the user is rejected is outputted to the pc 3 which is currently utilized by the user ( step s 60 ), and the display 27 is caused to indicate the rejection . additionally , when the printing for the current user is permitted ( yes in step s 58 ), a command for causing the display 27 to indicate the permission is outputted to the pc 3 which is currently utilized by the user ( step s 61 ). and , an upper limit value of number of printing sheets , which provides new restriction information , is calculated for the users other than the current user ( step s 62 ). in the above - described example , two sheets for the user b , and one sheet for the user c have been provided for the user a . thus , the upper limit value of number of printing sheets for the user b is changed from 150 sheets to 148 sheets , while the upper limit value of number of printing sheets for the user c is changed from 100 sheets to 99 sheets . and , with these calculated upper limit values of number of printing sheets in the restriction information , the user registration table is updated ( step s 63 ). after the above - stated processing is implemented , the current value of number of printing sheets , which is the user information for the current user , and the user history are sent to the other printers 2 with reference to the network addresses ( step s 64 ). in the above - described example , the user information after the update , which indicating that the current value of number of printing sheets for the user a is 53 sheets , and the user history after the updating , are sent . the processing implemented by the other printers 2 when this user information is received will be described later with reference to fig1 , while the processing implemented by the other printers 2 when the user history is received will be described later with reference to fig1 . and , it is determined whether the restriction information for each of the grouped users including the current user is re - calculated ( step s 65 ). when the step s 63 is implemented , such re - calculation is carried out ( yes in step s 65 ). thus , the re - calculated restriction information for all the users is sent to the other printers 2 ( step s 66 ). in the above - described example , the information of 53 sheets , 148 sheets , and 99 sheets , which are the upper limit values of number of printing sheets after the updating for the users a , b , and c , respectively , is sent . the processing of the printer 2 when this restriction information is received will be described later with reference to fig1 . after the above - stated processing is implemented , the printing processing by the printer engine 15 is performed ( step s 67 ). fig1 is a flowchart illustrating the processing which is implemented by the printer 2 when a certain printer 2 acquires user information updating data . first , when the printer 2 acquires user information updating data ( yes in step s 71 ), it is determined whether the user information is not yet updated , while the printer 2 is in the process of the printing job ( step s 72 ). in other words , for example , when a printing job for printing out one sheet is received from the user a , and it is being processed , the step s 72 gives a determination of yes . in this case , the user information is re - calculated ( step s 73 ). for example , in such a case when the user a has a current number of printing sheets of 40 sheets , and sends a printing job for printing out one sheet , and this job is being processed , re - calculation for adding one sheet to the current number of printing sheets of 40 sheets is carried out . in this way , when the printer 2 is in the process of the printing job and the user information is not yet updated ( yes in step s 72 ), the user information is re - calculated ( step s 73 ). otherwise ( no in step s 72 ), the user information is updated without re - calculating the user information ( step s 74 ). for example , in such a case when the user a has a current number of printing sheets of 40 sheets and sends a printing job for printing out one sheet , and this job is being processed , re - calculation for adding one sheet to the current number of printing sheets of 40 sheets is carried out . then , if the user information updating data indicates that the user a prints out 5 sheets with another printer 2 , the current number of printing sheets for the user a in the user registration table is updated with 46 sheets as a result of adding 5 sheets to 41 sheets . and , in the case where the user information updating data is inputted from the operation panel 17 , which provides the user interface for the printer 2 ( yes in step s 75 ), or in the case where it is inputted by a user having an administrative privilege ( yes in step s 76 ), or , when user information is re - calculated ( step s 73 , yes in step s 77 ), the user information is sent to the other printers 2 ( step s 78 ). this is for informing the other printers 2 of the user information that is changed as a result of the printing job being processed with the printer 2 . fig1 is a flowchart illustrating the processing which is implemented when the printer 2 acquires restriction information updating data for updating the upper limit value of number of printing sheets in the restriction information . in other words , when the printer 2 acquires restriction information updating data ( yes in step s 81 ), and in the case where the restriction information updating data is inputted from the operation panel 17 , which provides the user interface for the printer 2 , ( yes in step s 82 ), or in the case where it is inputted by a user having an administrative privilege ( yes in step s 83 ), the restriction information in the user registration table is updated with the restriction information updating data ( step s 84 ), and the restriction information updating data is sent to the other printers 2 ( step s 85 ). this is for informing the other printer 2 that the restriction information is changed . when this restriction information is acquired from another printer 2 ( no in step s 83 ), the restriction information in the user registration table is updated with the restriction information updating data ( step s 86 ). fig1 is a flowchart illustrating the processing which is implemented by the printer 2 when the printer 2 acquires a user history from another printer 2 . when the printer 2 acquires a user history from other printer 2 ( yes in step s 91 ), the difference between the user history acquired at this time and the user history held in the user registration table is calculated ( step s 92 ). and , when that difference is included only in the user history acquired at this time ( yes in step s 93 ), and is not included in the existing user history held in the user registration table , the information of the difference is added to or subtracted from the user history held in the existing user registration table ( step s 94 ). for example , if the user history for the user a is 49 sheets , while the user history for the user a acquired at this time is 50 sheets , the 50 sheets as a result of addition of one sheet is adopted as the data to be registered in the user registration table as the user history for the user a . additionally , when the difference is also included in the user history held in the existing user registration table ( no in step s 93 ), the information of the difference based on the user history acquired at this time is added to or subtracted from the user history held in the existing user registration table ( step s 95 ), and , that user history is sent to the other printers 2 ( step s 96 ). this is for informing the other printers 2 that the user history is changed as a result of the printing job being processed with the printer 2 . it should be noted that , in the second example , the processing as shown in fig9 described above is implemented . as is the case with the second example , the third example is also an example in which , even if the upper limit value of number of the printing sheets for the user is exceeded , when there is a margin in the limit value of number of printing sheets for other users , the user can use the margin of the other users to print out , while the total upper limit value of number of printing sheets for all the users in the group is maintained . however , unlike the first and second examples , in the third example , each printer 2 as a whole does not unifiedly limit the number of printing sheets for each user through synchronization of each of the printers 2 . therefore , the processing as described hereinbelow that is implemented by the printer 2 is a processing which is implemented by the individual printer 2 independently of the other printers 2 . in the third example , the hardware configuration , and the like , of the network system 1 are the same as those in the first example of the invention . thus , hereinbelow , the same signs and numerals will be used while a detailed description is omitted . additionally , the network address table is the same as that in fig4 , thus a detailed description is omitted . fig1 and fig2 are flowcharts illustrating the processing which is implemented by the printer 2 in the third example . in the same figure , the steps having the same signs and numerals as those in fig1 and fig1 are the same as those in the second example , thus a detailed description is omitted . it should be noted that , in the third example , the processing as shown in fig9 described above is implemented . the foregoing description of the exemplary embodiments of the present invention is provided for the purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise forms disclosed . obviously , many modifications and variations will be apparent to practitioners skilled in the art . the exemplary embodiments were chosen and described in order to best explain the principles of the invention and its practical applications , thereby enabling others skilled in the art to understand the invention for various embodiments and with the various modifications as are suited to the particular use contemplated . it is intended that the scope of the invention be defined by the following claims and their equivalents . | 6 |
according to this invention the conductive polymers developed herein act as a binder for the silicon particles used for the construction of the negative anode . they are mixed with the silicon nano sized silicon parties in a slurry process , then coated on a substrate such as copper or aluminum and thereafter allowed to dry to form the film electrode . though the silicon particles can range from micron to nano size , the use of nano sized particles is preferred as such results in an electrode material that can better accommodate volume changes . a fabrication method for the synthesis of one embodiment of the binder polymer of this invention is as set forth below . first presented is a means for preparing one of the monomers used in polymer formation , i . e . 2 , 5 - dibromo - 1 , 4 - benzenedicarboxylic acid , a reaction scheme for preparing this monomer illustrated at paragraph [ 0020 ], immediately below . when the benzenedicarboxylic acid staring material has only one ch 3 group , the reaction will end up with only one r = cooch 3 group in the final product . exemplary of a method for forming one of the polymers of this invention is provided with respect to one embodiment , according to the reaction scheme set forth at paragraph [ 0023 ], below . a mixture of 9 , 9 - dioctylfluorene - 2 , 7 - diboronic acid bis ( 1 , 3 - propanediol ) ester ( 0 . 83 g , 1 . 5 mmol ) commercially available from sigma - aldrich company , 2 , 7 - dibromo - 9 - fluorenone ( 0 . 50 g , 1 . 5 mmol ), ( pph 3 ) 4 pd ( 0 ) ( 0 . 085 g , 0 . 07 mmol ) and several drops of aliquat 336 in a mixture of 10 ml of thf ( tetrahydrofuran ) and 4 . 5 ml of 2 m na 2 co 3 solution was refluxed with vigorous stirring for 72 hours under an argon atmosphere . during the polymerization , a brownish solid precipitated out of solution . the solid was collected and purified by soxhlet extraction with acetone as solvent for two days with a yield of 86 %. a mixture of 9 , 9 - dioctylfluorene - 2 , 7 - diboronic acid bis ( 1 , 3 - propanediol ) ester ( 0 . 80 g , 1 . 43 mmol ), 2 , 7 - dibromo - 9 - fluorenone ( 0 . 24 g , 0 . 72 mmol ), methyl 2 , 5 - dibromobenzoate ( 0 . 21 g , 0 . 72 mmol ), ( pph 3 ) 4 pd ( 0 ) ( 0 . 082 g , 0 . 072 mmol ) and several drops of aliquat 336 in a mixture of 13 ml of thf ( tetrahydrofuran ) and 5 ml of 2 m na 2 co 3 solution was refluxed with vigorous stirring for 72 h under an argon atmosphere . after reaction stopped , the solution was concentrated by vacuum evaporation and the polymer was precipitated from methanol . the resulting polymer was further purified by precipitating from methanol twice . the final polymer was collected by suction filtration and dried under vacuum with a yield of 87 %. a mixture of pffomb ( 0 . 36 g ) and koh ( 2 g , 35 mmol ) in 20 ml of thf and 2 ml of h 2 o was refluxed for 48 h under an argon atmosphere . after reaction stopped , the solution was concentrated by vacuum evaporation and polymer was precipitated from methanol . the resulting polymer was suspended in 10 ml of concentrated h 2 so 4 with vigorous stirring for 12 hours . the final product was filtered , washed with water and dried with a yield of 96 %. reaction scheme for forming conductive polymer with — cooch 3 ( pffomb ) and — cooh ( pffoba ) groups on the side chains . it has been found that the presence of — cooh groups serves to increase the bindability of the polymer to the silicon particles of the electrode . in particular , one can position carboxylic acid groups in connection with the 9 th position of fluorene backbone . the below formula depicts the general structure of this type of polymer . wherein x = 0 , x ′ and y =& gt ; 0 , and z & lt ;= 1 , and x ′+ y + z = 1 , r 3 and r 4 can be ( ch 2 ) n cooh , n = 0 - 8 , and r 5 and r 6 can be any combination of h , cooh and cooch 3 . another variation is to adjust the number of cooh groups by copolymerizing x monomer into the main chains as illustrated in the formula shown below . by adjusting the ratio of x : x ′, the number of — cooh groups can be controlled without changing the electronic properties of the conductive binders . exemplary of such a composition is as illustrated below by the following formula . wherein , x , x ′, y & gt ; 0 , and z & lt ;= 1 , with x + x ′+ y + z = 1 . r 1 and r 2 can be ( ch 2 ) n ch 3 , n = 0 - 8 . r 3 and r 4 can be ( ch 2 ) n cooh , n = 0 - 8 . r 5 and r 6 can be any combination of h , cooh and cooch 3 ; and the “ x , x ′” unit is fluorene with either alkyl or alkylcarboxylic acid at the 9 , 9 ′ positions ; the “ y ” unit is fluorenone , the h positions of the back bone of fluorenon and fluorene also can be substituted with functional groups such as cooh , f , cl , br , so 3 h , etc . in still another embodiment , one can increase the flexibility of the polymer by introducing a flexible section between repeating units . this is illustrated as shown below where a flexible chain section such as alkyl or polyethylene can be used to connect a sections together to further improve elasticity , the structure illustrated by the below formula : 0 & lt ;= x , x ′, y and z & lt ;= 1 and x + x ′+ y + z = 1 . r 1 and r 2 can be ( ch 2 ) n ch 3 , n = 0 - 8 , r 3 and r 4 can be ( ch 2 ) n cooh , n = 0 - 8 , r 5 and r 6 can be any combination of h , cooh and cooch 3 . most of the highly conjugated conductive polymers have rigid backbones , and the elasticity of the polymers is low . in order to accommodate volume expansion incurred during the li interacalation and de - intercalation in the alloys , it is important that the conductive polymer binders have certain degree of elasticity . one method to increase flexibility is to synthetically introduce flexible units ( n ) into the polymer system as show above . unit n is a flexible alkyl or polyethylene portion . this flexible unit ( n ) can be one or many of — ch 2 units depending upon the requirements for a particular alloy system , or could be other types of liner units depending on the ease of synthesis . both x , x ′, y and z units could be one or many fluorene or fluorenone units . one possible structure is of a random copolymer with a few percent of flexible units distributed along the fluorene main chain . the r 1 - r 6 units could be either one of the choices , and it is not necessary they be all the same in a polymer chain . increasing the length of the side chains may also have an effect on the flexibility of the polymer binder . therefore , the number of units in r 1 - r 6 is also subject to change during an optimization process . one may change the number of units of the r 1 - r 6 , and look for improved cell cycling performance as indication of optimization . another issue is the stability and impedance of the interface between the active cathode material and electrolyte . the binder may cover ( that is , over - coat ) all the active materials at higher binder loadings . such over - coverage will modify the interface stability and impedance . varying the number of units in r 1 - r 6 will play a significant role in optimizing the charge transfer impedance at the interface . current polymer structures that have been synthesized and tested in lithium ion battery are shown as illustrated by the below . once the conductive polymers have been synthesized they can be mixed with the silicon particles , and coated onto a substrate such as copper and allowed to dry to form the electrode material . a more detailed discussion of electrode preparation is presented below . an advantage of the use of these conductive polymers of the present invention is that they are easily compatible with current slurry processes for making electrodes , thus requiring no special steps or equipment . si / conductive polymer mixtures were made by dissolving 0 . 09 g of the conductive polymer of fig1 ( i . e ., pffoba , wherein r 1 = r 2 =( ch 2 ) 7 ch 3 , r 5 = cooch 3 , r 6 = h , and x = 0 . 5 , x ′= 0 , y = 0 . 175 and z = 0 . 325 )) in 2 . 6 g of chlorobenzene . 0 . 18 g of si was dispersed in the polymer solution to meet the desired si : polymer ratios at 2 : 1 . to ensure the thorough mixing of the si nanoparticles into the polymer solution , a branson 450 sonicator equipped with a solid horn was used . the sonication power was set at 70 %. a continuous sequence of 10 second pulses followed by 30 second rests was used . the sonic dispersion process took about 30 min . all of the mixing processes were performed in ar - filled glove boxes . by way of comparison to the conductive polymers of this invention , illustrated in fig2 and 3 , slurries of ab : pvdf ( acetylene black / polyvinylidene fluoride ) at 0 . 2 : 1 ratios by weight were made by dissolving 5 g of pvdf in to 95 g of nmp to make a 5 % pvdf in nmp solution . proper amounts of ab were dispersed in the pvdf solution to meet the desired ab : pvdf ratios . to ensure the thorough mixing of the ab nanoparticles into the pvdf solution , the branson 450 sonicator equipped with a solid horn was used . the sonication power was set at 70 %. a continuous sequence of 10 s pulses followed by 30 s rests was used . the sonic dispersion process took ca . 30 min . all of the mixing processes were performed in ar - filled glove boxes . 0 . 86 g si was mixed with 7 . 16 g of the conductive glue ( pvdf : ab = 1 : 0 . 2 by weight in 95 % pvdf nmp solution ). to ensure the thorough mixing of the si nanoparticles into the glue solution , the branson 450 sonicator equipped with a solid horn was used . the sonication power was set at 70 %. a continuous sequence of 10 s pulses followed by 30 s rests was used . the sonic dispersion process took about 30 min . all of the mixing processes were performed in ar - filled glove boxes . all electrode laminates were cast onto a 20 μm thick battery - grade cu sheet using a mitutoyo doctor blade and a yoshimitsu seiki vacuum drawdown coater to roughly the same loading per unit area of active material . the films and laminates were first dried under infrared lamps for 1 h until most of the solvent was evaporated and they appeared dried . the films and laminates were further dried at 120 ° c . under 10 − 2 ton dynamic vacuum for 24 h . the film and laminate thicknesses were measured with a mitutoyo micrometer with an accuracy of ± 1 μm . the typical thickness of film is about 20 μm . the electrodes were compressed to 35 % porosity before coin cell assembly using a calender machine from international rolling mill equipped with a continuously adjustable gap . coin cell assembly was performed using standard 2325 coin cell hardware . a 1 . 47 cm diameter disk was punched out from the laminate for use in the coin cell assembly as a working electrode . lithium foil was used in making the counter electrode . the counter electrodes were cut to 1 . 5 cm diameter disks . the working electrode was placed in the center of the outer shell of the coin cell assembly and two drops of 1 m lipf 6 in ec : dec ( 1 : 1 weight ratio ) electrolyte purchased from ferro inc . were added to wet the electrode . a 2 cm diameter of celgard 2400 porous polyethylene separator was placed on top of the working electrode . three more drops of the electrolyte were added to the separator . the counter electrode was placed on the top of the separator . special care was taken to align the counter electrode symmetrically above the working electrode . a stainless steel spacer and a belleville spring were placed on top of the counter electrode . a plastic grommet was placed on top of the outer edge of the electrode assembly and crimp closed with a custom - built crimping machine manufactured by national research council of canada . the entire cell fabrication procedure was done in an ar - atmosphere glove box . the coin cell performance was evaluated in a thermal chamber at 30 ° c . with a maccor series 4000 battery test system . the cycling voltage limits were set at 1 . 0 v at the top of the charge and 0 . 01 v at the end of the discharge . all the starting chemical materials for synthesis of the conductive polymer were purchased from sigma - aldrich . battery - grade ab with an average particle size of 40 nm , a specific surface area of 60 . 4 m 2 / g , and a material density of 1 . 95 g / cm 3 was acquired from denka singapore private ltd . pvdf kf1100 binder with a material density of 1 . 78 g / cm 3 was supplied by kureha , japan anhydrous n - methylpyrrolidone nmp with 50 ppm of water content was purchased from aldrich chemical co . as described above , the conductive polymers of this invention can be used as electrically conductive binders for si nanoparticles electrodes . the electron withdrawing units lowering the lumo level of the conductive polymer make it prone to reduction around 1 v against a lithium reference , and the carboxylic acid groups provide covalent bonding with oh groups on the si surface by forming ester bonds . the alkyls in the main chain provide flexibility for the binder . results of the various tests that were conducted are as reported in the various plots of fig2 - 7 . fig2 shows the new conductive polymer binder in combination with si nanoparticles much improving the capacity retention compared to conventional acetylene black ( ab ) and polyvinylidene difluride ( pvdf ) conductive additive and binder as a control . fig3 illustrates the improved coulombic efficiency of the conductive binder / si electrode of the invention compared with the conventional ab / pvdf approach . fig4 illustrates results showing very similar voltage profiles of the conductive polymer / si electrode to the pure si film type of electrode . fig5 plots the rate performance of the conductive polymer / si electrode of the invention , showing good results . evan at a 10 c rate , there is still more than half of the capacity retention . fig6 illustrates cycleability of the silicon electrode made with the copolymer binder of the invention , which is very good at limited capacity range . there is no capacity fade in 100 cycles at 1200 mah / g and 600 mah / g fixed capacity cycling . fig7 illustrates cycling results for a pffomb binder using an electrolyte comprising 1 . 2 m lipf6 in ec / dec ( ethylene carbonate and diethylene carbonate ) plus 10 % fec ( fluoroethylene carbonate or fluorinated ethylene carbonate ), the fec additive serving as a stabilizer . this invention has been described herein in considerable detail to provide those skilled in the art with information relevant to apply the novel principles and to construct and use such specialized components as are required . however , it is to be understood that the invention can be carried out by different equipment , materials and devices , and that various modifications , both as to the equipment and operating procedures , can be accomplished without departing from the scope of the invention itself . | 7 |
fig1 shows a first exemplary embodiment , for which an outer case 10 is arranged above the conveyor belt 12 , which serves as a transporting means for this embodiment and conveys the substance s to be measured . inside this outer case 10 , an x - ray tube 20 that functions as an excitation source is installed inside a first case 22 . an x - ray beam y r that is directed so as to impinge on a measuring region 14 passes through an exit window 24 in the first case 22 . since the outer case 10 as a rule has relatively thick walls , for example is composed of stainless steel , the case underside is provided with an exit opening 16 for the x - ray radiation . to prevent dust and other particles from entering the inside of the outer case 10 , the exit opening is covered with a window , for example a beryllium film . as a result of this irradiation , x - ray fluorescence radiation y f is generated in the measuring region 14 , which is then measured by the x - ray fluorescence detector 30 that is also located inside the outer case 10 . from the second case 32 of the x - ray fluorescence detector 30 , a first tube 40 extends vertically downward and is open at its lower end . the first tube 40 is connected via a rubber bellows 41 to the second case 32 of the x - ray fluorescence detector 30 , wherein this connection is substantially gastight . the first tube 40 is composed totally or in part of zirconium . the use of an elastic rubber bellows serves to mechanically uncouple the first tube 40 from the x - ray fluorescence detector 30 . this is necessary since most x - ray fluorescence detectors are mechanically relatively sensitive . at its lower end , the first tube 40 is tightly connected to the outer case 10 . the x - ray fluorescence radiation generated in the measuring region 14 travels through the tube opening 42 into the first tube 40 and then travels through this tube to the entrance window 34 , through which it enters the x - ray fluorescence detector 30 . the entrance window 34 in that case can be open or can be covered with a film , for example , depending on the detector used . to prevent dust , ashes , or similar material from absorbing the x - ray fluorescence radiation along its path from the measuring region 14 to the x - ray fluorescence detector 30 , the first tube 40 is flushed with helium . for this , the first tube 40 is provided with a connection 44 , which connects the tube 40 to a helium source 46 that is usefully located outside of the outer case 10 . the connection 44 is preferably located in an upper section of the tube 40 , near the entrance window 34 . the helium flows from the connection 44 into the tube 40 where it flows in downward direction and subsequently leaves the tube 40 through the tube opening 42 . to achieve maximum intensity , the tube diameter should at least match the diameter of the measuring sensitive surface of the detector that is used . the tube preferably has an inside diameter of 10 to 50 mm . a relatively large tube diameter is furthermore important , so that the flushing gas connection can be attached . to reach high flow speeds for the flushing gas at the tube opening , it may be useful to taper the tube toward the tube opening ( fig1 a ). it is furthermore possible to arrange the exit opening 16 immediately adjacent to the tube opening 42 , so that the exit opening 16 can also be flushed with helium . it may be useful in that case to expand the tube 40 toward the tube opening 42 . in particular , it may be favorable in that case to embody the region around the tube opening 42 asymmetrical , such that flushing gas exiting the tube opening 42 is guided in the direction of the exit opening 16 . since helium is considerably lighter than air , a helium column is always present in the tube 40 to prevent air from entering . the use of a helium flushing operation thus has several effects . on the one hand , no window film or only an extremely thin window film is needed at the entrance window 34 of the x - ray fluorescence detector 30 , thereby resulting in a very low absorption by the measuring device itself . on the other hand , it prevents the depositing of dust , ashes , and the like on the window film , as well as the presence of dust , ashes , and the like in a large portion of the beam path for the x - ray fluorescence radiation . this not only reduces the total absorption , but also prevents absorption fluctuations , which could hinder the measuring operation in a manner that it is hard to reproduce . finally , a large portion of the radiation path is free of air , which also contributes to a strong reduction in the total absorption . furthermore , the spectral absorption of some air constituents , for example argon , is strongly reduced in some application cases . this effect can be important , particularly when measuring elements that are located adjacent to the absorbing constituent in the periodic system . with the exemplary embodiment shown in fig1 , it is possible for particles to be deposited on the cover for the exit opening 16 . because of the at least relatively high energy of the x - rays used , this is not very critical with regard to the required intensity , but can still lead to a distortion of the measuring result . in the exemplary embodiment shown in fig2 , the beam path of the exciting x - ray radiation therefore passes through the walls of the first tube 40 . in that case , the first tube 40 can be produced from a material that is pervious to the exciting x - ray radiation . rubber is one example for such a material , wherein rubber furthermore has the advantage of not transmitting vibrations to the x - ray fluorescence detector 30 even without installing a special rubber bellows in - between . a different option is shown in fig2 and consists of providing an opening 48 in the wall of the first tube 40 , through which the exciting x - ray radiation enters the first tube 40 . the opening 48 can be covered with a window , for example a beryllium film , to prevent leakage of the helium through this opening 48 . to minimize the measuring background , the window can also be replaced with a filter , through which only photons above a cutoff energy can travel . to further minimize scattering , an aperture 49 is preferably arranged above the opening 48 , for example an aperture of zirconium . as alternative to the embodiment shown in fig2 , the opening 48 can also be arranged directly adjacent to the tube end , so that it extends in the form of a recess from the open tube end into the tube wall . it is furthermore possible to connect the opening 48 and the exit window 24 of the x - ray tube with an x - ray conductor . the aperture 49 is located directly at the recess or opening 48 and is aligned parallel to the direction of irradiation for the excitation source . with the exemplary embodiment shown in fig3 , not only the largest portion of the beam path for the x - ray fluorescence radiation , but also the largest portion of the exciting x - ray radiation is located inside a helium - flushed tube . according to the exemplary embodiment shown in fig2 , the x - ray radiation coming from the x - ray tube 20 enters through the opening 48 into the first tube 40 . the second tube 50 , which is also connected via a different connection 54 to the helium source 46 , is located between this opening 48 and the exit window 24 in the x - ray tube 20 . as a result , the interfering absorption by air can be prevented in some cases . as an alternative to the embodiment shown in fig3 , it is also conceivable to keep the first and second tube completely separate , as shown in fig4 . to keep the operating costs as low as possible , the tube or tubes should be flushed with helium only during the active measuring operation . according to fig5 , a material sensor 60 that is installed upstream of the measuring region 14 is therefore proposed , which sensor detects whether or not the conveyor belt contains a substance to be measured . the signals from this material sensor 60 are transmitted to the control unit 64 . if no substance is detected on the conveyor belt , then the measurement is ended , if necessary with a time delay , and the valve 47 is closed . to prevent dirt from entering the first tube 40 during the time when no helium flushing takes place , a shutter 62 that is operated by a motor 66 is provided at the tube opening 42 . the shutter closes off the tube end once the valve 47 is closed . if a substance is again detected on the conveyor belt 12 , then the shutter 62 and the valve 47 are opened . as a result , the first tube 40 is pre - flushed , until the substance reaches the measuring region 14 and the measuring operation starts or is continued . the main object of the above - described exemplary embodiments is to reduce the absorption of x - ray fluorescence radiation . to be sure , in most application cases this will be the most important point , but the herein described principle of the “ open gas flushing ” can also be used , for example , exclusively for the beam path of the exciting radiation . | 6 |
in the following detailed description of the present embodiments , reference is made to the accompanying drawings that form a part hereof , and in which is shown by way of illustration specific embodiments in which the invention may be practiced . these embodiments are described in sufficient detail to enable those skilled in the art to practice the invention , and it is to be understood that other embodiments may be utilized and that process , electrical or mechanical changes may be made without departing from the scope of the present invention . the terms wafer or substrate used in the following description includes any base semiconductor structure . examples include silicon - on - sapphire ( sos ) technology , silicon - on - insulator ( soi ) technology , thin film transistor ( tft ) technology , doped and undoped semiconductors , epitaxial layers of a silicon supported by a base semiconductor structure , as well as other semiconductor structures well known to one skilled in the art . furthermore , when reference is made to a wafer or substrate in the following description , previous process steps may have been utilized to form regions / junctions in the base semiconductor structure , and the terms wafer and substrate include the underlying layers containing such regions / junctions . the following detailed description is , therefore , not to be taken in a limiting sense , and the scope of the present invention is defined only by the appended claims and equivalents thereof . the various embodiments of the invention relate to the integration of a logic device and a memory device . memory devices of various embodiments are adapted for communication directly with a logic device across a local bus . memory devices of the various embodiments may include non - buffered devices . the local bus is dedicated to bi - directional communication between the logic device and the memory device . voltages on the local bus are substantially at internal logic levels of the memory device . for one embodiment , the local bus includes a plurality of direct connections between the memory device and the logic device . for a further embodiment , each direct connection of the local bus is a wire bond connection between a bonding pad on the memory device and a bonding pad on the logic device . for an alternate embodiment , each direct connection of the local bus is a solder bump connection between a bonding pad on the memory device and a bonding pad on the logic device . for another embodiment , each direct connection is dedicated to communication exclusively between a single bonding pad or other coupling area on the memory device and a single bonding pad or other coupling area on the logic device . the local bus is distinct and isolated from the system bus . use of a dedicated local bus between a memory device and a logic device facilitates elimination or reduction of buffer circuitry on the memory device . input buffer circuitry adapted for level translation is normally included in a memory device to protect the device from voltage levels of a system bus . output buffer circuitry adapted for high drive and level translation is normally included in a memory device to drive the voltage and load levels of an external system bus . with the memory device isolated from the system bus and the local bus carrying voltage levels substantially at internal logic levels of the memory device , no input buffer circuitry is necessary . furthermore , the dedicated local bus has lower inductive , capacitive and resistive loads , thus reducing the sizing demands on the output buffer circuitry . as used herein , a signal will have a voltage level compatible with internal logic levels of a device if the expected maximum voltage of the signal is substantially equal to or below the highest acceptable voltage level of the internal logic levels of the device . elimination or reduction of buffer circuitry further facilitates semiconductor real estate efficiencies approaching those of a single - chip asic . furthermore , electronic systems containing memory and logic devices in accordance with the various embodiments have lower power consumption than typical multiple - device systems as communication between the memory device and the logic device is at voltage levels substantially at internal logic levels rather than higher system bus levels . while the local bus operates at voltages compatible with internal logic levels of the memory device such that elimination of input buffer circuitry is attainable , it may still be desirable to provide for signal conditioning of one or more of the input signals . such signal conditioning may include matching impedance between the memory device and the logic device to reduce reflections that become increasingly detrimental at higher transmission frequencies . however , without the need for level translation between system bus voltage levels and the memory device logic levels , the input buffer circuitry can make use of smaller transistors adapted for signal conditioning and substantially incapable of level translation . again , the reduction in input buffer size facilitates higher real estate efficiencies . fig2 a illustrates a simplified block diagram of an electronic system 200 a having a memory device 202 a and a logic device 204 a , wherein the memory device 202 a is coupled to the logic device 204 a through a local bus 275 . the memory device 202 a generally includes a memory core block 110 containing the memory cells and sensing circuitry ; a control , logic and interconnect block 112 , and an analog block 114 providing the various internal voltage potentials from the supply potential . the logic device 204 a generally includes a logic core block 116 ; a static random access memory ( sram ) block 118 for caching data between the logic core block 116 and the memory core block 110 ; an input / output ( i / o ) block 120 for interfacing with the system bus 250 ; and often a customer - specific block 122 containing customer - specific functionality . it is noted that the functionality of the sram block 118 may be replaced by what is termed pseudo - static ram . in pseudo - static ram , a dynamic ram ( dram ) array is automatically refreshed in the background such that it appears functionally as an sram array to external devices . this approach allows the use of dram technology in place of sram technology . the memory device 202 a is coupled to the logic device 204 a through a local bus 275 . the local bus 275 contains at least one conductive line for electrical communication of signals between the memory device 202 a and the logic device 204 a . some common examples of conductive lines include wire bond connections and solder bump connections well known in the art . for one embodiment , the local bus 275 may include one line for each address signal , data signal , and control signal communicated between the memory device 202 a and the logic device 204 a . for another embodiment , at least a portion of the signals communicated between the memory device 202 a and the logic device 204 a are multiplexed such that at least one line of the local bus 275 services two or more signals . fig2 b illustrates a functional block diagram of a memory device 202 b coupled to a logic device 204 b of an electronic system 200 b in accordance with one embodiment of the invention . fig2 b provides alternative detail of the memory device to more clearly describe the function of the local bus 275 . the memory device 202 b may , for example , be fabricated as an integrated circuit device on a semiconductor die of a semiconductor wafer . the memory device 202 b includes a memory array 206 . the memory cells ( not shown ) of the memory array 206 may be non - volatile floating - gate memory cells , such as in a flash memory device . row access circuitry 210 and column access circuitry 212 are provided to decode address signals provided on address signal lines a 0 - ax 214 from the local bus 275 . row access circuitry 210 and column access circuitry 212 provide access to the memory cells of the memory array 206 in response to the decoded address signals . an address latch circuit 208 is provided to latch the externally - applied address signals prior to decoding . data output driver circuit 220 is included for outputting data over a plurality of data ( dq ) signal lines 226 to the logic device 204 b across the local bus 275 . a data latch 224 is provided between the dq signal lines 226 and the memory array 206 for storing data values ( to be written to a memory cell ) received on the dq signal lines 226 from the logic device 204 b across the local bus 275 . command control circuit 216 decodes control signals provided on control signal lines 228 from the logic device 204 b across local bus 275 . the control signals are used to control the operations on the memory array 206 , including data read , data write , and erase operations . for one embodiment , the memory device 202 b is a nominally - buffered device . as used herein , a device or signal line will be nominally - buffered if it lacks buffer circuitry adapted for level translation , such as between a system bus level and an internal logic level , yet still permits other buffer circuitry for internal signal conditioning , such as impedance matching . for a further embodiment , the memory device 202 b is a non - buffered device as no input buffer circuitry is coupled to the dq signal lines 226 , the address signal lines 214 or the control signal lines 228 . in a typical memory device , input buffer circuitry for level translation is provided between the dq signal lines 226 and the data latch 224 , between the address signal lines 214 and the address latch circuit 208 , and between the control signal lines 228 and the command control circuit 216 . such level - translating input buffer circuitry is generally included to buffer or protect a device from input voltages that are detrimentally higher than the internal logic levels , such as those that might be utilized across a general - purpose system bus . as communications across the local bus 275 between the memory device 202 b and the logic device 204 b are at voltage levels associated with the internal logic levels of the devices , no input buffering is necessary for protection of the devices . however , as noted previously , impedance matching or other signal conditioning without level translation may be desirable . for one embodiment , at least one dq signal line 226 , at least one address signal line 214 , and / or at least one control signal line 228 is nominally - buffered . for a further embodiment , at least one dq signal line 226 , at least one address signal line 214 and / or at least one control signal line 228 is non - buffered . in addition to a reduction in input buffer circuitry , buffer circuitry of the data output driver circuit 220 may also be reduced . the local bus 275 as described herein has lower inductive , capacitive and resistive loads than a corresponding system bus 250 . as such , the data output driver circuit 220 would be called upon to drive a significantly smaller load . because of the smaller load , smaller output transistors may be used leading to lower power consumption and higher die efficiencies . the memory device 202 b has been simplified to facilitate a basic understanding of the features of the memory . a more detailed understanding of memory device functional components is known to those skilled in the art . fig3 a - 3c are a top , side and bottom view , respectively , of an electronic system 300 as a stacked package or multi - chip module in accordance with one embodiment of the invention . for the electronic system 300 , a logic device 204 is mounted to a memory device 202 . the memory device 202 may further be mounted to a printed circuit board ( pcb ) or other carrier 360 . the memory device 202 and the logic device 204 each have bonding pads or other coupling areas for providing electrical communication to various internal circuitry , such as control signal lines , address signal lines and dq signal lines . the coupling areas 362 of the memory device 202 and the coupling areas 364 of the logic device 204 are depicted as bonding pads . coupling areas 362 are coupled to coupling areas 364 through one or more direct connections 366 . the direct connections 366 collectively make up the local bus . the direct connections 366 are depicted as wire bonds , although other connections are known such as solder bump connections . the direct connections 366 have no intervening devices or other drops between a coupling area 362 of the memory device 202 and its corresponding coupling area 364 of the logic device 204 . advantageously , each direct connection 366 can thus be physically small , having relatively low power dissipation compared to a typical system bus . in general , the length of a typical system bus is at least one order of magnitude greater than the length of the direct connections 366 . for one embodiment , each direct connection 366 is less than about 2 mm in length . for a further embodiment , each direct connection 366 is less than about 1 mm in length . collectively , direct connections 366 form the dedicated local bus between the memory device 202 and the logic device 204 . for one embodiment , the memory device 202 receives an external clock signal and / or power supply potentials from the logic device 204 through the local bus . for another embodiment , the memory device 202 receives an external clock signal and / or power supply potentials through a connection ( not shown ) to the carrier 360 or other external device . the arrangement shown in fig3 a - 3c is particularly advantageous where the logic device 204 is smaller than the memory device 202 , facilitating placement of coupling areas 362 and 364 around the perimeter of each corresponding device . other arrangements are possible for electronic systems in accordance with the invention , including placing the memory device 202 on top of the logic device 204 , mounting the memory device 202 and the logic device 204 on opposite sides of a carrier 360 , and placing the memory device 202 and the logic device 204 substantially in the same plane , either adjoining or laterally spaced apart . in each case , coupling areas 362 and 364 should be accessible to simplify manufacture of the electronic system . fig3 a - 3b further show a portion of coupling areas 364 of the logic device 204 coupled to coupling areas 368 of the carrier 360 through connections 370 . the connections 370 , as with the direct connections 366 , are depicted as wire bonds . such coupling areas 364 may be coupled to a system bus through the connections 370 for communication with external devices or user interfaces , such as a keyboard , buzzer , microphone , speaker , display , etc ., of a wireless communication system . such coupling areas 364 may further receive power supply potentials or other external signals , such as an external clock signal , through such connections 370 . the connections 370 are generally coupled to these external devices , external signals or power supply potentials though external connections 372 , depicted in fig3 b - 3c as solder bump connections . the portion of coupling areas 364 of the logic device 204 coupled to connections 370 is separate and distinct from the portion of coupling areas 364 of the logic device 204 coupled to direct connections 366 . as shown in fig3 b , the electronic system 300 generally incorporates an encapsulant 374 to protect the devices and connections from such things as mechanical shock , harmful atmospheres , and electrical shorts . in electronic systems in accordance with the invention , designers may further eliminate electrostatic discharge ( esd ) protection in the memory device . as an example , in the electronic system 300 of fig3 a - 3b , the memory device 202 is isolated from a system bus by the interposing logic device 204 . furthermore , the direct connections 366 are insulated from external discharges by the encapsulant 374 . thus , the memory device 202 may be devoid of esd protection , relying instead on any esd protection contained in the logic device 204 or on the carrier 360 . with such close integration of a logic device and memory device as described herein , additional embodiments may further eliminate logic functions from the memory device , leaving only the memory array and access circuitry . the high bit - width , high - speed communication facilitated by the dedicated local bus allows use of the logic device to provide all logic functions to the memory device , such as command interpretation and address decoding . in this manner , decoded address signals may be sent from the logic device to the memory device for access of the memory array without further address decoding . similarly , decoded command signals may be sent from the logic device to the memory device for control of operations on the memory array without further command interpretation . memory devices and electronic systems having a memory device and a logic device have been described facilitating increased performance , reduced power consumption and reduced cost . memory devices of the various embodiments are adapted for communication across a dedicated local bus at voltages compatible with internal logic levels , thereby facilitating elimination or reduction of buffer circuitry . the various embodiments facilitate increased performance by supporting increased communication rates and larger word sizes between a memory device and a logic device . the various embodiments facilitate reduced power consumption by lowering voltages for communications between a separate memory device and a separate logic device to levels compatible with internal logic levels of the devices . the various embodiments facilitate reduced cost by allowing the memory portion of an electronic system to be produced using a relatively low - cost memory fabrication technique without detrimental impact on the logic portion of the electronic system , and by reducing semiconductor real estate usage to levels comparable to a single - chip asic device . the various embodiments of the invention and their adaptation for the use of a local bus for communications between a memory device and a logic device provide certain additional advantages . the local bus between the memory device and the logic device is generally orders of magnitude lower in length relative to a system bus , thereby resulting in lower power dissipation through lower resistive losses . in addition to lower power dissipation relative to a system bus , the local bus further provides faster communication rates . the local bus , due to its relative length and lack of intervening devices or drops , will exhibit lower ringing , thereby improving communication reliability and facilitating higher clock frequencies between the memory device and the logic device . the local bus can also provide faster communications through the use of higher levels of parallelism . as an example , an electronic system having a memory device and logic device each supporting a 64 - bit word can utilize a local bus including 64 dq signal lines , despite having a system bus that might be limited to a 16 - bit word . in this manner , the 64 - bit word can be transferred between the memory device and the logic device in a single transfer of 64 bits , rather than four sequential transfers of 16 bits each . by limiting the high - speed communication between a memory device and a logic device to the dedicated local bus , the system bus can be optimized for the relatively lower communication rates necessary for communications between the logic device and external devices or user interfaces . accordingly , the bit width of the system bus may be reduced without detrimentally impacting system performance . the number of connections between the logic device and these external devices and user interfaces via the system bus can also be reduced , thereby reducing the magnitude of buffer circuitry required on the logic device , i . e ., buffer circuitry for level translating can be limited to only those connections of the logic device coupled to the system bus . although specific embodiments have been illustrated and described herein , it will be appreciated by those of ordinary skill in the art that any arrangement that is calculated to achieve the same purpose may be substituted for the specific embodiments shown . many adaptations of the invention will be apparent to those of ordinary skill in the art . accordingly , this application is intended to cover any adaptations or variations of the invention . it is manifestly intended that this invention be limited only by the following claims and equivalents thereof . | 6 |
as shown in fig1 the conventional , preferably water - based coating , is formed by supplying as indicated at 10 the conventional ingredients ( including a carrier ) of the coating composition and adding a super absorbent as indicated at 12 to these ingredients in a mixer 14 wherein the coating ingredients , including the carrier , and the super absorbent are mixed and the super absorbent dispersed and its particle size defined . after the coating ingredients have been mixed and the super absorbent well dispersed throughout the coating , while retaining the particle size of super absorbent elements to produce swelled super absorbent particles the majority of which have a minimum dimension of less least 5 microns . if the particle size of the super absorbent in the coating is less than about 5 microns the resultant finished surface produce by drying of the coating will not be effective to achieve the required properties for printing of the board using conventional printing techniques as applied to uncoated multiply boards . the particle size of the superabsorbant material use must be such that the discrete void spaces left in the coating after the coating is set be in the range of at least 5 microns and preferably less than 100 microns . generally any suitable super absorbent material that swells significantly by absorption of the carrier and the shrinks substantially when the carrier is driven off is useable so that it tends to form a layer in the cavity formed , however super absorbent polyacrylates have been found particularly suitable . in particular a super absorbent formed of 100 % sodium polyacrylate in the form of a dry white powder or latex emulsion have been found to possess the required particle size and degree of swelling when saturated with water as the carrier in the coating composition . the viscosity of the coatings that were tried and were effective were noted to be significantly different from those that were not effective , as shown in fig2 wherein the viscosities of same basic coating formulations but containing different absorbents are shown . super absorbents a ( a dry powder type ) and b ( a latex type ) were the only ones found to perform satisfactory . the latex type had more uniform size and a greater number of smaller particles than the dry powder type . these measurements indicate that the superabsorbant containing coating should have a brookfield viscosity of at least about 500 cp when measured with a # 4 spindle operated at 30 rpm . in the tests reported in fig2 the carrier in the coating was water , the coating contained 40 % solids , and there were 1 . 5 parts of super absorbent ( based on 100 parts of pigment ). the blank sample is the base formulation without any super absorbant added . it is important that the swelled particle size or void size produced in the coating have a minimum dimension of at least 5 microns and preferably 10 to 60 microns . preferably this minimum dimension will not exceed 100 microns . if the swelled particle size is too large the rheology of the coating formulation will be adversely affected and coating uniformity will be affected . the swelled particles are generally spherical and thus the minimum and a maximum dimension of the swelled particles will be about the same . generally the super absorbent will be present in the coating formulation in the amount of between about 0 . 5 and 10 % w / w based on the dry solids in the coating . more preferably the super absorbent will be present in the range of between 0 . 5 and 3 %. in any event , once the coating has been properly mixed and the super absorbent dispersed therein as indicated at 14 , the coating is applied to coat a substrate as indicated at 16 . the amount of coating applied to the substrate will be any reasonable amount of coating as is normally used in coating board , but preferably the coating will be applied in the amount of 10 to 100 gm / m 2 , preferably about 15 to 25 gm / m 2 . after the carrier held by the super absorbent polymer has been driven off , the material or the coated board or substrate may then be printed as indicated at 22 . the type of coating apparatus used may be any suitable system such as an air knife coater or a rod type coater . the coating is then partially set as indicated at 18 and the carrier absorbed in the super absorbent material is then driven off as indicated at 20 after the coating has sufficiently set so that the void area formed by the driving off of the carrier obtained by the super absorbent material results in the formation of voids within the coating . it will be apparent that the super absorbent material tends to hold or retain the carrier and thus the carrier associated with the elements of the coating tends to be driven off or freed from these other elements before it is released by the super absorbent material , the net effect being that sufficient gelling or setting of the coating occurs before significant amount of the carrier ( water ) absorbed by the super absorbent material is released . the delayed release of this bound carrier forms voids within the coating and produces a significantly rougher surface on the coating and generally a more porous coated board as compared to that normally obtained when conventional coatings are applied . the coated surface may then be printed as indicated at 22 or converted as indicated at 24 and then printed as indicated at 22 . generally , the surface of the coating , when used to simulate a multiply matte white board , i . e . a linerboard having a layer of bleached pulp on its surface will have a ratio of sheffield smoothness ( ss ) to a parker print surf ( pps ), smoothness as illustrated in fig5 such that at a ss of at 290 ml / min the surface will have a pps of at least 6 . 5 pps units and at a ss of 330 ml / min a pps of at least 7 ( see fig5 ). the resultant product as indicated in photomicrograph of fig3 comprises a substrate 24 and a coating 26 . the line 25 has been added to the photomicrograph of fig3 to show the line of demarcation between the coating 26 and the substrate 24 . the coating is formed with a plurality of voids schematically indicated at 28 , many of which are adjacent to and exposed on the surface 30 thereby to form cavities 32 opening to the exposed surface 30 . these voids 28 ( and cavities 30 ) define the roughness of the surface 30 and are a major factor in determining the porosity of the coating 26 . fig4 is a photomicrograph showing a plan view of a portion of the surface 30 with cavities 32 showing as black spots on the surface . the porosity of the coated board is believed to be a significant property facilitating effective priming of the coated board . generally , the gurley porosity of the coated board should be less than about 3 , 500 sec / 100 ml preferably less than 3 , 000 se ./ 100 ml and most preferably less than 2 , 500 sec / 100 ml . the print length , as will be shown by the examples hereinbelow , will preferably be less than 12 cm and more preferably less than 10 . 5 cm measured on an mb print indicator . in printing the rate of absorption of the ink carrier into the substrate , i . e . perpendicular to the surface of the substrate , is important to the printing operation and to the quality of the printing as is the amount of lateral diffusion of the ink carrier along the surface of the substrate , i . e . parallel to the surface of the substrate . generally the former should be rapid and the later should be minimized for the best quality of printing . it is believed that the presence of the redried super absorbent in the pockets or voids in the coating increases the rate of ink carrier absorption directly into the substrate in a direction substantially perpendicular to the surface of the substrate thereby to increase absorption of carrier in a direction perpendicular to the surface which decreases the tendency for lateral diffusion of the carried along the surface . this increase in the rate of absorption perpendicular to the surface of the substrate also may reduce the amount of conventional drying required to dry the coating . in the following examples 1 to 7 a paper substrate ( 42 # unbleached linerboard ) was coated on one side only ( top side ) at a speed of 1000 fpm . the paper so coated was dried using a combination of infra red ( ir ) and heated air dryers . the dried coated papers produced has coat weights ranging from 6 to 45 g / m 2 . samples of the dried coated papers were conditioned in accordance with tappi standard t - 402 for a minimum of 12 hours . surface properties of the samples were evaluated in accordance with tappi standards ( when applicable ). tests included brightness ( t - 452 ), sheffield smoothness ( t - 538 ), and parker prim surface ( hard backing , 20 psi air pressure ). a series of bent blade coating trials was performed using an aqueous coating composition prepared by blending the following ingredients by weight : no void structure was observed when samples were examined under a microscope . 5 . cmc - 0 . 3 parts water added to total solids of 66 % a grooved rod metering device was used instead of a bent blade . no void structure was observed when samples were examined under a microscope . a grooved rod coating trial on commercial equipment using a commercial aqueous coating formulation supplied by michaelman . no void structure was observed when samples were examined under a microscope . the coated linerboard so produced was converted into a double face board , the coated linerboard being incorporated at the double backer as the outside linerboard . sheets were then primed and converted to boxes on a flexo - folder - gluer at the same time as sheets incorporating a mottled white linerboard in the outside linerboard position were being converted and printed . the samples incorporating the coated linerboard had poor print quality to due tracking and smearing of ink ( poor ink strike - in ) and to a high percentage (& gt ; 50 %) of bar code scan failures . rod coating trials were performed on commercial equipment using a coating formulation as recommended by the owner of the commercial equipment . the same coating formulation was applied using two different grooved rods . no void structure was observed when samples were examined under a microscope . the coated linerboard was converted into a double face board , the coated linerboard being incorporated at the double backer as the outside linerboard . sheets were then primed and converted to boxes on a three color press followed by a flat bed die cutter . a mottled white linerboard was converted and printed in an identical manner . samples incorporating the coated linerboard had poor print quality due to a high percentage (& gt ; 50 %) of bar code scan failures and to unacceptable print mottle in the solid print area . print mottle was measured as the standard deviation in print density for the solid primed areas , see table i . commercial coating trials at a custom coating facility using a bent blade ( precoat ) followed by an air knife and a commercial coating formulation . no void structure was observed when samples were examined under a microscope . the coated linerboard was converted into a double face board , the coated linerboard being incorporated at the double backer as the outside linerboard . sheets were then printed and converted to boxes on a flexo - folder - gluer . the samples incorporating the coated linerboard had poor print quality to due tracking and smearing of ink ( poor ink strike - in ) and to poor trapping of the yellow color by the black color . the same equipment and process conditions as example 4 except for the use of a dry powder sodium polyacrylate super absorbent polymer as the superabsorbant . the coated linerboard was converted and printed as in sample 5 . acceptable print quality was obtained . there was limited tracking and smearing of the ink . the yellow ink was trapped by the black . the printed images were also much more clearly defined in comparison to example 5 . commercial air knife coating using the same equipment as in example 5 except for no bent blade precoat . identical coating formulation as in example 6 . a similar pps to sheffield relationship to example 6 was obtained ( see fig5 ). a void structure in the coating was observed when the samples were examined under the microscope . coated linerboard was converted and printed similarly to example 4 . print quality equivalent to a mottled white linerboard was obtained . print mottle was comparable . table i______________________________________example liner tested print mottle (%) ______________________________________4 mottled white 1 . 44 coated board 4 . 27 mottled white 1 . 67 coated board 1 . 6______________________________________ as demonstrated in fig5 the parker print versus sheffield smoothness measurements for formulation 6 and 7 is similar to uncoated linerboard and is significantly different from example 1 through example 5 . a void structure in these coatings was observed when the samples were examined under the microscope . fig6 shows the ink drawdown measurements made on an mb print indicator for the products produced in examples 1 to 7 and for comparison similar test on the uncoated base stock and a typical mottled white board . it is apparent that the two examples that were successful had print lengths of less than 9 cm ; the product they are intended to replace had a print length of 10 . 4 and those that were unsuccessful had print lengths significantly longer than 12 cm indicating that print lengths less than about 12 may still produce the required result and that print lengths less than about 10 . 5 are preferred . test were conducted on two different boards , the first having a basis weight of 38 gm / m 2 and the second a basis weight of 69 gm / m 2 . the first and second boards had porosities before coating respectively of less than 66 sec / 100 ml and less than 28 sec / 100 ml and porosities after coating using a coating formulated in accordance with the present invention respectively of less than 2000 sec / 100 ml and 1000 sec / 100 ml . when the first board was coated with conventional coatings its porosity was greater than 4800 sec / 100 ml . it has been found that for a brighter product or to reduce the coat weight applied , titanium may be substituted for some of the delaminated clay . having described the invention , modifications will be evident to those skilled in the art without departing from the scope of the invention as defined in the appended claims . | 8 |
referring now to fig1 a block diagram of a typical plural printed document assembly apparatus is shown generally at 10 . assembly 10 includes a long conveyor 12 and 14 advancing signatures which are integrated and bound by binder 15 to form magazines , brochures or the like . several onserts or &# 34 ; tip - ons &# 34 ;, such as advertising material or leaflets , can be selectively added to the magazine along the way , as disclosed in the previously referenced patent to the assignee of the present invention . thereafter , the magazine and the onserts may be assembled together into a polybagger in preparation of mailing to a subscriber , or the like . this assembly is well known in the art . a plurality of ink - jet printers 16 print custom and personalized messages for the intended recipient on the signatures or the bound item as it passes , such as on an inside cover of a magazine . these printers 16 are controlled by a respective controller 18 located in a control room 20 located remote from the assembly apparatus , as will be discussed shortly . each of controllers 18 is controlled by binder real - time controller ( brtc ) 21 , this controller monitoring and controlling all i / o devices of assembly 10 . an ibm - pc ® 23 is also connected to controller 21 for allowing data input and additional data processing . a communication interface 22 , according to the preferred embodiment of the present invention comprises one line driver / receiver module 26 provided proximate each printer 16 , and one line driver / receiver module 24 is provided proximate each controller 18 in the control room 20 . interface 22 insures necessary control signals and data can be reliably transmitted therebetween up to distances of 1 , 000 feet . referring now to fig2 a schematic block diagram of communication interface 22 is shown . communication interface 22 interfaces data and control signals transmitted between the remotely located controllers 18 and printers 16 provided along the assembly conveyor 12 and 14 . printer controllers 18 are preferably comprised of an ektajet controller , model number ips 2000 upi and manufactured by ips printing systems limited of zofingen , switzerland . printers 16 are preferably comprised of a kodak ektajet 5000 printer manufactured by the kodak corporation . communication interface 20 is seen to include a plurality of communication line driver / receiver modules 24 , and a plurality of communication line driver / receiver modules 26 . line driver / receiver module 24 drives and receives both serial data and control signals at a respective printer controller 18 . a nine conductor cable 30 communicates the data and control signals from controller connector p1 to connector j1 of module 24 in a one - to - one pin connection . a separate cable 32 communicates encoder control signals from encoder p2 to connector j2 of module 24 . connector p1 is connected to an appropriate dynapar optical encoder 35 . again , these encoders monitor the conveyor 12 or 14 adjacent the particular printer 16 ( see fig1 ). the respective pin assignments are shown in fig2 . the data and control signals are amplified and buffered by line driver / receiver module 24 and outputted at connector p3 . these signals are then communicated via a long twisted - pair cable 36 to connector p4 of line driver / receiver module 26 . cable 36 is comprised of a plurality of twisted pair lines , each line being shielded and having a length of approximately 150 feet , but may extend up to 1000 feet . line driver / receiver module 26 amplifies and buffers these signals , and outputs these signals on respective connectors p5 and p6 . a multiconductor cable 40 communicates these control signals between connector p5 and connector p1 of printer 16 , and a two conductor cable 42 communicates control signals between module connector p6 and connector p2 of printer 16 . communication interface 22 is electrically transparent to both controller 18 and printer 16 , yet allows the data and control signals to be communicated for distances exceeding 150 feet . modules 24 and 26 provide for data to be communicated therethrough at high speeds , without creating data errors . in addition , the proprietary data format implemented by controller 18 and printer 16 is maintained since there is no format conversion of the data or control signals . line driver / receiver module 24 is positioned closely proximate respective controller 18 in the control room 20 , and communication line driver / receiver module 26 is located closely proximate respective printer 16 in the assembly area . the extended cable 36 is neatly located in cable trays ( not shown ) extending between the control room 20 and printers 16 , along with other cables extending therebetween so that the equipment can be remotely controlled from the control room . for proper operation of printer 16 by controller 18 , an additional 25 pin connector p8 of controller 18 needs to be connected to connector p9 of printer 16 . this is done by providing a 25 conductor cable 70 between connector p8 and connector p10 of a parallel line driver module 72 . module 72 converts parallel data to serial data . this module 72 is well known in the art , and is preferably identified as model number pl321a - r2 manufactured by the black box corporation if pittsburgh , pa . a parallel line receiver module 74 is provided at communication module 26 , and converts serial data back to parallel data . this device is also manufactured by the black box corporation and is preferably identified as part number pl322a - r2 . a cable 76 having a pair of twisted lines communicates the serial data between module 72 and module 74 , these connections being provided in a one - to - one pin connection . a standard 25 conductor cable 78 interfaces this data between connector p11 of module 74 and connector p9 of printer 16 . in summary , the signals communicated from connector p8 of controller 18 to connector p9 of printer 16 are converted from parallel to serial format , communicated via a 150 foot twisted pair cable 76 , and then converted back to parallel data and communicated to connector p9 of printer 16 . data is serially communicated over cable 76 such that the data can be shielded , thus , it will be less sensitive to ambient noise . referring now to fig3 a detailed electrical schematic diagram of one communication line driver / receiver module 24 is shown . data and control signals necessary to coordinate controller 18 with printer 16 are seen to be communicated between connectors j1 and j2 and output connector p3 via a plurality of integrated circuits . a tacho signal is a string of pulses generated by the separate dynapar optical encoder 35 ( see fig1 and 2 ) connected to connector j2 via cable 32 . these optical encoders 35 are directly coupled to and monitor conveyors 12 and 14 , and generate 480 reference pulses for every inch of belt travel . this signal is also referred to as the encoder signal , and is connected to the appropriate controller 18 at connector j1 , and also sent to the appropriate printer 16 . the pdi signal is a signal generated by an optical photo - eye 34 ( see fig1 ), one being located at the beginning of the conveyor 12 , and one at the beginning of conveyor 14 . this pdi signal is asserted when a document ( signature ) leading edge is present , and is commonly referred to as a label demand . this photo - eye is coupled to the brtc 21 , and also to appropriate controllers 18 , in a well - known manner , with the pdi signal then being provided to printer 16 . the brtc 21 and controller 18 count the reference tacho ( encoder ) pulses after the pdi signal is detected as asserted . since the printer locations ( distances ) relative to the appropriate photo - eye 34 is known , counting pulses ( each pulse corresponding to a known unit length ) allows the location of a document under a printer 16 to be determined and known at all times by the controller . printing or stroking the document is controlled in a closed - loop knowing the document location , with appropriate data signals being transmitted via cable 76 in a well - known manner . an rts ( status ) signal is generated by the printer 16 , and is asserted when the printer is ready to receive the instructions . this signal is communicated back to controller 18 . the tacho control signal is seen to be communicated from pin 6 of connector j1 and pin 3 of connector j2 to pin 7 of line driver microcircuit u1 . the pdi signal is communicated from pin 7 of connector j1 to pin 1 of microcircuit u1 . the tacho signal is output on pin 6 of chip u1 and communicated to pin 4 of connector p3 . the pdi signal is output on pin 2 of microcircuit u1 and communicated to pin 3 of connector p3 . the rts ( pok ) control signal received by module 24 , from printer 16 , on pin 1 of connector p3 . this control signal is communicated to pin 2 of line receiver microcircuit u2 . this signal is output on pin 3 of microcircuit u2 and communicated to pin 11 of voltage doubler microcircuit u3 . this signal is buffered , inverted , reduced from a + 10 volt high to a + 5 volt high , output on pin 14 of microcircuit u3 , and communicated to pin 4 of connector p1 . voltage doubler microcircuit u3 is implemented in addition to line receiver microcircuit u2 to maintain a high signal to noise ratio , and to convert a + 10 volt signal to 5 volts before communicated to connector j1 . the rts signal is sent to module 24 as a 10 volt high signal by module 26 , as will be discussed shortly . each of the rts , pdi , and tacho signals are all connected to an led circuit so one can visually ascertain that signals are being transmitted between the connectors of the module . specifically , the rts signal outputted on pin 3 of microcircuit u2 is also communicated through an inverting buffer microcircuit u4 , and then via a pull down resister r1 to the cathode of led d1 , this led being pulled high at the anode . therefore , when the rts data signal goes high , it will be inverted by chip u4 causing led d1 conduct and illuminate . similarly , the pdi data line is connected from pin 1 of microcircuit u1 to microcircuit u5 where it is buffered and inverted , and then connected via pull down resister r2 to the cathode of led d2 . when a high pdi signal is being sent , led d2 will illuminate as well . likewise , the tacho control signal is communicated from pin 7 of microcircuit u1 to microcircuit u6 , where it is inverted , buffered , and tied via pull down resister r3 to the cathode of led d3 . the ground signal for interface module 24 is provided from pin 1 of connector j1 , and the vcc + 5 volt signal is provided from pin 9 of connector j1 . this ground signal provides a reference for line driver microcircuit u1 and line receiver microcircuit u2 , this ground also being provided to pins 6 , 7 , 8 , and 9 of connector p3 . referring now to fig4 a detailed schematic diagram of one communication line driver / receiver module 26 is shown . control signals are seen to be received from cable 36 at connector p4 . the tacho signal is seen to be received at , and communicated from , connector p4 pin 4 to pin 6 of line receiver microcircuit u7 . the pdi ( cue - in ) signal is seen to be received at , and communicated from , pin 3 of connector p4 to pin 2 of line receiver microcircuit u7 . the tacho control signal is output from microcircuit u7 pin 5 and communicated to pin 3 of connector p5 . the pdi ( cue - in ) signal is output from pin 3 of microcircuit u7 to pin 6 of connector p5 . the rts signal , which is generated by printer 16 , is communicated from pin 19 of connector p6 to pin 13 of voltage doubler microcircuit u8 . this signal is buffered and inverted , and then an output on pin 12 . this rts signal is then communicated to pin 1 of line driver microcircuit u9 , output on pin 2 , and communicated to pin 1 of connector p4 . microcircuit u8 also doubles a 5 volt &# 34 ; high &# 34 ; signal to 10 volt before it is sent to connector p4 , and communicated via cable 36 to communication interface module 24 . as previously mentioned , this rts signal is inverted by microcircuit u3 of interface module 24 , and also reduced from a + 10 volt &# 34 ; high &# 34 ; potential to a + 5 volt potential . microcircuit u8 , in combination with microcircuit u3 , insures that the rts signal transmitted between interface 24 and 26 has a high signal to noise ratio by sending a 10 volt &# 34 ; high &# 34 ; signal rather than a 5 volt signal , and shielding this signal with ground . however , the signal is ultimately converted back to 5 volts before being communicated to controller 18 . each of the pdi , tacho and rts signals are coupled to a respective led d4 , d5 , and d6 via a buffer and inverting microcircuit u10 , u11 and u12 , respectively . thus again , one can visually ascertain that each of these signals is being transmitted through communication module 26 . preferably , line driver microcircuits u1 and u7 are identified as part number 75174 and manufactured by texas instruments . line receiver microcircuits u2 and u7 are identified as part number 75175 , also manufactured by texas instruments . voltage doubler microcircuits u3 and u8 are preferably identified as part number tc232 and manufactured by national semiconductor . finally , the buffer / inverter microcircuits u4 - u6 and u10 - u12 are identified as part number 4940 , manufactured by national semiconductor . this invention has been described herein in considerable detail in order to comply with the patent statutes and to provide those skilled in the art with the information needed to apply the novel principles and to construct and use such specialized components as are required . however , it is to be understood that the invention can be carried out by specifically different equipment and devices , and that various modifications , both as to the equipment details and operating procedures , can be accomplished without departing from the scope of the invention itself . | 1 |
as best illustrated in fig1 and 2 a preferred embodiment of the chimney damper 10 comprises a frame 20 having a peripheral lip extending along a edge thereof for mounting to a brick or concrete or metal flue pipe or chimney . a flange of skirt 25 extends from the peripheral edge of the frame 20 connecting to a short cylindrical base 23 extending upward therefrom sized in accordance with the flue pipe . the damper frame 20 includes an open window area 21 that is selectively opened and closed by moving a cap 30 upward or downward respectively away from and toward the frame 20 . as shown , frame 20 has a peripheral flange 24 configured to fit onto a square flue . the cap 30 is connected to a disk or plate 46 by a screw 34 extending from the bottom surface of the cap 30 which is inserted through a center hole of the plate and secured there through by a nut 32 . the plate or disk 46 is connected to frame 20 by a plurality of spring means 40 which are attached to the sides or bottom of the plate 46 and to the short cylindrical base 23 extending upward from a flange or skirt 25 adapted for connecting the peripheral frame 24 to the base 46 in order to biase the cap to it &# 39 ; s open position . the cylindrical base 23 , shirt 25 and peripheral frame 24 can be formed as individual members affixed together by welding , rivets , screws , or a friction fit ; however , the unit can easily be formed as an integral one piece design from a pressed or molded part . as shown in fig3 and 5 , cap 30 has been removed from disk 46 . spring means comprises a plurality of torsion springs 40 . as shown in the preferred embodiment four wire torsion springs 40 are employed , each one consisting of three arm portions 41 , 42 , 43 and a coiled portion 44 at one end . the arm portion 43 of the spring 40 is pivotally anchored to frame base 23 by a coiled portion 44 . the coiled portion 44 is held by a pin 22 secured to frame base 23 and projects into an open window area 21 . the coiled portion 44 of the spring 40 is held between two washers 60 . bracket 56 is fastened to frame 20 by pins 22 and 62 . lug 58 on bracket 56 acts as a stop for arm 43 preventing it from rotating up to a perpendicular attitude when damper 10 is open . therefore , lug 58 keeps arm portion 43 biased toward a closing attitude so that when the plate 46 and cap 30 is first urged toward frame 20 , it starts smoothly rotating in a controlled manner in a clockwise direction as viewed from above . the spring means 40 comprises four equal spaced wire springs 41 each having one of the opposite ends thereof fitting into an elongate sleeve secured to an inside corner of the frame base 23 and a stub leg at the other end that projects into and passes though a hole and is pivotally connected to a plate 46 . means for holding such as a ‘ c ’- clip ( or pressed on tight fit washer or the like ) on the outer end of the leg such as is illustrated in fig4 , keeps the leg and coupling inter - connected . an enlargement at the end such as a cap nut or the like retains the post on the cap member and a loose connection allows the post to oscillate during opening and closing of the damper . the other end of the post has the previously described through hole transverse to the axis of the post or alternatively a slot into which the end of the spring can project and loop around a pin . the wire springs bend and lie between the cap 30 and frame base 23 when the damper is in it &# 39 ; s closed state . to accomplish this it is necessary for the plate 46 to rotate a partial turn , ( approximately one quarter turn ), relative to the frame . the cap is mounted on the plate 46 by a coupling means and allowed to rotate with the plate 46 ; however , the cap 30 can be prevented from rotating with the plate 46 by use of a rotation preventing link connecting at one end thereof to the frame base 23 and at the other end to the coupling means . use of a biasing mechanism to prevent rotation of the cap 30 with respect to the plate 46 of the chimney damper 10 provides an embodiment suitable for use with rectangular chimney openings . moreover , the device can be modified for use with hexagonal , octagonal or other unusually shaped chimney openings . opening and closing the damper is accomplished by rotation of the plate 46 and compression of the springs and lowering the cap toward the frame base 23 . the pin 64 is attached to the bottom surface of the plate 46 . the cable 68 is attached to the pin 64 at its upper free end and extends down through the flue and into the upper fireplace where a handle 66 is connected at its lower free end . thus , a user can pull handle 66 to close or reduce the volume of the damper 10 . in its open position , when damper 10 is closed by pulling handle 66 , the arms 43 will be urged in a downward direction from a near vertical position toward a horizontal position which causes the plate 46 to rotate in a clockwise position and cap descend toward the frame base 23 . the cap may optionally utilize a seal means for example maybe a “ u ”- shape rubber , or the like gasket member 27 that fits onto the upper edge of the flange at the top of the frame base 23 . it provides sealing contact with the under face of the cap when the latter is in it &# 39 ; s closed position covering the open window of the frame . obviously the gasket could be made of suitable material such as graphite , silicon , soft metal , or synthetic polymer materials to withstand heat that would be encountered even when a chimney fire occurs . it is contemplated that cable 68 could be replaced with a chain , rod or any other attachment means appropriate for pulling cap 30 toward frame 20 . as shown best in fig3 , the spring arm portion 43 forms an approximate right angle to the torsion arm portion 42 . it is not necessary that this be a right angle , but it must be an angle that allows rotating arm 43 to twist and therefore apply a torque to arm portion 42 . likewise , torsion arm portion 42 forms an approximate right angle with stop arm portion 41 . and similarly , it is not necessary that this be a right angle , but it must be an angle that allows arm portion 41 to prevent torsion arm portion 42 from turning freely . arm portions 42 and 43 of spring 40 are pivotally attached to the plate 46 by a block 53 disposed on the upper surface close to the outer edge along the periphery of the plate . each one of the arm portions 42 and arm portions 41 are attached to a respective block 51 evenly spaced apart from one another along the periphery of the plate 46 . as the pin 64 is pulled toward frame 20 , arm 43 is rotated toward frame 20 because coil portion 44 rotates around pin 22 . this rotating motion causes torsion arm portion 42 to twist because arm portion 41 prevents arm 42 from rotating in blocks 51 and 53 . therefore a torsion effect is realized within arm portion 42 , which acts as a torsion spring . it is contemplated that blocks 51 - 54 may be replace with u - brackets , eyelets screws or any other suitable means that can pivotally attach spring portions 41 - 43 to disk 46 . as shown in fig4 , all four springs 40 react in the same way and therefore guide disk 46 and cap 30 down to frame 20 in a rotating manner . other embodiments could use three , five or more evenly spaced torsion springs to bias the cap assembly above the frame . also , note that with the torsion springs evenly spaced and pivotally connected to the frame as shown , no other guiding means is necessary . the springs keep the damper cap in alignment as it is urged down onto the window frame . frame 20 is shown in fig1 - 4 in a configuration wherein a round window 21 has been configured within frame 20 which fits a square flue . another embodiment contains a frame which is configured to fit a rectangular flue . the chimney cap maybe manufactured in rectangular or square configurations that fit conventional flues of the following nominal sizes : 8 ″× 8 ″; 8 ″× 17 ″; 9 ″× 13 ″; 13 ″× 13 ″; 13 ″× 18 ″; 18 ″× 18 ″ or any size circular flue as well . still another embodiment , shown in fig7 , contains a frame with flange 26 which is configured to fit a round flue . the foregoing detailed description is given primarily for clearness of understanding and no unnecessary limitations are to be understood therefrom , for modification will become obvious to those skilled in the art upon reading this disclosure and may be made upon departing from the spirit of the invention and scope of the appended claims . accordingly , this invention is not intended to be limited by the specific exemplification presented herein above . rather , what is intended to be covered is within the spirit and scope of the appended claims . | 5 |
fig1 shows a data processing system 100 that comprises an erp system 102 , which is coupled to a server computer 104 . the erp system 102 serves for administration of a manufacturing plant 106 , such as for the manufacturing of chemical or pharmaceutical substances . the erp system has at least one microprocessor 108 for execution of various program components that provide erp functionalities . these program components may include a human resources ( hr ) module 110 , customer relationship management ( crm ) module 112 , financials ( fi ) module 114 , and logistics module 116 . various additional erp functionalities can be provided by other program modules that are not shown in fig1 for ease of explanation . in addition , processor 108 executes a program module 118 that serves for initiating the collection of test data , receiving test reports and archiving the test reports in accordance with the respective official regulations and / or the internal rules of control of the company that runs the manufacturing plant 106 . such regulations or internal rules of control typically require that samples are taken from the running production or during goods receipt from external procurement or a number of other logistic processes in order to perform a specified number of tests on the samples . fig1 shows one such sample 120 by way of example . the sample 120 has an attached label 122 that carries a bar code . the bar code contains a sample identifier ( id ) that unequivocally identifies the sample 120 . the erp system 102 has storage 124 for storing a set 126 of method keys . each method key is assigned to a specific test method that has one or more method steps . the test methods and respective method steps are not specified in the erp system 102 . further , the storage 124 contains a database 128 that serves for storage of test results in compliance with the respective regulatory requirements . the server computer 104 has at least one processor 130 for the execution of various program components . for example , the processor 130 runs a table generation module 132 that serves for generating a tabular representation of test orders received from the erp system 102 . table filtering module 134 serves for implementation of various filter functions for filtering the tabular representation . for example , filtering is performed in order to filter out test orders assigned to a certain organisational entity or to filter out such test orders that can be executed by a given client computer . authentication module 136 serves for user authentication and can implement any suitable authentication method , such as password or ic - card implemented authentication methods or the identification of biometric features . storage module 138 serves for storage of intermediate results that are reported back from the client computers that are coupled to the server computer 104 . the intermediate results are stored in a database 140 , which is stored in storage 142 of the server computer 104 . audit trail module 144 serves to generate an audit trail 146 that is stored in storage 142 . each entry of the audit trail 146 identifies a transaction and the user that has initiated , performed or entered the respective transaction and / or intermediate result data including a time stamp and the reason for the action . report module 148 serves to generate a test report using the intermediate results stored in the database 140 . a set of database tables 150 that is stored in storage 142 contains a list of the method keys and the respective method steps and further data like information regarding appropriate laboratory instruments and / or result calculation rules (“ method definition ”). in other words , each method key has an assigned method definition . for example , a method definition is stored as a list of one or more method steps . the method steps , including evaluation and calculation rules , can be specified by respective code words or machine executable instructions . the tables can also include a flow control , such as “ if ” or “ if then else ” logic flow control method steps . an additional set of database tables 152 contains data descriptive of the available laboratory instruments and a set of database tables 154 that describes the available communication interfaces for communication with the laboratory instruments . the database tables 152 and 154 implement a relational database that describes the laboratory setup . table 156 is an example for a tabular output that is generated by table generation module 132 . table 156 contains a list of test orders received from the erp system and the method steps that need to be executed for performance of each test order . a number of client computers 158 , 160 , . . . is coupled to the server computer 104 , e . g . by means of a local area network ( lan ) 162 . for example , the server - client communication is performed using the tcp / ip protocol . the same or another network 163 , such as the internet or an intranet , can be used for coupling erp system 102 and server computer 104 . the client computer 158 has a bar code reader 164 for reading the bar code on label 122 when the sample 120 has been transported to the client computer location of client computer 158 . a number of laboratory instruments ( i ) 166 , 168 , . . . are coupled to the client computer 158 using various interconnection technologies . for example , laboratory instrument 166 is directly coupled to client computer 158 by means of a serial cable . laboratory instrument 168 is coupled to client computer 158 by means of a laboratory instrumentation bus or a field bus 170 . in operation the erp system 102 receives an event 172 . the event 172 is data that describes e . g . a logistics event , a customer request or an event reported from the manufacturing plant 106 that requires the testing of a sample in accordance with the applicable regulations and / or internal rules of procedure . the event 172 invokes program module 118 . program module 118 requests logistics module 116 to extract sample 120 from the running production and to assign a sample id to the sample 120 . program module 118 selects one of the method keys of the set 126 in accordance with the test method that is required by regulation or internal rule of control . the program module 118 generates a test order 174 that comprises at least a test order id , the sample id of the sample 120 , and the selected method key . the test order may include additional data , such as the measurement characteristic of interest , allowed measurement ranges and / or other additional information . the test order 174 is transmitted from erp system 102 to server computer 104 via network 163 . receipt of test order 174 by server computer 104 invokes table generation module 132 . the table generation module 132 reads the method key from the test order 174 and uses the method key in order to retrieve the method definition assigned to that method key in the database tables 150 . the method steps of the retrieved method definition are read from the database tables . the method steps are instantiated using the data contained in the test order , such as the measurement characteristic of interest . on this basis the table generation module 132 generates the table 156 that includes the test order 174 and previously received test orders as well as the respective instantiated method steps to be performed for the execution of these test orders . when a user logs in e . g . on client computer 158 he or she can view the table 156 . in order to reduce the size of the table 156 it can be filtered by means of table filtering module 134 in order to show only a subset of the test orders to the user that are relevant to the user and / or the client computer used for carrying out the current part of the test order . after user authentication by means of authentication module 136 the user can select one of the test orders e . g . by clicking on the respective row or rows of table 156 in order to initiate execution of the test order . the user utilizes the bar code reader 164 for reading the label 122 for identification of the sample 120 . this ensures that the test order is performed with respect to the correct sample as identified in the test order details containing the sample id . the method steps are communicated from the client computer 158 to the appropriate laboratory instrument 166 , 168 or another laboratory instrument using the communication interface as given in the database table 154 . the measurement results obtained from the laboratory instruments are transmitted from client computer 158 to the server computer 104 and stored by storage module 138 in the database 140 . after intermediate results have been received from laboratory instruments or have been entered manually , these results are stored in the database 140 . this is triggered by the user of client computer 158 digitally signing the set of intermediate results . calculations are carried out based on the method definitions contained in the test order as soon as all input parameters for a given calculation are present and again if any of these parameter changes later on . validation of the results requires a secondary digital signature by another user for approval of the intermediate results . this procedure is managed by report module 148 . report module 148 accepts a secondary digital signature only from a user that is not reported to be involved in the execution of the current test order in the audit trail 146 . on the basis of the intermediate results stored in the database 140 a final test report 176 is generated and transmitted from server computer 104 to erp system 102 where it is persistently stored in the database 128 for later reference and / or for further use in the process which triggered the inspection in the first place . it is important to note that only the method keys are stored in the erp system 102 but not the individual method steps . this ensures that only a minimal amount of complexity is added to the erp system 102 while the rest of the laboratory setup information is centrally stored on server 104 . this enables to seamlessly integrate lims functionalities into the erp system while keeping the administrative overhead at minimum . further , this enables a high degree of flexibility . for example , server computer 104 can be used as a hub that services two or more erp systems of the same or different companies . this will be explained in greater detail with respect to fig3 . fig2 shows a flow chart that illustrates a preferred mode of operation of the data processing system of fig1 . in step 200 an event is received by the erp system . in response a test order is generated using one or more method keys ( step 202 ). the test order is transmitted to the server computer in step 204 where the one or more method keys contained in the test order are utilized to retrieve the respective method steps ( step 206 ). in step 208 a tabular representation of test orders that have been received by the server computer is generated . the tabular representation includes the method steps to be performed for execution of each test order . in step 210 a user selects one of the test orders from the tabular representation . this initiates an automatic or semi - automatic performance of the respective method steps involving one or more laboratory instruments that are coupled to the client computer of the user ( step 212 ). in step 214 the measurement results that are obtained by the laboratory instruments are transmitted via the respective client computer to the server computer where the intermediate results are stored in the server computer &# 39 ; s database ( step 214 ). in step 216 a test report is generated on the basis of the intermediate results . the test report includes at least the actual measurement value or observation entered by laboratory staff that has been obtained for the measurement value of interest as specified in the test order . the test report is transmitted from the server computer to the erp system ( step 218 ) where it is persistently stored in the erp system &# 39 ; s database for later reference . fig3 shows an alternative embodiment where the server computer is used as a central hub for a plurality of erp systems . elements in the embodiment of fig3 that correspond to elements in the embodiment of fig1 are designated by similar reference numerals . the erp systems 302 , 302 ′, . . . can belong to the same or different companies . each of the erp systems 302 , 302 ′, . . . stores the same set 326 of method keys . this provides a common interface between the various erp system 302 , 302 ′, . . . and server computer 304 . in other words , the server computer 304 can receive test orders from any one of the erp systems and process these test orders as the same set of method keys is utilized across the entire data processing system 300 . | 6 |
one or more specific embodiments of the present disclosure will be described below . in an effort to provide a concise description of these embodiments , some features of an actual embodiment may be described in the specification . it should be appreciated that in the development of any such actual embodiment , as in any engineering or design project , numerous embodiment - specific decisions will be made to achieve the developers &# 39 ; specific goals , such as compliance with system - related and business - related constraints , which may vary from one embodiment to another . it should further be appreciated that such a development effort might be complex and time consuming , but would nevertheless be a routine undertaking of design , fabrication , and manufacture for those of ordinary skill having the benefit of this disclosure . one or more embodiments of the present disclosure may generally relate to securing an object about a bar located therethrough . more particularly , one or more embodiments of the present disclosure may relate to securing weight plates on exercise equipment . fig1 is a perspective view of an embodiment of a locking hub 100 . the locking hub 100 may include a first hub 102 and a second hub 104 . the first hub 102 and second hub 104 may have a sleeve 106 located therebetween . the first hub 102 and / or second hub 104 may be made of and / or include various materials including metals , plastics , ceramics , or combinations thereof . in an embodiment , the first hub 102 and / or second hub 104 may be made of and / or include a metal such as steel alloys , aluminum alloys , titanium alloys , other alloys , other metals , or combinations thereof . in another embodiment , the first hub 102 and / or second hub 104 may be made of and / or include a plastic such as a molded or machined thermoplastic such as styrenic block copolymers , elastomeric alloys , thermoplastic polyurethanes , thermoplastic copolyesters , or thermoplastic polyamides ; or thermosetting polymer such as polyurethane , fiberglass , or resins . the first hub 102 and / or second hub 104 may have one or more pads 108 contained therein . the pads 108 may be made of and / or include a molded or machined thermoplastic such as styrenic block copolymers , elastomeric alloys , thermoplastic polyurethanes , thermoplastic copolyesters , or thermoplastic polyamides . the first hub 102 and / or second hub 104 may include one or more retention members 110 . the retention members 110 may be connected to a surface of the first hub 102 and / or second hub 104 . in another embodiment the retention members 110 may be integrally formed with the first hub 102 and / or second hub 104 . in an embodiment , the retention members 110 may extend from an inner axial surface of the first hub 102 and / or second hub 104 . in another embodiment , the retention members 110 may be connected to or integrally formed with a radial surface of the first hub 102 and / or second hub 104 and extend axially . the retention members 110 may limit movement of the pads 108 relative to the retention members 110 and , therefore , limit movement of the pads 108 relative to the first hub 102 and / or second hub 104 . the retention members 110 may limit movement of the first hub 102 and second hub 104 relative to one another . in some embodiments , the retention members 110 may include mating features 109 located thereon . the mating features 109 may allow the retention members 110 to engage with and lock to one or more complimentary features 111 on another retention member 110 . for example , the retention members 110 may include a plurality of complimentary features 111 at various axial positions relative to the locking hub 100 such that the locking hub 100 may have a variable length such that it may accommodate varying lengths of a sleeve 106 . the adjustable length of locking hub 100 allows the locking hub 100 to be used with weight plates of varying thicknesses . the mating features 109 may engage with the complimentary features 111 by a press fit , a snap fit , a friction fit , an adhesive , a material bond , one or more threads , or combinations thereof . in other embodiments , the mating features 109 may engage with and lock to complimentary features 111 located on other components , such as a first hub 102 and / or second hub 104 . fig2 is an exploded view of a locking hub 200 . fig2 depicts the relative position of the components of the locking hub 200 . a sleeve 206 is located between a first hub 202 and second hub 204 . the first hub 202 and / or second hub 204 may include one or more retention members 210 . in some embodiments , the first hub 202 may include three retention members 210 and the second hub 204 may include three retention members 210 . each retention member 210 may align with and / or be associated with a pad 208 . each pad 208 may include a body 212 and wings 214 . in some embodiments , the body 212 and wings 214 may be integrally formed with one another . for example , in the depicted embodiment , the body 212 and wings 214 are injection molded as a continuous piece . the pad 208 may include a textured surface 216 such that a surface of the body 212 and / or wings 214 may have an increased coefficient of friction relative to an untextured surface . the body 212 of the pad 208 may align with a channel 220 in the retention member 210 . in some embodiments , the body 212 may protrude from the channel 220 . in other embodiments , the body 212 may be flush with a surface of the retention member 210 or recessed with the channel 220 . the wings 214 of the pad 208 may be aligned with and / or contact one or more sloped surfaces 218 of the retention member 210 . the sloped surface 218 may be curved and / or substantially planar . the sloped surface 218 may have a portion that forms an angle with a surface of the associated retention member 210 in a range having upper and lower values including 10 °, 20 °, 30 °, 40 °, 50 °, 60 °, 70 °, 80 °, or any value therebetween . for example , the sloped surface 218 may have a portion that forms an angle with a surface of the associated retention member 210 in a range between 20 ° and 70 °, between 30 ° and 60 °, or between 35 ° and 55 °. the sloped surfaces 218 may apply a radial force to the pad 210 to limit or , in some instances , prevent movement of the pad 210 in a radial direction relative to the sleeve 206 . the sloped surfaces 218 may apply a lateral force to the pad 210 to limit or , in some instances , prevent movement of the pad 210 in a lateral and / or rotational direction relative to the sleeve 206 . fig3 and 4 show cross - section views of locking hubs 300 , 400 , respectively . the cross - sectional view of locking hub 300 in fig3 depicts the locking hub 300 in a locked state . the locking hub 300 may have a locked state and an unlocked state . a sleeve 306 located between a first hub ( not shown ) and a second hub 304 has more than one inner radius . in particular , the sleeve 306 may include a one or more unlocked recesses 322 and one or more locked recesses 324 in an inner radial surface 326 . the one or more unlocked recesses 322 may be a portion of the inner radial surface 326 having a first radius . the one or more locked recesses 324 may be a portion of the inner radial surface 326 having a second radius . the first radius may be greater than the second radius . in other embodiments , the sleeve 306 may include one or more protrusions ( not shown ) extending radially inward from the inner radial surface 326 such that a first portion of the inner radial surface 326 has a first radius , and a second portion of the inner radial surface 326 has a second radius . in yet other embodiments a combination of both protrusions ( not shown ) and recesses 322 and / or 324 may be used to create varying radii for the inner radial surface 326 . the body 312 of the pad 308 may include one or more recesses ( not shown ). the recesses in the body 312 may complimentarily mate with the protrusions on the inner radial surface 326 when in the locked and / or unlocked position . the protrusions in the inner radial surface 326 may apply a force to the pads 308 when not aligned with the one or more recesses in the body 312 such that the pads are in a compressed state . when aligned with the one or more recesses in the body 312 , the one or more protrusions may apply less or substantially no force to the pads 308 such that the pads may be in a relaxed state . fig3 shows a pad 308 in a compressed state . in a compressed state , the sleeve 306 may be rotated relative to the locking hub 300 such that at least one of the locked recesses 324 is substantially aligned with a body 312 of a pad 308 . each pad 308 may be at least partially within a retention member 310 . the radial inner surface 326 of the sleeve 306 may apply a force to the pad 308 radially inward . the sloped surfaces 318 of the retention member 310 may apply a force to the pad 308 having a component radially outward and a component toward the body 312 . the pad 308 may compress at least partially due to the force applied by the sloped surface 318 . the pad 308 may compress and extend through the channel 320 of the retention member 310 . the channel 320 may be open and allow the pad 308 to extend beyond a surface of the retention member 310 such that the pad 308 may engage another object , such as a weight bar as will be described in relation to fig1 , and apply a frictional force thereto to limit motion of the locking hub 300 relative to the object . the body 312 of the pad 308 may include one or more relief cuts 328 in a surface thereof . the relief cuts 328 may facilitate preferred compression of a portion of the pad 308 against another , such as a bar . for example , the relief cuts 328 may be longitudinal cuts in a surface of the body 312 that allow for more lateral compression ( i . e ., perpendicular to the longitudinal cuts ) than compression in another direction relative to the body 312 . in other embodiments , the sleeve 306 may include unlocked recesses 322 and have a constant radius of the inner radial surface 326 therebetween . for example , the sleeve 306 may not include locked recesses 324 . in such an embodiment , the inner radial surface 326 may apply a force radially inward against the pads 308 such that the pads 308 may be in a compressed state . the unlocked recesses 322 may be distributed evenly about the circumference of the inner radial surface 326 of the sleeve . the unlocked recesses 322 may , therefore , provide one or more unlocked positions of the locking hub 300 in which the sleeve 306 is oriented at one or more predetermined positions relative to the first hub 302 and / or second hub 304 . all other positions of the sleeve 306 relative to the first hub 302 and / or second hub 304 may result in the locking hub 300 being in a locked state . fig4 shows a pad 408 in a relaxed state . in a relaxed state , a sleeve 406 of a locking hub 400 rotated relative to a first hub ( not shown ) and a second hub 404 such that at least one of the unlocked recesses 422 of the radial inner surface 426 is substantially aligned with a body 412 of the pad 408 . the unlocked recess 422 may have a radius that is larger than that of a locked recess 424 . when in a relaxed state , the pad 408 may be in an uncompressed or less compressed state relative to a pad in a compressed state . one or more relief cuts 428 may expand when a radially inward force on the pad 408 is reduced or removed . the expansion of the relief cuts 428 may encourage a preferred lateral expansion of the body 412 against the sloped surfaces 418 of the retention members 410 . the expansion of the body 412 against the sloped surface 418 of the retention member 410 may urge the pad 408 toward the sleeve 406 . in some embodiments , a portion of the pad 408 may protrude from the channel 420 . in other embodiments , a portion of the pad 408 may extend from the channel 420 and the body 412 may be flush with or recessed from radial inner surface of the retention members 410 . one or more of the locked recesses 424 and / or one or more of the unlocked recessed 422 may include a curved surface relative to the radial inner surface 426 . in an embodiment , one or more of the locked recesses 424 and / or one or more of the unlocked recessed 422 may be radially symmetrical relative to the sleeve 406 such that the pad 408 will expand and preferentially rest substantially centered in one or more of the locked recesses 424 and / or one or more of the unlocked recessed 422 . in such an embodiment , the sleeve 406 may be rotated relative to the first hub and / or second hub 404 in either rotational direction ( i . e ., clockwise and counterclockwise ). a force applied between the pads 408 and the sleeve 406 may be substantially equal in either direction . in another embodiment , one or more of the locked recesses 424 and / or one or more of the unlocked recessed 422 may be radially asymmetrical relative to the sleeve 406 such that compression of the pad 408 may be more gradual and / or easier when moving the sleeve 406 and pad 408 relative to one another in a first direction when compared to moving the sleeve 406 and the pad 408 relative to one another in a second direction . one or more of the locked recesses 424 and / or one or more of the unlocked recessed 422 being radially asymmetrical may create a tactile feel for a user that there is a preferred rotational direction for entering and / or exiting a locked and / or unlocked state of the locking hub 400 . fig5 is an exterior side view of a locking hub 500 . the locking hub 500 may include an axial bore 530 having a longitudinal axis 532 therethrough . the locking hub 500 may include first hub 502 having one or more engagement features 534 . the one or more engagement features 534 may be spaced evenly about a circumference of the first hub 502 . the one or more engagement features 534 may be separated by one or more engagement spaces 536 spaced evenly about the circumference of the first hub 502 and alternatingly with the engagement features 534 . in other embodiments , the engagement features 536 may be spaced or otherwise located unevenly about the circumference of the first hub 502 . it should be understood that while the engagement features 534 and the associated engagement spaces 536 are described and depicted in relation to the first hub 502 , the engagement features 534 and the associated engagement spaces 536 may also be located on a corresponding second hub as shown in fig6 . fig6 depicts a locking hub 600 having a first hub 602 and a second hub 604 . the first hub 602 may have a plurality of engagement features 634 and engagement spaces 636 . the second hub 604 may have a plurality of engagement features 634 and engagement spaces 636 . the first hub 602 may have an outer axial surface 638 and an inner axial surface 640 . the engagement features 634 and engagement spaces 636 may be located on the outer axial surface 638 and the inner axial surface 640 may be proximate and / or abutting a sleeve 606 . similarly , the second hub 604 may have an outer axial surface 638 and an inner axial surface 640 . the engagement features 634 and engagement spaces 636 may be located on the outer axial surface 638 and the inner axial surface 640 may be proximate and / or abutting a sleeve 606 . as shown in fig6 , the first hub 602 and second hub 604 may be similar or identical . in some embodiments , the first hub 602 and second hub 604 of the locking hub 600 may be substantially rotationally aligned . for example , the engagement features 634 of the first hub 602 may be substantially rotationally aligned ( i . e ., may fall along a common longitudinal line ) with the engagement features 634 of the second hub 604 . in other embodiments , the first hub 602 and second hub 604 may not be similarly rotationally aligned . for example , the engagement features 634 of the first hub 602 may substantially align with the engagement spaces 636 of the second hub 604 . in yet other embodiments , the engagement features 634 of the first hub 602 and second hub 604 may not align with any feature or space on the first hub 602 and / or second hub 604 . fig7 depicts a pair of locking hubs 700 - 1 , 700 - 2 engaged with one another . in an embodiment , a first locking hub 700 - 1 and a second locking hub 700 - 2 may be similar or identical to one another . for example , first locking hub 700 - 1 may share all components with second locking hub 700 - 2 , such that first locking hub 700 - 1 and / or second locking hub 700 - 2 may engaged in the described fashion with any number of similar locking hubs a user may use . the first locking hub 700 - 1 and / or second locking hub 700 - 2 may each have a first hub 702 - 1 , 702 - 2 and a second hub 704 - 1 , 704 - 2 , respectively . in the depicted embodiment , the first hub 702 - 1 , 702 - 2 and a second hub 704 - 1 , 704 - 2 may be identical and / or interchangeable ( e . g ., first locking hub 700 - 1 may be inverted without altering the function of the first locking hub 700 - 1 ) and , therefore , it should be understood that “ first hub ” and “ second hub ” are merely used as directional indicators relative to depicted positions . the first locking hub 700 - 1 may engage with the second locking hub 700 - 2 . engagement features 734 - 1 of the first locking hub 700 - 1 may engage with the engagement features 734 - 2 of the second locking hub 700 - 2 . in the depicted embodiment , the engagement features 734 - 1 of the first locking hub 700 - 1 may substantially mate with the engagement spaces 736 - 2 of the second locking hub 700 - 2 . the engagement features 734 - 2 of the second locking hub 700 - 2 may substantially mate with the engagement spaces 736 - 1 of the first locking hub 700 - 1 . the interlocking engagement of the locking hubs 700 - 1 , 700 - 2 may facilitate the locking / unlocking of the hubs 700 - 1 , 700 - 2 . for example , the interlocking engagement of the locking hubs 700 - 1 , 700 - 2 may rotationally fix the first hub 702 - 1 of the first locking hub 700 - 1 with the second hub 704 - 2 of the second locking hub 700 - 2 . while the first hub 702 - 1 of the first locking hub 700 - 1 is engaged with the second hub 704 - 2 of the second locking hub 700 - 2 , the second locking hub 700 - 2 may be moved into a locked state and / or an unlocked state without a user manually fixing the position of the first hub 702 - 2 and / or second hub 704 - 2 ( e . g ., when a plurality of locking hubs are aligned and engaged in series when on a weight bar as will be described in more detailed in relation to fig1 ). fig8 and 9 are cutaway views of locking hubs 800 , 900 that include visual indicators 842 , 942 to indicate when the locking hub 800 , 900 is in a locked state and / or an unlocked state . as shown in fig8 , the locking hub 800 may include a visual indicator 842 . in some embodiments , the visual indicator 842 may include an opening and a pattern , color , light , other selectable visual cue , or combinations thereof visible through the opening . in other embodiments , the visual indicator may include a pattern , color , light , display , readout , or other selectable visual cue located on a surface of the locking hub . in fig8 , the locking hub 800 is depicted in an unlocked state with a pad in a relaxed state flush with and / or recessed within a surface of a retention member 810 . a first visual cue 844 may be visible in the visual indicator 842 when the locking hub 800 is in an unlocked state . as shown in fig9 , a second visual cue 946 may be visible through a visual indicator 942 when a locking hub 900 is in a locked state . a pad 908 may be in a compressed state and protrude from a retention member 910 when the second visual cue 946 is visible through the visual indicator . for example , the first visual cue 844 in fig8 and the second visual cue 946 in fig9 may be located on a sleeve ( not shown ). when the sleeve is moved relative to the visual indicator 842 , 942 , the first visual indicator 844 and the second visual indicator 946 may move with the sleeve , becoming selectively visible in association with the relative position of the sleeve . the relative position of the sleeve may at least partially determine whether the pad 908 is in a compressed or relaxed state and , hence , whether the locking hub 900 is in a locked or unlocked state . the visual indicator 942 may thereby provide a visual indication as to the state of the locking hub 900 . fig1 depicts a system 1050 including a locking hub 1000 located between a weight plate 1048 and a weight bar 1052 . the weight bar 1052 may include a weight portion 1054 and a grip portion 1056 . a user may load weight plates 1048 onto the weight portion 1054 of the weight bar 1052 prior to a weight training exercise while the locking hub 1000 is in an unlocked state . the weight bar 1052 may include a weight stop 1058 that is positioned between the grip portion 1056 and the weight portion 1054 . the weight stop 1058 may include one or more bar engagement features 1060 and / or bar engagement spaces 1062 on an outer axial surface thereof . the bar engagement features 1060 may be configured to engage with the engagement features 1034 and / or engagement spaces 1036 of the locking hub 1000 . the locking hub 1000 may be located within an axial bore of the weight plate 1048 . in an embodiment , the locking hub 1000 may be connected to the weight plate 1048 by a press fit , a friction fit , an adhesive , one or more threads , a material bond , or combinations thereof such that the weight plate 1048 and a sleeve ( not shown ) may be rotationally fixed relative to one another . in other embodiments , the locking hub 1000 may be at least partially integrally formed with the weight plate 1048 . for example , the sleeve may be integrally formed with the weight plate 1048 and / or an inner radial surface of the weight plate 1048 may directly contact the pads ( not shown ) of locking hub 1000 . the weight plate 1048 and locking hub 1000 may be placed on the weight portion 1054 of the weight bar 1052 such that the weight portion 1054 extends through an axial bore of the locking hub 1000 ( see axial bore 530 in fig5 ). the weight plate 1048 and locking hub 1000 may be advanced on the weight portion 1054 until the locking hub 1000 contacts the weight stop 1058 . in some embodiments , the engagement features 1034 of the locking hub may engage the bar engagement features 1060 when the locking hub 1000 is adjacent the weight stop 1058 . the bar engagement features 1060 may rotationally fix the engagement features 1034 of the locking hub 1000 relative to the weight bar 1052 . a user may then rotate the weight plate 1048 relative to the weight bar 1052 until the locking hub 1000 reaches a locked state , which may be indicated by a visual indicator such as described in relation to fig8 and 9 , or until the user feels a tactile change in the resistance of the locking hub 1000 as the pads move between unlocked and locked recesses as described in relation to fig3 and 4 . in an embodiment including a plurality of weight plates 1048 on a weight portion 1054 , an outermost weight plate 1048 may partially or substantially limit the lateral movement of one or more inner weight plates . in such an embodiment , the interlocking engagement of the plurality of locking hubs 1000 may rotationally fix all of the first and / or second hubs relative to the weight bar 1052 ( as described in relation to fig7 ). the outermost weight plate 1048 may be rotated relative to the weight bar 1052 to move the locking hub 1000 to a locked state . a method 1164 of use , as shown in fig1 , may include providing 1166 a locking hub according to the present disclosure in an unlocked state and positioning 1168 the locking hub on a bar or other object extending through an axis of the locking hub . the method 1164 may include rotating 1170 a first hub of the locking hub relative to a sleeve and compressing 1172 a pad against the bar or other object and thereby restricting 1174 or substantially preventing lateral movement of the locking hub relative to the bar or other object . the method 1164 may also include rotating the first hub of the locking device and relaxing the pad from the bar or other object to ease movement of the locking hub relative to the bar or other object . in doing so , a locking hub according to the present disclosure may effectively and reliably retain one or more weight plates on a weight bar with an integrated locking mechanism . the articles “ a ,” “ an ,” and “ the ” are intended to mean that there are one or more of the elements in the preceding descriptions . the terms “ comprising ,” “ including ,” and “ having ” are intended to be inclusive and mean that there may be additional elements other than the listed elements . additionally , it should be understood that references to “ one embodiment ” or “ an embodiment ” of the present disclosure are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features . numbers , percentages , ratios , or other values stated herein are intended to include that value , and also other values that are “ about ” or “ approximately ” the stated value , as would be appreciated by one of ordinary skill in the art encompassed by embodiments of the present disclosure . a stated value should therefore be interpreted broadly enough to encompass values that are at least close enough to the stated value to perform a desired function or achieve a desired result . the stated values include at least the variation to be expected in a suitable manufacturing or production process , and may include values that are within 5 %, within 1 %, within 0 . 1 %, or within 0 . 01 % of a stated value . a person having ordinary skill in the art should realize in view of the present disclosure that equivalent constructions do not depart from the spirit and scope of the present disclosure , and that various changes , substitutions , and alterations may be made to embodiments disclosed herein without departing from the spirit and scope of the present disclosure . equivalent constructions , including functional “ means - plus - function ” clauses are intended to cover the structures described herein as performing the recited function , including both structural equivalents that operate in the same manner , and equivalent structures that provide the same function . it is the express intention of the applicant not to invoke means - plus - function or other functional claiming for any claim except for those in which the words ‘ means for ’ appear together with an associated function . each addition , deletion , and modification to the embodiments that falls within the meaning and scope of the claims is to be embraced by the claims . the terms “ approximately ,” “ about ,” and “ substantially ” as used herein represent an amount close to the stated amount that still performs a desired function or achieves a desired result . for example , the terms “ approximately ,” “ about ,” and “ substantially ” may refer to an amount that is within less than 5 % of , within less than 1 % of , within less than 0 . 1 % of , and within less than 0 . 01 % of a stated amount . further , it should be understood that any directions or reference frames in the preceding description are merely relative directions or movements . for example , any references to “ up ” and “ down ” or “ above ” or “ below ” are merely descriptive of the relative position or movement of the related elements . the present disclosure may be embodied in other specific forms without departing from its spirit or characteristics . the described embodiments are to be considered as illustrative and not restrictive . the scope of the disclosure is , therefore , indicated by the appended claims rather than by the foregoing description . changes that come within the meaning and range of equivalency of the claims are to be embraced within their scope . | 0 |
the invention will now be described in more detail by way of example with reference to the embodiments shown in the accompanying figures . it should be kept in mind that the following described embodiments are only presented by way of example and should not be construed as limiting the inventive concept to any particular physical configuration , shape , size , or order . fig1 illustrates basic components of an exemplary embodiment of the present invention , in which an electrical receptacle 100 can include an electrical interface 110 , a switch 120 , at least one electrical socket 130 , a user interface 140 , and a timer 150 . electrical interface 110 can be coupled to electrical wires 160 that carry electrical current . coupling can be effectuated via any manner that conductively connects electrical interface 110 to electrical wires 160 . for example , for direct connection with respective electrical wires 160 , electrical interface 110 can include plural terminals having color - coded screws , such as , for example and not in limitation , one or more brass screws for black ( or “ hot ”) wire ( s ), one or more silver screws for white ( or “ neutral ”) wire ( s ), and a green screw for a ground wire . additionally , electrical interface 110 is connected to switch 120 , such that the electrical current is carried thereto . switch 120 is conductively connected to electrical socket 130 , and thereby allows the electrical current from the electrical interface to flow to electrical socket 130 when switch 120 is in a closed state . when in an open state , however , switch 120 does not allow the electrical current to reach electrical socket 130 . optionally , switch 120 can have a default open state . electrical socket 130 is adapted to conductively engage with an electrical plug of a desired electrical device , such as a transformer , a light , a clothes iron , etc . user interface 140 allows a user to functionally control timer 150 . user interface 140 includes at least one input device for receiving an activation command , and at least one output device for sending an activation signal . an input device can be one or more buttons , for example and not in limitation ; and an output device can be one or more display devices , such as an lcd or led screen ( with or without back - lighting ), or an led bulb ( for example , to signal that one or more electrical sockets are “ hot ”); and / or an audible device , such as a speaker , for example . timer 150 triggers the closing and opening of switch 120 . when switch 120 is closed , electrical current from electrical wires 160 conductively flows through switch 120 to electrical socket 130 . conversely , when switch 120 is open , the electrical current does not flow to electrical socket 130 . as shown in fig2 , conventional electrical receptacles generally come in two shapes : standard and décor . while the electrical receptacle provided by the present invention can be similarly or identically shaped , it is not so limited . therefore , the present invention can be provided in alternative shapes to the extent desired . for example , an exemplary embodiment of the present invention can provide a receptacle having the same height of a décor or standard receptacle , but having a portion thereof that is wider , so as to provide additional surface area for placement of one or more components of the user interface and / or timer , which may extent beyond the width of a conventionally sized receptacle . likewise , another exemplary embodiment of the present invention can provide a receptacle having the same width of a décor or standard receptacle , but taller . notably , the shape of a corresponding faceplate of the present invention can deviate , in a complementary manner , from that of a standard or décor variety faceplate to accommodate variations in height and / or width of a receptacle of the present invention . further , a corresponding faceplate may include plural apertures or holes through which a user interface may be accessible , whether physically , visually , audibly , or otherwise . further , the present invention can be embodied in a regular or gfi (“ ground fault interrupter ”) receptacle . fig3 illustrates a front view an exemplary embodiment of the present invention , in which receptacle 300 is provided with a décor shape and a duplex ( dual electrical sockets ) configuration 310 , 320 . as illustrated , user interface can include start - button 330 , stop - button 340 , and display 350 . as further illustrated , a complementary faceplate 360 can engage receptacle 300 so as to provide a more visually pleasing appearance . it should be noted that a single user interface can be associated with one or more sockets , in an independent or similar manner . fig4 illustrates a front view of another exemplary embodiment of the present invention , in which receptacle 400 is also provided with a décor shape and a duplex configuration 410 , 420 . as illustrated , user interface , in whole or in part , can be located on faceplate 460 , which can be desirable to allow easier user access whilst an electrical plug is engaged with electrical sockets 410 , 420 . notably , respective user interfaces are provided for each of electrical sockets 410 , 420 ; and therefore , each user interface can be communicatively connected to respective switches for each socket . further , it should be noted that to the extent desired , a single user interface can be utilized to control a single or plurality of switches for a respective single or plurality of sockets , with the switches being controlled either independently or similarly by the single user interface . also notably , according to the present invention , faceplate 460 need not conform in dimensions to that of a conventional faceplate , and therefore , may be larger or smaller , and / or be shaped differently ( i . e ., any shape other than rectangular ). faceplate 460 can be a separate component attachable to receptacle 400 , or an integral part of receptacle 400 . in the former case , a receptacle of the present invention may optionally include a receptacle interface for at least one of electrical and communicative connection with the receptacle interface , with any portion of a user interface located on such a faceplate being appropriately connected to the faceplate interface . in the latter case , faceplate 460 can be formed or attached to receptacle 400 in a manner that is intended to be mostly permanent to the extent desired . according to the present invention , a user interface includes an input device and an output device . via an input device , a user can initiate an activation command ( and optionally , a deactivation command ) to be sent to the timer . via an output device , a user can be notified of a particular state of the present invention by way of an activation signal . an input device includes at least one button . many functions , input modes , and data entry techniques can be readily implemented via a single button . for example , and not in limitation , ones may be based on the number ( i . e ., “ double - pressing ”), duration , sequence , and / or combination of button presses . for example , a user may press a button for a long period of time ( e . g ., 2 seconds ) in order to put the timer into a particular “ state ” or “ mode ” such as an always - on or always - off state . additionally , a particular state of the timer can be an enter - start - time or enter - end - time state . therefore , it should be understood that numerous functions and data entry techniques can be effectuated via a single button . however , plural buttons can be utilized to provide a means for simplifying , or avoiding overly complex , operating logistics for a user . further , additional functionality can be provided via inclusion of a switch ( e . g ., an n - way mode switch : timer , schedule , always - on / off modes and / or socket selection ), a dial , etc ., for example and not in limitation . in one exemplary embodiment , the receptacle of the present invention is , by default , in an “ off ” state . in other words , by default , no current is passed to one or more electrical sockets via one or more switches . via the user interface , the user can initiate a timed “ on ” state , with the state being for a predetermined amount of time . for example , a user can depress a “ start ” button one or more times to add increments of time , which can be fifteen (“ 15 ”) minutes increments , for example and not in limitation . in such a case , the timer triggers the switch ( es ) to close for this amount of time and current is passed to the socket ( s ). when the amount of time lapses , the switch or switches return to their default state ( s ), “ open ” and current in no longer so passed to one or more sockets . notably , a user may add to the predetermined amount of time during the timed “ on ” state by depressing the same or different button , thereby creating a new predetermined amount of time . in another exemplary embodiment , a user may additionally have the option of placing the receptacle in an “ always on ” mode . for example , the user may depress a button ( as noted above ) for an extended period of time , such as , for example and not in limitation , for about two (“ 2 ”) seconds , which places the timer in the “ always on ” mode . likewise , a user may place the receptacle in an “ always off ” mode ( or return the receptacle to its default off state ), by depressing the same or a different button for an extended period of time . this toggling manner of interacting with the receptacle is an example of the plural functions a single button can provide . in another exemplary embodiment of the present invention , a user can place the timer into a “ schedule ” mode , and correspondingly , the timer can further include a clock having a set time for reference . for example , the user may depress a button for an extended period of time , such as , for example and not in limitation , for about two (“ 2 ”) seconds , which places the timer into the “ schedule ” mode . thereafter , the user may depress the same or a different button to cycle through time digits ( e . g ., hours , minutes ) until a desired time representing a start time is reached . in an exemplary aspect , a user may hold down a button to more quickly cycle through time digits . likewise , the user may enter a stop time . accordingly , the timer can thereby set to close the electrical switch upon the start time , and to close the electrical switch upon reaching the stop time . notably , multiple modes can be available in a single embodiment of the present invention . for example , an extended depressing of a button can cycle through available modes , with an output device indicating the active mode . an activation command can take one or more forms depending on the particular mode and functionality desired , and effectively , triggers the timer to cause the current switch to close . a deactivation command can also take one or more forms , and effectively causes the current switch to open . an output device can include a display device , such as an light emitting diode (“ led ”) or liquid crystal display screen , for example and not in limitation . in one exemplary embodiment , a display device displays a numeric value , which can be a digit or a unit ( e . g ., a lighted bar or bars represent time ). additionally , a display device can provide a visual indication of a particular mode or state the receptacle is in . for example and not in limitation , a display device can display an indicator associated with a particular mode , such as always - on , awaiting input , error , etc . in another exemplary embodiment , a display device can alternatively or additionally include a light , such as an led . for example , an led can be a single or dual colored light or lights , such as “ green ” and “ red ” colored , and / or glow in various blinking manners and / or glow in a steady manner . in another exemplary embodiment , a display device can optionally be back - lighted . for example , back - lighting can render the display device more easily readable . also , back - lighting can be activated when a socket is powered , and therefore , such activating can serve as a visual indication to the user that the socket is energized . an activation signal informs a user whether a socket is activated , or in other words , whether electrical current is being passed to a socket , and can include , for example and not in limitation , an amount of time remaining or a powered led light . in an exemplary embodiment of the present invention , such a signal may be an amount of time shown via a display device , and / or a powered led glowing “ red ” to indicate that the current switch is closed or glowing “ green ” to indicate that the current switch is open , for example and not in limitation . alternatively or additionally , an audible signal may be provided to the extent desired , and accordingly , a speaker and sound generator can be provided . power for the present invention can be provided via a battery and / or the electrical current provided from the electrical wires . notably , a receptacle of the present invention can optionally include a reset mechanism that resets the receptacle during a power outage . further , optionally , a battery backup can be provided to preserve data stored in any volatile memory , such as a clock , for example and not in limitation . it will be apparent to one skilled in the art that the manner of making and using the claimed invention has been adequately disclosed in the above - written description of the exemplary embodiments and aspects taken together with the drawings . it should be understood , however , that the invention is not necessarily limited to the specific embodiments , aspects , arrangement , and components shown and described above , but may be susceptible to numerous variations within the scope of the invention . accordingly , the specification and drawings are to be regarded in an illustrative and enabling , rather than a restrictive , sense . therefore , it will be understood that the above description of the embodiments of the present invention are susceptible to various modifications , changes , and adaptations , and the same are intended to be comprehended within the meaning and range of equivalents of the appended claims . | 7 |
fig1 and 2 show the basic elements of a resonator according to the invention , namely a piezoelectric crystal 1a , 2a , for example a quartz crystal , supporting means 5 , 6 for crystal 1a , 2a , electrical conductors 14a , 15a and electrodes 26 , 27 connected to conductors 14a , 15a respectively by metal paths 28 , 29 deposited on the crystal . the sealed enclosure constituting the resonator body and within which are diposed the above - defined elements is not shown in the drawings and may be constituted in conventional manner by a metal box or glass bulb for example . within said enclosure is formed a high vacuum or a residual atmosphere ( hydrogen , helium , nitrogen , etc ). conductors 14a , 15a connected to the edge of crystal 2a , for example by thermocompression bonding t or by cementing respectively to the metal paths 28 , 29 corresponding to electrodes 26 , 27 may also serve as a supporting means 5 , 6 for crystal 1a , 2a in the sealed enclosure . conductor wires 14a , 15a pass to the outside of the enclosure via insulated openings . crystal 1a , 2a may have different configurations , which depend on the envisaged applications . thus , it is possible to use crystals which are flat convex , biconvex , biplanar , etc . fig1 and 2 show as an example a flat convex circular crystal having a lower planar face 41 and an upper convex face 40 . the surface of crystal 1a , 2a must be carefully prepared and must have a minimum of faults . in order that the properties of the parts of the crystal adjacent to the surface are as close as possible to the properties of the inside of the crystal , processes which geometrically form the surface ( grinding , polishing ) are alternated with processes which clean and chemically attack it . in conventional manner , the said crystal shaping processes are followed by cleaning and then chemical attack . finally , crystal 1a , 2a is , according to conventional processes , carefully rinsed and cleaned in solvents such as distilled water , pure acetone and absolute alcohol , prior to the deposition of electrodes 26 , 27 and connecting paths 28 , 29 , for example by vacuum evaporation . electrodes 26 , 27 which are located on either side of crystal 1a respectively on faces 40 and 41 are in the form of disks in fig2 but could naturally have other configurations . in the embodiment of fig1 and 2 the central portion 1a of crystal 1a , 2a between the two electrodes 26 , 27 constitutes the active part of the crystal , whilst the peripheral portion 2a constitutes an immobilised part ensuring the suspension of the active central zone 1a . an intermediate portion 34 , 35 , 36 , 37 connects the peripheral portion 2a to the central active zone 1a . the crystal is tapered level with the intermediate portion 34 , 35 , 36 , 37 ( fig1 ) in such a way that grooves 83 , 83a , 86 , 86a are respectively formed in the upper face 40 and the lower face 41 of crystal 1a , 2a . naturally , the shape of grooves 83 , 83a , 86 , 86a can be varied in accordance with the envisaged applications . grooves 83 , 83a , 86 , 86a of the intermediate portion 34 , 35 , 36 , 37 form a boundary between the active central portion 1a which is able to vibrate and the peripheral portion 2a which is immobile and integral with the resonator body via supporting means 5 , 6 . thus , the active portion 1a of the crystal is autosuspended , because no outside element connects it to the peripheral portion 2a forming a suspension ring . the intermediate portion 34 to 37 introduces no structural discontinuity in the vicinity of the active portion 1a , whilst bringing about a certain mechanical separation from said active portion 1a . the tapered intermediate portion 34 to 37 obtained for example by grinding is advantageously circular , but may also be given other configurations , in particular as a function of the configuration of the electrodes and the nature of the crystal . according to a special embodiment of the invention , recesses 36 , 37 are made for example by ultrasonic machining in part of the retracted portions separating the central portion 1a and the peripheral portion 2a of the crystal . the active portion 1a of the crystal is thus suspended by two crystalline bridges 34 , 35 which connect it to the peripheral portion 2a . however , the crystal may have more than two bridges 34 , 35 . thus , the intermediate portion between the central and peripheral portions which has a reduced thickness over at least part of the distance between the active central portion 1a and the peripheral portion 2a may have a varied number of bridges , as a function of the desired mechanical adaptation . if no recess 36 , 37 is provided in the intermediate tapered portion and if as a result a single thin bridge extending angularly over an angle of 360 ° completely surrounds the active portion 1a , the machining of the crystal is extremely easy . rotary machining , without any complementary ultrasonic machining , may be sufficient and it may even be possible to provide an annular groove 83 , 83a in the intermediate portion of the crystal on only a single side , for example on the side of face 40 of the crystal , whereby the opposite annular groove 86 , 86a is then eliminated . the thin bridges 34 , 35 constitute suspension points for the active part 1a of the crystal and can be positioned with great accuracy both with regard to the edge of vibrating crystal 1a and angularly on its periphery . in particular , it is possible to realise the perfectly symmetrical suspension or having certain symmetry characteristics . according to the envisaged applications , it is possible to individually modify a large number of parameters , such as the thickness of the bridge or bridges 34 , 35 , their heightwise positioning relative to the crystal edge , their width , length , shape , positioning in azimuth , etc . in the case of two thin bridges 34 , 35 it is however generally preferable to position these in accordance with the axis zz &# 39 ; of the crystal , when the piezoelectric crystal comprises a quartz crystal of section at . in general terms , no difficulty is encountered in realising the intermediate portion 34 to 37 of the crystal in such a way that it has an even number of bridges 34 , 35 , ensuring a suspension symmetry of the active portion of the crystal . bridges 34 , 35 are advantageously disposed relative to the edge of the crystal in such a way that the centre of the bridges essentially coincides with the nodal reference plane of the crystal , which is located approximately in the centre of the thickness of the crystal . in fig6 it can be seen that the bridges 34 , 35 left between recesses 36 and 37 and connecting the central active portion 1a to the fixed peripheral portion 2a of the crystal are radial . however , fig7 shows an embodiment in which end 34b , 35b respectively of a bridge 34 , 35 located on the side of peripheral portion 2a is displaced by a certain angle β around the sectional axis relative to end 34a , 35a located respectively on the side of the active central portion 1a , whereby the lateral faces 34c , 34d respectively 35c , 35d of each of the bridges 34 and 35 being curved and having the same direction of curvature . in the same way , in order to reduce or eliminate residual stresses at the suspension points of the crystal by its peripheral and intermediate portions , it is possible to subject crystal 1a , 2a to treatment prior to its fitting . for example , it is advantageous for the crystal to undergo annealing at approximately 480 ° c ., after which it undergoes a very slight bifluoride attack . on referring to fig1 and 2 , it can be seen that means 5 , 6 for supporting the peripheral portion 2a of the crystal are fixed at points which are preferably remote from connecting bridges 34 , 35 between central portion 1a and peripheral portion 2a . the fixing points of the conductor wired 14a , 15a to the edge of peripheral portion 2a are also preferably located as far as possible from the connecting bridges . the metal paths 28 , 29 respectively connecting electrodes 26 , 27 to conductors 14a , 15a are deposited on faces 40 , 41 of the crystal at the same time as electrodes 26 , 27 . metal paths 28 , 29 traverse the intermediate portion of the crystal level with thin bridges 34 , 35 . to facilitate electrical continuity , it is preferable for grooves 83 , 86a not to be too deep . fig3 to 5 correspond to a second embodiment of the invention . as in the case of fig1 and 2 , the piezoelectric crystal 1a , 2a of fig3 to 5 comprises a central portion 1a connected to a peripheral portion 2a by an intermediate portion which is tapered relative to central portion 1a and peripheral portion 2a . like parts in the embodiment of fig1 and 2 and in the embodiment of fig3 to 4 are given the same references and all that has been described hereinbefore relative to crystals 1a , 2a and the intermediate portion thereof also applies to the embodiments of fig3 to 5 . the basic structure of the piezoelectric resonator shown in fig3 to 5 differs from that of fig1 and 2 essentially through the fact that electrodes 126 , 127 located on either side of the crystal on faces 140 , 141 respectively are disposed over the peripheral portion 2a of the crystal , which thus becomes the active part of the resonator , whilst the supporting means 5 , 6 of the crystal , which are advantageously constituted by conductors 114a , 115a for the power supply of the electrodes 126 , 127 are fixed to the central portion 1a of the crystal , which thus becomes the immobilised part of the resonator . electodes 126 , 127 disposed on the active peripheral portion 2a have a substantially annular configuration and are connected to conductors 114a , 115a by metal paths 128 , 129 respectively , which are disposed on faces 140 , 141 of the crystal at the same time as electrodes 126 , 127 and traverse the intermediate portion level with thin bridges 34 , 35 . the retaining means 5 , 6 , for the crystal are preferably fixed to the centre of the central portion 1a thereof , whereby said immobilised central portion 1a can have a greater thickness than the active peripheral portion 2a . peripheral portion 2a of the crystal may be limited on the upper face 140 and lower face 141 by planar portions ( fig5 ) or may have at least one convex portion , for example on the upper face 140 ( fig3 ), in such a way that the corresponding annular electrode 126 can be located in a maximum thickness zone where energy trapping is better . the embodiment of fig3 to 5 with an outer active portion has the advantage of permitting the retaining of the crystal by means of two fixing bridges located in the centre of the crystal and which is particularly easy to realise . thus , there is no difficulty in forming a crystal 1a , 2a having a very thin active peripheral portion 2a and a thinner central portion 1a capable of ensuring a completely adequate support for the complete crystal ( fig3 ). the presence of two electrical conductors , which serve as retaining means and which are disposed on either side of the central portion of the crystal and specifically in the centre thereof give symmetry to the system and ensure a better resistance to accelerations . fig4 shows a crystal , whose intermediate portion has two perpendicular axes of symmetry with four bridges 34 , 34a , 35 , 35a separated by recesses 36 , 36a , 37 , 37a . this configuration , which is also applicable to the embodiment of fig1 and 2 , is in no way limitative . fig8 to 10 show variants of a resonator having an active central portion . in these variants , the suspension of the whole crystal 1a , 2a , which comprises retaining means 5 , 6 cooperating with peripheral portion 2a of the crystal , is strictly symmetrical relative to the nodal reference plane of the crystal , located approximately in the centre of the thickness of the crystal . thus , the lack of sensitivity to accelerations is greatly improved compared with conventional devices in which the retaining means are entirely located on the same side of the piezoelectric crystal . in fig8 to 10 , elements of the resonator which are similar to elements of devices of fig1 to 7 carry the same references . in the embodiment of fig8 and 9 , crystal 1a , 2a is suspended by retaining means 5 , 6 formed by wires 214a , 215a , 214 , 215 which can be constituted by tapes , cylindrical wires , bifilar wires , or double wires are fixed to the edge of the peripheral portion 2a of the crystal by cementing or preferably by thermocompression bonding level with fixing points t . wires 214 , 215 and 214a , 215a are stretched on a supporting frame 200 . the tensions of the strands of wires located on one side of the crystal are the same as the tensions of the strands of wires located on the other side of the crystal , in such a way that in both tension and length each of the wires stretched over frame 200 is symmetrical to the reference nodal plane of the crystal . in fig9 it is possible to see a crystal 1a , 2a having four bridges 34 , 34a , 35 , 35a in the form of a cross for connecting the active central portion 1a of the crystal to its peripheral portion 2a . the crystal retaining means 5 , 6 comprise wires 214a , 215a which at the same time serve as power supply wires for electrodes 26 , 27 , and wires 214 , 215 . the attachment points t of the various suspension wires 214a , 214 , 215a , 215 are in a 45 ° cross arrangement with bridges 34 , 34a , 35 , 35a . the resonator of fig8 and 9 with its crystal , electrodes and suspension means has two rectangular axes of symmetry located in the plane of the crystal . these axes are preferably xx &# 39 ; and zz &# 39 ; axes in the case of a section at . the preferred axes may by analogy be calculated for other types of sections , such as for example a section sc . the resonator of fig8 and 9 also has the plane of symmetry as the nodal reference plane of the crystal , i . e . the nodal plane which is closest to the centre of the thickness of the crystal . this configuration , which has a very large number of symmetries , is particularly beneficial in as much as it reduces in a significant manner the sensitivity of the resonator to accelerations . naturally , the symmetry of the device could be a little less elaborate . for example , the retaining wires 214 , 215 could be eliminated . in the case of a crystal having only two diametrically opposite bridges 34 , 35 in the intermediate portion , wires 214a , 215a for the power supply of the electrodes and for retaining the crystal are advantageously located in each case at 90 ° from one of the bridges 34 , 35 , in such a way that the lever arm constituted by the part of peripheral portion 2a located between fixture t of a wire 214a , 215a and a bridge 34 , 35 makes it possible to transmit only greatly reduced stresses to the active central portion 1a . the symmetry of wires 214a , 215a relative to the plane of the crystal also ensures a greater lack of sensitivity to accelerations , as in the case of fig8 and 9 . in the case of the device of fig1 , the wires 314a , 315a for supplying the electrodes and which also serve to maintain the crystal in position are located in the nodal reference plane of the crystal or , in the case of bifilar wires , in symmetrical manner relative to said reference nodal plane . wires 314a , 315a are , as in the case of the embodiment of fig8 and 9 , stretched over a frame 300 . the strands of wires 314a , 315a located on either side of the points t of fixing the wires to the edge of the peripheral portion 2a of the crystal are of equal length and are subject to the same mechanical tension . as in the case of the other embodiments , fixing points t are preferably located in the zones of portion 2a which are most remote from connecting bridges 34 , 34a , 35 , 35a . the invention is not limited to the embodiments described and represented hereinbefore and various modifications can be made thereto without passing beyond the scope of the invention . | 7 |
the u . s . patent application ser . nos . 10 / 855 , 287 , 10 / 857 , 714 , 10 / 857 , 280 , 10 / 983 , 353 , 10 / 778 , 281 , 10 / 806 , 299 , 10 / 822 , 414 , 10 / 896 , 141 , 10 / 914 , 474 , 10 / 934 , 133 , 10 / 979 , 568 , 10 / 979 , 619 , 10 / 979 , 624 , 10 / 979 , 612 , 11 / 072 , 296 , and 11 / 076 , 688 are incorporated by reference into this disclosure as if fully set forth herein . fig1 illustrates the principle of the fresnel lens and micromirror array lens 11 . there are two conditions to make a perfect lens . the first is the converging condition that all lights scattered by one point of an object should converge into one point of the image plane . the second is the same phase condition that all converging light should have the same phase at the image plane . to satisfy the perfect lens conditions , the surface shape of conventional reflective lens 12 is formed to have all lights scattered by one point of an objective to be converged into one point of the image plane and have the optical path length of all converging light to be same . fig2 illustrates the in - plane view of the axis - symmetric micromirror array lens 21 . the micromirror 22 has the same function as a mirror . therefore , the reflective surface of the micromirror 22 is made of metal , metal compound , multi - layered dielectric material , or other materials with high reflectivity . many known microfabrication processes can make the surface with high reflectivity . each micromirror 22 is electrostatically and / or electromagnetically controlled by the actuating components 23 as known . in case of an axis - symmetric lens , the micromirror array lens 21 has a polar array of the micromirrors 22 . each of the micromirrors 22 has a fan shape to increase an effective reflective area , which increases optical efficiency . the micromirrors are arranged to form one or more concentric circles to form an axis - symmetric lens and the micromirrors on the same concentric circle can be actuated by the same electrodes or independently controlled by known semiconductor microelectronics technologies such as mos or cmos . the mechanical structure upholding each reflective micromirror 22 and the actuating components 23 are located under the micromirrors 22 to increase the effective reflective area . electric control circuits to operate the micromirrors can be replaced with known semiconductor microelectronics technologies such as mos and cmos . also , the control circuitry can be made by at least one wire layer as described in u . s . patent application ser . no . 11 / 072 , 296 . applying the microelectronics circuits under micromirror array , the effective reflective area can be increased by removing necessary area for electrode pads and wires used to supply actuating power . fig3 illustrates how the micromirror array lens 31 makes an image . arbitrary scattered lights 32 , 33 are converged into one point p of the image plane by controlling the positions of the micromirrors 34 . the phases of arbitrary light 32 , 33 can be adjusted to be same by translating the micromirrors 34 . the required translational displacement is at least half of the wavelength of light . it is desired that each micromirror 34 has a curvature because the ideal shape of a conventional reflective lens 12 has a curvature . if the size of the flat micromirror is small enough , the aberration of the lens including flat micromirrors 34 also becomes small enough . in this case , the micromirror does not need a curvature . the focal length f of the micromirror array lens 31 is changed by controlling the rotation and the translation of each micromirror 34 . parallel ray with 0 degree of view angle ( or scanning angle for the scanning device ) is converged into one point by parabolic surface . by the way , practical optical system requires continuous view angle ( or scanning angle ) in field of view ( or scanning range ). therefore , the required surface is not simple parabolic , which is usually polynomial function . the optimal surface for continuous field of view ( or scanning angle ) can be generally found by optical simulation software . as explained in fig1 , the optimal surface can be made by micromirror array using fresnel lens principle . in present , there is no optical software to find the optimal rotation and translation of each micromirror of mmal . therefore , the rotation and translation of each micromirror should be calculated from the optimal aspheric surface function found by optical simulation software . fig4 shows a micromirror reproducing a part of the axis - symmetric reflective surface . the aspheric surface 41 can be expressed in where z is profile of aspheric surface 41 and r is a radial component in cylindrical coordinate system . rotation of micromirror 42 , θ is calculated from the gradient of z , dz / dr . direction of ray 43 reflected by the aspheric surface 41 is same with the direction of ray 44 reflected by the micromirror because r - directional gradient of the aspheric surface at the point p is reproduced by rotation of micromirror 42 . if the aspheric surface is not axis - symmetric , it can be expressed in where z is profile of aspheric surface and x and y is in - plane coordinate . in this case , two degree - of - freedom rotation is necessary , which is x - directional and y - directional rotation . because micromirror 42 is fabricated by microfabrication process , they are arranged in a flat plane 45 as shown in fig4 . therefore , the optical path length of ray reflected the aspheric surface is different with the one of ray reflected by the micromirror 42 . the optical path length difference is caused by height difference , δz between the aspheric surface and the micromirror , which is expressed in even though the opd of converging light is different , the phase of two lights can be matched by adjusting the opd to be m times wavelength because the phase of light is periodic , where m is an integer . fig5 shows two examples of aspheric surface , u shape 51 and w shape 52 . they can be reproduced by mmal 53 as shown in fig5 . fig6 shows dual focal length mmal 61 . two aspheric surfaces 62 , 63 with different focal length can be reproduced into one mmal 61 . multiple focal length mmal also possible in one mmal . fig7 shows two degree of freedom rotations and one degree of freedom translation of the micromirror 71 . the array including micromirrors 71 with two degree of freedom rotations 72 , 73 and one degree of freedom translation 74 , which are controlled independently can make a lens with arbitrary aspheric surface . incident lights can be modulated arbitrarily by forming an arbitrary aspheric surface . to do this , it is required that incident lights are deflected to an arbitrary direction by controls of two degree of freedom rotations 72 , 73 . independent translation 74 of each micromirror is also required to satisfy the phase condition . in fig8 a , 8 b , 9 and 10 , the rotational amount and direction of a micromirror are represented by length of arrow 82 and the profile gradient direction to represent a rotational direction of a micromirror is represented by direction of arrow 82 . fig8 a shows a variable focal length cylindrical lens including hexagonal micromirrors 81 . fig8 b shows a variable focal length circular lens 83 including hexagonal micromirrors 81 . shape , position and size of the variable focal length circular lens 83 can be changed by independent control of micromirrors 81 with two dof rotations and one dof translation . in fig8 b and 10 , micromirrors 85 which are not elements of the lens are controlled to make lights reflected by the micromirrors 85 not have influence on imaging or focusing . even though fig8 a – 8 b show hexagonal micromirrors 81 , fan shape , rectangle , square , and triangle micromirrors array can be used . an array including fan shape micromirrors is appropriate to an axisymmetric lens . fig9 shows a variable focal length cylindrical lens 91 including rectangular micromirrors 92 . an array including square or rectangle micromirrors 92 is appropriate to a symmetric lens about one in - plane axis such as cylindrical lens 91 . the micromirrors with same rotation are actuated by the same electrode or controlled by known semiconductor microelectronics technologies such as mos or cmos independently . fig1 shows a variable focal length circular lens 101 including triangular micromirrors 102 . an array including triangular micromirrors 102 is appropriate to a lens with arbitrary shape and / or size lens like an array including hexagonal micromirrors . the micromirror array lens is an adaptive optical component because the phase of light can be changed by controlling the translations 74 and rotations 72 , 73 of micromirrors independently . adaptive optical micromirror array lens requires two - dimensional arrays of individually addressable micromirrors . to achieve this , it is necessary to combine the micromirrors with on - chip electronics . in order to do this , wafer - level integration of micromirrors with the known microelectronics circuits is necessary . the micromirror array lens can correct the phase errors since an adaptive optical component can correct the phase errors of light due to the medium between the object and its image , and / or correct the defects of a lens system that cause its image to deviate from the rules of paraxial imagery . for example , the micromirror array lens can correct the phase error due to optical tilt by adjusting the translations 74 and rotations 72 , 73 of micromirrors . the same phase condition satisfied by the micromirror array lens contains an assumption of monochromatic light . therefore , to get a color image , the micromirror array lens is controlled to satisfy the same phase condition for each wavelength of red , green , and blue ( rgb ), respectively , and the imaging system can use bandpass filters to make monochromatic lights with wavelengths of red , green , and blue ( rgb ). if a color photoelectric sensor is used as an imaging sensor in the imaging system using a micromirror array lens , a color image can be obtained by processing electrical signals from red , green , and blue ( rgb ) imaging sensors with or without bandpass filters , which should be synchronized with the control of micromirror array lens . to image red light scattered from an object , the micromirror array lens is controlled to satisfy the phase condition for red light . during the operation , red , green , and blue imaging sensors measure the intensity of each red , green , and blue light scattered from an object . among them , only the intensity of red light is stored as image data because only red light is imaged properly . to image each green or blue light , the micromirror array lens and each imaging sensor works in the same manner as the process for the red light . therefore , the micromirror array lens is synchronized with red , green , and blue imaging sensors . alternatively , the same phase condition for a color image is satisfied by using the least common multiple of wavelengths of red , green , and blue lights as an effective wavelength for the phase condition . in this case , the micromirror array lens is not necessary to be controlled to satisfy the phase condition for each red , green , and blue light individually . instead , the phase condition for the least common multiple of the wavelengths should be satisfied . for the simpler control , the translation of each micromirror is only controlled to satisfy the phase condition for one light among red , green , and blue lights or is not controlled to satisfy the phase condition for any other lights of red , green , and blue . even though the micromirror array lens cannot satisfy the phase condition for multi - wavelength due to different phase error of lights , still the lens can be used as a variable focal length lens with low quality . fig1 shows imaging system using the mmal with free surface 110 . the imaging system 111 is one example of optical system using the mmal with free surface . because the mmal is reflective lens , the mmal is usually positioned with tilt to deflect the light into a sensor 114 as shown in fig1 . because conventional refractive lenses 112 are positioned to be perpendicular about optical axis 113 , surface profile of the lens is generally axis - symmetric . but , the surface profile of the mmal is only symmetric about y - axis if the mmal 110 is positioned with a rotation about x - axis . while the invention has been shown and described with reference to different embodiments thereof , it will be appreciated by those skilled in the art that variations in form , detail , compositions and operation may be made without departing from the spirit and scope of the invention as defined by the accompanying claims . | 6 |
please refer to fig1 . fig1 is a flow chart illustrating a method for fabricating a polyaniline / c - mwnt nano - composite according to an embodiment of the invention . the polyaniline / c - mwnt nanocomposite fabricated by means of the method of the embodiment could be coated on shielding casings of electronic devices as a material for electromagnetic shielding or anti - static shielding . as illustrated in fig1 , the fabricating method of the embodiment includes the following steps . in step s 10 , carbon nanotubes are carboxylated to form carboxylic carbon nanotubes . in step s 12 , the carboxylic carbon nanotubes are mixed with a solvent to form a first carbon nanotube solution . in step s 14 , aniline monomers are mixed with the first carbon nanotube solution to form a second carbon nanotube solution . in step s 16 , an ammonium persulfate solution is mixed with the second carbon nanotube solution to form a third carbon nanotube solution . finally , in step s 18 , the third carbon nanotube solution is air - extracted and filtered to obtain the polyaniline / c - mwnt nanocomposite , and the polyaniline / c - mwnt nanocomposite is cleaned and baked . practically , all of the solutions formed in the steps mentioned above could be processed a treatment , depending on the requirement , to help the aniline monomers and the carboxylic carbon nanotubes dissolved therein . for example , the first carbon nanotube solution could be agitated for a night to make the carboxylic carbon nanotubes dissolved therein . moreover , the second carbon nanotube solution could be ice bathed and agitated for 0 . 5 hour to make the aniline monomers dissolved therein . furthermore , the third carbon nanotube solution could be ice bathed and agitated for 3 hours to make the ammonium persulfate solution completely mixed with the second carbon nanotube solution mentioned above . in the embodiment , because there is no interaction force existing between the carbon nanotubes and the polymer composite , and also there is no functional group on the surface of the carbon nanotube , the carbon nanotube is difficultly dispersed in the polyaniline and combined with the polyaniline . in the step s 10 , after carboxylating the carbon nanotubes , the carboxylic carbon nanotubes possesses higher solvability because of the — cooh functional groups on the surface thereof which helps the carboxylic carbon nanotube dispersed in the polyaniline and combined with the polyaniline . please refer to fig2 . fig2 is a flow chart illustrating the process of carboxylating the carbon nanotubes in fig1 . as illustrated in fig2 , the process includes the following steps . in step s 100 , the carbon nanotubes are mixed with a sulfuric acid / nitric acid solution to form a mixed solution . in step s 102 , the mixed solution is ultrasonic vibrated . in step s 104 , the mixed solution is filtered to obtain the carboxylic carbon nanotubes , and the carboxylic carbon nanotubes obtained is cleaned and baked . practically , the carbon nanotubes mentioned above could be , but not limited to , multi - wall carbon nanotubes . the ratio of the sulfuric acid to the nitric acid of the sulfuric acid / nitric acid solution in the step s 100 could be 3 : 1 in practical applications , wherein the concentration of the sulfuric acid therein could be 90 % wt and that of the nitric acid therein could be 70 % wt . the process of ultrasonic vibrating the mixed solution in the step s 102 could be under the temperature range of 20 ± 5 ° c . in the embodiment , however , the range of the temperature could depend on the requirement of users , but not limited to the embodiment of the invention . moreover , the ultrasonic vibrating time could depend on users &# 39 ; requirement as well , but not limited to a specific period of time . for example , the mixed solution could be ultrasonic vibrated under the temperature range of 20 ± 5 ° c . for 4 , 8 , 12 , or 24 hours . please notice that the ultrasonic vibrating is for assisting the carbon nanotube in forming — cooh functional groups on the surface of the carbon nanotubes to increase solvability of the carbon nanotubes in the solvent . thus , the longer the ultrasonic vibrating time is , the easier it is for the carboxylic carbon nanotube to be dissolved in the solvent . however , forming — cooh functional groups on the surface of the carbon nanotubes means that the sp2 bonding thereon would be damaged , thus the longer the ultrasonic vibrating time is , the lower the conductivity of the carboxylic carbon nanotubes is . please refer to fig3 . fig3 illustrates the structure of part surface of a carboxylic carbon nanotube 2 according to an embodiment of the invention . as illustrated in fig3 , the surface of the carboxylic carbon nanotube 2 is constructed by hexagonal structure 20 . the difference between the carboxylic carbon nanotube 2 and the common carbon nanotube is that some of the sp2 bonding of the hexagonal structure 20 is damaged and connected with — cooh functional group 22 . practically , the longer the ultrasonic vibrating time is , the larger the number of the — cooh functional group 22 is . the filtered carboxylic carbon nanotubes in the step s 106 in the embodiment could be cleaned by deionized water and methanol repeatedly for several times and then baked in an oven under 60 ° c . for 24 hours to get rid of extra water of the carboxylic carbon nanotubes . similarly , the cleaning fluid , the temperature of the oven and the baking time could be adjusted according to the requirement of users , but not limited to the embodiment of the invention . please refer to fig1 again . the composition of the solvent mixed with the carboxylic carbon nanotubes in the step s 12 in fig1 could be hydrogen chloride . subsequently , in the step s 14 the aniline monomers are mixed with the first carbon nanotube solution in the step s 12 to form a second carbon nanotube solution . in the step s 16 the ammonium persulfate solution is mixed with the second carbon nanotube solution to form a third carbon nanotube solution . in the step s 18 the polyaniline / c - mwnt nanocomposite is filtered and obtained from the third carbon nanotube solution and then cleaned and baked . in the embodiment , the polyaniline formed from the aniline monomers by means of the steps mentioned above is an emeraldine base form of polyaniline . a common emeraldine base form of polyaniline has conjugated double bonds . however , such form of polyaniline lacks of free charge resulting in bad conductivity , so the polyaniline needs providing with free charge on the conjugated double bonds by means of doping to improve its conductivity . in the embodiment , the first carbon nanotube solution which is mixed with the aniline monomers includes hydrogen chloride ( namely , polyaniline dopant ). the polyaniline doped with low ph value protic acid has much higher conductivity and is suitable for electromagnetic shielding or anti - static shielding . similarly , the doped protic acid , as a dopant which increases the conductivity of the polyaniline , could be other inorganic acids such as phosphoric acid in practical applications . on the other hand , the ammonium persulfate in the step s 16 of the embodiment is used as an initiator to assist the aniline monomers with polymerization to form the polyaniline . in the embodiment , the ammonium persulfate solution is a mixture of ammonium persulfate and hydrochloric acid . according to another embodiment , the polymer composite of the invention could include a polyaniline / c - mwnt nanocomposite , wherein the polyaniline / c - mwnt nanocomposite further includes a polyaniline and carboxylic carbon nanotubes dispersing in the polyaniline , which could be formed by means of the fabricating method disclosed above , so the details of the fabricating method are not described again here . in the embodiment , there are functional groups on the surfaces of the carboxylic carbon nanotubes so that the carboxylic carbon nanotubes could disperse in the polyaniline during the process of fabricating the polymer composite , unlike uncarboxylic carbon nanotubes untwine each other which are difficultly dispersed . moreover , during the process of fabricating the polyaniline of the polyaniline / c - mwnt nanocomposite , an inorganic acid , such as hydrogen chloride or phosphoric acid , is doped to provide the polyaniline with free charge on the conjugated double bonds thereof to improve the conductivity of the polyaniline . because a polymer composite will have the characters of the original materials , the polyaniline / c - mwnt nanocomposite of the embodiment will have good conductivity as the doped polyaniline and the carbon nanotube . the polyaniline / c - mwnt nanocomposite could be coated on casings of electronic devices for electromagnetic shielding or anti - static shielding to protect electronic devices against the disturbance of electromagnetic waves or static electricity . otherwise , the polyaniline / c - mwnt nanocomposite keeps the physical characteristics and chemical characteristics of the polyaniline and the carbon nanotube those make the polyaniline / c - mwnt nanocomposite could be applied to their original application domains respectively . compared to the prior art , the polymer composite and the fabricating method for making the same of the invention could provide functional groups on the surfaces of the carboxylic carbon nanotubes that help the carboxylic carbon nanotubes with dispersing in the polyaniline to form the polyaniline / c - mwnt nanocomposite . the polyaniline is doped with low ph value protic acid while fabricating that makes it has much higher conductivity . moreover , the carbon nanotube itself has good conductivity as well . all that makes the polyaniline / c - mwnt nanocomposite suitable as a conductive coating material to protect electronic devices against the disturbance of electromagnetic wave or static electricity , so as to affectively extend the lifetime of electronic devices . although the present invention has been illustrated and described with reference to the preferred embodiment thereof , it should be understood that it is in no way limited to the details of such embodiment but is capable of numerous modifications within the scope of the appended claims . | 2 |
referring now to fig1 , a system 12 for controlling the suspension of the vehicle 10 and embodying the principles of the present invention is provided . the system 12 includes an electronic control unit 16 , a digital displacement pump motor ( ddpm ) 18 , compressible fluid struts ( cfs ) 14 , and displacement sensors 15 . a suspension system of this general type is generally disclosed in u . s . patent application ser . no . 10 / 688 , 095 , filed on oct . 17 , 2003 , which is hereby incorporated by reference . electronic control unit 16 interfaces with the displacement sensors 15 to collect strut relative displacement information . the strut displacement sensors are of the type well known in the industry and therefore need not be discussed in greater detail herein . utilizing the strut relative displacement information , the electronic control unit 16 selects a control strategy to optimize the suspension performance and calculates the desired strut pressure information to implement the control strategy . the desired strut pressure is utilized to operate the ddpm 18 thereby tuning the stiffness and damping characteristics of each compressible fluid strut 14 in accordance with the control strategy . now referring to fig2 , the displacement sensors 15 provide the strut relative displacement 22 to a control algorithm 20 contained in the electronic control unit 16 . block 24 receives the strut relative displacement signals and converts the strut relative displacement signals to body relative velocities 26 . in addition , block 24 also generates strut relative velocities 25 to be used in calculating the desired strut pressure 34 , 36 , 38 . block 28 receives the body relative velocities 26 and performs a frequency decoding algorithm to generate the effective frequencies 30 . block 32 then generates the desired strut pressure 34 , 36 , 38 based on the strut relative displacement 22 , the strut relative velocity 25 , and the effective frequencies 30 . the desired strut pressure 34 , 36 , 38 is received by block 40 to calculate the combined desired strut pressure 42 for each strut 14 . the combined desired strut pressure 42 is provided to the digital displacement pump motor 18 to effectuate a desired control strategy by adjusting the pressure in each strut 14 . various portions of the control algorithm 20 will be discussed in more detail below . now referring to fig3 , the details of block 24 are provided . the strut relative displacement signals 22 ( d if , d ir , d rf and d rr ) are received by the derivative filter 50 , and the derivative filter 50 generates the strut relative velocities 25 ( vs if , vs ir , vs rf , and vs rr ). the strut relative velocities 25 are independently used to calculate the desired strut pressure as discussed later . further , the strut relative velocities 25 are received by block 53 to generate the body relative velocities 26 , or more specifically the body relative heave , pitch , and roll velocity ( v h , v p and v r ). for a specific vehicle , wheelbase ( l ) and tread ( t ) are known and used to calculate the body relative heave , pitch and roll velocities according to the relationship v h =( v lf + v lr + v rf + v rr )/ 4 , v p =( v lf − v lr + v rf − v rr )/( 2 * l ), and v r =( v lf + v lr − v rf − v rr )/( 2 * t ). after the body relative velocity v i ( i = h , p and r ) is calculated , each signal can be used to extract the effective frequency ω ie1 ( i = h , p , r ) for ride control . now referring to fig4 , the frequency decoding algorithm 28 is applied at the vehicle body mode frequency range . accordingly , the body relative velocity 26 is provided to a high - pass filter 60 and a low - pass filter 62 . the vehicle body mode frequency is ω 1 (= 2πf 1 ), therefore , a lower frequency ω 0 ( about two or three times less than ω 1 ) can be selected , along with an intermediate frequency ω 01 between ω 0 and ω 1 . these frequencies can be used as break frequencies for the high - pass filter 60 and the low - pass filter 62 . the high - pass filtered body relative velocity 61 is used to extract a first frequency amplitude 65 ( a 1 ) at the selected frequency ω 1 , as denoted by block 64 . similarly , the low - pass filtered body relative velocity 63 is used to extract a second frequency amplitude 67 ( a 0 ) at the selected frequency ω 0 , as denoted by block 66 . in block 68 , the first frequency amplitude 65 in the second frequency amplitude 67 are combined according to the relationship a 1 / a 0 to generate the effective frequency 30 . now referring to fig5 , a description of the algorithm to extract the frequency amplitude at the selected frequency such as in blocks 64 and 66 , is provided in reference to selection of the first frequency amplitude 65 ( a 1 ). the high - pass filtered body relative velocity 61 is provided to a washout filter in block 70 . the washout filter modifies the high - pass filtered body relative velocity 61 according to certain washout factors 76 . the selected frequency 80 ( ω 1 ), along with the result of the washout filter 70 , is provided to a band - pass filter in block 72 . the results from the band - pass filter 72 and the washout filter 70 are provided to an integrator 74 . the result of the integrator 74 is provided , along with the result of the band - pass filter 72 and the selected frequency 80 , to a modal generator in block 78 . utilizing the selected frequency information 80 the modal generator result is provided to a smoothing filter 82 , which results in the frequency amplitude 65 ( a 1 ). similarly , the above - described algorithm to extract the frequency amplitude at a selected frequency may be applied to the second frequency amplitude 67 ( a 0 ) in the same manner . referring again to fig4 , the effective frequency ω ie1 ( i = h , p , r ) is used for integrating different control strategies required for different frequency ranges . similarly , the above procedure can be applied to the frequency range around the wheel - hop mode frequency ω ie2 ( i = h , p , r ). for illustrative purposes the control algorithm for the low - band - width active suspension system is provided . for the low bandwidth active suspension , a bandwidth of 5 to 7 hz is targeted due to the limited capability of the ddpm with a limited power supply . therefore , if the suspension dynamics dominate in the frequency range beyond the bandwidth , the control algorithm will set the ddpm to idle to save power and let the cfs work in a passive state . if the effective frequencies of the suspension dynamics are less than the bandwidth , the control algorithm can select different strategies to better isolate the vehicle body from the subjected vibrations . those strategies can be stiff stiffness , soft stiffness , soft rebound damping , hard compression damping or variations thereon . in addition , a traditional passive shock absorber damping capability exists in the cfs , such as , hard damping for rebound and soft damping for compression . based on the effective frequencies ωie 1 and ω ie2 ( i = h , p , r ), strategy mappings can be determined for stiffness control and damping tuning with different effective frequencies as described in tablel below . for example , if the heave body mode is 1 . 4 hz , then the ω he1 - based strategy mapping can be − 1 ( representing stiff stiffness ) for ω he1 less than 0 . 9 hz , 1 for ω he1 near 1 . 4 hz ( and beyond ), and a linearly interpolated value ( or other curves ) for ω he1 between 0 . 9 and 1 . 4 hz . the control signals may be reduced beyond the given bandwidth by : ( 1 ) directly forcing the ω h31 - based strategy mapping to close to 0 if ω he1 is close to 5 to 7 hz and 0 beyond the bandwidth , ( 2 ) using ω he2 to identify the high frequencies so that the ω he2 - based strategy mapping is 1 below 5 to 7 hz and becomes 0 beyond the bandwidth . the product of two strategy mappings , ω he1 84 and ω he2 86 , for the stiffness control are shown in fig6 . similarly the strategy mappings for heave damping can be properly derived from table 1 . now referring to fig7 , the desired strut pressure algorithm 32 is provided in more detail . the strut relative displacements 22 are provided to the transfer function f ( d i ) as provided in block 88 . further , f ( d i ) ( i = lf , lr , rf and rr ) is a function of the strut relative displacements , always no less than zero , and the outputs are desired pressures for each of the cfs . the strategy mapping is also used to decide whether a stiff or soft stiffness should be required for the feedback . the effective frequency 30 ( ω ie1 and ( ω ie2 ) is provided to the strategy mapping for stiffness heave control as denoted by block 90 . in block 92 , the product of the transfer function from block 88 and the strategy mapping for stiffness heave control from block 90 is used to generate the desired strut stiffness heave pressure 93 . the strut relative velocity 22 is provided to the transfer function f ( v h ) as provided in block 106 . effective frequency 30 ( ω ie1 and ω ie2 ) is provided to the strategy mapping for heave damping control as denoted by block 108 . in block 110 , the product of the transfer function from block 106 and the strategy mapping for heave damping control from block 108 is used to generate the desired strut heave damping pressure 111 . the desired strut stiffness heave pressure 93 and the desired strut heave damping pressure 111 are combined in block 112 to generate the desired strut heave pressure 34 . for pitch control , the strut pitch relative velocity from the strut relative velocity 22 is provided to the transfer function f ( v p , l / 2 ), where l is the wheelbase , as provided in block 94 . the effective frequency 30 ( ω he1 and ω he2 ) is provided to the strategy mapping for pitch control as denoted by block 96 . in block 98 , the product of the transfer function from block 94 and the strategy mapping for pitch control from block 96 is used to generate the desired strut pitch pressure 36 . similarly , for roll control , the strut roll relative velocity from the strut relative velocity 22 is provided to the transfer function f ( v p , t / 2 ), where t is the tread , as provided in block 100 . the effective frequency 30 ( ω he1 and ω he2 ) is provided to the strategy mapping for roll control as denoted by block 102 . in block 104 , the product of the transfer function from block 100 and the strategy mapping for roll control from block 102 is used to generate the desired strut roll pressure 38 . as a person skilled in the art will readily appreciate , the above description is meant as an illustration of implementation of the principles this invention . this description is not intended to limit the scope or application of this invention in that the invention is susceptible to modification , variation and change , without departing from spirit of this invention , as defined in the following claims . | 1 |
[ 0032 ] fig3 contains a block diagram of the tis system airborne component . the airborne component of fig3 may comprise an avionics system carried aboard the aircraft as part of the aircraft &# 39 ; s suite of avionics , or optionally may be included in a handheld or other portable device carried aboard the plane by the crew which interfaces with the aircraft transponder . in the diagram of fig3 the tis airborne component includes an antenna 50 and a transponder 52 for receiving mode s signals broadcast from a ground station containing the tis data for nearby aircraft . the tis data received by mode s transponder 52 is then forwarded via a communication data bus 54 to a mode s airborne data link processor , or adlp , 60 . the adlp processor 60 comprises a bi - directional transponder interface which processes each tis message received and presents the message contents to a tis processor via an interface 98 . as explained in greater detail below , the tis message includes transponder data for up to eight nearby aircraft including aircraft bearing , range , relative altitude , ground track , as well as own aircraft ground track . in a preferred embodiment of the invention , interface 98 comprises a mode s specific protocol as described in the above referenced rtca document d0 - 239 . the tis processor 94 drives a tis display 100 for displaying to the pilot traffic in the vicinity of the aircraft . in a preferred embodiment of the invention , tis display 100 displays traffic using the symbology used on a conventional tcas display as shown in fig2 . the tis display , however , does not display resolution advisory information since the tis system merely displays traffic and does not include the collision avoidance algorithms present in tcas systems . the tis display 100 may be a multipurpose display also used for displaying , for example , weather data , terrain data , and / or navigation data . when the pilot wishes to view tis data , the pilot so indicates by initiating a request using a pilot interface 102 . in a preferred embodiment of the invention , interface 102 may comprise a select button or switch that signals to the tis processor 104 that tis information should be displayed on display 100 . in response to the tis data request received at interface 102 , tis processor 98 instructs airborne data link processor 60 to downlink a request for such data in the mode s communications broadcast to the ground by transponder 52 . as shown in fig3 a data link 104 known as a gicb , or ground initiated comm - b , link encodes the tis data request for inclusion in the downlink broadcast by transponder 52 . the tis message uplinked from the ground has the structure given in table i below . each uplinked message consists of 56 bits with each message field having the bit widths shown in table i . table i tis uplink message structure header message type traffic block 1 traffic block 2 8 6 21 21 as shown in table i , each tis uplink message contains two 21 bit traffic blocks . each of these traffic block fields contain six subfields as documented in table ii below . the six subfields describe the bearing , range , relative altitude , altidute rate and heading for a single intruder aircraft . hence , data for a maximum of two aircraft can be uplinked in a single tis messge . up to four tis messages may be uplinked to any given aircraft in a single scan . thus , data for eight intruder aircraft can be sent to the requesting aircraft in response to an active tis request . the traffic bearing field is a six bit field containing the bearing angle from the own - aircraft to the alert aircraft quantitized in six degree increments . the bearing angle is defined with respect to the own aircraft ground track . table ii traffic information block data fields traffic traffic relative traffic bearing range altitude altitude rate heading traffic status 6 4 5 2 3 1 three types of tis messages can be contained in the uplinked message . the three types of message are : “ keep - alive ,” “ good - bye ,” and traffic data . the particular type of message is specified by the value of the bits contained in the message type field as given in table iii below . table iii message type field values message type value tis message uplink type 0 & lt ; oh & lt ; 60 traffic data , first segment 60 traffic data , intermediate segment ( s ) 61 traffic data , final segment 62 goodbye 63 keep - alive the “ first segment ” traffic data message contains the mode s derived ground track of the aircraft receiving the tis uplinked message . the ground track is given in six degree increments and referenced to magnetic north . the “ oh ,” or own heading , value in the message field is provided to permit the display processor to correct for differences between the aircraft ground track and the aircraft heading as would occur when the aircraft is maneuvering or crabbing into the wind . however , the oh correction can only be used when an airborne heading sensor is utilized . smaller aircraft of the type envisioned to use the tis system may not have the capability to provide this sensor input to the tis system . in addition , hand - held or portable tis units would receive own aircraft data from a gps which provides ground track only and does not include aircraft heading data . the present invention permits the correct orientation of the intruder aircraft on the display relative to the own aircraft when an airborne heading sensor is not available . the present invention thus permits the display to show the correct orientation of intruduer aircraft when maneovering . fig4 depicts a flow chart for correcting intruder aircraft orientation in the absence of own heading data according to an embodiment of the present invention . in the flow chart of fig4 the aircraft actual track data is received from , for example , an onboard or portable gps device . the tis uplink message contains the own aircraft track heading as derived from the downlinked mode s data . the actual track 200 received from the on board gps device and the uplinked track data 202 received in the uplinked data message are compared in step 206 . if the two tracks are substantially equal then the aircraft is not likely to be maneovering and no correction need to be applied to the display . the uplinked track heading may therefore be used to depict intruder aircraft relative to the own aircraft as shown in step 208 . if the uplinked track and the actual track differ , then a correction equal to the difference between the two measures is calculated in step 210 . in step 212 this correction is applied to the uplinked intruder aircraft positions to better depict the positons of these aircraft relative to the own aircraft on the display . the correction logic of fig4 may be implemented as software , executable code , firmware , or as a microelectronic circuit . in a preferred embodiment of the invention , the invention is implemented as code stored in a flash memory device and located in the tis display processor . however , the invention may be implemented as part of any general purpose processor located aboard the aircraft . for example , the invention may be hosted in transponder 52 , or alternatively , in mode s adlp 60 . the invention has now been described with reference to the preferred embodiments . variations and modifications will be readily apparent to those of ordinaryskill in the art . for these reasons , the invention is to be interpreted in viewof the claims . | 6 |
the following provides an explanation of the linear motion rolling guide unit of the present invention with reference to the attached drawings . as indicated in fig5 the linear motion rolling guide unit claimed in the present invention has respective first and second relative motion members in the form of bed 11 and table 12 . this bed 11 and table 12 are obtained by , for example , bending processing and punching processing and so on using sheet steel for the material . said bed 11 and table 12 are formed so that the shape of their cross - sections , at a right angle with respect to their lengthwise shape direction , are substantially u - shaped . as is particularly clear from fig6 track grooves 11a and 12a , having substantially v - shaped cross - sections , are formed in the outsides on the left and right sides of bed 11 and on the insides of both the left and right sides of table 12 , respectively . bed 11 and table 12 are arranged so that bed 11 is inside table 12 so that these track grooves 11a and 12a mutually oppose each other . cage 15 , formed substantially into the shape of a rectangular plate and having a long shape , is juxtaposed between said track grooves 11a and 12a . fig7 through 12 indicate the details of this cage 15 . furthermore , cage 15 is comprised of an elastic substance such as synthetic resin or synthetic rubber and so forth . as is indicated in fig6 and fig8 through 12 , a plurality of circular openings 15a are formed in a row in cage 15 . rolling elements in the form of balls 16 are inserted into each of said openings 15a . these balls 16 roll over said track grooves 11a and 12a accompanying linear movement of bed 11 and table 12 . furthermore , as indicated in fig5 end caps 17 and 18 are provided on both the front and back ends of bed 11 and table 12 ( only one end of bed 11 and table 12 is shown in the drawing ) to prevent cage 15 and balls 16 from coming out . as indicated in fig5 through 12 , a plurality of projections 15b and 15c are formed into a single structure in both primary surfaces 15e of cage 15 so as to face said openings 15a and be in a state of protruding from said primary surfaces 15e . these projections are provided in the lengthwise direction of cage 15 to be arranged on a straight line from one end to the other end of said cage 15 . furthermore , those projections provided between mutually adjacent openings 15a are given the reference numeral 15b , while the two projections arranged on both ends of cage 15 are given the reference numeral 15c . each of said projections 15b and 15c perform the action of preventing balls 16 , inserted into openings 15a , from coming out . projections 15b are formed continuously between two openings 15a on both sides , while projections 15c are formed continuously from opening 15a , located in the vicinity of end surface 15d in the lengthwise direction of cage 15 , to said end surface 15d . thus , each of projections 15b and 15c are formed continuously between two mutually adjacent openings 15a and from openings 15a to end surface 15d of cage 15 , respectively , thus making it difficult for cage 15 to become warped due to the resulting increased rigidity . however , as is particularly clear from fig9 and 10 , each of said projections 15b and 15c are formed corresponding only to prescribed range h ( indicated in fig9 ), and not to the entire circumference of each opening 15a , in the direction at a right angle to the lengthwise direction of cage 15 , or in other words , the direction of the width of cage 15 . thus , since the range formed by each projection 15b and 15c does not cover the entire circumference of openings 15a , but only a prescribed range , the surface area in mutual contact between each of said projections 15b and 15c and balls 16 is held to a low amount , thus reducing slipping resistance . in addition , as is clear from fig6 and 12 , the shapes of the cross - sections of each of projections 15b and 15c at a right angle to the lengthwise direction of cage 15 are trapezoidal . due to said cross - sectional shape , it is difficult for these projections to interfere with each of the corresponding track grooves 11a and 12a of bed 11 and table 12 as indicated in fig6 . in addition , rigidity is increased making each of said projections 15b and 15c durable . furthermore , as indicated in fig6 each of projections 15c ( 15b ) are formed to a height at which their ends enter the insides of each of track grooves 11a and 12a of bed 11 and table 12 by only the amount of dimension e . as a result of having this structure , said projections 15b and 15c are easily able to prevent balls 16 from falling out of cage 15 , and balls 16 and cage 15 can be prepared prior to assembly of said linear motion rolling guide unit in the form of a ball and cage assembly by incorporating said balls 16 in said cage 15 . the following provides a detailed description of the form of each of the openings 15a as well as projections 15b and 15c formed in cage 15 . as is clear from fig1 , each of openings 15a is formed so that its diameter d 1 is slightly larger than the diameter of balls 16 that are inserted therein . with respect to each of projections 15b and 15c provided so as to face each of said openings 15a , the intervals between adjacent projections 15b or the intervals between projection 15b and projection 15c are smaller than the diameter of balls 16 , and are equal to dimensions m and m so as to differ on both sides of openings 15a . moreover , these intervals differ in alternating fashion in the lengthwise direction of cage 15 . furthermore , the relationship between each of these dimensions is as follows : d & gt ; m & gt ; m . the dimensional relationship described above is the result of injection molding of said cage 15 . the following provides an explanation of the method for manufacturing cage 15 . firstly , pins 20 , of a shape of a barrel in which both ends are chamfered as indicated in fig1 , are arranged at a constant pitch inside a metal mold ( not shown ) for manufacturing of the cage . molten synthetic resin and so on is then injected into said metal mold followed by cooling and solidification . the mold is then separated and the resulting molded article is removed . pins 20 are removed in the opposite direction in alternating fashion as indicated by arrow p , thus resulting in cage 15 . when pins 20 are being removed as described above , the portion on the side of the direction in which they are removed is spread apart . this results in the larger interval m described above . as described above , by pulling out pins 20 in the opposite direction in alternating fashion , different intervals m and m are arranged in a row in alternating fashion in the lengthwise direction of cage 15 . thus , although cage 15 is able to rotate about the center of the axis that passes through each of balls 16 , it does not move in the horizontal direction , and an increase in sliding resistance , caused by full - surface contact by said cage 15 with the outside surface of bed 1 and the inside surface of table 12 , is prevented . furthermore , although a rolling guide unit for linear motion is indicated in the embodiment described above , the present invention can also be applied to , for example , an arc - shaped rolling guide unit that follows a curved path . in addition , although rolling elements in the form of balls 16 are indicated in the embodiment described above , the present invention is not limited to such , but rather may also be of a constitution wherein rollers and so forth are used . according to the present invention as explained above , since projections , that prevent rolling elements from coming out of a plurality of openings formed in a row for insertion of rolling elements , are formed continuously between each opening , the cage is less susceptible to warping due to its increased rigidity , thus offering a first advantage of achieving a smooth operating state of the rolling guide unit . in addition , since the range over which said projections are formed is not over the entire circumference of said openings , but rather only over a prescribed range , the surface area at which there is mutual contact between said projections and the rolling elements is held to a small amount and reduces the amount of slipping resistance , thus offering a second advantage of even smoother sliding . | 5 |
the present invention is directed to a modular ivr overlay system to supplement an interactive voice response (“ ivr ”) system for the processing of calls , and a method for processing calls using the modular ivr system in conjunction with an ivr system . fig1 is an illustration of an exemplary embodiment of a system 100 that may be used at call - centers for the processing of calls . the system 100 may include a typical ivr system 110 integrated with a modular ivr overlay system 140 according to an embodiment of the present invention . the system 100 may receive a call from a caller on a phone 112 or 114 . the call may be connected to the ivr system 110 at the call - center through a telephone carrier &# 39 ; s switching network or some other type of network infrastructure represented by the communications connections 116 and 118 . the ivr system 110 may include a server 120 running various applications such as a voice extensible markup language (“ vxml ”) browser , a voice synthesizer software application , and a voice recognition software application . the ivr system 110 may also include a database 122 to store voice data so that voice recognition can be performed by the ivr system 110 . to supplement the ivr system 110 , the modular ivr overlay system 140 is deployed with the ivr system 110 . the deployment of the ivr overlay system 140 may involve a local or remote connection to the ivr system 110 . this connection may be made through virtually any type of network connection , including an ethernet connection , a t1 connection , a wireless connection , fiber optics , the internet , wide area network , (“ wan ”), local area network (“ lan ”), etc . the modular ivr overlay system 140 includes an application server 142 and a plurality of agent workstations 144 , 146 and 148 . although the embodiment illustrated in fig1 only shows a single application server and three agent workstations , different implementations of modular ivr overlay system 140 may have various designs and configurations . the various configurations may vary the number of application servers and agent workstations , their locations and connections . the agent workstations 144 , 146 , and 148 are networked to the application server 142 . the network connection may be made via virtually any type of network connection including an ethernet connection , a t1 connection , a wireless connection , fiber optics , the internet , wide area network , (“ wan ”), local area network (“ lan ”), etc . the modular ivr overlay system 140 also includes a graphical user interface (“ gui ”) application ( not shown ) running at each of the agent workstations . the gui presents call - data associated with calls to live agents , and receives commands from the live agents to efficiently and accurately process calls . during operation of the system 100 , the ivr system 110 performs its regular functions of prompting callers for information and receiving the utterances spoken by the callers in response . as a caller is speaking utterances in response to the prompts , the ivr system 110 generates call - data associated with each utterance , including a recording of the utterance , a computer generated estimate of the utterance , and a confidence score associated with the estimate . this call - data may be stored on the server 120 . as this call - data is being gathered by the ivr system 110 , the application server of the modular ivr overlay system 140 uses “ hooks ” to request the call - data . the hooks may include standalone software applications or software scripts that run in a browser , and may reside on the application server 142 . further , the application server 142 includes an agent messaging system ( not shown ) that determines the allocation of calls among the agent workstations 144 , 146 and 148 , and transmits the call - data to the corresponding workstation . the call - data is presented to an agent at the assigned workstation via the gui . after analyzing the call - data presented by the gui , the agent can take actions to correct or confirm the call - data associated with the utterance , instruct the ivr system 110 to re - prompt the caller for the information via the application server 142 , or transfer the caller to a live agent . the system can present all of the call - data associated with a single call to a single agent . alternatively , the system can present distribute the call - data from a single call to multiple agents so that no one agent is presented all the call - data associated with a single call . this is useful for applications such as the reset of passwords where it may be undesirable for a single agent to see all of a caller &# 39 ; s sensitive data . fig2 is an exemplary flow diagram of a call - flow 200 being processed by an ivr system with a modular ivr overlay system according to an embodiment of the present invention . the elements of fig2 will be described with reference to the elements and features of the system 100 depicted in fig1 , and an embodiment where all the call - data associated with a single call is processed by a single agent . however , the call - flow 200 of fig2 is not confined to the system 100 as shown in fig1 , or the embodiment where a single agent processes all the call - data associated with a single call , but is representative of a call - flow of a call being processed by an implementation of a modular ivr overlay system with an ivr system according to the present invention . accordingly , alternative embodiments in accordance with the present invention where the call - data associated with a single call is distributed among multiple agents may be implemented . in the call - flow 200 , the prompts 202 , 204 , 206 , 208 , 210 , and 212 are exemplary prompts that the ivr system 110 may present to a caller in acquiring information from the caller in order to process a call . in response to each of the prompts , the caller may speak an utterance to answer each prompt . the “ vr hooks ” 214 , 216 , 218 , 220 , 222 , and 224 may include software applications or scripts utilized at the application server 142 of the modular ivr overlay system 140 to request and receive call - data that is generated by the ivr system 110 for each utterance . the call - data for each utterance is illustrated as the call - data blocks 226 , 228 , 230 , 232 , 234 , and 236 . each of the call - data 226 - 236 generated by the ivr system 110 includes a recording of the utterance , an estimate of the utterance in text form , and a confidence score associated with the respective utterance . the hooks 214 - 224 enable the call - data 226 - 236 associated with each utterance to be transmitted to the application server 142 of the modular ivr overlay system 140 . at the application server 142 , the call - data 226 - 236 can be saved in a database 244 . the call - data 226 - 236 is then forwarded to an agent messaging system 240 that assigns the call to a specific agent , and transmits one or more of the call - data 226 - 236 to the workstation 242 of the assigned agent . the workstation 242 may be any of the agent workstations 144 - 148 in the system 100 of fig1 . in selecting a specific agent to process any of the call - data 226 - 236 , the agent messaging system 240 implements an algorithm to generate a priority score for each available agent . first , the agent messaging system 240 determines the status of each agent ( e . g ., “ active ,” “ on break ,” “ logging out ,” etc .). for each “ active ” agent , a priority score is generated . to generate the priority score for each agent , the agent messaging system 240 may consider various statistical information associated with each “ active ” agent . examples of statistical information include the number of active calls , the number of failed utterances , the number of failed utterances in a wait - state , a ratio of completed utterances to total number of utterances , agent response times , caller hold times , and caller satisfaction indicators . these data points can then be combined as a weighted average to calculate the priority score . the priority scores can be used to determine which agent will be assigned a call as it is received in real - time , or an ordered priority queue listing all the available agents can be constructed and continuously updated periodically . after an agent has been selected , the call - data 226 - 236 is transmitted to the agent workstation 242 and may populate a gui ( not shown ) at the agent workstation 242 . in an exemplary embodiment , each call - data 226 - 236 associated with a specific utterance may populate different fields of the gui . in addition to presenting the call - data 226 - 236 to the agent on the agent workstation 242 , the gui is configured so that the assigned agent is able to take certain actions for any of the call - data 226 - 236 . the agent is able to see the confidence score associated with the utterance , listen to the recorded utterance , and see the estimate generated by the ivr system 110 . based on the actions the agent opts to take for each call - data 226 - 236 , the agent may correct the estimate if necessary , confirm that the estimate is correct , instruct the ivr system 110 to re - prompt the caller for the specific utterance , or instruct the ivr system 110 to transfer the call to a live agent . the action taken by the agent is transferred back to the application server 142 . the agent action regarding the call - data 226 - 236 is used to instruct the ivr system 110 how to proceed in the call - flow 200 . if the agent has confirmed and / or corrected all the estimates included in each of the call - data 226 - 236 , the ivr system 110 may confirm the utterances with the caller as shown in block 248 , and complete the call . however , if the caller does not confirm the utterances presented in block 248 , the caller may be prompted to state the mistake , generating a call - data 250 for the utterance stating the mistake . the call - data 250 is transmitted to the application server 142 , and the process is repeated . additionally , if the utterances are unconfirmed in step 248 , the ivr system 110 and the application 142 may be notified that the call is placed on hold , and indicate that the call - data 250 is urgent . in a situation where the agent is not able to correct or confirm the estimate of a specific call - data for a specific utterance , the agent can instruct the ivr system 110 to re - prompt the caller for the specific utterance . the ivr system 110 will re - prompt the caller as shown with arrow 246 . although arrow 246 is depicted re - prompting the caller for the prompt 202 , this is merely exemplary , and the caller may be re - prompted for any of the prompts 202 - 212 . furthermore , the re - prompt can be executed so that the caller is only required to repeat the one utterance for the specific prompt and not all the prompts in the call - flow 200 . after the caller has been re - prompted and the utterance is received by the ivr system 110 , the process is repeated for the call - data generated for the re - prompted utterance . fig3 is an exemplary flow diagram of a method 300 illustrating the processing of an individual utterance stored as call - data being processed by an ivr system with a modular ivr overlay system according to an embodiment of the present invention . fig3 will be described with reference to the elements and features of the system 100 and the call - flow 200 depicted in fig1 and 2 . however , the method 300 of fig3 is not limited to the system 100 and call - flow 200 as shown in fig1 and 2 , and is only representative of call - data being processed by an exemplary implementation of a modular ivr overlay system with an ivr system according to the present invention . during step 305 , the call - data is received by the ivr overlay system 140 . the call - data is saved in the ivr overlay system database 142 during step 310 . during step 315 , the agent messaging system 240 determines which agent to assign the call - data . the call - data is then transmitted to the assigned agent &# 39 ; s workstation , and populates a gui at the agent &# 39 ; s workstation during steps 320 and 325 . during steps 330 and 335 , the agent analyzes the call - data by evaluating the confidence score , the estimate and listening to the recording of the utterance . based on the assessment of the call - data , it is determined during step 340 whether the generated estimate is correct . if the estimate is correct , it is confirmed and saved during step 345 . however , if the estimate is incorrect , the agent determines whether or not it can be corrected based on the recording . if a determination can be made , the agent edits the estimate to accurately reflect the utterance of the caller during step 355 , and proceeds to save and confirm the edited estimate . if the agent cannot make a determination , the agent considers whether the call should be transferred to a live agent during decision block 360 . this determination may be based on , for example , the complexity of the information requested , the complexity of the reason for the call , the quality of the call and / or recording , availability of live agents , etc . based on this determination , the call is either transferred to a live agent during step 365 , or the agent instructs the ivr system 110 to re - prompt the caller for the information during step 370 . fig4 is an exemplary screen shot of a graphical user interface (“ gui ”) 400 that is configured to display call - data and receive agent commands on agent workstations . the elements of fig4 will be described with reference to the elements and features of system 100 depicted in fig1 , the call - flow 200 of fig2 and method 300 of fig3 . however , the gui 400 of fig4 is not limited to the descriptions used in reference to fig1 , 2 , and 3 , and may be representative of a gui according to any implementation of a modular ivr overlay system with an ivr system according to the present invention . the gui 400 may be a browser - based script as shown in fig4 , or a separate stand alone software application . the gui 400 may include several session tabs 402 , 404 , 406 , and 408 , where each session tab corresponds to a different call . the agent workstation 242 receives the call - data 226 - 236 from the agent messaging system 240 . the call - data 226 - 236 populates fields 420 , 422 , 424 , 426 , 428 , 430 , 432 , 434 , and 436 associated with the call corresponding to session tab 406 . each field 420 - 436 may be populated with call - data associated with a single utterance , and may include an entry 446 containing the estimate generated by the ivr system 110 . further , the call - data associated with each utterance populates the gui 400 in a logical application - specific manner based on the type of call being processed for efficient processing of the call . examples of such groupings include : name and address ; various call - data associated with credit card information ( e . g ., credit card number , expiration date , etc . ); various call - data associated with account information ( e . g ., account number , social security number , etc . ); various call - data associated with employee information ( e . g ., employee identification , date of birth , social security number , etc . ); and various call - data associated with date information ( e . g ., month , day , year , etc .). furthermore , the gui 400 may also include audio buttons 444 that allow the agent to listen to the recorded utterance included in the call - data 226 - 236 . the gui 400 may further include a status indicator 442 , that may be based on the confidence score contained in the call - data 226 - 236 . the gui 400 may also include action buttons 450 that allow the agent to take actions in response to the call - data for each utterance . the agent can confirm the estimate is correct or enter a corrected utterance in a form 448 . alternatively , the agent can instruct the ivr system 110 to re - prompt the caller for the specific utterance , or transfer the call to a live agent . in addition to the features of the gui 400 that allow the agents to process the calls and the call - data , the gui 400 may also include “ sign - off ,” and “ break ” functions , as shown in fig5 - 9 . fig5 - 8 show various screen shots of an implementation of the gui 400 showing the status of the agent . fig5 shows the status of an agent in the signing - off process . fig6 shows the status of an agent who is in the process of going on break . fig7 shows the status of an agent who is on break . fig8 shows the status of an agent who is active . further , fig9 shows an exemplary flow diagram of a method 900 illustrating the steps that may be implemented in executing a “ sign - off ” or “ break ” request according to an embodiment of the present invention . the “ sign - off ” and “ break ” features of the gui 400 work in conjunction with the agent messaging system 240 and the method 200 . an agent can activate the “ sign - off ” or “ break ” feature via the gui 400 as shown in steps 905 and 910 . next , the agent &# 39 ; s status will be changed to “ logging off ” or “ pausing ”, respectively , as shown in steps 915 and 920 . this ensures that the agent messaging system 240 is aware that the agent is either going on break or in the process of signing off , and will not direct any more calls to the agent during steps 925 and 930 . after all of the agent &# 39 ; s calls have been processed , the agent &# 39 ; s status is changed to unavailable or “ on break ” during steps 965 and 970 . optionally , as shown in decision blocks 935 and 940 and step 975 , the agent messaging system 240 can pull calls already assigned to an agent workstation from an agent in the process of logging out or going on break to expedite this process , and re - assign the calls to “ active ” agents . further , the gui 400 may include an autocue feature ( not shown ). the autocue feature of the gui 400 prioritizes to ensure that the calls or utterances with the highest priority are processed efficiently and effectively . autocue enables the agent to work passively , allowing the agent to wait for the gui to prioritize the work flow and present the agent with the next utterance to be processed . in an exemplary embodiment in accordance with the present invention , the autocue feature analyzes all of the currently active call - data blocks currently in each agent &# 39 ; s queue to determine the age of each of the blocks . based on this information , the autocue feature generates a queue so that the older calls are given a higher priority . the active call - data blocks are then arranged according to the queue so that the older , and thus higher priority calls , are processed first . other factors that may be considered in prioritizing the calls is the importance of each call , and an estimated time that is required to complete processing of the call . this feature reduces wait times that callers may experience , and also processing times associated with calls . to further assist the agent , the autocue feature may optimize the configuration of the gui screen presented to the agent for each utterance that is prioritized according to the autocue that is being processed by the agent . in an exemplary embodiment , a “ first name ” field included in the gui may be highlighted and selected as the utterance is being played for the agent . this may allow the agent to immediately edit the field without first selecting the field via a keystroke or a click with a computer mouse . additionally , after the agent completes processing an utterance prioritized by the autocue feature , the autocue feature may select and prepare the utterance with the next highest priority in a similar manner to allow seamless processing of the prioritized list of utterances by the agent . thus , the autocue feature allows the agent to focus on utterances in an order of decreasing priorities . additionally , call - data that has been confirmed by a caller or entered by an agent may be stored to optimize the voice - recognition capabilities of the ivr . the stored data may include the call - data , including an utterance and an accurate interpretation of the utterance . this data may be compiled and archived and may be accessed by the ivr to improve and expand the speech recognition capabilities of the ivr . thus , while there have been shown , described , and pointed out fundamental novel features of the invention as applied to several embodiments , it will be understood that various omissions , substitutions , and changes in the form and details of the illustrated embodiments , and in their operation , may be made by those skilled in the art without departing from the spirit and scope of the invention . substitutions of elements from one embodiment to another are also fully intended and contemplated . the invention is defined solely with regard to the claims appended hereto , and equivalents of the recitations therein . | 7 |
consideration of the factors discussed above results in the identification of certain design goals which are achieved by the prosthetic heart valve of the present invention . first , the prosthetic heart valve must have enough material in the leaflet for wide opening and low closing , but more than this amount increases the energy barrier to opening . to ensure that there is sufficient , but not an excess of material , a draping analysis discussed in more detail below is used . second , to ensure sufficient material for wide opening and low closing , the valve can only be manufactured in a partially open position : ( a ) by deforming the stent posts outwards during manufacture ; ( b ) by introducing multiple curves in the leaflet free edge ( but see below ); ( c ) by making the closed position asymmetric ; and ( d ) combinations of the above . third , if there is enough material for low closing and wide opening , the energy barrier to opening may be high enough to prevent opening of all leaflets at low flow . the energy barrier can be minimized by : ( a ) introducing multiple curves in the leaflet ; ( b ) making the leaflet asymmetric ; and combinations of the above . fourth , open commissures are needed for blood handling and closed commissures are needed for regurgitation , so the valve should have partially open commissures . in particular the included angle between adjacent leaflet free edges at the valve commissures ( for example see angle α of the symmetric leaflets shown in fig1 ) should be in the range of 10 - 55 °, preferably in the range 25 - 55 °. as discussed above , the use of multiple curves in the leaflet helps assure wide opening and more complete closure of the valve and to minimize the energy barrier to opening of the valve . however , the introduction of multiple curves of more than 1 . 5 wavelengths to the leaflet can be a disadvantage . while there may be sufficient material in the leaflet to allow full opening , in order for this to happen , the bends in the leaflet must straighten out completely . the energy available to do this arises only from the pressure gradient across the open valve , which decreases as the leaflets becomes more open , i . e ., as the valve orifice area increases . this energy is relatively small ( the more successful the valve design the smaller it becomes ), and does not provide enough energy to remove leaflet curves of more than 1 . 5 wavelengths given the stiffness of the materials available for valve manufacture . the result is they do not straighten out and the valve does not open fully . a draping analysis is used as a first approximation to full finite element analysis to determine if the starting shape of a membrane is such that it will take on a desired final shape when placed in its final position . from a durability standpoint the focus is on the closed position , and the desired shape of the leaflet in its closed position is defined . draping analysis allows the leaflet to be reformed in a partially open position . draping analysis assumes that very low energy deformation is possible ( in reality any form of deformation requires energy ). in order for this to occur the bending stiffness of the leaflet / membrane must be small , each element of the membrane should be free to deform relative to its neighbour , and each element should be free to change shape , i . e ., the shear modulus of the material is assumed to be very low . in applying the draping analysis , it is assumed that the leaflet can be moved readily from an original defined closed position to a new position in which it is manufactured . when the valve is actually cycled , it is assumed that the leaflet when closing will move from the manufactured position to the originally defined closed position . this allows the closed position to be optimised from a stress distribution aspect , and the manufactured position to be optimised from the point of view of reducing the energy barrier to opening . both symmetric and asymmetric shapes of the leaflet can allow incorporation of sufficient material in the leaflet free edge to allow full opening . fig1 is a diagrammatic view comparing the shape of symmetric ( solid line ) and asymmetric ( dashed line ) leaflets and also showing the commissure area 12 where the leaflets connect to the frame . an advantage of the asymmetric shape is that a region of higher radius of curvature 14 is produced than is achieved with a symmetric curve having a lower radius of curvature 16 . this region can buckle more readily and thereby the energy barrier to opening is reduced . an asymmetric leaflet also reduces the energy barrier through producing unstable buckling in the leaflet . during opening symmetric leaflets buckle symmetrically i . e ., the leaflet buckles are generally mirrored about the centerline of the leaflet thus balancing the bending energies about this centerline . in the asymmetric valve the region of higher radius buckles readily , and because these bending energies are not balanced about the center line , this buckle proceeds to roll through the leaflet producing a sail - like motion producing a low energy path to open . an additional feature of the asymmetric valve is that the open position is also slightly asymmetric , as a result of which it offers a somewhat helical flow path , and this can be matched to the natural helical sense of the aorta . suggested benefits of this helical flow path include reduction of shear stress non - uniformity at the wall , and consequent reduction of platelet activation . first and second embodiments of the valve prosthesis will be described with reference to the accompanying drawings . fig2 is a perspective view of a heart valve prosthesis made in accordance with the present invention . the valve 10 comprises a stent or frame 1 and attached leaflets 2 a , 2 b , and 2 c . the leaflets are joined to the frame at scallops 5 a , 5 b , and 5 c . between each scallop is post 8 , the most down - stream part of which is known as a stent tip 6 . leaflets 2 a , 2 b , and 2 c have free edges 3 a , 3 b , and 3 c , respectively . the areas between the leaflets at the stent tips 6 form commissures 4 . the following describes a particular way of designing a first embodiment of a valve of the present invention . other different design methodology could be utilized to design a valve having the structural features of the valve disclosed herein . five computational steps are involved in this particular method : ( 1 ) define the scallop geometry ( the scallop , 5 , is the intersection of the leaflet , 2 , with the frame , 1 ); ( 2 ) geometrically define a valve leaflet in the closed position c ; ( 3 ) map and compute the distribution of area across the leaflet in the closed position ; ( 4 ) rebuild the leaflet in a partially open position p ; and ( 5 ) match the computed leaflet area distribution in the partially open or molded position p to the defined leaflet in the closed position c . this ensures that when an increasing closing pressure is applied to the leaflets , they eventually assume a shape which is equivalent to that defined in closed position c . this approach allows the closed shape of the leaflets in position c to be optimised for durability while the leaflets shaped in the molded partially open shape p can be optimised for hemodynamics . this allows the use of stiffer leaflet materials for valves which have good hemodynamics . an xyz co - ordinate system is defined as shown in fig2 , with the z axis in the flow direction of blood flowing through the valve . the leaflets are mounted on the frame , the shape of which results from the intersection of the aforementioned leaflet shape and a 3 - dimensional geometry that can be cylindrical , conical or spherical in nature . a scallop shape is defined through intersecting the surface enclosed by the following equations with a cylinder of radius r ( where r is the internal radius of the valve ): x ell = e so − e sj .√{ square root over ( 1 −( z / e sn ) 2 )} h sj = e so − e sj √{ square root over (( 1 −( z / e sn ) 2 ))}− h so x hyp = h so + h sj √{ square root over (( 1 −( y / h sn ) 2 ))} the shape of the scallop can be varied using the constants e s0 , e sj , h s0 , ƒ ( z ). the definition of parameters used in these and the other equations herein are contained in table 4 . the shape of the leaflet under back pressure ( i . e ., in the closed position c ) can be approximated mathematically using elliptical or hyperbolic co - ordinates , or a combination of the above in an xyz co - ordinate system where xy is the plane of the valve perpendicular to the blood flow and z is the direction parallel to the blood flow . the parameters are chosen to define approximately the shape of the leaflet under back pressure so as to allow convenient leaflet re - opening and minimize the effect of the stress component which acts in the direction parallel to the blood flow , whilst also producing an effective seal under back pressure . the closed leaflet geometry in closed position c is chosen to minimize stress concentrations in the leaflet particularly prone to occur at the valve commissures . the specifications for this shape include : ( 1 ) inclusion of sufficient material to allow a large open - leaflet orifice ; ( 2 ) arrangement of this material to minimize redundancy ( excess material in the free edge , 3 ) and twisting in the centre of the free edge , 3 ; and ( 3 ) arrangement of this material to ensure the free edge , 3 , is under low stress i . e ., compelling the frame and leaflet belly to sustain the back - pressure . fig3 is a partial sectional view ( using the section 3 - 3 shown in fig2 ) showing only the intended position of the leaflet in the closed position . the shape of this intended position is represented by the function x closed ( z ). this function can be used to arrange the shape of the leaflet in the closed position c to meet the aforementioned specification . the curve is defined using the following equation and manipulated using the constants e cj , e co , z co and the functions e cn ( z ) and x t ( z ). x closed ( z ) = - [ e cj · ( 1 - ( z - z e o e c n ( z ) ) 2 ) ] 0 . 5 + e co - x t ( z ) where e cn is a function changing linearly with z and x t ( z ) is a function changing nonlinearly with z thus the scallop shape and the function x closed ( z ) are used to form the prominent boundaries for the closed leaflet in the closed position c . the remaining part of the leaflet is formed using contours s ( x , y ) n sweeping from the scallop to the closed leaflet belly function x closed ( z ), where n is an infinite number of contours , two of which are shown in fig4 b . the length of the leaflet ( or contours s ( x , y ) n ) in the circumferential direction ( xy ) is calculated and repeated in the radial direction ( z ) yielding a function l ( z ) which is used later in the definition of the geometry in the partially open position p . the area contained between respective contours is also computed yielding a function k ( z ) which is also used in the definition of the geometry in position p . the area contained between contours is approximated using the process of triangulation as shown in fig4 b . this entire process can be shortened by reducing the number of contours used to represent the surface ( 100 & lt ; n & lt ; 200 ). the aforementioned processes essentially define the leaflet shape and can be manipulated to optimise for durability . in order to optimise for hemodynamics , the same leaflet is molded in a position p which is intermediate in terms of valve opening . this entails molding large radius curves into the leaflet which then serve to reduce the energy required to buckle the leaflet from the closed to the open position . the large radius curves can be arranged in many different ways . some of these are outlined herein . the leaflet may be molded on a dipping former as shown in fig1 . preferably the former is tapered with an included angle θ so that the end 29 has a diameter which is greater than the end 22 . ( this ensures apposition of the frame and former during manufacture .) in this case , the scallop shape , defined earlier , is redefined to lie on a tapered geometry ( as opposed to the cylindrical geometry used in the definition of the closed leaflet shape ). this is achieved by moving each point on the scallop radially , and in the same movement , rotation of each point about an x - y plane coincident with the bottom of the scallop , until each point lies on the tapered geometry . the geometry of the leaflet shape can be defined as a trigonometric arrangement ( or other mathematical function ) preferably sinusoidal in nature in the xy plane , comprising one or more waves , and having anchoring points on the frame . thus the valve leaflets are defined by combining at least two mathematical functions to produce composite waves , and by using these waves to enclose the leaflet surface with the aforementioned scallop . one such possible manifestation is a composite curve consisting of an underlying low frequency sinusoidal wave upon which a second higher frequency sinusoidal wave is superimposed . a third wave having a frequency different from the first and second waves could also be superimposed over the resulting composite wave . this ensures a wider angle between adjacent leaflets in the region of the commissures when the valve is fully open thus ensuring good wash - out of this region . the composite curve , and the resulting leaflet , can be either symmetric or asymmetric about a plane parallel to the blood flow direction and bisecting a line drawn between two stent tips such as , for leaflet 2 a , the section along line 3 - 3 of fig2 . the asymmetry can be effected either by combining a symmetric underlying curve with an asymmetric superimposed curve or vice versa . the following describes the use of a symmetric underlying function with an asymmetric superimposed function , but the use of an asymmetric underlying function will be obvious to one skilled in the art . the underlying function is defined in the xy plane and connects the leaflet attachment points to the scallop at a given height from the base of the valve . this underlying function shown in fig5 , can be trigonometric , elliptical , hyperbolic , parabolic , circular , or other smooth analytic function or could be a table of values . using sine functions , one possible underlying wave is shown in fig5 and is defined using the following equation . the superimposed wave is defined in the xy plane , and connects the attachment points of the leaflet to the scallop at a given height above the base of the valve . the superimposed wave is of higher frequency than the underlying wave , and can be trigonometric , elliptic , hyperbolic , parabolic , circular , or other smooth analytic function , or a table of values . using sine functions , one possible symmetric leaflet design is formed when the underlying wave is combined with a superimposed wave formed using the following equation . a s can be varied across the leaflet to produce varying wave amplitude across the leaflet , for example lower amplitude at the commissures than in the leaflet centre . b s can be varied to adjust the length of the wave . the superimposed wave is shown in fig6 . the composite wave formed by combining the underlying wave ( fig5 ) with the superimposed wave ( fig6 ) is shown in fig7 . using sine functions , one possible asymmetric leaflet design is formed when the underlying wave ( fig5 ) is combined with a superimposed wave formed using the following equation . a s can be varied across the leaflet to produce varying wave amplitude across the leaflet , for example lower amplitude at the commissures than in the leaflet centre . b s ( y ) can be varied to adjust the length of the wave . the superimposed wave is shown in fig8 . the resulting asymmetric composite wave is shown in fig9 . the composite wave w ( x c , y c ) n is created by offsetting the superimposed wave normal to the surface of the underlying wave ( fig7 , 9 ). while the general shape of the leaflet in position p has been determined using the composite wave , at this stage it is not specified in any particular position . in order to specify the position of p , the shape of the partially open leaflet position can be defined as x open ( z ). this is shown as reference numeral 7 in fig1 . in order to manipulate the composite wave to produce the belly shape x open ( z ) the respective amplitudes of the individual sine waves can be varied from the free edge to the leaflet base . for example , the degree of ‘ openness ’ of the leaflet in position p can be varied throughout the leaflet . the composite wave is thus defined to produce the molded “ buckle ” in the leaflet , and x open ( z ) is used to define the geometry of the leaflet at position p . at this stage it may bear no relation to the closed leaflet shape in position c . in order to match the area distribution of both leaflet positions , ( thus producing essentially the same leaflet in different positions ) the composite wave length is iterated to match the length of the relevant leaflet contour in position c . thus the amplitude and frequency of the individual waves can be varied in such a manner as to balance between : ( a ) producing a resultant wave the length of which is equal to the relevant value in the length function l ( z ) thus approximating the required closed shape when back pressure is applied , and ( b ) allowing efficient orifice washout and ready leaflet opening . also the area contained between the contours in the open leaflet is measured using the same process of triangulation as in the closed position c , and is iterated until it matches with the area contained between relevant contours in position c ( denoted k ( z )) ( through tilting the contours in p relative to each other ). thus the composite waves ( p ( x , y ) n ) pertaining to the contour n and length l ( z ) can be tilted at an angle to the xy plane about attachment points x ( n , 0 ) . y ( n , 0 ) and x ( n , 0 ), − y ( n , 0 ) until the correct area is contained between p ( x , y ) n and p ( x , y ) n - 1 ( see fig1 & amp ; 11 ). this process identifies the values of b s , a u and the contour tilt angle to be used in constructing the mold for the valve leaflet . as long as the constants such as b s and a u , and the tilt angle of the contours relative to the xy plane , are known , the surface of the leaflet in its molded position can be visualised , enclosed and machined in a conventional manner . as a result of this fitting process the composite wave retains the same basic form but changes in detail from the top of the leaflet to the bottom of the leaflet . a composite wave can be defined in the leaflet surface as the intersection of the leaflet surface with a plane normal to the z axis . this composite wave will have the same general form as the composite wave used in the leaflet design but will differ from it in detail as a result of the tilting process described above . in summary therefore one possible method of designing the leaflet of the first embodiment of the present invention is in the following way : ( 1 ) define a scallop shape ; ( 2 ) define a shape approximating the shape of the closed leaflet using elliptical , hyperbolic , parabolic or circular functions , smooth analytical functions or table of values ; ( 3 ) compute the functions l ( z ) and k ( z ), which define the length of the leaflet in the xy plane along the z axis and the area distribution of the leaflet along the z axis ; ( 4 ) use one or more associated sine waves to generate a geometry which is partially - open , which pertains to a leaflet position which is between the two extreme conditions of normal valve function , i . e ., leaflet open and leaflet closed ; ( 5 ) vary the frequency and amplitude of the sinewaves to fit to the length function l ( z ) and the angle at which the contour is tilted to the xy plane to fit to the area function k ( z ); and ( 6 ) the respective amplitudes of the individual sine waves can be varied from the free edge to leaflet base , for example the degree of ‘ openness ’ of the leaflet can be varied throughout the leaflet . examples 1 and 2 set forth hereafter are examples of how the invention of the first embodiment can be put into practice . using the scallop constants in table 1 , the constants required to produce an example of a symmetric leaflet valve ( example 1 , fig1 ) and an example of an asymmetric leaflet valve ( example 2 , fig1 ) are given in table 2 and table 3 respectively . these constants are used in conjunction with the aforementioned equations to define the leaflet geometry . with one leaflet described using the aforementioned equations , the remaining two leaflets are generated by rotating the geometry about the z axis through 120 ° and then through 240 °. these leaflet shapes are inserted as the leaflet forming surfaces of the dipping mold ( otherwise known as a dipping former ), which then forms a 3 - dimensional dipping mold . the composite wave described in the aforementioned equations , therefore substantially defines the former surface which produces the inner leaflet surface . as seen in fig1 the dipping mold 20 is slightly tapered so that the end 29 has a diameter which is greater than the end 22 , and has a first end 22 having an outside diameter slightly smaller than the inside diameter of the frame . the former includes at least two and preferably three leaflet forming surfaces 24 which are defined by scalloped edges 26 and flats 28 . sharp edges in the manufacturing former and on the frame are radiused to help reduce stress concentrations in the finished valve . during the dip molding process the frame is inserted over end 22 of the former so that the scallops 5 and stent posts 8 of the frame align with the scalloped edges 26 and flats 28 of the former . the leaflet forming surfaces 24 are configured to form leaflets during the molding process which have the geometry described herein . this mold can be manufactured by various methods , such as , machining , electrical discharge machining , injection molding . in order that blood flow is not disturbed , a high surface finish on the dipping mold is essential . for the frame there are preferably three posts with leaflets hung on the frame between the posts . a crown - like frame or stent , 1 , is manufactured with a scallop geometry , which matches the dipping mold scallop . the frame scallop is offset radially by 0 . 1 mm to allow for the entire frame to be coated with a thin layer of leaflet material to aid adhesion of the leaflets . leaflets may be added to the frame by a dip - molding process , using a dipping former machined or molded to create the multiple sinewave form . the material of preference should be a semi - rigid fatigue - and creep - resistant frame material such as polyetheretherketone ( peek ), high modulus polyurethane , titanium , reinforced polyurethane , or polyacetal ( delrin ) produced by machining or injection - molding etc . alternatively , a relatively low modulus polymer may be used , which may be fibre - reinforced , to more closely mimic the aortic wall . the frame can be machined or injection molded , and is manufactured preferably from peek or polyacetal ( delrin ). the frame is treated by exposure to a gas plasma or other methods to raise its surface energy above 64 mn / m ( millinewtons / meter ). then the frame is dipped in a polyurethane solution ( preferably elast - eon ™ manufactured by aortech biomaterials pty , sydney australia ) in order to apply a coating of approximately 0 . 1 mm thick . having dried the frame with applied coating in an oven overnight , it is placed on the dipping former and aligned with the former scallops . the combination of frame and three dimensional dipping mold is then dipped into polyurethane solution , which forms a coating of solution on frame and mold . this coating flows slowly over the entire mold surface ensuring a smooth coating . the new coating on the frame and dipping mold solvates the initial frame coating thus ensuring a good bond between leaflet and frame . the dipping mold with polyurethane covering is dried in an oven until all the solvent has been removed . one or more dips may be used to achieve a leaflet with a mean thickness between 40 μm and 500 μm . the shape of the former , and the viscosity and solvent interactive properties of the polyurethane solution , control the leaflet thickness and the distribution of thickness over the leaflet . a dipping process does not allow precise control of leaflet thickness and its variation across a leaflet . in particular , surfaces that are convex on the dipping former result in reduced leaflet thickness when compared with surfaces that are concave . additionally the region of the leaflet adjacent to the frame essentially provides a very small concave radius which traps further polymer solution and this results in thickening of these regions . the shape of the former is substantially defined by the composite wave . radiusing and polishing of the former can both contribute to some variation of the shape . the shape of the inner surface of the leaflets will closely replicate the shape of the former . the shape of the outer surface of the leaflets will be similar to the shape of the inner surface but variations will result from the processing properties of the polymer solution and details of the dipping process used to produce the valve . the leaflet may be formed from polyurethanes having a young &# 39 ; s modulus less than 100 mpa , preferably in the range 5 to 50 mpa . the valve is next removed from the dipping mold . the stent posts , which had been deflected by the taper on the former , now recover their original position . the shape of the leaflets changes slightly as a result of the movement of the stent posts . at this stage the dipping mold and frame is covered with an excess of polyurethane due to the drain - off of the polymer onto the region of the mold known as the drain - off area 30 . leaflet free edges may be trimmed of excess material using a sharp blade rotated around the opened leaflets or using laser - cutting technology . an alternate valve manufacturing method is injection molding . a mold is constructed with a cavity which allows the valve frame to be inserted in the mold . the cavity is also designed with the leaflet geometry , as defined above , as the inner leaflet surface . a desired thickness distribution is defined for the leaflet and the outer leaflet surface of the mold is constructed by adding the leaflet thickness normally to the inner leaflet surface . the leaflet may be of uniform thickness throughout , in the range 40 to 500 microns , preferably 50 to 200 microns , more preferably 80 to 150 microns . the leaflet may be thickened towards its attachment to the frame . alternatively the thickness of the leaflet , along a cross - section defined by the intersection of a plane perpendicular to the blood flow axis and the leaflet , can change gradually and substantially continuously from a first end of the cross - section ( i . e ., first edge of the leaflet ) to a second end of the cross - section ( i . e ., second edge of the leaflet ) in such a way that the mean thickness of the first half of the leaflet is different from the mean thickness of the second half of the leaflet . this mold is inserted in a conventional injection molding machine , the frame is inserted in the mold and the machine injects molten polymer into the cavity to form the leaflets and bond them to the frame . the polymer solidifies on cooling and the mold is opened to allow the complete valve to be removed . the leaflets may also be formed using a reaction - molding process ( rim ) whereby the polymer is synthesized during the leaflet forming . a mold is constructed as described above . this mold is inserted in a reaction - injection molding machine , the frame is inserted in the mold and the machine injects a reactive mixture into the cavity . the polymer is produced by the reaction in the cavity to form the leaflets and bond them to the frame . when the reaction is complete , the mold is opened to allow the complete valve to be removed . yet a further option is to compression mold a valve initially dipped . this approach allows the leaflet thickness or thickness distribution to be adjusted from that initially produced . by varying the thickness of the leaflets the dynamics of the valve opening and closing can be modified . for example , the thickness of the leaflet along a cross - section defined by the intersection of a plane perpendicular to the blood flow axis and the leaflet can be varied so that the thickness changes gradually and substantially continuously from a first end of the cross - section ( i . e ., first edge of the leaflet ) to a second end of the cross - section ( i . e ., second edge of the leaflet ) in such a way that the mean thickness of the first half of the leaflet is different from the mean thickness of the second half of the leaflet . this will result in the thinner half of the leaflet opening first and creating a sail - like opening motion along the free edge of the leaflet . leaflet shape resulting from conventional injection molding , reaction injection molding or compression molding , is substantially defined by the composite wave described above . it will differ in detail for many of the same reasons identified for dip molding . the valves of the present invention are manufactured in the neutral position or close to it and are therefore substantially free of bending stresses in this position . as a result when the leaflet is moved to its closed position the total bending energy at the leaflet center free edge and at the commissures is reduced compared to a valve made according to u . s . pat . no . 5 , 376 , 113 ( jansen et al .). the valves of the present invention may be used in any required position within the heart to control blood flow in one direction , or to control flow within any type of cardiac assist device . the following examples 1 and 2 use the same scallop geometry described using the constants set forth in table 1 : while the examples described herein relate to one valve size , the same method can be used to produce valves from a wide range of sizes . this can be carried out by modifying the constants used in the equations , by resealing the bounding curves such as x closed ( z ) and computing and iterating in the normal fashion or by rescaling the leaflet . the parameters described in the preceding sections are assigned the values set forth in table 2 and are used to manufacture a symmetric valve . the included angle between adjacent leaflet free edges at the valve commissure for this valve is approximately 50 °. the parameters described in the preceding sections are assigned the values set forth in table 3 and are used to manufacture an asymmetric valve . the included angle between adjacent leaflet free edges at the valve commissure for this valve is approximately 48 °. the following describes another particular way of designing a second embodiment of a valve of the present invention . other different design methodology could be utilized to design a valve having the structural features of the valve disclosed herein . five computational steps are involved in this particular method : ( 1 ) define the scallop geometry ( the scallop , 5 , is the intersection of the leaflet , 2 , with the frame , 1 ); ( 2 ) define a contour length function l ( z ) and use this function to define a valve leaflet in the closed position c and optimize the stress distribution on the valve . the stress distribution can be confirmed using finite element analysis ( fea ). thus the resulting stress distribution results from the length function l ( z ) and fea is used to confirm the optimal l ( z ); ( 3 ) rebuild the leaflet in a partially open position p ; and ( 4 ) match , using contour lengths , the computed leaflet area distribution in the partially open or molded position p to the defined leaflet in the closed position c . this ensures that when an increasing closing pressure is applied to the leaflets , they eventually assume a shape which is equivalent to that defined in closed position c . this approach allows the closed shape of the leaflets in position c to be optimised for durability while the leaflets shaped in the molded partially open shape p can be optimised for hemodynamics . this allows the use of stiffer leaflet materials for valves which have good hemodynamics . an xyz coordinate system is defined as shown in fig2 , with the z axis in the flow direction of blood flowing through the valve . the leaflets are mounted on the frame , the shape of which results from the intersection of the aforementioned leaflet shape and a 3 - dimensional geometry that can be cylindrical , conical or spherical in nature . the leaflets are mounted on the frame , the shape of which results from the intersection of the aforementioned leaflet shape and a 3 - dimensional geometry that can be cylindrical , conical or spherical in nature . a scallop shape is defined through cutting a cylinder of radius r ( where r is the internal radius of the valve ) with a plane at an inclined angle . the angle of the cutting plane is dictated by the desired height of the leaflet and the desired distance between the leaflets at the commissures . the closed leaflet geometry in closed position c is chosen to minimize stress concentrations in the leaflet particularly prone to occur at the valve commissures . the specifications for this shape include : ( 1 ) inclusion of sufficient material to allow a large open - leaflet orifice ; ( 2 ) arrangement of this material to minimize redundancy ( excess material in the free edge , 3 ) and twisting in the centre of the free edge , 3 ; and ( 3 ) arrangement of this material to ensure the free edge , 3 , is under low stress i . e ., compelling the frame and leaflet belly to sustain the back - pressure . the closed leaflet geometry is formed using contours s ( x , y ) n sweeping from attachment points on one side of the scallop to the congruent attachment point on the opposite side of the scallop , where n is an infinite number of contours , two of which are shown in fig4 b . the geometry of the contours s ( x , y ) n can be simple circular arcs or a collection of circular arcs and tangential lines ; the length of each contour is defined by l ( z ). hence the geometry is defined and modified using the length function l ( z ). thus the scallop shape and the contours s ( x , y ) n are used to form the prominent boundaries for the closed leaflet in the closed position c . this process can be shortened by reducing the number of contours used to represent the surface ( 5 & lt ; n & lt ; 200 ). for design iteration , the ease with which the leaflet shape can be changed can be improved by reducing the number of contours to a minimum ( i . e ., n = 5 ), although the smoothness of the resulting leaflet could be compromised to some extent . upon optimising the function l ( z ) for stress distribution , the number of contours defining the leaflet can be increased to improve the smoothness of the resulting leaflet ( 100 & lt ; n & lt ; 200 ). the function l ( z ) is used later in the definition of the geometry in the partially open position p . the aforementioned processes essentially define the leaflet shape and can be manipulated to optimise for durability . in order to optimise for hemodynamics , the same leaflet is molded in a position p which is intermediate in terms of valve opening . this entails molding large radius curves into the leaflet which then serve to reduce the energy required to buckle the leaflet from the closed to the open position . the large radius curves can be arranged in many different ways . some of these are outlined herein . as previously described with respect to the first embodiment the leaflet may be molded on a dipping former as shown in fig1 . however , in this embodiment to aid removal of the valve from the former and reduce manufacturing stresses in the leaflet the former is preferably not tapered . the geometry of the leaflet shape can be defined as a circular and trigonometric arrangement ( or other mathematical function ) preferably circular and sinusoidal in nature in the xy plane , comprising one or more waves , and having anchoring points on the frame . thus the valve leaflets are defined by combining at least two mathematical functions to produce composite waves , and by using these waves to enclose the leaflet surface with the aforementioned scallop . one such possible manifestation is a composite curve consisting of an underlying circular arc or wave upon which a second higher frequency sinusoidal wave is superimposed . a third wave having a frequency different from the first and second waves could also be superimposed over the resulting composite wave . this ensures a wider angle between adjacent leaflets in the region of the commissures when the valve is fully open thus ensuring good wash - out of this region . the composite curve , and the resulting leaflet , can be either symmetric or asymmetric about a plane parallel to the blood flow direction and bisecting a line drawn between two stent tips such as , for leaflet 2 a , the section along line 3 - 3 of fig2 . the asymmetry can be effected either by combining a symmetric underlying curve with an asymmetric superimposed curve or vice versa , or by utilising a changing wave amplitude across the leaflet . the following describes the use of a symmetric underlying function with an asymmetric superimposed function , but the use of an asymmetric underlying function will be obvious to one skilled in the art . the underlying function is defined in the xy plane and connects the leaflet attachment points to the scallop at a given height from the base of the valve . this underlying function shown in fig1 , can be trigonometric , elliptical , hyperbolic , parabolic , circular , or other smooth analytic function or could be a table of values . the superimposed wave is defined in the xy plane , and connects the attachment points of the leaflet to the scallop at a given height above the base of the valve . the superimposed wave is of higher frequency than the underlying wave , and can be trigonometric , elliptic , hyperbolic , parabolic , circular , or other smooth analytic function , or a table of values . one possible asymmetric leaflet design is formed when the underlying wave formed using a circular arc is combined with a superimposed wave formed using the following equation . a circular arc is defined by its cord length , 2y ( n , o ) , and amplitude , a u , as shown in fig1 . a s can be varied across the leaflet to produce varying wave amplitude across the leaflet , for example lower amplitude in one commissure than the opposite commissure . b s can be varied to adjust the length of the wave . the superimposed wave is shown in fig1 . the composite wave formed by combining the underlying wave ( fig1 ) with the superimposed wave ( fig1 ) is shown in fig1 . the composite wave w ( x c , y c ) n is created by offsetting the superimposed wave normal to the surface of the underlying wave ( fig1 ). positive γ is defined as the direction of the normal to the underlying wave relative to the x - axis . when y is positive , the composite curve is created by offsetting in the direction positive γ and where y is negative the composite curve is created by offsetting in the direction negative γ ( the offset direction is shown by arrows for a positive y point and a negative y point in fig1 . while the general shape of the leaflet in position p has been determined using the composite wave , at this stage it is not specified in any particular position . in order to specify the position of p , the shape of the partially open leaflet position can be defined using the ratio of the amplitude of the circular arc a u to the amplitude of the sinusoidal wave b s . a large ratio results in a leaflet which is substantially closed and vice versa . in this example the ratio changes from 10 at the base of the leaflet to 4 at the free edge of the leaflet . the result of this is a leaflet which effectively is more open at the free edge than at the base of the leaflet . in this way , the degree of ‘ openness ’ of the leaflet in position p can be varied throughout the leaflet . the composite wave is thus defined to produce the molded “ buckle ” in the leaflet , and the amplitude ratio is used to define the geometry of the leaflet at position p . at this stage it may bear no relation to the closed leaflet shape in position c . in order to match the area distribution of both leaflet positions , ( thus producing essentially the same leaflet in different positions ) the composite wave length is iterated to match the length of the relevant leaflet contour in position c . thus the amplitude and frequency of the individual waves can be varied in such a manner as to balance between : ( a ) producing a resultant wave the length of which is equal to the relevant value in the length function l ( z ) thus approximating the required closed shape when back pressure is applied , and ( b ) allowing efficient orifice washout and ready leaflet opening . this process identifies the values of a u and b s to be used in constructing the mold for the valve leaflet . as long as the constants such as a u and b s are known , the surface of the leaflet in its molded position can be visualised , enclosed and machined in a conventional manner . as a result of this fitting process the composite wave retains the same basic form but changes in detail from the top of the leaflet to the bottom of the leaflet . a composite wave can be defined in the leaflet surface as the intersection of the leaflet surface with a plane normal to the z axis . in summary therefore one possible method of designing the leaflet of the second embodiment of the present invention is in the following way : ( 1 ) define a scallop shape ; ( 2 ) define a shape representing the closed leaflet using a contour length function l ( z ); ( 3 ) use circular arcs and sine waves to generate a geometry which is partially - open , which pertains to a leaflet position which is between the two extreme conditions of normal valve function , i . e ., leaflet open and leaflet closed ; ( 5 ) vary the amplitude of the arcs and the sinewaves to fit to the length function l ( z ); and ( 6 ) the respective amplitudes of the circular arcs and sine waves can be varied from the free edge to leaflet base , for example the degree of ‘ openness ’ of the leaflet can be varied throughout the leaflet . example 3 set forth hereafter is an example of how the invention of the second embodiment can be put into practice . using the scallop constants in table 5 , the constants required to produce an example of an asymmetric leaflet valve are given in table 6 . these constants are used in conjunction with the aforementioned equations to define the leaflet geometry . with one leaflet described using the aforementioned equations , the remaining two leaflets are generated by rotating the geometry about the z axis through 120 ° and then through 240 °. these leaflet shapes are inserted as the areas of the dipping mold ( otherwise known as a dipping former ), which form the majority of the leaflet forming surfaces , and which then forms a 3 - dimensional dipping mold . the composite wave described in the aforementioned equations , therefore substantially defines the former surface which produces the inner leaflet surface . a drain - off area 30 is also created on the former to encourage smooth run - off of polymer solution . the drain - off region 30 is defined by extruding the leaflet free edge away from the leaflet and parallel to the flow direction of the valve for a distance of approximately 10 mm . the transition from leaflet forming surface of the dipping mold 24 to the drain - off surface of the dipping mold 30 is radiused with a radius greater than 1 mm and preferably greater than 2 mm to eliminate discontinuities in the leaflet . the details of the manufacture of the valve of the second embodiment are similar to those previously described with respect to the valve of the first embodiment until the valve is removed from the dipping mold . since the former used in making the valve of the second embodiment is not tapered the stent posts are not deflected by the former and do not move or change the leaflet shape when the valve is removed from the mold . at this stage the dipping mold and frame is covered with an excess of polyurethane due to the drain - off of the polymer onto the region of the mold known as the drain - off area 30 . to maintain the integrity of the frame coating , the leaflet is trimmed above the stent tips at a distance of between 0 . 025 to 5 mm preferably 0 . 5 mm to 1 . 5 mm from the stent tip . thus part of the surface of the leaflet is formed on the drain - off region 30 which is substantially defined using the composite wave w ( x c , y c ) 0 . leaflet free edges may be trimmed of excess material using a sharp blade rotated around the opened leaflets or using laser - cutting technology or other similar technology . the valve of the second embodiment may be used in any required position within the heart to control blood flow in one direction , or to control flow within any type of cardiac assist device . the following example 3 uses the same scallop geometry described using the constants set forth in table 5 : while the example 3 described herein relates to one valve size , the same method can be used to produce valves from a wide range of sizes . this can be carried out by modifying the constants used in the equations , and computing and iterating in the normal fashion or by rescaling the leaflet . the parameters described in the preceding sections are assigned the values set forth in table 6 and are used to manufacture an asymmetric valve according to the second embodiment . the included angle between adjacent leaflet free edges at the valve commissure for this valve is approximately 30 °. | 8 |
in describing the preferred embodiments of the invention illustrated in the drawings , specific terminology will be used for the sake of clarity . however , the invention is not intended to be limited to the specific terms so selected , and it is to be understood that each specific term includes all technical equivalents that operate in a similar manner to accomplish a similar purpose . referring to the drawings wherein like reference numerals represent like elements , there is shown in fig1 a flat screen display system generally designated by reference numeral 100 . the system 100 includes an electronic device such as a flat screen display 102 , a quick interconnection system generally designated by reference numeral 104 and an articulating support arm generally designated by reference numeral 106 . other electronic devices include notebook computers , crt displays , vcr &# 39 ; s or the like . the articulating support arm 106 includes a support bracket 108 adapted to rotationally support the support arm 106 on a supporting surface . one suitable support bracket 108 for this purpose is disclosed in applicant &# 39 ; s copending patent application ser . no . 09 / 406 , 531 entitled “ configurable mount ” filed on sep . 27 , 1999 , the disclosure of which is incorporated herein by reference . the other end of the support arm 106 includes , by way of example , a tilter 110 . the tilter 110 is adapted to be coupled to the flat screen display 102 to enable its rotation and tilting about two perpendicular axes . one known tilter 110 is disclosed in u . s . pat . no . 6 , 505 , 988 , entitled “ tilter for positioning electronic device ”, the disclosure of which is incorporated herein by reference . known articulating arms 106 are disclosed in applicant &# 39 ; s u . s . pat . no . 6 , 409 , 134 entitled “ arm apparatus for mounting electronic devices with cable management system ”; application ser . no . 10 / 061 , 880 entitled “ modular mounting arm ” filed on feb . 1 , 2002 ; u . s . pat . no . 6 , 478 , 274 entitled “ arm apparatus for mounting electronic devices ”; and u . s . pat . no . 6 , 076 , 785 , entitled “ ergonomic sit / stand keyboard support mechanism ”; the disclosures of which are incorporated herein by reference . the quick interconnection system 104 generally includes three components , an electronic device mounting bracket 112 , a quick release plate 114 and a connector block 116 . the mounting bracket 112 is , by way of one example , a u - shaped bracket having a pair of upstanding side walls 118 , 120 spaced apart by a flat plate 122 . in the embodiment disclosed in fig1 , an attachment device in the nature of , for example , three pins 124 having enlarged heads or ends are attached to extend outwardly from the plate 122 in a triangular orientation . the mounting bracket 112 is attached to the back of the flat screen display 102 by means of the side walls 118 , 120 . typically , the side walls 118 , 120 will have lateral flanges through which a bolt , screw or other fastening device may attach to a threaded opening provided within the back of flat screen display 102 . the quick release plate 114 , as best shown in fig2 and 3 , is constructed from a rectangular member having a short leg 125 and a long leg 126 arranged parallel thereto by a short transversely arranged connecting leg . the short leg 125 is provided with a number of openings which allow the short leg to be fixedly attached to the connector block 116 using bolts , screws and the like received within corresponding threaded openings within the connector block . the long leg 126 is also provided with a plurality of openings 127 to allow the plate 114 to be attached to the tilter 110 , also using suitable bolts or screws . the long leg 126 is provided with a key hole - shaped opening 128 and a pair of spaced apart u - shaped openings 130 , 132 disposed along the leading edge 133 of the long leg 126 . the key hole - shaped opening 128 and u - shaped openings 130 , 132 are spaced apart in a triangular arrangement to correspond to the spaced apart arrangement of the connector pins 124 which protrude from the mounting bracket 112 . the plate 114 is also provided with a spring biased locking pin 134 which , in the preferred embodiment , is normally biased to extend outwardly . the locking pin 134 is alignable with a hole 136 provided within the mounting bracket 112 . the connector block 116 is shown in fig4 in accordance with one embodiment of the present invention . the connecting block 116 includes a front wall 138 and spaced apart top and bottom walls 140 , 142 . in the embodiment shown , three recessed openings 144 , 146 , 148 are cut into the front wall 138 and extend to corresponding openings provided in the top and bottom walls 140 , 142 . the number of openings 140 , 146 , 148 will depend upon the number of connectors required for the particular electronic device to be used with the quick interconnection system 104 in accordance with the present invention . in the case of the flat screen display 102 , it is contemplated that three openings will be provided . in this regard , opening 144 is adapted to receive connector 150 for supplying dc power to the flat screen display 102 . opening 146 is adapted to receive connector 152 for supplying digital video signals to the flat screen display 102 . opening 148 is configured so as to accept connector 154 for supplying analog video signals to the flat screen display 102 . each of the connectors 150 , 152 , 154 have corresponding protruding portions 156 , 158 , 160 which extends above the top wall 140 . the protruding portions 156 , 158 , 160 are configured to mate with corresponding connectors 162 , 164 , 166 provided on the back of the flat screen display 102 as shown in fig1 . by way of example , the connectors may be in the nature of rca connectors , male pin connectors , female pin connectors and the like . each of the connectors 150 , 152 , 154 are provided with electrical cables 168 which extend outwardly through the openings provided in the bottom wall 142 . each of the cables 168 will be provided with an end connector ( not shown ) at its terminal end for connection to the computer for operation of the flat screen display . the connectors 150 , 152 , 154 may be secured within the openings 144 , 146 , 148 by any suitable means . by way of example , a plurality of small clips 170 are secured to the front wall 138 of the connector block 166 using suitable screws or bolts . each of the clips 170 have a portion which extends overlying a portion of the connector 150 , 152 , 154 so as to secure same within its corresponding opening 144 , 146 , 148 . if desired , the front wall 138 may be provided with a recessed portion sized and shaped to receive a corresponding clip 170 thereby orienting the location of the clip at a predetermined location . as previously described , the connector block 116 is attached to the plate 114 , which in turn , is connected to the tilter 110 . the mounting bracket 112 is attached to the back of the flat screen display 102 . the flat screen display 102 is coupled to the quick connection system 104 by first aligning the connecting pins 124 with a corresponding one of the u - shaped openings 130 , 132 and key hole - shaped opening 128 . at the same time , the locking pin 134 is aligned with its corresponding hole 136 within the mounting bracket 112 . the flat screen display 102 is advanced until the mounting bracket 112 is approximate or in contact with the plate 114 . at this point , the connecting pins 124 will be extended through a corresponding one of the openings 128 , 130 , 132 , with the connectors 162 , 164 , 166 on the flat display screen 102 overlying and in alignment with the connectors 150 , 152 , 154 within the connector block 116 . the downward movement of the flat screen display 102 will result in mating of the connectors with the locking pin 134 engaging the hole 136 thereby locking the flat screen display in electrical and mechanical connection to the connector block 116 as shown in fig5 . the key hole - shaped opening 128 ensures that the connectors on the flat screen display 102 and connector block 116 mate during downward displacement of the flat screen display . the u - shaped openings 130 , 132 are used for alignment purposes so as to effect the alignment with the connecting pins 124 . the flat screen display 102 can be detached from the connector block 116 using the reverse procedure . in this regard , the locking pin 134 is retracted from its spring biased position so as to withdraw same from within the hole 136 within the mounting bracket 112 . the flat screen display 102 is then raised vertically to disconnect the connectors as well aligning the enlarged head of the connector pin 124 with the enlarged opening in the key hole - shaped opening 128 . the flat screen display 102 is now disconnected whereupon a new flat screen display may be replaced and electrically connected to the computer via the quick interconnect system 104 as previously described . it should be appreciated that replacing a defective flat screen display 102 using the quick interconnection system 104 of the present invention is relatively quick and takes a minimal amount of time . referring now fig6 and 7 , there is disclosed a quick interconnection system 172 constructed in accordance with another embodiment of the present invention . in the interconnection system 172 , the previously described plate 114 and connector block 116 are integrally formed into a single connector mounting bracket 174 . the connector mounting bracket 174 includes a generally flat rectangular plate 176 having a similarly arranged key hole - shaped opening 128 , a pair of spaced apart u - shaped openings 130 , 132 and a locking pin 134 as thus far described . an elongated connector support plate 178 is attached to the bottom edge 177 of the plate 176 . the connector support plate 178 which functions as a connector block can be integrally formed with the plate 176 being arranged traversely thereto by bending . however , the connector support plate 178 may be formed as a separate component from plate 176 , being joined thereto by , for example , welding , brazening or other suitable means . the connector support plate 178 is provided with a plurality of spaced apart openings 180 , 182 , 184 which communicate with the front edge 186 of the connector support plate . the openings 180 , 182 , 184 are sized and shaped to accommodate passage of cables 168 and to receive the body portion of connectors 188 , 190 , 192 . a peripheral portion of the connectors 188 , 190 , 192 , via a respective flange 194 , overlies a portion of the connector support plate 178 . each of the flanges 194 are provided with openings for attaching the connectors 188 , 190 , 192 to the connector support plate 178 using suitable screws or bolts threadedly engaging corresponding openings . it should therefore be appreciated that the configuration , shape and number of openings 180 , 182 , 184 will be so determined based upon the construction and nature of the connectors 188 , 190 , 192 to be used with respect to the electronic device , and in particular , the flat screen display 102 . the connector mounting bracket 174 is attached to the tilter 110 in a manner as previously described . the flat screen display 102 can be electrically coupled to the connectors 188 , 190 , 192 in the manner as previously described with respect to the operation of the quick interconnection system 104 . although the invention herein has been described with reference to particular embodiments , it is to be understood that these embodiments are merely illustrative of the principles and applications of the present invention . for example , although the attachment device has been described as constructed of three pins 124 and corresponding openings ; other arrangements are contemplated to provide the same function , for example , posts and restricted ball sockets and the like . it is therefore to be understood that numerous modifications may be made to the illustrative embodiments and that other arrangements may be devised without departing from the spirit and scope of the present invention . | 8 |
antimicrobial activity and protease stability of proteins comprising fluorinated amino acids peptides were synthesized manually using the in - situ neutralization protocol for t - boc chemistry on a 0 . 075 mmol scale with mbha and boc - lys ( 2 - cl - z )- merrifield resins . the dinitrophenyl protecting group on histidine was removed using a 20 - fold molar excess of thiophenol . peptides were cleaved from the resin by treatment with hf / anisole ( 90 : 10 ) at 0 ° c . for 2 h and then precipitated with cold et 2 o . crude peptides were purified by rp - hplc [ vydac c 18 , 10 μm , 10 mm × 250 mm ]. the purities of peptides were more than 95 % as judged by analytical rp - hplc [ vydac c 18 , 5 μm , 4 mm × 250 mm ]. the molar masses of peptides were determined maldi - tof ms . peptide concentrations were determined by quantitative amino acid analysis . m2 ( seq id no 1 ) and buforin ii [ 1 - 21 ] ( bii1 ) ( seq id no 2 ), two of the most potent antimicrobial peptides known , were chosen as templates for fluorination . while both peptides are capable of exerting their bactericidal activity at low micromolar concentrations , their modes of action are quite distinct . although both are initially drawn to negatively charged bacterial membranes by electrostatic interactions , m2 causes cell lysis by forming torodial pores in lipid bilayers , while bii1 penetrates into the cell and kills bacteria by binding intracellular dna and rna . both pore formation and translocation of bii1 into cells seem to be controlled by hydrophobic interactions . we envisaged that incorporation of the super - hydrophobic hexafluoroleucine at selected positions would simultaneously increase membrane affinity and provide greater protease stability . a third template , bii5 ( seq id no 3 ) employed in our study was an n - terminal truncated buforin ii ( 5 - 21 ) that has higher antimicrobial activity compared to bill . the sequences of peptides and the fluorinated analogues are shown in fig1 . since these peptides adopt amphipathic helical conformations , sites of fluorination were selected on the nonpolar face of helices with the help of helical wheel diagrams ( fig2 ). the antimicrobial activity was assessed as a minimal inhibitory concentration ( mic ) using turbidity assays against both gram - positive ( b . subtilis ) and gram - negative ( e . coli ) bacteria ( fig3 ). all fluorinated peptides have comparable or more potent antimicrobial activities relative to the parent peptides with the exception of m2f5 . m2f2 exhibited similar mic values as m2 and m2f5 is 4 - and 16 - fold less active against b . subtilis and e . coli respectively . on the other hand , the buforin analogues are at least as potent ( bii1f2 ) or 4 - fold more potent ( bii5f2 ) than the respective controls . these data clearly demonstrate that the antimicrobial activity is either retained or enhanced upon fluorination . the selectivity with which the peptides are able to lyse bacterial cells compared to mammalian cells was interrogated by a hemolysis assay against human red blood cells ( hrbc ). the two buforin analogues had hemolytic activity essentially the same as that of the control peptides suggesting that passage across the membrane was not compromised by fluorination ( fig3 , table 1 ). m2f2 was slightly more hemolytic than m2 , whereas m2f5 was significantly more hemolytic than the parent peptide . it has been demonstrated previously that increased hydrophobicity correlates with hemolytic activity . our results are consistent with this trend . these data point to a maximum hydrophobicity of the parent peptide (& gt ; 75 % solvent b required for elution in rp - hplc under the conditions specified in fig1 ) beyond which fluorination may not result in retention of selectivity for bactericidal activity over mammalian cell permeabilization . the cationic peptides used in this study were tested for cleavage by trypsin , which catalyzes hydrolysis of c - terminal amide bonds of lysine and arginine . all fluorinated peptides were similar or more stable to proteases ( fig4 ). the buforin ii analogue bii5f2 was ˜ 3 fold more resistant to hydrolysis , while bii1f2 was similar to bii1 . furthermore , the initial p1 site of cleavage was different in bii1f2 ( r14 ) than bii1 ( r17 ). in addition , the initial cleavage fragment bii1f2 ( 6 - 21 ) accumulated and persisted much longer than bii1 ( 6 - 2 1 ). in both cases , the presence of hexafluoroleucine at the p1 ′ and p2 ′ sites seems to confer protection to the r17 cleavage site . a similar trend was observed for the magainin analogues . m2f2 was more stable to proteolysis by a factor ˜ 1 . 2 relative to m2 , whereas m2f5 was fiercely resistant to degradation , with & gt ; 78 % of the peptide remaining in solution after 3 h . in contrast , m2 is completely hydrolyzed in 33 mins . the initial fragment resulting from cleavage , m2f2 ( 1 - 14 ) accumulated in higher amounts than m2 ( 1 - 14 ) and only underwent minimal proteolytic degradation over 3 h . the presence of a single hexafluoroleucine residue ( p2 ′ site ) at position 6 in m2f2 ( 1 - 14 ) confers a dramatic advantage in protecting the k4 amide bond . unlike fluoromethylketone or β - fluoro α - keto ester and acid terminated peptides , the fluorine substitution in this instance is not proximal to the hydrolysis site . while an electronic perturbation may still be operational , it is more likely that the protease protection is a result of steric occlusion of the peptide from the active site or because of increased conformational stability of folded entities that deny protease access to the labile amide . circular dichroism ( cd ) spectroscopy was used to probe secondary structure . all peptides with the exception of m2f5 were random coil in aqueous solutions . however , with increasing amounts of trifluoroethanol ( tfe ), the peptides adopted an α - helical structure . at 50 % tfe , both m2 and m2f2 were ˜ 60 % helical . in contrast , m2f5 was helical to the same extent in buffered aqueous solutions with no tfe . furthermore , m2 was monomeric as judged by analytical ultracentrifugation while both m2f2 and m2f5 had a tendency to populate multiple oligomeric states . indeed , m2f5 appears to form helical bundles providing an explanation for both decreased antimicrobial activity and greatly enhanced protease stability . influence of selective fluorination of glp - 1 on proteolytic stability and biological activity peptide design . glp - 1 binds to the glp - 1r on the pancreatic β cells and the hydrophobic interactions are likely the major driving force responsible for the association of this amphiphilic α - helical peptide to its receptor . structural studies on glp - 1 both in a dodecylphosphate choline micelle and in 35 % tfe by 2d nmr showed that glp - 1 consists of a n - terminal random coil segment ( 7 - 13 ), two helical segments ( 13 - 20 and 24 - 37 ), and a linker region ( 21 - 23 ). the c - terminal helix is more stable than the n - terminal helix determined by amide proton exchange experiments and was an essential contributor of binding to glp - 1r . replacements of phe 28 and ile 29 to alanine led to the dramatic lose of the binding affinity to glp - 1r . these two residues along with trp 31 , leu 32 , gly 35 are conserved between glp - 1 and exendin 4 , a synthetic glp - 1r agonist with high affinity and are located on the c - terminal hydrophobic surface . in an attempt to improve the binding affinity of glp - 1 to glp - 1r , phe 28 , ile 29 and leu 32 were selectively substituted by hexafluoroleucine under the consideration that increased hydrophobicity of hexafluoroleucine would possibly lead to an enhanced binding affinity . the trp 31 was kept unchanged not only because this chromophore will be used for determining the peptide concentration but also it has a large side chain volume . the gly 35 was also remained since the flexibility it provided has been proposed essential for the receptor binding . to render the resistance towards dpp iv , the primary enzyme for the rapid deactivation of glp - 1 , the n - terminal residues ( p1 , p1 ′ and / or p2 ′ positions ) were substituted by hexafluoroleucine , namely , ala 8 , glu 9 , gly 10 and both ala 8 and glu 9 to generate four fluorinated analogs . the his 7 was kept unchanged since its particularly crucial role for sending signal to the receptor . in short , the n - terminal replacements were aimed to enhance enzymatic stability and the c - terminal substitutions were intended to test fluorination effect on binding affinity to receptor . the total seven - fluorinated analogs , the wild type glp - 1 , and [ 125 i ]- exendin ( 9 - 39 ) amide are listed in fig3 . binding assay . the binding affinity of fluorinated analogs was measured by a competition - binding assay using [ 125 i ]- exendin ( 9 - 39 ) amide as a radioligand . this bolton - hunter labeled peptide was assumed to have a similar affinity to hglp - 1r as exendin ( 9 - 39 ) amide since the modification at lys 12 side - chain does not damage the receptor binding . the homologous antagonist competitive binding experiments showed that the binding of exendin ( 9 - 39 ) amide has a dissociation constant of 2 . 9 nm ( three independent experiments in triplicate ), comparable to previous reported data . all 7 fluorinated glp - 1 analogs bound to the hglp - 1r expressed on cos - 7 cells , which lack of endogenous glp - 1r . f9 had a 2 . 7 - fold decreased binding affinity compared to wt glp - 1 ( ic 50 5 . 1 nm vs 1 . 9 nm , fig1 and table 1 ), while f29 and f28 displayed 7 - fold and 9 . 9 - fold decreased affinity . f8 , f89 , f10 , and f32 lost the binding affinity by 27 ˜ 60 fold . the carboxylate of glu 9 has been proved important for the receptor binding as substitution by lys 9 resulted in a dramatic lose in terms of binding affinity . its substitution by ala 9 led to relatively poor receptor binding ( 30 ˜ 100 - fold higher ic 50 ), while substitution by asp 9 did not exhibit remarkable changes in receptor binding ( about same ic 50 ). these facts , together with the similar binding affinity showed by f9 , glu 9 was replaced by hexafluoroleudcine , led to a plausible explanation that the “ polar hydrophobicity ” of hexafluoroleucine is probably responsible for the no apparent lose of binding affinity or the bulky hydrophobic side chains at this position are well tolerated . these data here indicate that fluorination led to a slightly to moderate decrease of binding affinity to glp - 1r . the n - terminal modifications , except for f9 , resulted in pronounced decrease of binding affinity , while the c - terminal modifications were well tolerated . formation of camp . to examine whether the fluorinated analogs remain to be functional as full agonists , partial agonists or antagonists , cos - 7 cells with hgpl - 1r were stimulated by peptides and the production of camp were measured by a radioimmunoassay . all fluorinated peptides remain as full agonists except for f89 and subsequent the dose - response was measured for all peptides ( fig2 ). f9 , f32 , f29 , and f28 had a 2 . 1 , 2 . 4 , 3 . 6 , and 5 . 4 - fold decreased potency while remaining the important efficacy as wt glp - 1 ( fig2 and table 1 ). f8 and f10 showed moderate 68 and 73 . 8 - fold lower potency with slightly decreased the efficacy , which were not statistically significant byp - test . unexpected , f89 turned out to be a partial agonist and had a dramatic decrease of potency , 378 - fold lower than wt glp1 , while conserving the similar binding ability to receptor as f10 in the range of tested concentrations . since the histidine residue of n - terminal random coil is responsible for initiating the signal to the receptor , the change of the secondary structure at this portion may have apparent influence on the stimulation of camp production . or , the side chains of hexafluoroleucine disturb the receptor conformational change . overall , analogs with a lower receptor affinity were , by and large , exhibited a higher ec 50 value with respect to activation of adenylyl cyclase . proteolytic stability . wt glp - 1 is rapidly inactivated by ubiquitous enzyme dpp iv , setting the obstacle up for native glp - 1 as a therapeutic agent ( in human t 1 / 2 ≈ 1 ˜ 3 mins ). dpp iv has a relative specific requirement for substrate residues at p2 , p1 , p1 ′ and p2 ′ positions regarding the scissile ala - glu amide bond . especially , at p1 position , pro and ala are highly favored . in contrast , other amino acids and derivatives at this 8 position enhanced the peptide stability , as the reported case gly 8 , aib 8 , ser 8 , thr 8 , leu 8 . from our previous studies , incorporation of hexafluoroleucine close to the scissile bond is able to modulate the resistance of peptides towards hydrolytic protease . under the selected experimental conditions , as expected , replacement by hexafluoroleucine at 8 , 9 , 10 positions endowed dpp iv resistance to different extent . f8 and f89 showed dramatic resistance as no fragments were detected after 24 h incubation . to further examine the stability , fs was incubated with dpp iv at a 10 - fold higher concentration , no fragments were detected after 1 h . f9 and f10 exhibited ˜ 1 . 2 - fold and 2 . 9 - fold resistance by comparing the initial first - order rate constants ( fig3 ), and hplc analysis showed the formation of only one other major peak , which was identified by esi - ms as corresponding peptide fragment glp - 1 ( 9 - 36 ) amide . the kinetic data reported here for the fluorinated glp - 1 analogs could plausiblely correlate to the prolonged metabolic stability in vivo , which has been established by deacon et . al . in their study , daily administration of val 8 - glp - 1 resulted in the increased insulin level and reduced plasma glucose more than wt glp - 1 . taken together , f8 , f9 , f10 , and f29 showed promising potential as candidates for further animal glucose tolerance study . as seen in fig1 , both enzymatic kinetic studies on glp - 1 analogs with mutation at position 8 and the x - ray crystal structural investigation of human dpp iv with a decapeptide substrate or an inhibitor show that the enzyme demands an amino acid with a small side to chain at 8 position to fit in the binding pocket . while the hexafluoroleucine ( bearing a large side chain functionality ) was incorporated at n - terminal modifications , the resistance against dpp iv was observed . the result here is in good agreement with previous kinetic and structural studies . the f9 and f10 containing hexafluoroleucine at p1 ′ and p2 ′ positions also displayed moderate enhanced resistance to dpp iv . in contrast to other methodologies employed for prolonging the half - life time of therapeutic peptides / proteins , such as pegylation , glycosylation , and conjugation to serum protein albumin , incorporation of fluorinated amino acid clearly proves their potential usages especially when small peptides are the targets to be modified as these non - natural amino acids can be rapidly incorporated by solid phase peptide synthesis . the changes of potency of fluorinated analogs could be due to slightly structural variations at the n - terminal random region . the c - terminal modifications were motivated to enhance binding affinity to the receptor , which were not achieved ; rather , slightly decreased binding affinity was observed . these results may not be surprising since the elegant interactions between glp - 1 and its receptor have evolved by nature over million years so that minor structural change of ligand will possibly lead to the decreased affinity of the ligand . however , this lock - and - key type interaction could be strengthened by design if detailed structural information of ligand and receptor is available , or by a large library screening . thus alternations in the n - terminus of glp - 1 with hexafluoroleucine confer dpp iv resistance while retaining the biological activity in terms of in vitro efficacy , suggesting that using fluorinated amino acids is a promising methodology to make bioactive peptides more metabolically stable with a retain and only slightly decreased biological activity ( fig1 ). for convenience , certain terms employed in the specification , examples , and appended claims are collected here . the term “ heteroatom ” as used herein means an atom of any element other than carbon or hydrogen . preferred heteroatoms are boron , nitrogen , oxygen , phosphorus , sulfur and selenium . as used herein , the definition of each expression , e . g ., amino acid , m , n , etc ., when it occurs more than once in any structure , is intended to be independent of its definition elsewhere in the same structure . the phrase “ protecting group ” as used herein means temporary substituents which protect a potentially reactive functional group from undesired chemical transformations . examples of such protecting groups include esters of carboxylic acids , silyl ethers of alcohols , and acetals and ketals of aldehydes and ketones , respectively . the field of protecting group chemistry has been reviewed ( greene , t . w . ; wuts , p . g . m . protective groups in organic synthesis , 2 nd ed . ; wiley : new york , 1991 ). as used herein , “ natural ” or “ wild type ” refers to a protein or a polypeptide , which is found in nature , and “ artificial ” refers to a protein or a polypeptide that comprises non - natural sequences and / or amino acids . the term “ amino acid ” is used herein in its broadest sense , and includes naturally occurring amino acids as well as non - naturally occurring amino acids , including amino acid analogs and derivatives . the latter includes molecules containing an amino acid moiety . one skilled in the art will recognize , in view of this broad definition , that reference herein to an amino acid includes , for example , naturally occurring proteogenic l - amino acids ; d - amino acids ; chemically modified amino acids such as amino acid analogs and derivatives ; naturally occurring non - proteogenic amino acids , and chemically synthesized compounds having properties known in the art to be characteristic of amino acids . as used herein , the term “ non - natural amino acid ” refers to an amino acid that is different from the twenty naturally occurring amino acids ( alanine , arginine , glycine , asparagine , aspartic acid , cysteine , glutamine , glutamic acid , serine , threonine , histidine , lysine , methionine , proline , valine , isoleucine , leucine , tyrosine , tryptophan , phenylalanine ) in its side chain functionality . the term “ hydrophobic ” when used in reference to amino acids refers to those amino acids which have nonpolar side chains . hydrophobic amino acids include valine , leucine , isoleucine , cysteine methionine , phenylalanine , tyrosine and tryptophan . as used herein , the term “ fluorinated amino acid ” refers to an amino acid that differs from the naturally occurring amino acid via incorporation of fluorine in place of one or more hydrogens in its side chain functionality . exemplary fluorinated amino acids may include trifluoroleucine , 4 , 4 , 4 - trifluorovaline , 5 , 5 , 5 - trifluoroleucine , trifluorovaline , hexafluorovaline , trifluoroisoleucine , trifluoronorvaline , hexafluoroleucine , 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine , trifluoromethionine , trifluoromethylmethionine and fluorophenylalanine . the term “ polypeptide ” when used herein refers to two or more amino acids that are linked by peptide bond ( s ), regardless of length , functionality , environment , or associated molecule ( s ). typically , the polypeptide is at least four amino acid residues in length and can range up to a full - length protein . as used herein , “ polypeptide ,” “ peptide ,” and “ protein ” are used interchangeably . certain compounds of the present invention may exist in particular geometric or stereoisomeric forms . the present invention contemplates all such compounds , including cis - and trans - isomers , r - and s - enantiomers , diastereomers , ( d )- isomers , ( l )- isomers , the racemic mixtures thereof , and other mixtures thereof , as falling within the scope of the invention . additional asymmetric carbon atoms may be present in a substituent such as an alkyl group . all such isomers , as well as mixtures thereof , are intended to be included in this invention . if , for instance , a particular enantiomer of a compound of the present invention is desired , it may be prepared by asymmetric synthesis , or by derivation with a chiral auxiliary , where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers . alternatively , where the molecule contains a basic functional group , such as amino , or an acidic functional group , such as carboxyl , diastereomeric salts are formed with an appropriate optically - active acid or base , followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art , and subsequent recovery of the pure enantiomers . for purposes of this invention , the chemical elements are identified in accordance with the periodic table of the elements , cas version , handbook of chemistry and physics , 67th ed ., 1986 - 87 , inside cover . when used herein , the term “ biologically active ” refers to an ability to exhibit a biological function . the phrase “ pharmaceutically acceptable ” is employed herein to refer to those compounds , materials , compositions , and / or dosage forms which are , within the scope of sound medical judgment , suitable for use in contact with the tissues of human beings and animals without excessive toxicity , irritation , allergic response , or other problem or complication , commensurate with a reasonable benefit / risk ratio . as used herein , “ pharmaceutically acceptable salts ” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof . examples of pharmaceutically acceptable salts include , but are not limited to , mineral or organic acid salts of basic residues such as amines ; alkali or organic salts of acidic residues such as carboxylic acids ; and the like . the pharmaceutically acceptable salts include the conventional non - toxic salts or the quaternary ammonium salts of the parent compound formed , for example , from non - toxic inorganic or organic acids . for example , such conventional non - toxic salts include those derived from inorganic acids such as hydrochloric , hydrobromic , sulfuric , sulfamic , phosphoric , nitric and the like ; and the salts prepared from organic acids such as acetic , propionic , succinic , glycolic , stearic , lactic , malic , tartaric , citric , ascorbic , pamoic , maleic , hydroxymaleic , phenylacetic , glutamic , benzoic , salicylic , sulfanilic , 2 - acetoxybenzoic , fumaric , toluenesulfonic , methanesulfonic , ethane disulfonic , oxalic , isethionic , and the like . the term “ treating ” refers to : ( i ) preventing a disease , disorder or condition from occurring in an animal which may be predisposed to the disease , disorder and / or condition but has not yet been diagnosed as having it ; ( ii ) inhibiting the disease , disorder or condition , i . e ., arresting its development ; and ( iii ) relieving the disease , disorder or condition , i . e ., causing regression of the disease , disorder and / or condition . in certain embodiments , the invention relates to a method for preparing a modified peptide , comprising ( a ) identifying a natural or non - natural peptide ; and ( b ) synthesizing a modified peptide based on the sequence of said natural or non - natural peptide ; wherein at least one amino acid of the natural or non - natural peptide is replaced by at least one fluorinated amino acid in said modified polypeptide ; and said modified polypeptide has increased stability relative to said natural or non - natural peptide . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , thermal , or proteolytic . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and said stability is increased by less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 0 . 1 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 0 . 5 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 1 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 3 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 5 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 7 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 9 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is chemical , and the increase is greater than about 11 kcal / mol and less than or equal to about 15 kcal / mol when measured as δδg ° unfolding . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 1 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 5 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 10 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 15 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 20 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 25 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 30 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 35 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 40 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is thermal , and t m is increased by greater than about 45 ° c . and less than or equal to about 50 ° c . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 1 . 1 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 2 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 4 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 50 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 2 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 3 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 4 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 5 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 6 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 7 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said increased stability is proteolytic , and said stability is increased by greater than a factor of about 10 8 and less than or equal to a factor of about 10 9 . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one fluorinated amino acid is selected from the group consisting of trifluoroleucine , 4 , 4 , 4 - trifluorovaline , 5 , 5 , 5 - trifluoroleucine , trifluorovaline , hexafluorovaline , trifluoroisoleucine , trifluoronorvaline , hexafluoroleucine , 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine , trifluoromethionine , trifluoromethylmethionine and fluorophenylalanine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is trifluoroleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is trifluorovaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is trifluoroisoleucine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is trifluoronorvaline . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is trifluoromethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is leucine ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is isoleucine ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is alanine ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is valine ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glycine ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is glutamic acid ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said at least one amino acid is phenylalanine ; and said at least one fluorinated amino acid is trifluoromethylmethionine . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence gigkflhaakkfakafvaeimns . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence raglqfpvgrvhrllrk . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence trssraglqfpvgrvhrllrk . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence qhwsyllrp . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence kcntatcatqrlanflvhssnnfgpilpptnvgsnty . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence hgegtftsdlskqmeeeavrxiewlknggpssgappps . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence haegtftsdvssylegqaakefiawlvkgr . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence spkmvqgsgcfgrkmdrissssglgckvlrrk . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence ytslihslieesqnqqelneqelleldkwaslwnwf . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence vvytdctesgqnlclcegsnvcgqgnkcilgsdgeknqcvtgegtpkpqshndgd feeipeeylq . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence mplwvfffviltlsnsshcsppppltlrmrryadaiftnsyrkvlgqlsarkllqdi msrqqgesnqergararlgrqvdsmwaeqkqmelesilvallqkhsrnsqg . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence mkpiqkllaglilltscvegcssqhwsyglrpggkrdaenlidsfqeivkevgqlae tqrfectthqprsplrdlkgaleslieeetgqkki . in certain embodiments , the invention relates to the aforementioned method , wherein said natural or non - natural polypeptide has the sequence malwmrllpllallalwgpdpaaafvnqhlcgshlvealylvcgergffytpkt rreaedlqvgqvelgggpgagslqplalegslqkrgiveqcctsicslyqlenycn . in certain embodiments , the invention relates to a polypeptide comprising at least one fluorinated amino acid wherein said polypeptide has a sequence selected from the group consisting of gigkfxhaakkfakafvaexmns ; gigkfxhaxkkfxkafxaexmns ; raglqfpvgrvhrxxrk ; trssraglqfpvgrvhrxxrk ; hxegtftsdvssylegqaakefiawlvkgr ; haxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxegtftsdvssylegqaakexiawlvkgr ; haxgtftsdvssylegqaakefxawlvkgr ; and hxegtftsdvssylegqaakefiawxvkgr ; wherein x is a fluorinated amino acid . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence gigkfxhaakkfakafvaexmns . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence gigkfxhakfxkafxaexmns . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence raglqfpvgrvhrxxrk . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence trssraglqfpvgrvhrxxrk . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has a sequence selected from the group consisting of hxegtftsdvssylegqaakefiawlvkgr ; haxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxegtftsdvssylegqaakexiawlvkgr ; haxgtftsdvssylegqaakefxawlvkgr ; and hxegtftsdvssylegqaakefiawxvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence hxegtftsdvssylegqaakefiawlvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence haxgtftsdvssylegqaakefiawlvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence hxxgtftsdvssylegqaakefiawlvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence hxxgtftsdvssylegqaakefiawlvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence hxegtftsdvssylegqaakexiawlvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence haxgtftsdvssylegqaakefxawlvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said polypeptide has the sequence hxegtftsdvssylegqaakefiawxvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the fluorinated amino acid x is selected from the group consisting of trifluoroleucine , 4 , 4 , 4 - trifluorovaline , 5 , 5 , 5 - trifluoroleucine , trifluorovaline , hexafluorovaline , trifluoroisoleucine , trifluoronorvaline , hexafluoroleucine , 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine , trifluoromethionine , trifluoromethylmethionine and fluorophenylalanine . in certain embodiments , the invention relates to a polypeptide , comprising at least one fluorinated amino acid replacement for at least one replaced natural amino acid , wherein said at least one fluorinated amino acid replacement is selected from the group consisting of trifluoroleucine , 4 , 4 , 4 - trifluorovaline , 5 , 5 , 5 - trifluoroleucine , trifluorovaline , hexafluorovaline , trifluoroisoleucine , trifluoronorvaline , hexafluoroleucine , 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine , trifluoromethionine , trifluoromethylmethionine and fluorophenylalanine ; and said polypeptide is selected from the group consisting of : gigkflhaakkfakafvaeimns , raglqfpvgrvhrllrk , trssraglqfpvgrvhrllrk , qhwsyllrp , kcntatcatqrlanflvhssnnfgpilpptnvgsnty , hgegtftsdlskqmeeeavrxiewlknggpssgappps , haegtftsdvssylegqaakefiawlvkgr , spkmvqgsgcfgrkmdrissssglgckvlrrk , ytslihslieesqnqqelneqelleldkwaslwnwf , vvytdctesgqnlclcegsnvcgqgnkcilgsdgeknqcvtgegtpkpqshndgd feeipeeylq , mplwvfffviltlsnsshcsppppltlrmrryadaiftnsyrkvlgqlsarkllqdi msrqqgesnqergararlgrqvdsmwaeqkqmelesilvallqkhsrnsq , mkpiqkllaglilltscvegcssqhwsyglrpggkrdaenlidsfqeivkevgqlae tqrfectthqprsplrdlkgaleslieeetgqkki , and malwmrllpllallalwgpdpaaafvnqhlcgshlvealylvcgergffytpkt rreaedlqvgqvelgggpgagslqplalegslqkrgiveqcctsicslyqlenycn . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine , isoleucine , valine and alanine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said at least one fluorinated amino acid replacement is 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine , isoleucine , valine and alanine ; and said at least one fluorinated amino acid replacement is 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine ; and said at least one fluorinated amino acid replacement is 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to a polypeptide , comprising at least one fluorinated amino acid replacement , wherein said at least one fluorinated amino acid replacement is selected from the group consisting of trifluoroleucine , 5 , 5 , 5 - trifluoroleucine , hexafluoroleucine , and 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine ; each instance of x is independently leucine or a fluorinated amino acid replacement ; and said polypeptide is selected from the group consisting of : gigkfxhaakkfakafvaeimns , ragxqfpvgrvhrxxrk , trssragxqfpvgrvhrxxk , qhwsyxxrp , kcntatcatqrxanfxvhssnnfgpixpptnvgsnty , hgegtftsdxskqmeeeavrxiewxknggpssgappps , haegtftsdvssyxegqaakefiawxvkgr , spkmvqgsgcfgrkmdrissssgxgckvxrrk , ytsxihsxieesqnqqexneqexxexdkwasxwnwf , vvytdctesgqnxcxcegsnvcgqgnkcixgsdgeknqcvtgegtpkpqshndg dfeeipeeyxq , mpxwvfffvixtxsnsshcsppppxtxrmrryadaiftnsyrkvxgqxsarkxxq dimsrqqgesnqergararxgrqvdsmwaeqkqmexesixvaxxqkhsrnsqg , mkpiqkxxagxixxtscvegcssqhwsygxrpggkrdaenxidsfqeivkevgqx aetqrfectthqprspxrdxkgaxesxieeetgqkki , and maxwmrxxpxxaxwgpdpaaafvnqhxcgshxveaxyxvcgergffytp ktrreaedxqvgqvexgggpgagsxqpxaxegsxqkrgiveqcctsicsxyqxen ycn . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said at least one fluorinated amino acid replacement is selected from the group consisting of 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to a polypeptide , comprising at least one fluorinated amino acid replacement for at least one replaced natural amino acid , wherein said at least one fluorinated amino acid replacement is selected from the group consisting of trifluoroleucine , 4 , 4 , 4 - trifluorovaline , 5 , 5 , 5 - trifluoroleucine , trifluorovaline , hexafluorovaline , trifluoroisoleucine , trifluoronorvaline , hexafluoroleucine , 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine , trifluoromethionine , trifluoromethylmethionine and fluorophenylalanine ; each instance of x is independently a fluorinated amino acid replacement ; and said polypeptide is selected from the group consisting of hxegtftsdvssylegqaakefiawlvkgr ; haxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxegtftsdvssylegqaakexiawlvkgr ; haxgtftsdvssylegqaakefxawlvkgr ; and hxegtftsdvssylegqaakefiawxvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine , isoleucine , alanine , glycine , glutamic acid , and phenylalanine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said at least one fluorinated amino acid replacement is 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine , isoleucine , alanine , glycine , glutamic acid , and phenylalanine ; and said at least one fluorinated amino acid replacement is 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein the at least one replaced natural amino acid is selected from the group consisting of leucine ; and said at least one fluorinated amino acid replacement is 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to a polypeptide , comprising at least one fluorinated amino acid replacement , wherein said at least one fluorinated amino acid replacement is selected from the group consisting of trifluoroleucine , 5 , 5 , 5 - trifluoroleucine , hexafluoroleucine , and 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine ; each instance of x is independently leucine or a fluorinated amino acid replacement ; and said polypeptide is selected from the group consisting of hxegtftsdvssylegqaakefiawlvkgr ; haxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxxgtftsdvssylegqaakefiawlvkgr ; hxegtftsdvssylegqaakexiawlvkgr ; haxgtftsdvssylegqaakefxawlvkgr ; and hxegtftsdvssylegqaakefiawxvkgr . in certain embodiments , the invention relates to the aforementioned polypeptide , wherein said at least one fluorinated amino acid replacement is selected from the group consisting of 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- hexafluoroleucine . in certain embodiments , the invention relates to a polypeptide comprising at least one radiolabeled amino acid wherein said polypeptide has the sequence dlsk * qmeeeavrlfiewlknggpssgappps ; wherein k * is a radiolabeled amino acid . the invention now being generally described , it will be more readily understood by reference to the following examples , which are included merely for purposes of illustration of certain aspects and embodiments of the present invention , and are not intended to limit the invention . typical procedure for the coupling reaction : to a stirred solution of the garner aldehyde 1 ( 7 . 0 g , 31 . 0 mmol ) and pph 3 ( 57 g , 217 mmol ) in dry et 2 o ( 300 ml ) was added 2 , 2 , 4 , 4 - tetrakis -( trifluoromethyl )- 1 , 3 - dithietane ( 39 . 5 g , 108 . 5 mmol ) at − 78 ° c . under argon . the mixture was stirred for 3 d while being slowly warmed to room temperature . the reaction slowly accumulated an insoluble white solid which was filtered and the filtrate concentrated . the residue was further dissolved in n - pentane ( 300 ml ) and filtered again to remove insoluble impurities . after removal of the solvent , the residue was subjected to flash column chromatography using n - pentane / et 2 o ( 6 / 1 ) as eluant to give pure 2 as a pale yellow oil ( 10 . 4 g , 92 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 6 . 70 ( d , 1h , j = 8 . 7 hz ), 4 . 81 ( bs , 1h ), 4 . 23 ( dd , 1h , j = 6 . 9 hz , 9 . 3 hz ), 3 . 79 ( dd , 1h , j = 3 . 9 hz , 9 . 3 hz ), 1 . 65 ( s , 3h ), 1 . 56 ( s , 3h ), 1 . 42 ( s , 9h ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 65 . 01 ( d , 3f , j = 5 . 9 hz ), − 58 . 44 ( d , 3f , j = 5 . 9 hz ); ft - ir ( film , ν max , cm − ) 2983m , 2935m , 2885w , 1713s , 1479w , 1460w , 1379s , 1230s , 1165s , 1110m , 971m ; [ α ] d 26 . 1 + 12 . 3 ° ( c 1 . 7 , chcl 2 ); gc - ms ( ci , ch 4 ): 364 ( 1 , [ m + 1 ] + ), 336 ( 18 ), 308 ( 100 ), 288 ( 98 ), 264 ( 37 ), 102 ( 2 ), 57 ( 9 ). a 500 ml round bottomed flask was charged with a solution of 2 ( 10 . 3 g , 28 . 3 mmol ) in thf ( 250 ml ) and 10 % pd / c ( 40 g ). the reaction flask was purged with argon and hydrogen sequentially and stirred under hydrogen at room temperature until uptake of h 2 ceased ( 24 hours ). the catalyst was then separated from the reaction mixture by filtration ( and can be used again ). the filtrate was dried over anhydrous mgso 4 and concentrated by rotary evaporation to give 3 ( 10 . 1 g , 98 % yield ) as a pale yellow oil . 1 h nmr ( 300 mh , cdcl 3 ) δ 4 . 23 ( 4 . 05 ) ( m , 1h ), 4 . 00 ( dd , 1h , j = 5 . 4 hz , 9 . 3 hz ), 3 . 73 ( d , 1h , j = 9 . 3 hz ), 3 . 58 ( 3 . 05 ) ( m , 1h ), 2 . 18 ( 2 . 01 ) ( m , 2h ), 1 . 62 ( 1 . 58 ) ( s , 3h ), 1 . 48 ( br . s , 12h ); 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 153 . 22 ( 151 . 51 ) ( c ═ o ), 123 . 89 ( q , 2 × cf 3 , 1 j cf = 284 . 0 ), 94 . 47 ( 94 . 03 ) ( c ), 80 . 85 ( 80 . 73 ) ( c ), 67 . 26 ( 66 . 65 ) ( ch 2 ), 55 . 58 ( 55 . 12 ) ( ch ), 45 . 44 ( 45 . 12 ) ( quintet , ch , 2 j cf = 27 . 2 hz ), 28 . 98 ( 28 . 00 ) ( ch 2 ), 28 . 25 ( 3 × ch 3 ), 27 . 58 ( 26 . 90 ) ( ch 3 ), 24 . 15 ( 22 . 86 ) ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 67 . 68 -− 68 . 42 ( m ); ft - ir ( film , ν max , cm − 1 ): 2984m , 2941m , 2884w , 1704s , 1457m , 1393s , 1258s , 1168s , 1104s , 847m ; [ α ] d 22 . 4 =+ 17 . 5 ° ( c 0 . 4 , chcl 3 ); gc - ms ( ci , ch 4 ): 366 ( 4 , [ m + 1 ] + ), 338 ( 16 ), 310 ( 100 ), 290 ( 48 ), 266 ( 48 ), 57 ( 8 ). to a solution of 3 ( 10 . 1 g , 27 . 6 mmol ) in ch 2 cl 2 ( 30 ml ) was added 10 ml of trifluoroacetic acid ( tfa ). the reaction mixture was stirred at room temperature for 5 min . after removal of the solvent and tfa , the residue was partitioned between 150 ml of ethyl ether and 100 ml of h 2 o . the organic layer was washed with water ( 20 ml × 4 ), dried over mgso 4 , and concentrated to give 4 ( 7 . 2 g , 80 % yield ) as a white solid . the aqueous layers contain a completely deprotected product due to cleavage of the boc moiety as evidenced by ninhydrin active material . this hexafluoroamino alcohol can be converted back to 4 by protecting the free amine group as a boc amide . 1 h nmr ( 300 mhz , cdcl 3 ) δ5 . 03 ( d , 1h , j = 8 . 1 hz ), 3 . 84 ( m , 1h ), 3 . 70 ( m , 2h ), 3 . 20 ( m , 1h ), 3 . 10 ( br . s , 1h ), 1 . 98 ( m , 2h ), 1 . 45 ( s , 9h ); 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 156 . 57 ( c ═ o ), 124 . 00 ( q , 2 × cf 3 , 1 j cf = 284 . 0 hz ), 80 . 58 ( c ), 66 . 08 ( ch 2 ), 50 . 57 ( ch ), 45 . 09 ( m , ch , 2 j cf = 28 . 1 hz ), 28 . 38 ( 3 × ch 3 ), 26 . 44 ( ch 2 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 67 . 96 ( m ), − 68 . 46 ( m ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3397s ( br ), 3253s , 3068m , 2981s , 2948m , 1686s , 1552s , 1369s , 1289s , 1174s , 1145s , 1055s ; [ α ] d 22 . 9 =− 14 . 4 ° ( c 1 . 0 , ch 3 oh ); gc - ms ( ci , ch 4 ): 326 ( 8 , [ m + 1 ] + ), 298 ( 14 ), 270 ( 100 ), 226 ( 20 ), 57 ( 2 ); m . p .= 114 - 115 ° c . a mixture of 4 ( 7 . 1 g , 21 . 8 mmol ) and pyridinium dichromate ( 33 g , 88 mmol ) in dmf ( 150 ml ) was stirred under argon at room temperature for 24 hrs . before 150 ml of h 2 o was added . the mixture was then extracted with ethyl ether ( 400 ml × 2 ). the combined ether layers were washed with 1 n hcl ( 80 ml × 2 ) and concentrated until about 150 ml of solution left . this solution was washed with 5 % nahco 3 ( 150 ml × 3 ). the combined aqueous layers were acidified to ph 2 with 3 n hcl , extracted with ether again ( 400 ml × 2 ). the ether layers were then dried over mgso 4 and concentrated to give 5 ( 5 . 2 g , 70 %) as a white solid . 1 h nmr ( 300 mhz , cdcl 3 ) δ 7 . 36 ( 5 . 21 ) ( d , 1h , j = 6 . 3 hz ), 4 . 41 ( m , 1h ), 3 . 37 ( m , 1h ), 2 . 43 - 2 . 11 ( br . m , 2h ), 1 . 47 ( s , 9h ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 67 . 87 -− 68 . 23 ( m ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3358 - 2500m ( br . ), 3245s , 3107m , 2989s , 2980m , 1725s , 1712s , 1657s , 1477s , 1458s , 1404s , 1296s , 1277s , 1258s , 916m ; [ α ] d 21 . 8 =− 23 . 0 ° ( c 1 . 0 , ch 3 oh ); gc - ms ( ci , ch 4 ): 3 40 ( 21 , [ m + 1 ] + ), 312 ( 7 ), 284 ( 100 ), 264 ( 16 ), 240 ( 19 ), 57 ( 39 ); m . p .= 85 - 91 ° c . a solution of 5 ( 581 mg , 1 . 7 mmol ) in 5 ml of tfa / ch 2 cl 2 ( ⅔ ) was stirred for 30 min . after removal of the solvents , the residue was partitioned between 1 n hcl ( 10 ml × 3 ) and ethyl ether ( 10 ml ). the combined aqueous layers were freeze dried to give 6 ( 446 mg , 95 % yield ) as a white solid . to a stirred solution of 5 ( 11 mg , 0 . 03 mmol ) in anhydrous dmf ( 1 ml ) was added diisopropyl ethyl amine ( 13 mg , 0 . 1 mmol ), hbtu ( 13 mg , 0 . 03 mmol ), and h - ser ( t - bu )- ome . hcl ( 14 mg , 0 . 065 mmol ) sequentially . the mixture was stirred at room temperature for 40 min before 6 ml of h 2 o was added . the reaction mixture was extracted with ether ( 15 ml ) and the organic layer was further washed with 1 n hcl ( 5 ml × 2 ) and 5 % nahco 3 solution ( 5 ml ), dried over mgso 4 , and concentrated to afford 8 ( 13 mg , 87 % yield ) as a white solid . 1 h nmr ( 300 mhz , cdcl 3 ) ε 6 . 68 ( d , 1h , j = 8 . 1 hz ), 5 . 21 ( d , 1h , j = 8 . 1 hz ), 4 . 64 ( m , 1h ), 4 . 40 ( m , 1h ), 3 . 86 ( dd , 1h , j = 2 . 7 hz , 9 . 3 hz ), 3 . 76 ( s , 3h ), 3 . 56 ( dd , 1h , j = 3 . 3 hz , 9 . 3 hz ), 3 . 50 ( m , 1h ), 2 . 33 - 2 . 10 ( br . m , 2h ), 1 . 45 ( s , 9h ), 1 . 14 ( s , 9h ). to a suspension of boc - dl - trifluorovaline ( 1 . 30 g , 4 . 79 mmol ) and nahco 3 ( 1 . 21 g , 14 . 37 mmol ) in 20 ml of dry dmf was added 0 . 33 ml of ch 3 i ( 5 . 27 mmol ) at room temperature under argon . the resulting mixture was stirred for 5 h and then partitioned between 75 ml of ethyl acetate and 50 ml of water . the organic layer was washed with water ( 3 × 50 ml ), dried over mgso 4 , and concentrated to yield 1 . 36 g ( 95 %) of the boc - dl - trifluorovaline methyl ester as a pale - yellow oil . the boc - tfv methyl ester ( 855 mg , 3 mmol ) was dissolved in 20 ml of methanol , and nabh 4 ( 681 mg , 18 mmol ) was added in small portions at 0 ° c . the reaction mixture was stirred overnight at room temperature and then diluted with 80 ml of ethyl acetate , washed with water ( 3 × 50 ml ), and dried over mgso 4 . after removal of the solvent , the crude product ( boc - trifluorovalinol ) was chromatographed on a silica gel column ( silica gel , 300 g ) using n - pentane / et 2 o ( 1 : 1 ) as eluant to give 452 mg of 2a as a pale - yellow solid ( 58 %) and 214 mg of 2b as a white solid ( 28 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 5 . 04 ( d , 1h , j = 9 . 3 hz ), 4 . 02 ( m , 1h ), 3 . 62 ( m , 3h ), 2 . 61 ( m , 1h ), 1 . 44 ( s , 9h ), 1 . 15 ( d , 3h , j = 7 . 2 hz ); 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 156 . 20 ( c ═ o ), 127 . 83 ( q , cf 3 , 1 j cf = 279 . 9 hz ), 80 . 26 ( c ), 62 . 78 ( ch 2 ), 51 . 09 ( ch ), 38 . 47 ( q , ch , 2 j cf = 25 . 6 hz ), 28 . 40 ( 3 × ch 3 ), 8 . 76 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 70 . 63 ( d , 3f , j = 9 . 0 hz ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3435s , 3300s , 2990s , 2979m , 2954m , 1691s , 1539s , 1537s , 1265s , 1172s , 1125 ; gc - ms ( ci , ch 4 ): 258 ( 14 , [ m + 1 ] + ), 242 ( 4 ), 202 ( 100 ), 158 ( 37 ), 57 ( 14 ). 1 h nmr ( 300 mhz , cdcl 3 ) δ 5 . 11 ( d , 1h , j = 8 . 4 hz ), 3 . 80 ( m , 1h ), 3 . 66 ( m , 2h ), 3 . 45 ( t , 1h , j = 5 . 7 hz ), 2 . 53 ( m , 1h ), 1 . 42 ( s , 9h ), 1 . 15 ( d , 3h , j = 7 . 2 hz ); 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 156 . 43 ( c ═ o ), 127 . 91 ( q , cf 3 , 1 j cf = 280 . 2 hz ), 80 . 30 ( c ), 62 . 92 ( ch 2 ), 52 . 56 ( ch ), 38 . 89 ( q , ch , 2 j cf = 24 . 8 hz ), 28 . 40 ( 3 × ch 3 ), 10 . 59 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ 68 . 76 ( d , 3f , j = 8 . 5 hz ); ft - ir ( film , v max , cm − 1 ): 3436s , 3302s , 3012m , 2990m , 2954m , 1691s , 1532s , 1265s , 1172s , 1127s ; gc - ms ( ci , ch 4 ): 258 ( 14 , [ m + 1 ] + ), 242 ( 4 ), 202 ( 100 ), 182 ( 8 ), 57 ( 14 ). a solution of alcohol 2a ( 257 mg , 1 mmol ) in 4 ml of dry dmf was treated with pdc ( 2 . 26 g , 6 mmol ) at room temperature under argon and stirred overnight . the reaction mixture was then diluted with 20 ml of diethyl ether / 30 ml of saturated nahco 3 solution . the organic layer was washed with 10 ml of saturated nahco 3 . the combined aqueous layers were acidified to ph 2 with 3 n hcl and extracted with diethyl ether ( 2 × 50 ml ). the combined organic layers were dried over mgso 4 and concentrated to yield 176 mg of the corresponding boc - trifluorovaline ( 65 %). boc - tfv ( 176 mg , 0 . 65 mmol ) was treated with 4 ml of 40 % trifluoroacetic acid in ch 2 cl 2 for 10 min . after removal of the solvent , the residue was dissolved in 2 ml of water , treated with naoh ( 260 mg , 6 . 5 mmol ) at 0 ° c ., followed by dropwise addition of acetic anhydride ( 0 . 13 ml , 1 . 3 mmol ). the reaction mixture was stirred at 0 ° c . for 30 min before it was allowed to warm to room temperature . after stirring for another 1 . 5 h , the mixture was diluted with 10 ml of water , acidified to ph 2 with 1 n hcl , and extracted with ethyl acetate ( 2 × 60 ml ). the combined organic layers were dried over mgso 4 and concentrated to give the desired product 3a as a white solid ( 132 mg , 95 %). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 96 ( d , 1h , j = 3 . 0 hz ), 3 . 07 ( m , 1h ), 2 . 04 ( s , 3h ), 1 . 15 ( d , 3h , j = 7 . 2 hz ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 71 . 63 ( d , 3f , j = 8 . 8 hz ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3397s ( br ), 3253s , 3068m , 2981s , 2948m , 1686s , 1552s , 1369s , 1289s , 1174s , 1145s , 1055s ; gc - ms ( ci , ch 4 ): 214 ( 100 , [ m + 1 ] + ), 196 ( 9 ), 172 ( 33 ), 82 ( 33 ), 57 ( 6 ). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 67 ( d , 1h , j = 3 . 3 hz ), 3 . 07 ( m , 1h ), 2 . 04 ( s , 3h ), 1 . 17 ( d , 3h , j = 7 . 2 hz ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 69 . 43 ( d , 3f , j = 8 . 8 hz ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3397s ( br ), 3253s , 3068m , 2981s , 2948m , 1686s , 1552s , 1369s , 1289s , 1174s , 1145s , 1055s ; gc - ms ( ci , ch 4 ): 214 ( 100 , [ m + 1 ] + ), 196 ( 9 ), 172 ( 33 ), 101 ( 10 ), 82 ( 33 ), 57 ( 6 ). to a solution of 3a ( 107 mg , 0 . 5 mmol ) in 1 ml of ph 7 . 9 aq . lioh / hoac was added porcine kidney acylase i ( 10 mg ) at 25 ° c . the mixture was stirred at 25 ° c . for 48 h ( ph was maintained at 7 . 5 by periodic addition of 1 n lioh ). the reaction was then diluted with 5 ml of water , acidified to ph 5 . 0 , heated to 60 ° c . with norit , and filtered . the filtrate was acidified to ph 1 . 5 and extracted with ethyl acetate ( 2 × 10 ml ). the aqueous layer was freeze - dried to give 49 mg of 4a ( 95 %). the combined organic layers were concentrated , and the residue refluxed in 3 n hcl for 6 h , then freeze - dried to yield 50 mg of 4c ( 98 %). the other two diastereomers , 4b and 4d , were obtained from 3b using the same procedure . 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 24 ( dd ; 1h , j = 2 . 1 , 3 . 9hz ), 3 . 23 ( m , 1h ), 1 . 30 ( d , 3h , j = 7 . 2 hz ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 71 . 69 ( d , 3f , j = 9 . 3 hz ); [ α ] d 23 . 7 =+ 7 . 2 ° ( c 0 . 75 , 1 n hcl ). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 35 ( t , 1h , j = 2 . 7 hz ), 3 . 27 ( m , 1h ), 1 . 22 ( d , 3h , j = 7 . 5 hz ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 70 . 04 ( d , 3f , j = 9 . 0 hz ); [ α ] d 23 . 3 =+ 12 . 8 ° ( c 0 . 5 , 1 n hcl ). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 24 ( dd , 1h , j = 2 . 1 , 3 . 9 hz ), 3 . 23 ( m , 1h ), 1 . 30 ( d , 3h , j = 7 . 2 hz ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 70 . 04 ( d , 3f , j = 9 . 0 hz ). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 35 ( t , 1h , j = 2 . 7 hz ), 3 . 27 ( m , 1h ), 1 . 22 ( d , 3h , j = 7 . 5 hz ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 71 . 69 ( d , 3f , j = 9 . 3 hz ). a mixture of boc - dl - trifluoroleucine ( 1 . 25 g , 4 . 38 mmol ), iodomethane ( 0 . 3 ml , 4 . 82 mmol ), nahco 3 ( 1 . 1 g , 13 . 15 mmol ), and dry dmf ( 20 ml ) was stirred at room temperature under argon for 6 h , then diluted with 200 ml of ethyl acetate , and washed with water ( 4 × 100 ml ). the organic layer was dried over na 2 so 4 and concentrated to give 1 . 25 g of product as a pale - yellow oil ( 95 %). column chromatography on silica gel ( 500 g ) using et 2 o / n - pentane ( 1 : 4 ) as eluant afforded 420 mg of ( 2s , 4r )-, ( 2r , 4s )- n - boc - 5 , 5 , 5 - trifluoroleucine methyl ester ( 6a ) ( 32 %), 347 mg of ( 2s , 4s )-, ( 2r , 4r )- n - boc - 5 , 5 , 5 - trifluoroleucine methyl ester ( 6b ) ( 27 %), and 337 mg of the mixture of 6a and 6b ( 26 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 5 . 29 ( d , 1h , j = 6 . 9 hz ), 4 . 32 ( m , 1h ), 3 . 70 ( s , 3h ), 2 . 31 ( m , 1h ), 2 . 12 ( m , 1h ), 1 . 58 ( m , 1h ), 1 . 37 ( s , 9h ), 1 . 11 ( d , 3h , j = 6 . 9 hz ); 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 172 . 72 ( c ═ o ), 155 . 29 ( c ═ o ), 128 . 09 ( q , cf 3 , 1 j cf = 278 . 9 hz ), 80 . 27 ( c ), 52 . 54 ( ch 3 ), 51 . 70 ( ch ), 35 . 13 ( q , ch , 2 j cf = 26 . 4 hz ), 32 . 98 ( ch 2 ), 28 . 30 ( 3 × ch 3 ), 13 . 17 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 74 . 15 ( d , 3f , j = 8 . 2 hz ); ft - ir ( film , ν max , cm − 1 ) 3360m , 2984m , 2938m , 1747s , 1716s , 1520s , 1368s , 1269s , 1168s , 1133m ; gc - ms ( ci , ch 4 ): 300 ( 2 , [ m + 1 ] + ), 284 ( 7 ), 244 ( 100 ), 200 ( 66 ), 82 ( 21 ), 57 ( 24 ). 1 h nmr ( 300 mhz , cdcl 3 ) δ 5 . 02 ( d , 1h , j = 8 . 7 hz ), 4 . 38 ( m , 1h ), 3 . 76 ( s , 3h ), 2 . 32 ( m , 1h ), 1 . 91 - 1 . 74 ( br . m , 2h ), 1 . 44 ( s , 9h ), 1 . 20 ( d , 3h , j = 6 . 9 hz ); 13 c nmr ( 75 . 7 mhz , cdcl 3 ) δ 173 . 03 ( c ═ o ), 155 . 86 ( c ═ o ), 128 . 24 ( q , cf 3 , 1 j cf = 278 . 9 hz ), 80 . 57 ( c ), 52 . 80 ( ch 3 ), 50 . 83 ( ch ), 35 . 02 ( q , ch , 2 j cf = 26 . 9 hz ), 33 . 00 ( ch 2 ), 28 . 42 ( 3 × ch 3 ), 12 . 28 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 74 . 03 ( d , 3f , j = 8 . 7 hz ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3368s , 3014m , 2983s , 2961m , 1763s , 1686s , 1527s , 1265s , 1214s , 1170s , 1053s , 1028s ; gc - ms ( ci , ch 4 ): 300 ( 2 , [ m + 1 ] + ), 284 ( 7 ), 244 ( 100 ), 224 ( 30 ), 200 ( 66 ), 57 ( 24 ). to a solution of 6a ( 420 mg , 1 . 4 mmol ) in methanol ( 10 ml ) was added nabh 4 ( 531 mg , 14 . 0 mmol ) in small portions . the reaction mixture was stirred at room temperature for 1 h before removal of the solvent . the residue was partitioned between 100 ml of ethyl acetate and 50 ml of water . the aqueous layer was extracted with 100 ml of ethyl acetate . the combined organic layers were dried over na 2 so 4 and concentrated to yield 357 mg of the desired product as a white solid ( 94 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 4 . 74 ( m , 1h ), 3 . 71 ( m , 2h ), 3 . 58 ( m , 1h ), 2 . 31 ( m , 1h ), 2 . 14 ( m , 1h ), 1 . 92 ( m , 1h ), 1 . 45 ( s , 9h ), 1 . 17 ( d , 3h , j = 7 . 0 hz ). 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 156 . 26 ( c ═ o ), 128 . 41 ( q , cf 3 , 1 j cf = 279 . 4 hz ), 80 . 14 ( c ), 64 . 78 ( ch 2 ), 50 . 73 ( ch ), 35 . 59 ( q , ch , 2 j cf = 29 . 6 hz ), 31 . 74 ( ch 2 ), 28 . 52 ( 3 × ch 3 ), 13 . 71 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 73 . 84 ( br . s , 3f ); gc - ms ( ci , ch 4 ): 272 ( 100 , [ m + 1 ] + ), 216 ( 68 ), 172 ( 26 ), 57 ( 11 ). 1 h nmr ( 300 mhz , cdcl 3 ) δ 4 . 58 ( m , 1h ), 3 . 79 ( m , 1h ), 3 . 68 ( m , 1h ), 3 . 58 ( m , 1h ), 2 . 27 ( m , 1h ), 2 . 05 ( m , 1h ), 1 . 80 ( m , 1h ), 1 . 45 ( s , 9h ), 1 . 18 ( d , 3h , j = 6 . 6 hz ). 13 c nmr ( 75 . 5 mhz , cdcl 3 ) δ 156 . 47 ( c ═ o ), 128 . 56 ( q , cf 3 , 1 j cf = 278 . 7 hz ), 80 . 20 ( c ), 66 . 31 ( ch 2 ), 49 . 49 ( ch ), 35 . 15 ( q , ch , 2 j cf = 26 . 7 hz ), 31 . 71 ( ch 2 ), 28 . 50 ( 3 × ch 3 ), 12 . 56 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 73 . 98 ( d , 3f , j = 8 . 5 hz ); gc - ms ( ci , ch 4 ): 272 ( 100 , [ m + 1 ] + ), 172 ( 26 ), 57 ( 11 ). a mixture of ( 2s , 4r )-, ( 2r , 4s )- n - boc - 5 , 5 , 5 - trifluoroleucinol ( 330 mg , 1 . 23 mmol ), pdc ( 4 . 62 g , 12 . 3 mmol ), and dry dmf ( 2 . 5 ml ) was stirred at room temperature under argon for 4 h , then diluted with 50 ml of ethyl acetate and 50 ml of water . the organic layer was washed with 30 ml of 1n hcl and 2 × 30 ml of water , dried over mgso 4 , and concentrated to give 198 mg of ( 2s , 4r )-, ( 2r , 4s )- n - boc - 5 , 5 , 5 - trifluoroleucine as a pale - brownish oil ( 60 %). a solution of the above product ( 180 mg , 0 . 63 mmol ) in 2 ml of ch 2 cl 2 was treated with 0 . 5 ml of trifluoroacetic acid for 30 min at room temperature . after removal of the solvent , the yellowish residue was dissolved in 2 ml of water , treated with naoh ( 126 mg , 3 . 15 ) at 0 ° c ., and acetic anhydride ( 0 . 12 ml , 1 . 26 mmol ) was then added dropwise . the reaction mixture was stirred at 0 ° c . for 30 min , then allowed to warm to room temperature . after stirring for another 1 h , the mixture was diluted with 30 ml of water , acidified to ph 2 with 3 n hcl , and extracted with ethyl acetate ( 2 × 90 ml ). the combined organic layers were dried over na 2 so 4 and concentrated to yield 136 mg of 7a as a white solid ( 95 %). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 48 ( dd , 1h , j = 6 . 1 , 8 . 8 hz ), 2 . 51 ( m , 1h ), 2 . 27 ( m , 1h ), 2 . 06 ( s , 3h ), 1 . 79 ( m , 1h ), 1 . 18 ( d , 3h , j = 7 . 0 hz ); 13 c nmr ( 75 . 5 mhz , d 2 o ) δ 175 . 48 ( c ═ o ), 174 . 60 ( c ═ o ), 128 . 53 ( q , cf 3 , 1 j cf = 278 . 9 hz ), 51 . 24 ( ch ), 34 . 88 ( q , ch , 2 j cf = 26 . 6 hz ), 31 . 21 ( ch 2 ), 21 . 90 ( ch 3 ), 13 . 03 ( ch 3 ); 19 f nmr ( 282 . 8 mhz , d 2 o / cf 3 co 2 h ) δ − 73 . 68 ( d , 3f , j = 9 . 0 hz ); ft - ir ( k1br pellet , ν max , cm − 1 ) 3343s , 3063 - 2487m ( br . ), 2932m , 2894m , 1709s , 1613s , 1549s , 1266s , 1179s , 1137s ; gc - ms ( ci , ch 4 ): 228 ( 100 , [ m + 1 ] + ), 211 ( 47 ), 186 ( 26 ), 140 ( 16 ), 57 ( 11 ). 1 h nmr ( 300 mhz , d 2 o ) δ 4 . 48 ( dd , 1h , j = 3 . 8 , 11 . 6 hz ), 2 . 41 ( m , 1h ), 2 . 07 ( s , 3h ), 2 . 15 - 1 . 91 ( br . m , 2h ), 1 . 16 ( d , 3h , j = 6 . 9 hz ); 13 c nmr ( 75 . 5 mhz , d 2 o ) δ 178 . 35 ( c ═ o ), 177 . 38 ( c ═ o ), 131 . 09 ( q , cf 3 , 1 j cf = 278 . 3 hz ), 52 . 72 ( ch ), 37 . 31 ( q , ch , 2 j cf = 26 . 6 hz ), 33 . 06 ( ch 2 ), 24 . 50 ( ch 3 ), 13 . 90 ( ch 3 ); 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 73 . 87 ( d , 3f , j = 8 . 5 hz ); ft - ir ( kbr pellet , ν max , cm − 1 ) 3336s , 2977m , 2949m , 2897m , 2615m , 2473s , 1711s , 1628s , 1551s , 1276s , 1250s , 1127s , 1095s ; gc - ms ( ci , ch 4 ): 228 ( 100 , [ m + 1 ] + ), 211 ( 47 ), 186 ( 26 ), 140 ( 16 ), 120 ( 3 ), 57 ( 11 ). to a solution of 7a ( 136 mg , 0 . 6 mmol ) in 2 ml of ph 7 . 9 aqueous lioh / hoac was added porcine kidney acylase i ( 18 mg ) at 27 ° c . the mixture was stirred at 27 ° c . for 48 h ( ph was maintained at 7 . 5 by periodic addition of 1 n lioh ). it was further diluted with 5 ml of water , acidified to ph 5 . 0 , heated to 60 ° c . with norit , and filtered . the filtrate was acidified to ph 1 . 5 and extracted with ethyl acetate ( 2 × 50 ml ). the aqueous layer was freeze - dried to give 63 mg of 8a ( 95 %). the combined organic layers were concentrated , and the residue refluxed in 3 n hcl for 6 h , then freeze - dried to yield 64 mg of 8c ( 96 %). the other two diastereomers , 8b and 8d , were obtained from 7b using the same procedure . 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 74 . 33 ( d , 3f , j = 9 . 0 hz ); [ α ] d 22 . 9 =+ 21 . 6 ° ( c 0 . 5 , 1n hcl ). 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 74 . 11 ( d , 3f , j = 8 . 2 hz ); [ α ] d 23 . 6 =− 4 . 0 ° ( c 0 . 8 , 1n hcl ). 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 74 . 33 ( d , 3f , j = 9 . 0 hz ). 19 f nmr ( 282 . 6 mhz , d 2 o / cf 3 co 2 h ) δ − 74 . 11 ( d , 3f , j = 8 . 2 hz ). to a stirred solution of ( 2s , 4s )- 5 , 5 , 5 - trifluorovaline ( 4b ) ( 5 mg , 0 . 02 mmol ) in dmf ( 1 ml ) was added diisopropylethyl amine ( diea , 0 . 01 ml , 0 . 06 mmol ), o -( benzotriazol - 1 - yl )- n , n , n ′, n ′- tetramethyluronium hexafluorophosphate ( hbtu , 8 mg , 0 . 02 mmol ), and the hcl salt of ( 2s )- h - ser ( ot - bu )- ome ( 9 mg , 0 . 04 mmol ), sequentially . the mixture was stirred at room temperature for 20 min before dilution with water ( 5 ml ) and extraction with diethyl ether ( 15 ml ). the organic layer was washed with 1 n hcl ( 2 × 5 ml ) and 5 % nahco 3 ( 2 × 8 ml ), dried over mgso 4 , and concentrated to give 7 mg of the dipeptide ( 88 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ 6 . 92 ( d , 1h , j = 7 . 8 hz ), 5 . 16 ( d , 1h , j = 8 . 7 hz ), 4 . 65 ( m , 1h ), 4 . 39 ( dd , 1h , j = 5 . 1 , 8 . 8 hz ), 3 . 81 ( dd , 1h , j = 2 . 7 , 9 . 0 hz ), 3 . 74 ( s , 3h ), 3 . 56 ( dd , 1h , j = 3 . 0 , 9 . 0 hz ), 3 . 04 ( m , 1h ), 1 . 46 ( s , 9h ), 1 . 23 ( d , 3h , j = 7 . 2 hz ), 1 . 14 ( s , 9h ); 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 8 . 57 ( d , 3f , j = 8 . 7 hz ). 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 71 . 36 ( d , 3f , j = 7 . 9 hz ). 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 71 . 48 ( d , 3f , j = 8 . 5 hz ). 19 f nmr ( 282 . 6 mhz , cdcl 3 / cfcl 3 ) δ − 68 . 49 ( d , 3f , j = 9 . 0 hz ). peptides were synthesized manually using the in - situ neutralization protocol 2 for t - boc chemistry on a 0 . 075 mmol scale . mbha and boc - lys ( 2 - cl - z )- merrifield resins were used for peptides m2 ( seq id no 1 ), m2f2 and m2f5 and peptides bii1 ( seq id no 2 ), bii1f2 , bii5 ( seq id no 3 ) and bii5f2 , respectively . the dinitrophenyl protecting group on histidine was removed using a 20 - fold molar excess of thiophenol . peptides were cleaved from the resin by treatment with hf / anisole ( 90 : 10 ) at 0 ° c . for 2 h and then precipitated with cold et 2 o . crude peptides were purified by rp - hplc [ vydac c 18 , 10 μm , 10 mm × 250 mm ]. the purities of peptides were more than 95 % as judged by analytical rp - hplc [ vydac c 18 , 5 μm , 4 mm × 250 mm ]. the molar masses of peptides were determined maldi - tof ms . peptide concentrations were determined by quantitative amino acid analysis . m2 : m / z calcd ( m ) 2476 . 4 , obsd 2496 . 1 ( m + na + ). m2f2 : m / z calcd ( m ) 2692 . 3 , obsd 2693 . 6 ( m + h + ). m2f5 : m / z calcd ( m ) 3114 . 2 , obsd 3115 . 5 ( m + h + ). bii1 : m / z calcd ( m ) 2432 . 4 , obsd 2434 . 9 ( m + h + ). bii1f2 : m / z calcd ( m ) 2649 . 3 , obsd 2650 . 7 ( m + h + ). bii5 : m / z calcd ( m ) 2002 . 2 , obsd 2003 . 5 ( m + h + ). bii5f2 : m / z calcd ( m ) 2218 . 1 , obsd 2218 . 9 ( m + h + ). glp - 1 m / z calcd ( m ) 3295 . 6 , obsd 3297 . 6 ( m + h + ); f8 m / z calcd ( m ) 3445 . 7 , obsd 3447 . 3 ( m + h + ); f9 m / z calcd ( m ) 3389 . 7 , obsd 3398 . 8 ( m + h + ); f89 m / z calcd ( m ) 3537 . 7 , obsd 3540 . 0 ( m + h + ); f10 m / z calcd ( m ) 2476 . 4 , obsd 2496 . 1 ( m + na + ); f28 m / z calcd ( m ) 2692 . 3 , obsd 2693 . 6 ( m + h + ); f29 m / z calcd ( m ) 3114 . 2 , obsd 3115 . 5 ( m + h + ); f32 m / z calcd ( m ) 3114 . 2 , obsd 3115 . 5 ( m + h + ). minimal inhibitory concentrations ( mic ) were measured against gram - negative escherichia coli ( atcc 23716 ) and gram - positive bacillus subtilis ( smy ) using mid - logarithmic phase cells . bacteria from a single colony were grown overnight in luria broth at 37 ° c . with agitation . an aliquot was taken and diluted ( 1 : 50 ) in fresh broth and cultured for ˜ 2 h . the cells ( od 590 = 0 . 5 ) were diluted to a concentration of 5 × 10 5 colony forming units / ml ( cfu / ml ) for m2 , m2f2 and m2f5 or a concentration of 5 × 10 4 cfu / ml for bii series peptides . the colony forming units per ml were quantitated by spreading 10 - fold serially diluted cell suspensions onto agar plates in triplicate . two - fold serial dilution of peptide solutions was performed in a sterile 96 - well plate ( microtest ™) in duplicate to a final volume of 50 μl in each well , followed by addition of 50 μl cell suspension . the plate was incubated at 37 ° c . for 6 h . the absorbance at 590 nm was monitored using a microtiterplate reader ( versamax ). the mic was recorded as the concentration of peptide required for the complete inhibition of cell growth ( no change in absorbance ). fresh human red blood cells ( hrbcs ) were centrifuged at 3 , 500 rpm and washed with pbs buffer until the supernatant was clear . the hrbcs were then resuspended and diluted to a final concentration of 1 % ( v / v ) in pbs and stored at 4 ° c . two - fold serial dilution of peptides in pbs in a 96 - well plate resulted in a final volume of 20 μl in each well , to which 80 μl hrbcs was added . the plate was incubated at 37 ° c . for 1 h , followed by centrifugation at 3 , 500 rpm for 10 min using a sorvall tabletop centrifuge . an aliquot ( 50 μl ) of supernatant was transferred to a new 96 - well plate containing 50 μl h 2 o in each well . the absorbance at 415 nm was measured using a plate reader . wells containing melittin at 100 - 400 μg / ml served as positive controls , and wells containing only buffer and hrbcs served as negative controls . the percentage hemolysis was calculated using the equation : where complete hemolysis is defined as the average absorbance of all wells containing 100 - 400 μg / nl melittin . the proteolytic stability of peptides towards trypsin ( from bovine pancreas , ec 3 . 4 . 21 . 4 ) was determined by an analytical rp - hplc assay . a standard substrate , n - α - benzoyl - l - arginine ethyl ester ( babe ), was used to check enzymatic activity by measuring absorbance at 254 nm . the enzyme concentration ( in 1 mm hcl ) was determined by absorbance at 280 nm . in a typical trypsinization experiment , 0 . 25 mm peptide in 200 μl of pbs buffer ( ph 7 . 4 , 10 mm po 4 3 − , 150 mm nacl ) and 1 μg trypsin for m2 , m2f2 and m2f5 , and 0 . 5 μg trypsin for bii1 , bii5 , bii1f2 and bii5f2 ( 0 . 19 mm ) were used . the amount of enzyme was optimized so that kinetics of proteolytic reactions could be assayed by rp - hplc ( detection at 230 nm ). the peptides were incubated with trypsin at 37 ° c . over a period of 3 h . aliquots ( 10 μl ) were taken at different reaction times , diluted with 0 . 2 % tfa ( 440 μl ) and stored at − 80 ° c . a c 18 analytical column [ j . t . baker c 18 , 5 μm , 4 mm × 250 mm ] was used for separation and quantitation of digested products . the remaining full - length peptide concentration was normalized with respect to the initial concentration . kinetic data after 3 h were fitted using an exponential decay function using igor pro 5 . 03 : pseudo first order rate constants were then obtained as the fitted value ± one standard deviation by fitting data (& lt ; initial 20 mins ) using the equation : where a is the normalized concentration of peptides ; k is the pseudo first order rate constant ; t is the reaction time in mins ; and [ a ] 0 is the initial concentration of peptides . each fragment cleaved from the full - length peptides was identified by esi - ms so that cleavage patterns could be established and compared . circular dichroism spectra were recorded at 25 ° c . on a jasco j - 715 spectropolarimeter fitted with a ptc - 423s single position peltier temperature controller using a 1 cm pathlength cuvette . tfe titrations were carried out in pbs buffer by changing the percentage of tfe while keeping the concentration of peptides constant ( 10 μm ). four scans were acquired per sample and averaged to improve the s / n ratio . a baseline was recorded and subtracted after each spectrum . mean residue ellipticities ([ θ ], deg · cm 2 · dmol − 1 ) were calculated using the equation : where θ obs is the measured signal ( ellipticity ) in millidegrees , l is the optical pathlength of the cell in cm , c is the concentration of the peptide in mg / ml and mrw is the mean residue molecular weight ( molecular weight of the peptide divided by the number of residues ). for the glp - 1 studies , spectra were recorded at 5 ° c . on a jasco j - 715 spectropolarimeter fitted with a ptc - 423s single position peltier temperature controller using a 1 mm pathlength cuvette . peptides were dissolved in 20 mm sodium phosphate , 20 mm sodium phosphate containing 35 % tfe , or 40 mm dodecylphosphate choline at ph 7 . 4 to deliver a final concentration of 10 μm . four scans were acquired per sample and averaged to improve the s / n ratio at 20 nm / min scanning speed . a baseline was recorded and subtracted for each spectrum . mean residue ellipticities ([ θ ], deg · cm 2 · dmol − 1 ) were calculated using the equation : where θ obs is the measured signal ( ellipticity ) in millidegrees , l the optical pathlength of the cell in cm , c the peptide concentration in mol / l and n is the number of residues in protein . sedimentation equilibrium experiments were performed for m2 , m2f2 and m2f5 at 25 ° c . on a beckman xl - i ultracentrifuge . peptides dissolved in pbs were loaded into equilibrium cells at three different concentrations ( 25 , 50 , 100 μm for m2 and m2f5 ; 50 , 100 , 200 μm for m2f5 ). absorbance data at 230 nm were acquired at three different rotor speeds ( 35 , 000 , 40 , 000 and 45 , 000 rpm ) after equilibration for 18 hrs . data obtained were fitted using the following equation that describes the sedimentation of a single ideal species using igor pro 5 . 03 : where abs = absorbance at radius x , a ′= absorbance at reference radius x 0 , h =( 1 − v ρ ) ω 2 / 2rt , v = partial specific volume ( 0 . 7673 ml / g ), ρ = density of solvent ( 1 . 0017 g / ml ), ω = angular velocity in radians / second , r = gas constant ( 83 , 144 , 000 g / mol · k ), t = absolute temperature ( 298 k ), m = apparent molecular weight ( da ), and b = solvent absorbance ( blank ). the partial specific volume of peptides was estimated according to the amino acid composition using the program sednterp . a crystal of 5 , 5 , 5 , 5 ′, 5 ′, 5 ′- 2s - hexafluoroleucine was grown in meoh and data were collected at 86 ( 2 ) k using a bruker / siemens smart apex instrument ( mo kα radiation , λ = 0 . 71073 å ) equipped with a cryocool neverice low temperature device . data were measured using omega scans of 0 . 3 ° per frame for 20 seconds , and a full sphere of data was collected . the structure was solved by direct methods and refined by least squares method on f 2 using the shelxtl program package . cos - 7 cells were cultured in dme supplemented with 10 % fbs , penicillin g sodium ( 100 units / ml ) and streptomycin sulfate ( 100 μg / ml ), 26 mm sodium bicarbonate , ph 7 . 2 at 37 ° c ., 5 % co 2 , and highly humidified atmosphere . cos - 7 cells ( 0 . 8 × 10 6 cells ) were plated in 10 - cm dish a day before transfection . cells were transiently transfected using the diethylaminoethyl - dextran ( deae - dextran ) method , with 5 μg of pcdna1 vector containing the full - length cdna encoding the wild type human glp - 1 receptor ( hglp1 - r ) ( kindly provided by dr . beinborn martin , tufts - new england medical center , ma ). this genetic construct has been sequenced and confirmed the identity . cos - 7 cells ( 10 k cells / well ) were subcultured onto 24 - well tissue culture plates ( falcon , primaria ®, bd sciences , ca ) a day after transfection . the next day , competition - binding experiments were carried out at 25 ° c . for 100 min using 17 pm [ 125 i ]- exendin ( 9 - 39 ) amide as radioligand . the tested peptides had a final concentration ranging from 3 × 10 − 6 to 3 × 10 − 11 m in 270 μl buffer . non - specific binding was determined in the presence of 1 μm unlabeled peptides . fresh binding buffer was prepared in hanks &# 39 ; balanced salt solution , containing 0 . 2 % bsa , 0 . 15 mm phenylmethylsulfonyl fluoride ( pmsf ), 25 mm hepes , ph 7 . 3 . cell monolayers were carefully washed one time before and three times after the incubation with 1 ml binding buffer . cells were hydrolyzed in 1 n naoh , washed by 1 n hcl , and transferred to polypropylene tubes ( sigma ) for gamma counting using a beckman gamma counter 5500b . cos - 7 cells ( 100 k cells / well ) were passaged onto 24 - well plates a day after transfection and cultured for another 24 h . cells were stimulated with glp - 1 and analogs at 25 ° c . for 1 h in dulbecco &# 39 ; s modified eagle &# 39 ; s medium ( without phenol red ) supplemented with 1 % bovine serum albumin , 1 mm isobutyl - methylxanthine ( ibmx ), 0 . 4 μm pro - boro - pro , and 25 mm hepes , ph 7 . 4 . pro - boro - pro ([ 1 -( 2 - pyrrolidinylcarbonyl )- 2 - pyrrolidinyl ] boronic acid ), a potent dpp iv inhibitor , was kindly provided by dr . w . w . bachovchin ( tufts university , ma ). the final concentrations of tested peptides were 10 - fold increased from 1 × 10 − 6 to 1 × 10 − 11 m in 270 μl buffer . upon removal of incubation buffer , the cells were lysed by freeze - thaw method in liquid nitrogen ( 80 s ), followed by addition of 200 μl m - per to ensure the total lysis of cells . the camp was acetylated using acetic anhydride / diea and its concentration were determined by competitive binding with [ 125 i ]- camp using a flashplate ® kit ( perkinelmer life sciences ). plate - bound radioactivity was measured using a packard topcount ® proximity scintillation counter . the proteolytic stability of peptides towards dpp iv ( from porcine kidney , ec 3 . 4 . 14 . 5 ) was determined by analytical rp - hplc assay ( detection at 230 nm ). a chromogenic substrate , gly - pro - p - nitroanilide , was employed to calibrate specific activity by measuring absorbance at 410 nm using δε = 8800 m − 1 · cm − 1 in 100 mm tris - hcl , ph 8 . 0 . at enzyme concentration of 20 unit / l , the peptides ( 8 . 3 μm ) were separately incubated with dpp iv in 50 mm tris - hcl , 1 mm edta , ph 7 . 6 at 37 ° c . over 1 h . reactions were quenched with 600 μl of 0 . 2 % tfa at time intervals and stored on dry ice until the analysis . an analytical c 18 column [ j . t . baker c 18 , 5 μm , 4 mm × 250 mm ] was used for separation and quantitation of intact and digested peptides with a binary solvent system can / h 2 o / 0 . 1 % tfa . first order rate constants were obtained as the fitted value ± one standard deviation by fitting with the equation : where a is the concentration of peptides ; k the first order rate constant ; t the reaction time in min ; and [ a ] 0 the initial concentration of peptides . the fragments derived from the full - length peptides were manually collected and identified by esi - ms . radioligand competition binding and camp production concentration - response curves were fitted using graphpad prism software version 3 . 0 ( graphpad , san diego , calif .). normalizations were relative to wt glp - 1 for both binding assays and camp assays . ic 50 and ec 50 values were fitted using nonlinear regression with build - in single - site competition model or sigmoidal model . data are reported as mean ± s . e . m . peptides h and f were designed to form parallel dimeric coiled coils . these peptides have an identical sequence except that all seven of the core leucine ( l ) residues in h are replaced by 5 , 5 , 5 , 5 ′, 5 ′- s - hexafluoroleucine ( x ) in f : accordingly the fluorinated peptide ff contains seven hexafluoroleucine residues per helix . the free energy of unfolding for a non - fluorinated peptide hh was determined by assuming a two state equilibrium between folded and unfolded states . where f hh is the folded species and u hh represents the fully unfolded hh . data were obtained by monitoring [ θ ] 222 as a function of gdn . hcl concentration . data were analyzed by the linear extrapolation method to yield the free energy of unfolding . the equilibrium constant and therefore δg are easily determined from the average fraction of unfolding . assuming that the linear dependence of δg ° with denaturant concentration in the transition region continues to zero concentration , the data can be extrapolated to obtain δgh ° h2o , the free energy difference in the absence of denaturant . previously reported sedimentation equilibrium experiments suggest ff is a tetramer ( dimer of the disulfide bonded dimer ) in the 2 - 15 μm concentration range . therefore , an unfolded monomer - folded dimer equilibrium can be used to calculate δg ° of unfolding : where k d =[ u ff ] 2 /[ f ff ] ( u ff = unfolded ff and f ff = folded dimer of ff with 4 helices ). since the total peptide concentration po can be given by p t = 2 ][ f ff ]+[ u ff ], the observed cd signal y obs can be described in terms of folded and unfolded baselines , y folded and y unfolded , respectively , by the following expression : additionally , k d can be expressed in terms of the free energy of unfolding . assuming that the apparent free energy difference between folded f ff and unfolded u ff states is linearly depended on the gdn . hcl concentration , δg ° unfolding can be written as : where δg ° h2o is the free energy difference in the absence of denaturant and m is the dependency of the unfolding transition with respect to the concentration of gdn . hcl . the data was fit for two parameters , namely δg ° h2o and m by nonlinear least squared fitting ( kaliedagraph v 3 . 5 ). all of the u . s . patents and u . s . patent application publications cited herein are hereby incorporated by reference . expressly incorporated by reference in its entirety is u . s . patent application ser . no . 10 / 468 , 574 , filed feb . 25 , 2002 . those skilled in the art will recognize , or be able to ascertain using no more than routine experimentation , many equivalents to the specific embodiments of the invention described herein . such equivalents are intended to be encompassed by the following claims . | 2 |
the discovery of micrornas ( mirnas ), which are key regulators of gene expression involved in diverse cellular processes , was a breakthrough in the field of molecular biology . aberrant expression of micrornas ( mirnas ), small ˜ 22 nucleotide non - coding rnas , is involved in the initiation and progression of human cancer . mirnas can act as either tumor suppressors or oncogenes by disrupting the expression of their target oncogenes or tumor suppressor genes , respectively . molecular mirna profiling has identified several mirnas that act as either tumor suppressors by down - regulating oncogenes or as oncogenes by down - regulating tumor suppressor genes . the knockdown of an oncogene is a common strategy for gene therapy in cancer but most approaches target only one gene or one pathway , unlike sirna ( short interfering rna ), each mirna targets multiple genes . therefore , a vector containing multiple tumor suppressor mirnas are able to knockdown multiple target genes and pathways from a single transcript and could suppress tumorigenesis in an additive or synergistic manner . a flexible rna polymerase ii promoter - driven vector which expressed a single transcript containing three mirna members of the mir - 34 family has been developed . this multiple mirna expression vector suppressed cancer cells in a synergistic manner compared to expression vectors with each mirna individually . likewise , the construction of an expression vector that contains multiple mirnas not just from one family but containing multiple families or clusters of mirnas ( 10 to 12 mirnas total ) that target different pathways involved in tumorigenesis has been developed . the present invention allows for the creation of a new class of vector for gene therapy based on mirnas , providing the first steps towards the clinical application of mirna therapy in cancer patients . the development of a high throughput assay allows for the identification of target genes of mirnas and for gathering of important information about the exact biological effects of potential therapy in addition to providing an invaluable tool to the mirna field . by using a combination of tumor suppressor mirnas to target multiple pathways involved in tumorigenesis the mirna vector has the potential to be a universal cancer therapy . many micrornas ( mirnas ) have had their functional roles during tumorigenesis confirmed by in vitro and / or in vivo studies and are therefore considered to be strong candidate tumor suppressors and oncogenes . the invention allows for the development of novel classes of vectors for gene therapy based on mirnas that are able to target multiple oncogenes and / or tumorigenic pathways in cancer . additionally , the inclusion of a combination of mirna families and clusters allows for expression vectors that are not specific to any cancer type but instead could be a universal cancer therapy . using this approach , the inventors provide exciting steps towards the clinical application of mirna therapy in cancer patients . the development a multiple mirna expression vector with synergistic inhibitory effects on cancer cells compared to individual mirnas . the key step for the mirna processing machinery to produce mature mirnas seems to be the recognition of the hairpin structure and not the sequence outside of the pre - mirna ( 73 ), implying that the sequence requirement for mature mirna expression from an expression vector could be as little as a few base pairs in either direction of the pre - mirna . due to the small size of the pre - mirna genes , it is technically simple to clone many pre - mirna genes into the same expression vector . therefore , it is possible to clone multiple tumor suppressor mirnas into one vector able to affect many different pathways involved in tumorigenesis , creating a powerful mirna - based universal cancer therapy . the inventors cloned the mir - 34 tumor suppressor family ( mir - 34a , mir - 34b and mir - 34c ), which is regulated by p53 , into a single expression vector in order to determine whether it had a stronger inhibitory effect on cancer cell lines in comparison to the individual mirnas . mir - 34a is located at chromosome 1p36 , while mir - 34b and mir - 34c are located at chromosome 11q23 , about 500 bp apart . previous studies have shown that restored expression of individual mirnas from the mir - 34 family can induce apoptosis in cancer cell lines and inhibit cell growth ( 12 ). because mir - 34a , mir - 34b , and mir - 34c have similar roles when they are activated by p53 , our strategy is to establish a synergistic expression vector by expressing 3 mirnas ( mir - 34a , mir - 34b , and mir - 34c ) from one single transcript . to create a multiple mirna expression vector , approximately 50 by surrounding the pre - mirnas for mir - 34a , mir - 34b , and mir - 34c were amplified by pcr and then cloned into pcdna3 . 1 (+) either individually or all three together in one transcript of approximately 450 bp . when hct116 colon cancer cells , which have low levels of mir - 34a , mir - 34b , and mir - 34c ( 12 ), were transfected , the mir - 34abc vector yielded mature mirnas at a level similar to each individual mirna vector ( fig1 a ) as measured by stem - loop real - time pcr . of the individual mir - 34 family members , only mir - 34a and mir - 34b inhibited cell proliferation and colony formation , respectively ( fig1 b and c ). however , the mir - 34abc vector strongly inhibited both cell proliferation and colony formation , indicating that although each mir - 34 might not have a strong effect individually when expressed together they have a powerful synergistic effect ( fig1 b and c ). in addition , the inventors constructed an expression vector containing the mir - 127 cluster , which consists of mir - 431 , mir - 433 , mir - 127 , mir - 432 , and mir - 136 within a 4 kb genomic region . the inventors have previously shown that this cluster of mirnas is expressed in normal tissues but not in bladder , colon or prostate cancers ( 10 ). one of these , mir - 127 , is embedded in a cpg island and was highly induced from its own promoter after treatment with the dna methylation inhibitor and chromatin - modifying drugs 5 - aza - cdr and pba , respectively . the invetors study also indicated that mir - 127 can down - regulate the pro - oncogene bcl6 , making it a potential tumor suppressor mirna ( 10 ). since the mir - 127 cluster , not mir - 127 alone , is silenced in cancer , we established an expression vector with an insert of ˜ 800 bp containing the 5 mirnas in a single transcript to compare its efficacy to mir - 127 alone in the bladder cancer cell line t24 , which does not express the mir - 127 cluster . once again , the vector expressing the mir - 127 cluster strongly inhibited both cell proliferation and colony formation when compared with mir - 127 alone ( fig2 a and b ). taken together , these results confirm that expression of multiple mirnas is more effective at inhibiting cancer cell lines than individual mirnas . the next step is to determine whether expression of multiple families or clusters of mirnas have stronger inhibitory effects in cancer cells than single mirna families or clusters . the inventors believe that these findings represent a new way to treat cancer . in order to understand more fully the biological impact this multiple mirna expression vector have as a cancer therapy , a high - throughput method to identify additional mrna targets of the included tumor suppressor mirnas is used . the development of approaches for in vivo delivery of short interfering rna ( sirna ) to silence a single target gene has established techniques that are also useful for mirna delivery . the inventors have focused on the ability of a single mirna to down - regulate many crucial genes or pathways involved in the aggressive behavior of cancer . by linking many mirnas together into a single vector , the inventors are able to suppress vast numbers of target genes at once . two multiple mirna expression vectors containing the mir - 34abc or the mir - 127 cluster , both of which had a synergistic inhibitory effect on cancer cell lines compared to expression vectors containing individual mirnas have been successfully made ( fig1 and 2 ). an expression vector containing between 10 to 12 mirnas from multiple mirna families and clusters allows for more robust anti - cancer effects in cancer cell lines and in a mouse model has been created . furthermore , the development of a high - throughput target validation assay allows for the identification of mirna target genes using the multiple mirna expression vectors . development of a mirna expression vector containing multiple mirna families and clusters that target different oncogenic pathways and confirm the synergistic effects of the multiple microrna expression vector over single mirna vectors in various human cancer cell lines . preliminary studies , show successful synergistic effects of multiple mirna expression vectors are made by ligating individual mirnas of a tumor suppressor microrna family or cluster into one expression vector . the inventors have created expression vectors containing multiple mirna families and clusters . then synergistic inhibitory effects of the vectors in various human cancer cell lines including bladder cancer ( t24 , umuc3 , rt4 ), prostate cancer ( pc3 , lncap , du145 ), colon cancer ( hct116 , lovo , rko ), breast cancer ( mcf7 , mda - mb - 453 , mda - mb - 361 ), lung cancer ( a549 , h1299 ), and leukemia ( k562 , jurkat , u937 ) are tested . normal cell lines such as ld419 are included in this experiment as controls for the unintended effects of mirnas . studies have indicated that mirna expression profiles vary by tissue and by cancer type ( 74 , 1 ). therefore , different cancer cell lines have different responses to a single mirna or even to a single mirna cluster or family . the final goal is to combine multiple tumor suppressor mirnas found to be involved in many different types of cancer into one expression vector that has robust anti - tumor effects on most , if not all , cancers . cell lines . bladder cancer ( t24 , umuc3 , rt4 ), prostate cancer ( pc3 , lncap , du145 ), colon cancer ( hot116 , lovo , rko ), breast cancer ( mcf7 , mda - mb - 453 , mda - mb - 361 ), lung cancer ( a549 , h1299 ), and leukemia ( k562 , jurkat , u937 ) cell lines will be used in this study . some of the cell lines such as t24 , umuc , rt4 , and mcf7 , pc3 are available in the lab ; the others are obtained from american type culture collection ( rockville , md .). culture conditions will follow the instructions of atcc . create expression vectors with multiple mirna tumor suppressors . expression vectors are made by pcr amplifying 50 to 100 by surrounding the pre - mirnas ( 10 to 12 ) and cloning these separately into multiple restriction sites of pcdna3 . 1 (+) ( invitrogen ) resulting in an insert of less than 2 kb containing 10 to 12 mirnas . the inventors only include let - 7b and let - 7e as members of the let - 7 family because they are the most divergent ( 77 ) of the 16 family members . cellular proliferation . the comparison of colony and cell counts between empty vector control and mirna expression vectors are done using dunnet &# 39 ; s method ( 78 ). briefly , the analysis is based on log - transformed data where means and 95 % confidence intervals are calculated and transformed back to the original scale . cell doubling time and a focus - forming assay is performed to measure cell growth in the cells with or without multiple mirna expression vectors to identify tumor supressor properties in vivo ( 79 , 80 ). the cell proliferation assays are conducted in triplicate as described previously ( 81 ). each well is trypsinized and equal cell numbers plated onto 10 cm dishes with medium containing g418 ( sigma ). medium is changed every 3 - 4 days and total cell numbers counted after 13 - 14 days . colony formation assays are conducted as described previously ( 82 ). 48 hours after transfection equal numbers of cells are plated in triplicate into 6 - well dishes containing medium with g418 ( sigma ) at the same concentrations as the cell proliferation assay . medium is changed every 3 - 4 days and colonies counted after 13 - 14 days by washing with pbs , fixing with methanol and staining with giemsa . dna fragmentation and apoptosis assay . as mentioned before , some of mirnas including in the expression vector can induce apoptosis . apoptosis is measured in various cancer cell lines with or without multiple mirnas expression vector using the in site cell death detection kit ( tunel assay ) from roche . invasion assay . cellular potential for invasiveness is determined using six - well matrigel invasion chambers ( bd biosciences discovery labware ). cells are seeded into upper inserts at 2 × 105 per insert in serum - free dmem and outer wells are filled with dmem containing 5 % fbs as chemoattractant . cells are incubated at 37 ° c . with 5 % carbon dioxide for 48 h , and then noninvading cells are removed by swabbing the top layer of the matrigel with a q - tip . the membrane containing invading cells is stained with hematoxylin for 3 min , washed , and mounted on slides . the entire membrane with invading cells are counted under a light microscope at 40 × objective . western blots . cells are harvested by treatment with trypsin and resuspended in wa buffer . the resuspended cells are lysed by 2 cycles of sonication for 15 sec . equal amounts of protein ( 20 - 50 μg ) are separated on sds - polyacrylamide gels and transferred to pvdf membranes . the blot is probed with antibodies against the potential target protein and control protein and image of individual proteins are visualized using ecl detection system ( amersham biosciences , piscataway , n . j .) ( 80 ). reverse transcription and taqman real - time pcr . rna is isolated from cell lines using trizol ( invitrogen , carlsbad , calif .) according to the manufacturer &# 39 ; s protocol . all reagents for mirna taqman assays to detect mature mirnas are purchased from applied biosystems ( foster city , calif .) and used according to the manufacturer &# 39 ; s protocol ( 83 ). u6 is used as the internal control and all reactions are done in duplicate . confirmation of the synergistic effect of a multiple microrna expression vector over single microrna vectors on cancer in vivo using mouse models . based on the results from above , 4 to 6 different cancer cell lines that are able to form xenograft tumors into nude mice after transfection with the multiple mirna expression vector to test the effects in vivo are injected into mice . the animal experiments used are standardized . animal experiments . animal studies are performed according to institutional guidelines . cancer cell lines of different tissue types ( 4 - 6 cell lines ) are transfected in vitro with 100 nm ( final concentration ) of the control expression vector or the multiple mirna expression vector dna by using lipofectamine 2000 reagent ( invitrogen ), according to the protocol of the manufacturer . at 48 after transfection , 0 . 5 to 3 × 106 cells ( injection ) are inoculated subcutaneously into the right and left flanks ( along the midaxillary lines ) of 4 - to 6 - week - old male balb / c nu / nu mice ( harlan , san diego , calif .). in order to obtain statistically meaningful results , at least six mice per group ( control and 6 cancer cell lines ) are used . tumor diameters are measured 7 days after injection and every 5 days thereafter . after 3 weeks ( the days might be various based on the cell lines ), mice are killed and tumors are weighted after necropsy . tumor volumes are determined using the equation v ( in mm3 )= a × b2 / 2 , where a is the largest diameter and b is the perpendicular diameter . tumors are removed and each tumor is divided into two separate portions . one portion is immediately fixed with neutral buffered formalin , embedded in oct compound , frozen , and then sectioned . the frozen sections are stained with hematoxylin and eosin . all histologic examinations are carried out by light microscopy using a leica dm lb microscope ( leica microsystems , inc ., bannockburn , ill .). the other potion of each tumor is used for isolating dna and total rna for analysis of dna methylation by ms - snupe , which was developed in the inventors lab ( 84 ), and of mirnas and related gene expression by stem loop rt - pcr or real - time rt - pcr , respectively . identification of target genes of the tumor suppressor micrornas from our multiple microrna expression vector by transfecting cells , screening for down - regulated menas by microarray , and enriching target mrnas using risc immunoprecipitation ( rip ) and identifying the mrnas by microarray ( rip on chip ). confirmation of potential target genes from microarray results by prediction algorithms , western blot , real - time rt - pcr , and luciferase assay . although the inventors expect the multiple mirna expression vector to inhibit tumor cell growth , knowing the exact gene targets of the tumor suppressor mirnas helps to understand the mechanism behind any synergistic effects . furthermore , since the final goal is to use this expression vector for treatment for human cancers , identifying potential target genes helps to predict the consequences of this therapy such as any potential side - effects due to up - regulating harmful genes or down - regulating beneficial genes in normal cells . experimental validation of mirna targets is challenging because of the low accuracy (˜ 30 %) of mirna target prediction algorithms ( 58 ). there is a need for a simple and high - throughput assay for biologically validating mirna targets . the mirna : mrna association is mediated by the risc complex , the most important member of which is ago2 . the inventors are able to identify de novo mirna : mrna interactions by immunoprecipitating ago2 and isolate the accompanying rna ( 63 , 85 ). as described above , the inventors interrogate the enriched mrna with an expression array in order to determine potential target genes and screen out background levels using mrna from cells transfected with the empty control vector . potential targets are confirmed by real time rt - pcr , western blots , microrna target prediction algorithms , and / or luciferase assay . this approach allows for the establishment of a novel high - throughput assay for validating mirna targets and be especially useful in identifying the exact targets of the tumor suppressor mirnas in the expression vector . coimmunoprecipitation of ago2 and mrna targets . this assay takes advantage of the risc - mirna - mrna interaction necessary for gene repression and coimmunoprecipitates ago - 2 , a component of the risc complex , and target mrnas containing mirna binding sites ( 64 ). cells with either the multiple mirna expression vector or a control vector and prepare extracts are transfected . cells are harvested 48 h after transfection and washed in pbs followed by hypotonic lysis buffer [ 10 mm tris , ph 7 . 5 , 10 mm kcl , 2 mm mgcl2 , 5 mm dtt , and 1 tablet per 10 ml of protease inhibitors , edta - free ( roche )]. cells are incubated in lysis buffer for 15 min and lysed by douncing . immediately after doucing , the lysates are supplemented with 5 × atp depletion mix [ 4 units / μl rnasein ( promega ), 100 mm glucose , 0 . 5 unites / μl hexokinase ( sigma ), 1 mg / ml yeast trna ( invitrogen ), 450 mm kcl ] to a final concentration of 1 ×. the lysates are cleared by centrifugation at 16 , 000 × g for 30 min at 40c . before immunoprecipitation , anti ago2 ( elf2c ) ( sc - 32877 , santa cruz biotechnology , inc ) is pre - blocked for 30 min in wash buffer [ 0 . 5 % nonidet p - 40 , 150 mm nacl , 2 mm mgcl2 , 2 mm cacl2 , 20 mm tris , ph 7 . 5 , 5 mm dtt , and 1 tablet per 10 ml of protease inhibitors ] supplemented with 1 mg / ml yeast trna and 1 mg / ml bsa , followed by a wash in wash buffer . one volume of wash buffer is added to the lysates , and ago2 is immunoprecipitated with pre - blocked beads for 4 h at 4 ° c . the beads are washed once with wash buffer and twice in wash buffer containing 650 mm nacl , the slurry is transferred to a new tube on the last wash , and bound rna is extracted with trizol . mieroarray analysis . total rna or rna from ago2 coimmunoprecipiation is isolated from cells transfected with either the multiple mirna expression vector or a control vector using trizol . to look at global gene expression rna is hybridrized to the human 6 v2 expression beadchip ( illumina ) and data analysis is performed using illumina software by the epigenome center on a fee - for service - basis . microrna target prediction algorithms . the potential target genes are first confirmed by the following four prediction algorithms : mirnaviewer ( http :// cbio . mskcc . org / mirnaviewer /); pictar ( http :// pictar . bio . nyu . edu /); targetscan4 . 1 ( http :// www . targetscan . org ; and pita ( http :// genie . weizmann . ac . il / pubs / mir07 / mir07_data . html ). this analysis is performed by the epigenome center on a fee - for service - basis . real - time rt - pcr . targets are be confirmed by real - time rt - pcr . rna is reverse - transcribed using 2 μg of rna and random hexamers , deoxy nucleotide triphosphates ( boehringer mannheim , germany ) and superscript ii reverse transcriptase ( life technologies , inc ., palo alto , calif .) in a 50 μl reaction . the mixture is placed at room temperature for 10 min , 42 ° c . for 45 min , and 90 ° c . for 3 min , then rapidly cooled to 0 ° c . the resulting cdna is amplified with primers specific to the gene of interest with β - actin or gapdh as a control . quantitative pcr is performed on the dna engine opticon system ( mj research , cambridge , mass .) using amplitaq gold dna polymerase ( applied biosystems ) with 2μl cdna , gene specific primers , and fluorescently labeled taqman probes synthesized by bioresarch . all pcrs is carried out under the same conditions : 95 ° c . for 15 s and 59 ° c . for 1 min for 45 cycles ( 86 ). luciferase assay . the luciferase assay is performed in order to further confirm the identity of mirna target genes and determine the mirna binding site in the target gene . this assay has been used in the inventors &# 39 ; lab ( 10 ). briefly , luciferase constructs are made by ligating oligonucleotides containing the wild type or mutant target site of the identified gene &# 39 ; s 3 ′ utr into the xbai site of pgl3 - control vector ( promega ). cells both with and without expression of the mirna is transfected with 0 . 4 μg of firefly luciferase reporter vector containing a wild - type or mutant target site and 0 . 02 μg of the control vector containing renilla luciferase , prl - cmv ( promega ), using lipofectamine 2000 ( invitrogen ). luciferase assays are performed 48 h after transfection using the dual luciferase reporter assay system ( promega ). firefly luciferase activity is normalized to renilla luciferase . many modifications and variation of the invention as hereinbefore set forth can be made without departing from the spirit and scope thereof and therefore only such limitations should be imposed as are indicated by the appended claims . all patent and literature references cited in the present specification are hereby incorporated by reference in their entirety . 1 . galin g a , croce c m . microrna signatures in human cancers . nat rev cancer 2006 ; 6 ( 11 ): 857 - 66 . 2 . valencia - sanchez m a , liu j , hannon g j , parker r . control of translation and mrna degradation by mirnas and sirnas . genes dev 2006 ; 20 ( 5 ): 515 - 24 . 3 . vasudevan s , tong y , steitz j a . switching from repression to activation : micrornas can up - 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223 by the aml1ieto oncoprotein . cancer cell 2007 ; 12 ( 5 ): 457 - 66 . 38 . lu l , katsaros d , de la longrais i a , sochirca o , yu h . hypermethylation of let - 7a - 3 in epithelial ovarian cancer is associated with low insulin - like growth factor - ii expression and favorable prognosis . cancer res 2007 ; 67 ( 21 ): 10117 - 22 . 39 . meng f , wehbe - janek h , henson r , smith h , patel t . epigenetic regulation of microrna - 370 by interleukin - 6 in malignant human cholangiocytes . oncogene 2007 . 40 . lujambio a , ropero s , ballestar e , fraga m f , cerrato c , setien f , et al . genetic unmasking of an epigenetically silenced microrna in human cancer cells . cancer res 2007 ; 67 ( 4 ): 1424 - 9 . 41 . hayashita y , osada h , tatematsu y , yamada h , yanagisawa k , tomida s , et al . a polycistronic microrna cluster , mir - 17 - 92 , is overexpressed in human lung cancers and enhances cell proliferation . cancer res 2005 ; 65 ( 21 ): 9628 - 32 . 42 . he l , thomson j m , hemann m t , hernando - monge e , mu d , goodson s , et al . a microrna polycistron as a potential human oncogene . nature 2005 ; 435 ( 7043 ): 828 - 33 . 43 . hammond s m . micrornas as oncogenes . curr opin genet dev 2006 ; 16 ( 1 ): 4 - 9 . 44 . woods k , thomson j m , hammond s m . direct regulation of an oncogenic micro - rna cluster by e2f transcription factors . j biol chem 2007 ; 282 ( 4 ): 2130 - 4 . 45 . tam w , ben - yehuda d , hayward w s . bic , a novel gene activated by proviral insertions in avian leukosis virus - induced lymphomas , is likely to function through its noncoding rna . mol cell biol 1997 ; 17 ( 3 ): 1490 - 502 . 46 . vigorito e , perks k l , abreu - goodger c , bunting s , xiang z , kohlhaas s , et al . microrna - 155 regulates the generation of immunoglobulin class - switched plasma cells . immunity 2007 ; 27 ( 6 ): 847 - 59 . 47 . eis p s , tam w , sun l , chadburn a , li z , gomez m f , et al . accumulation of mir - 155 and bic rna in human b cell lymphomas . proc nati acad sci usa 2005 ; 102 ( 10 ): 3627 - 32 . 48 . yanaihara n , caplen n , bowman e , seike m , kumamoto k , yi m , et al . unique microrna molecular profiles in lung cancer diagnosis and prognosis . cancer cell 2006 ; 9 ( 3 ): 189 - 98 . 49 . iorio m v , ferracin m , liu c g , veronese a , spizzo r , sabbioni s , et al . microrna gene expression deregulation in human breast cancer . cancer res 2005 ; 65 ( 16 ): 7065 - 70 . 50 . gironella m , seux m , xie m j , cano c , tomasini r , gommeaux j , et al . tumor protein 53 - induced nuclear protein 1 expression is repressed by mir - 155 , and its restoration inhibits pancreatic tumor development . proc nati aced sci usa 2007 ; 104 ( 41 ); 16170 - 5 . 51 . voorhoeve p m , le sage c , schrier m , gillis a j , stoop h , nagel r , et al . a genetic screen implicates mirna - 372 and mirna - 373 as oncogenes in testicular germ cell tumors . cell 2006 ; 124 ( 6 ): 1169 - 81 . 52 . chan j a , krichevsky a m , kosik k s . microrna - 21 is an antiapoptotic factor in human glioblastoma cells . cancer res 2005 ; 65 ( 14 ): 6029 - 33 . 53 . volinia s , calin g a , liu c g , ambs s , cimmino a , petrocca f , et al . a microrna expression signature of human solid tumors defines cancer gene targets . proc nati acad sci usa 2006 ; 103 ( 7 ): 2257 - 61 . 54 . frankel l b , christoffersen n r , jacobsen a , lindow m , krogh a , lund all . programmed cell death 4 ( pdcd4 ) is an important functional target of the microrna mir - 21 in breast cancer cells . j biol chem 2007 . 55 . asangani i a , rasheed s a , nikolova d a , leupold j h , colburn n h , post s , et al . microrna - 21 ( mir - 21 ) post - transcriptionally downregulates tumor suppressor pdcd4 and stimulates invasion , intravasation and metastasis in colorectal cancer . oncogene 2007 . 56 . zhu s , si m l , wu h , mo y y . microrna - 21 targets the tumor suppressor gene tropomyosin 1 ( tpm1 ). j biol chem 2007 ; 282 ( 19 ): 14328 - 36 . 57 . lai e c . micro rnas are complementary to 3 ′ utr sequence motifs that mediate negative post - transcriptional regulation . nat genet 2002 ; 30 ( 4 ): 363 - 4 . 58 . chaudhuri k , chatterjee r . microrna detection and target prediction : integration of computational and experimental approaches . dna cell biol 2007 ; 26 ( 5 ): 321 - 37 . 59 . doench j g , petersen c p , sharp p a . sirnas can function as mirnas . genes dev 2003 ; 17 ( 4 ): 438 - 42 . 60 . pillai r s , bhattacharyya s n , artus cg , zoller t , cougot n , basyuk e , et al . inhibition of translational initiation by let - 7 microrna in human cells . science 2005 ; 309 ( 5740 ): 1573 - 6 . 61 . chen j f , mandel e m , thomson j m , wu q , callis t e , hammond s m , et al . the role of microrna - 1 and microrna - 133 in skeletal muscle proliferation and differentiation . nat genet 2006 ; 38 ( 2 ): 228 - 33 . 62 . schratt g m , tuebing f , nigh e a , kane c g , sabatini m e , kiebler m , et al . a brain - specific microrna regulates dendritic spine development . nature 2006 ; 439 ( 7074 ): 283 - 9 . 63 . easow g , teleman a a , cohen s m . isolation of microrna targets by mirnp immunopurification . rna 2007 ; 13 ( 8 ): 1198 - 204 . 64 . karginov f v , conaco c , xuan z , schmidt b h , parker j s , mandel g , et al . a biochemical approach to identifying microrna targets . proc nati acad sci usa 2007 ; 104 ( 49 ): 19291 - 6 . 65 . akao y , nakagawa y , naoe t . let - 7 microrna functions as a potential growth suppressor in human colon cancer cells . biol pharm bull 2006 ; 29 ( 5 ): 903 - 6 . 66 . scott g k , goga a , bhaumik d , berger c e , sullivan c s , benz c c . coordinate suppression of erbb2 and erbb3 by enforced expression of micro - rna mir - 125a or mir - 125b . j biol chem 2007 ; 282 ( 2 ): 1479 - 86 . 67 . devi g r . sirna - based approaches in cancer therapy . cancer gene ther 2006 ; 13 ( 9 ): 819 - 29 . 68 . abbas - terki t , blanco - bose w , deglon n , pralong w , aebischer p . lentiviral - mediated rna interference . hum gene ther 2002 ; 13 ( 18 ): 2197 - 201 . 69 . lu p y , xie f , woodle m c . in vivo application of rna interference : from functional genomics to therapeutics . adv genet 2005 ; 54 : 117 - 42 . 70 . tong a w . small rnas and non - small cell lung cancer . curr mol med 2006 ; 6 ( 3 ): 339 - 49 . 71 . doench j g , sharp p a . specificity of microrna target selection in translational repression . genes dev 2004 ; 18 ( 5 ): 504 - 11 . 72 . stark a , brennecke j , bushati n , russell r b , cohen s m . animal micrornas confer robustness to gene expression and have a significant impact on 3 ′ utr evolution . cell 2005 ; 123 ( 6 ): 1133 - 46 . 73 . han j , lee y , yeom k h , nam j w , heo i , rhee j k , et al . molecular basis for the recognition of primary micrornas by the drosha - dgcr8 complex . cell 2006 ; 125 ( 5 ): 887 - 901 . 74 . bommer g t , gerin i , feng y , kaczorowski a j , kuick r , love r e , et at p53 - mediated activation of mirna34 candidate tumor - suppressor genes . curr biol 2007 ; 17 ( 15 ): 1298 - 307 . 75 . brown b d , cantore a , annoni a , sergi l s , lombardo a , della valle p , et al . a microrna - regulated lentiviral vector mediates stable correction of hemophilia b mice . blood 2007 ; 110 ( 13 ): 4144 - 52 . 76 . egger g , jeong s , escobar s g , cortez c c , li t w , saito y , et al . identification of dnmt1 ( dna methyltransferase 1 ) hypomorphs in somatic knockouts suggests an essential role for dnmt1 in cell survival . proc nati acad sci usa 2006 ; 103 ( 38 ): 14080 - 5 . 77 . lee y s , dutta a . the tumor suppressor microrna let - 7 represses the hmga2 oncogene . genes dev 2007 ; 21 ( 9 ): 1025 - 30 . 78 . dunnet c w . a multiple comparisons procedure for comparing several treatments with a control . journal of the american statistical association 1955 ; 50 : 1096 - 1121 . 79 . cheng j c , yoo c b , weisenberger d j , chuang j , wozniak c , liang g , et al . preferential response of cancer cells to zebularine . cancer cell 2004 ; 6 ( 2 ): 151 - 8 . 80 . cheng j c , weisenberger d j , gonzales f a , liang g , xu g l , hu y g , et al . continuous zebularine treatment effectively sustains demethylation in human bladder cancer cells . mol cell biol 2004 ; 24 ( 3 ): 1270 - 8 . 81 . robertson k d , jones p a . tissue - specific alternative splicing in the human ink4a / arf cell cycle regulatory locus . oncogene 1999 ; 18 ( 26 ): 3810 - 20 . 82 . kim t y , zhong s , fields c r , kim j h , robertson k d . epigenomic profiling reveals novel and frequent targets of aberrant dna methylation - mediated silencing in malignant glioma . cancer res 2006 ; 66 ( 15 ): 7490 - 501 . 83 . chen c , ridzon d a , broomer a j , zhou z , lee dh , nguyen j t , et al . real - time quantification of micrornas by stem - loop rt - pcr . nucleic acids res 2005 ; 33 ( 20 ): e179 . 84 . gonzalgo m l , liang g . methylation - sensitive single - nucleotide primer extension ( ms - snupe ) for quantitative measurement of dna methylation . nat protoc 2007 ; 2 ( 8 ): 1931 - 6 . 85 . schwarz d s , zamore p d . why do mirnas live in the mirnp ? genes dev 2002 ; 16 ( 9 ): 1025 - 31 . 86 . liang g , lin j c , wei v , yoo c , cheng j c , nguyen c t , et al , distinct localization of histone h3 acetylation and h3 - k4 methylation to the transcription start sites in the human genome . proc nati acad sci usa 2004 ; 101 ( 19 ): 7357 - 62 . | 2 |
the following detailed description is directed to a kit , container assembly and method for retaining and organizing thoughts expressed in the form of indicia provided from loved ones or holidays or special occasions . the present inventions are susceptible of embodiment in many different forms . there is no intent to limit the principles of the present inventions to the particular disclosed embodiments . in the following detailed description , references are made to the accompanying drawings that form a part hereof and in which are shown by way of illustration specific embodiments or examples . referring to the drawings , in which like numerals represent like elements throughout the several figures , aspects of the present disclosure will be presented . in one or more embodiments the present invention is a kit or container assembly of components or parts used and arranged to enable reflection upon a past special occasion or holiday . for example , the kit or container may be provided as a gift for a birthday , anniversary , or for an expecting mother . thoughts , well wishes or words of encouragement can be conveyed to someone on the special day or holiday which are then archived in a storage compartment of a container such as a pillow or plush toy . preferably , the container is flexible , but the storage compartment is rigidly defined and configured so that any contents are not damaged while the container is being handled , displayed or stored . the pillow or plush toy may be in the form of a teddy bear or some other animal or shape . also , the container may be themed as a result of its configuration , color , decorations and / or writing included on its exterior . fig1 a and 1b illustrate one embodiment of a plush toy in the form of a teddy bear 10 . the teddy bear 10 includes an internal storage compartment 12 for receiving and retaining media . for example , a plurality of paper sheets such as notecards 14 may be received and retained within the storage compartment 12 . alternatively , the media may take other forms suitable for receiving and recording indicia from a writing implement such as a pen or pencil . for example , someone can purchase the teddy bear 10 as part of a kit that includes the notecards 14 , at least one writing implement 16 , and instructions 18 which include information on how the notecards 14 are to be used . the instructions could include examples of indicia which guests may include on one or more of the notecards 14 . preferably , more than one writing implement is included so that multiple notecards 14 may be completed at the same time . the notecards 14 , writing implement 16 and instructions 18 may be included in the storage compartment 12 when purchasing the teddy bear 10 as a gift . alternatively , the notecards 14 , writing implement 16 and instructions 18 may be included as part of the purchase but separate from the storage compartment 12 of the teddy bear 10 . all or a portion of the plurality of notecards 14 may be blank or a portion of the plurality of notecards 14 may include a partial sentence or phrase for prompting or suggesting how to write out thoughts or to personalize the notecards 14 . during an event one or more of the notecards 14 are provided to other users such as friends and family members which are present for an event . as explained in the instructions 18 , these users can then utilize the writing implement 16 to personalize the notecards 14 by providing indicia on the notecard 14 that corresponds with their personalized thoughts or well wishes for another person that will ultimately be receiving the teddy bear 10 . notecards 14 that already include some indicia prompt the user to complete the sentence or thought . the instructions 18 may include examples of how to complete the notecards 14 . upon each user completing their notecard 14 , the completed notecard 14 is placed within the storage compartment 12 of the teddy bear 10 . for example , as shown in fig1 b , the notecard is folded and the zipper 20 is unzipped in order for the folded notecard 14 to be placed within the storage compartment 12 . preferably , the notecards 14 are initially larger than the opening to the storage compartment 12 and therefore may be pre - folded or scored so that all the notecards 14 when completed would be the same size when received and retained within the storage compartment 12 . other means for keeping the storage compartment 12 closed may also be used such as fasteners . also , the completed and folded notecards 14 may first be placed inside a bag and then the bag with the notecards 14 inside may be placed inside the storage compartment 12 . alternatively , completed and folded notecards 14 may be first placed in a box or some other secondary container which is then placed inside the storage compartment 12 . for example , the folded notecards 14 may be collected in the bag or box and then at the end of the event or afterwards the bag or box may be placed inside the storage compartment 12 . in other words , the bag or box may be nested inside the container 10 . in another embodiment , the collected notecards 14 may be removed from the bag or box at the end of the event or afterwards and then placed inside the storage compartment 12 . in one or more embodiments , the storage compartment 12 may include an indicator such as an alarm , a displayed date or blinking light that indicates or reminds someone to open the storage compartment 12 in order to provide the opportunity to recall the event by reading the notecards 14 again . also , in one or more embodiments , a window may be provided so that it is possible to see notecards 14 inside the storage compartment 12 . thus , a collection of completed notecards 14 , with indicia there on , are received and retained within the storage compartment 12 of the teddy bear 10 . upon the conclusion of the event , the teddy bear 10 may then be visually displayed in a prominent manner by the user for which the notecards 14 were intended . in one or more embodiments , the container such as the teddy bear 10 is provided with internal structural members so that the teddy bear 10 remains sitting upright even when having completed notecards 14 inside the storage compartment 12 . sometimes a plush toy with such an internal structure is referred to as having a skeleton or as “ boned .” the storage compartment 12 may then be opened on an anniversary of the special occasion , holiday or event to retrieve the notecards 14 . thus , the completed notecards 14 are retained inside the teddy bear 10 in a safe and organized manner but may then be subsequently removed from the storage compartment 12 and read in order to reflect upon the past special occasion , holiday or event . instead of a teddy bear , the container with an internal storage compartment may take other shapes such as , but not limited to , an apple 26 for a teacher as illustrated in fig2 , a heart 30 with the zipper 20 on the side for valentine &# 39 ; s day as illustrated in fig3 , a tooth 40 as illustrated in fig4 a and 4b , or a bag 50 as illustrated in fig5 a and 5b . the tooth 40 may also include a pocket 42 for holding a tooth that has fallen out which may be exchanged for money during the night . the bag 50 may have a christmas theme and drawstrings 52 for closing the bag 50 as shown in fig5 b . the bag 50 may also include a pocket 54 . another example may be a ball configured for a particular sport . in addition to the kit and container assembly , the present inventions also includes a method for retaining and organizing thoughts expressed in the form of indicia provided from loved ones on holidays or special occasions . the method includes the steps of receiving via a first user a container having a storage compartment ; providing to a plurality of other users a plurality of paper sheets , a writing implement and instructions comprising information on how the plurality of sheets are to be used including examples of indicia which may be included on one or more of the plurality of paper sheets ; providing , via one or more of the plurality of other users utilizing the writing implement , indicia on one or more of the plurality of paper sheets ; configuring one or more of the plurality of paper sheets having indicia thereon to be received and retained within the storage compartment of the container ; and visually displaying the container with the one or more of the plurality of paper sheets having indicia thereon retained within the storage compartment of the container . the method may also include removing the one or more paper sheets having indicia . for example , the method may further include opening the storage compartment of the container on an anniversary of a special occasion , holiday or event to retrieve the one or more of the plurality of paper sheets having indicia thereon . the step of configuring one or more of the plurality of paper sheets having indicia thereon may include folding each of the one or more of the plurality of paper sheets having indicia thereon . unless otherwise indicated , more or fewer operations may be performed than shown in the figures and described herein . additionally , unless otherwise indicated , these operations may also be performed in a different order than those described herein . the subject matter described above is provided by way of illustration only and should not be construed as limiting . various modifications and changes may be made to the subject matter described herein without following the example embodiments and applications illustrated and described , and without departing from the true spirit and scope of the present disclosure , which is set forth in the following claims . | 0 |
according to the top view of fig1 a , the protective collar according to the invention comprises an annular part 10 which is interrupted or open 15 on one side in the non - assembled condition . the substantially flat annular part 10 consists of non - woven felt in the illustrated embodiment . alternatively , the collar may consist of a flat inlay , of slight inherent stability , or of a flat cushion or the like filled with a filling material . the annular part 10 comprises a circular inner opening 20 having a diameter d which after assembly around the child &# 39 ; s neck is substantially filled up by the latter , it being understood that the diameter d of the annular part 10 decreases of course a little during assembly . the slot - shaped opening 15 on one side of the annular part 10 serves to enable the collar 10 to be placed around the neck of a very small child . to this end , the annular part 10 comprises a usually two - part velcro fastener 25 ′, 25 ″ in the area of the opening 15 , in the preferred embodiment at the two annular ends 17 , 18 , reference numeral 25 ′ defining the hook fleece , while reference numeral 25 ″ defines the associated loop fleece . it goes without saying that the described fastening means 25 ′, 25 ″, instead of being arranged directly at the annular ends 17 , 18 may of course also be arranged at a certain distance from the annular ends 17 , 18 . using the velcro fastener 25 ′, 25 ″, the annular part 10 can be joined around the neck of a very small child , as illustrated diagrammatically in fig2 , in the form shown in fig1 b and can then be assembled as illustrated in fig2 . fig1 b further illustrates the way in which the protective collar 10 is held together by the two parts 25 ′, 25 ″ of the velcro fastener . further , the inner , substantially circular opening 20 developing during assembly is illustrated by broken lines in that figure , being hidden behind the outer front wall of the annular part 10 in that figure . according to another embodiment , not shown in the drawing , the annular part 10 consists of an inner part having a certain inherent stiffness and a detachable envelop made from a fabric or plastic material , or the like , intended to be placed on top , the envelope being made from a material that can be easily cleaned or washed . this two - part design of the annular part 10 permits the relatively high demands , that are placed on hygiene aspects especially in hospitals , to be met without any problems . the protective collar is deformable so that no disturbing and unnatural posture of the child &# 39 ; s head will be provoked for example if a very small child sleeps lying on one side . the elasticity of the protective collar then is such that on the one hand the sleeping child will be disturbed either not at all or only to a very little degree , while on the other hand any contact with the face is rendered impossible in that sleeping position . moreover , fastening means ( also not shown in the figure ) may be provided in the inner area of the annular part 10 ( which later faces the child &# 39 ; s neck ) for fastening or fixing a preferably tube - shaped therapeutic device , for example a probe device ( stomach probe , etc .) or an infusion tube . it thereby can be ensured that the very small child can reach that device with his / her hands or fingers either not at all or only with very great difficulty so that the device is protected from being moved , displaced or even torn off or torn apart . fig2 further illustrates the way in which the protective collar adapts itself closely to the child &# 39 ; s neck in the assembled condition . that arrangement guarantees that the collar will not slip or tilt to the rear and that the child is effectively prevented , in any position , i . e . when lying or standing , from reaching his / her face when rising his / her arm 30 ″, not even if his / her forearm should be angled , as illustrated diagrammatically in the drawing . the before - mentioned non - slipping feature of the collar finally is assisted by the fact that due to its shape , resembling a truncated cone , the protective collar is substantially fixed in the position in which it was attached , in the direction of the neck , which effect is further supported by the shape of the child &# 39 ; s head ( chin , etc . ). | 0 |
referring to fig1 a torque absorber 10 in accord with the provisions of this invention is shown bondingly associated with the socket 12 of a prosthetic device 14 . it can be seen from fig1 , 5 and 6 that prosthetic device 14 is comprised of endoskeletal elements which may include , for example , an upper pylon 16 or 16 &# 39 ;, a knee joint 18 , and a lower pylon 20 . in fig1 the torque absorber 10 is shown associated with a pylon which may be pylon 16 but more probably is pylon 20 as denoted in fig1 and applicable for a below - the - knee amputation . referring specifically to the structure in fig1 it can be seen that torque absorber 10 is made up of means such as a hollow cylindrical member 22 for fixture to the skeletal portion of a prosthesis about which an elastomeric member 24 may be bondingly associated and to which a socket 12 may be bonded . interior of hollow cylindrical member 22 is an elongated cylindrical member 26 having a flanged end 28 and a threaded opposite end 30 . threaded opposite end 30 is of lesser diameter than the unthreaded mid - portion 29 . disposed between the elongated cylindrical member 26 and the hollow cylindrical member 22 is a press - fitted bushing 32 adjacent to the hollow cylindrical member 22 and a friction reducing plastomeric sleeve 34 between the elongated cylindrical member and the plastomeric sleeve . such friction reducing material is well known in the art and will not further be described . disposed between flanged end 28 and the press - fitted bushing 32 is a friction reducing plastomeric washer 36 . similarly , at the opposite end of the elongated cylindrical member 26 and proximate threaded end 30 is a second friction reducing plastomeric washer 37 . a retainer 40 having a threaded axial bore 42 is threadably positionable on threaded end 30 . retainer 40 has spatially separated flanges 44 and 46 , the purpose of which will become apparent in the subsequent discussion . elastomeric member 24 is also formed with spatially separated flanges 48 and 50 , with the flange 50 located at the end proximate retainer 40 and defining a plurality of grooves or serrations 52 circumferentially oriented about the elastomeric member . it is desirable , although not necessary , that elastomeric member 24 extend above the end of press - fitted bushing 32 . furthermore , it is desirable , but not necessary , that the unthreaded mid - portion 29 of elongated cylindrical member 26 be sufficiently long to extend above the press - fitted bushing 32 , but not to the height of the elastomeric member 24 . finally , the plastomeric washer 37 may be thinner than the stepped portion of elongated cylindrical member 26 formed by the unthreaded mid - portion 29 extending above the press - fitted bushing 32 . the purpose of these dimensions is so that retainer 40 may be tightened on the threaded end 30 contacting first the elastomeric member 24 to seal the plastomeric washer 37 and press - fitted bushing 32 from plastomeric material utilized to construct socket 12 . this will become more apparent in the discussion that follows . in view of the turning moment which may be imposed upon elastomeric member 24 , it is desirable to include a metallic gripping portion fixedly associated with the first cylindrical portions 54 of hollow cylindrical member 22 . the metallic gripping portion 56 may be constructed of a plurality of flexible links in the form of a chain for bonding with first cylindrical portion by welding or the like . the hollow cylindrical member 22 extends downwardly below the elastomeric member 24 and has formed at the lower end thereof clamping means 60 for fixture to pylon 20 . referring to fig5 the same torque absorber 10 is shown relative an articulated knee joint 18 . this structure is in the event of a long upper stump remaining on the amputee with only the loss of the knee joint and the lower limb and is preferable in any above - the - knee amputation when used in conjunction with the foamed plastic pylon 16 &# 39 ; shown in fig6 . in this instance , the hollow cylindrical member 22 is affixed directly to the knee joint 18 by welding or the like . the method for affixing the knee joint to a lower pylon 20 is the subject of co - pending application ser . no . 805 , 058 . it will become apparent in the subsequent discussion that it is necessary to lock the retainer 40 relative the hollow cylindrical member during the molding process of a socket 12 &# 39 ;. consequently , when utilized in a knee joint application such as illustrated in fig5 it is appropriate to provide a set screw 64 which may be tightened against flanged end 28 . finally , it is appropriate to lock retainer 40 to threaded end 30 before molding socket 12 . accordingly , a set screw 66 has been found appropriate to accomplish this end . set screw 66 is radially oriented between flange 44 and 46 and may be of the socketed variety . in operation , the torque absorber is envisioned being used as follows . during the manufacture of the prosthesis , the socket 12 must be molded to a male mold of the amputee &# 39 ; s stump . accordingly , retainer 40 may be positioned a relatively small distance away from a male mold ( not shown ) so that the socket 12 may be molded thereabout ( see particularly fig1 and 5 ). socket 12 encompasses the upper portion of elastomeric member 24 and also encompasses the entire exposed surface of retainer 40 , in particular , the flanges 44 and 46 . as previously noted , during the molding process of socket 12 , flange 46 is tightened down against the upper end of elongated cylindrical member 26 so that the elastomeric member 24 serves to seal the area at the top of the bushing 32 and plastomeric sleeve 34 . this sealing prevents inadvertent seepage of plastomeric material into that area , which could lock retainer 40 in a fixed relationship with hollow cylindrical member 22 and defeat the purpose of the torque absorber . once the molding process is complete for socket 12 &# 39 ; in the embodiment illustrated in fig5 the set screw 64 , which is of assistance to enable retainer 40 to be tightened , may be relieved . in the embodiment shown in fig1 the flange 28 is accessible , hence a similar set screw is not necessary . it should now be apparent to those skilled in the art that socket 12 may rotate through the motion of retainer 40 which is lockingly associated with elongated cylindrical member 26 rotatably mounted in the hollow cylindrical member 22 . the resiliency of elastomeric member 24 serves to return socket 12 to the neutral or center position once the prosthesis is lifted from the ground when used by an amputee . comparison between the embodiments depicted in fig4 and 6 is appropriate in that the torque absorber 12 is positioned at opposite ends of the above knee or upper pylon . the embodiment in fig6 is preferred even though the mass of the torque absorber is located adjacent the knee rather than adjacent the socket . this embodiment may use a relatively light - weight plastic foam pylon 16 &# 39 ; which is affixed to torque absorber 10 by , for example , an epoxy adhesive . the socket 12 &# 34 ; which may be of glass fiber material is then formed about pylon 16 &# 39 ; and torque absorber 10 . the important feature seen in all the embodiments is the ability to mold the socket or socket extension over the elastomeric member 24 which is resiliently associated with prosthetic extremity by cylinder 22 while simultaneously bonding the same socket to retainer 40 which is rotatable in cylinder 22 and about the axis of the prosthetic extremity . the result provides for rotational movement of the socket relative the prosthetic foot with a simple resilient return arrangement . although this torque absorber has been shown in relation to a pylon or a knee joint , it is envisioned that the torque absorber may also be used in other positions in prostheses and should not be considered limited to the two applications nor to the particular embodiments described . furthermore , it is to be understood that variations to the torque absorber are to be considered within the scope of this disclosure and are limited only by the following claims . | 0 |
fig1 shows an embodiment of the document management system of the present invention . the system shown in fig1 includes the following constituent elements , namely , a display 10 to display thereon a retrieval result , a keyboard 20 to input therefrom commands for registration and retrieval operations , a central processing unit ( cpu ) 30 to execute registration processing and retrieval processing , a floppy disk driver 40 to read data from a floppy disk , a floppy disk 50 on which document data to be registered to a database is stored , a main memory 60 to temporarily store therein programs and data for the registration and retrieval operations , and a magnetic disk 70 to store therein various data items and programs and a bus 80 to connect these units to each other . in the main memory 60 , there are loaded from the magnetic disk 70 a system control program 100 , a registration control program 110 , a retrieval control program 120 , a text registration program 130 , a data creation and registration program for document retrieval 140 , an access control table creation and registration program 150 , a document retrieval program 160 , and an access control program 170 . moreover , a work area 190 is reserved in the memory 60 . additionally , on the magnetic disk 70 , there are reserved a text registration area 200 , a data registration area for data retrieval 210 , a registration area for various programs 230 , and a registration area for various tables 240 . although the embodiment includes a magnetic disk , the present invention is not restricted by this embodiment . namely , there may be used any device in which the areas above can be provided . in this regard , although these registration areas are reserved on the magnetic disk 70 in this embodiment , it may also possible to reserve these areas in another secondary storage such as a magneto - optical disk device . next , description will be given of the processing flow of this embodiment . in the embodiment , when databases are created , the system control program 100 beforehand generates a group control table shown in fig2 and a user control table shown in fig3 and stores these tables in the table registration area 240 . in other words , to the group control table , identification numbers of groups for which an access control operation is conducted in the document management system and an outline of each of the groups are beforehand registered . furthermore , stored in the user management table is information to identify groups to which each user belongs . that is , for each user registered to the system , ‘ 1 ’ is registered to a bit corresponding to a group to which the user belongs . in this connection , it may also be possible that a bit corresponding to a group to which the user belongs is set to ‘ 0 ’ and a bit corresponding to a group to which the user does not belong is set to ‘ 1 ’. namely , it is only necessary to discriminate groups to which the user belongs from those to which the user does not belong . that is , the user management table of fig3 indicates that a user , “ suzuki ” belongs to groups 1 and 2 , and the group control table of fig2 indicates that group 1 is a manager group of the document management system and group 2 is a group of in - house users in the organization of the system . subsequently , description will be given of processing procedures of document registration and retrieval operations in the document management system of this embodiment . first , in response to a registration command inputted from the keyboard 20 , the system control program 100 initiates operation of the registration control program 110 to start document registration processing . processing of the document retrieval operation will be described by referring to pad shown in fig4 . first , the program 110 activates the text registration program 130 in step 1000 . the program 130 registers text data of the registration document to the text registration area 200 on the magnetic disk 70 . the registration control program 110 then invokes the data creation and registration program for retrieval data 140 in step 1010 . the program 140 produces retrieval data in accordance with the text data stored in the area 200 and then registers the data to the area 210 on the disk 70 . finally , the program 110 starts the access control creation and registration program 150 in step 1020 . the program 150 registers bit information for documents which can be accessed by users belonging to respective groups as shown in fig8 to thereby create an access control table and then registers the table to the area 220 on the disk 70 and then terminates operation of the program 110 . subsequently , description will be given of the contents of processing of the registration program by referring to a specific example . first , the text registration program 130 reads , in step 110 as shown in fig5 text data of the registration document from the floppy disk 50 installed in the floppy disk drive 40 and loads the data in the work area 190 . thereafter , the program 130 registers in step 1110 the data loaded in the work area 190 to the area 200 on the disk 70 to thereby terminate processing of the program 130 . in this connection , although this embodiment includes a floppy disk , there may be used any other storage media on which information can be stored . moreover , in this embodiment , the registration document may be inputted not only from the floppy disk 50 but also from another apparatus , for example , by use of a communication line ( not shown in fig1 ) in the configuration of the embodiment . next , the retrieval data creation and registration program 140 reads , in step 1200 as shown in fig6 text data of the registration document stored in the area 200 of the disk 70 and loads the data in the work area 190 . the program 140 then creates in step 1210 retrieval data in the area 190 for the text data read in the area 190 . the retrieval data in this case is retrieval data for any one of various retrieval methods . for example , the data may be an index file to which words extracted from text data for index retrieval are registered or a learning file for a neurons - retrieval . moreover , the data may conform to an n - gram method in which an index is created for partial character strings ( n - gram ) extracted from a text . when the retrieval data is completely created , the program 140 registers in step 1220 the retrieval data created in the work area 190 to the area 210 of the disk 70 to thereby terminate processing of the program 140 . finally , the access control table creation and registration program 150 reads in step 1300 as shown in fig7 the group control table shown in fig2 and loads the table in the area 190 . furthermore , the program 150 loads in step 1310 the access control table shown in fig8 in the area 190 . the program 150 then executes in step 1320 processing of step 1330 for all registration documents . that is , in step 1330 , the program 150 refers to each entry of the group control table for each registration document and displays an outline of groups in step 1340 . the program 150 then determines in step 1350 whether or not the access is allowed for the pertinent group . when the access is to be allowed , the program 150 sets in step 1360 ‘ 1 ’ to the pertinent bit in the access control table , namely , there is recorded information that users belonging to the group are allowed to access the pertinent document . in other words , when the access right information is set to group 1 in association with a document with document number 7 , ‘ 1 ’ is set to an entry of group 1 corresponding to document number 7 ; whereas , ‘ 0 ’ is kept unchanged in entries of other groups . incidentally , it may also be possible that ‘ 0 ’ is set to the pertinent bit and ‘ 1 ’ is set to the other bits . only the pertinent bit is required to be discriminated from the other bits . when the processing above is completely finished for all registration documents , the program 150 deletes in step 1370 the group control table from the work area 190 . finally , t he program 150 registers in step 1380 the access control table generated in the area 190 to the area 220 on the disk 70 to thereby terminates the registration processing . in this regard , it may also be possible to beforehand assign information identifying a group to a document to be registered such that in accordance with information assigned to a registration document to identify a group , the program 150 executes the access control determination processing . the contents of processing in the document registration have been described . when a retrieval command is inputted by a user via a network to the document management system in accordance with the present invention , the system control program 100 initiates the retrieval control program 120 to start document retrieval processing . processing of document retrieval will be described by referring to pad shown in fig9 . first , the program 120 invokes the document retrieval program 160 in step 2000 . the program 160 refers to retrieval data under a retrieval condition specified by the user , obtains as a result of retrieval a list of documents associated with the retrieval condition , and stores the list in the work area 190 . next , the program 120 initiates the accessible document list creation program 170 in step 2010 to attain an accessible document list , i . e ., a list of documents which can be accessed by the user , and then stores the list in the area 190 . finally , the program 120 starts the access control program 180 in step 2020 . the program 180 accomplishes a disjunction operation between the list of retrieved documents created and stored in the area 190 by the document retrieval program and the accessible document list created and stored in the work area 190 by the program 170 to generate a list of retrieved documents after the access control determination , and returns the list to the user to thereby terminate the program 120 . next , the contents of processing of the retrieval program will be described by referring to a concrete example in a case in which a retrieval operation is conducted by a user with user name “ suzuki ”. first , the document retrieval program 160 analyzes a retrieval condition specified by the user in step 2100 as shown in fig1 and refers to retrieval data in accordance with the retrieval condition to conduct document retrieval processing . the retrieval processing can be carried out in any kinds of retrieval methods such as an index retrieval , neuro - retrieval , and an n - gram retrieval methods . in addition , two or more kinds of retrieval methods may be employed in the document retrieval processing . thereafter , the program 160 stores in step 2110 the list of documents obtained as a result of retrieval in the work area 190 and then terminates processing of the program 160 . next , as shown in fig1 , the program 170 reads in step 2200 a user control table shown in fig3 and stored in the area 240 on the disk 70 and loads the table in area 190 of the memory 60 . thereafter , the program 170 accomplishes collation for a retriever name in a field of the user name of the user control table in the area 190 to extract a group number of a pertinent entry so as to obtain a group number associated with an access right of the retriever . namely , in the case of this example , “ suzuki ” is obtained through the collation from the entry of the user name in the user control table to attain groups 1 and 2 as the pertinent group numbers . additionally , the program 170 refers in step 2220 to an entry in the access control table associated with the group number extracted in step 2210 to thereby obtain a list of documents which can be accessed by use of an access right of each group number . that is , in this example , the list of accessible documents is obtained by referring to entries of group numbers 1 and 2 in the access control table . moreover , the program 170 executes in step 2230 a conjunction operation between the lists of documents extracted in step 2220 . namely , in the case of “ suzuki ”, the operation is conducted between a document list corresponding to group 1 and a document list associated with group 2 to thereby create an accessible document list which is a list of documents which can be accessed by the retriever . thereafter , the program 170 stores in step 2240 the accessible document list to the area 190 . thereafter , the program deletes in step 2250 the user control table from the area 190 and then terminates the accessible document list creation program . finally , as shown in fig1 , the access control program 180 conducts a disjunction operation between the document list created in the area 190 in step 2300 as a result of retrieval by the document retrieval program 160 and the accessible document list created by the list creation program 170 to obtain a retrieval result of the access control processing . the program 180 then returns in step 2310 the retrieval result of the processing to the retrieval control program 130 . finally , the program 180 deletes in step 2320 the retrieval result document list and the accessible document list from the area 190 to thereby terminate the access control processing . on receiving the retrieval result created through the access control processing , the retrieval control program 120 returns the retrieval result via the system control program 100 to the retriever and then terminates the retrieval processing . description has been given of the contents of processing of document retrieval in the present embodiment . although the access control table is established for each group in this embodiment , the table may be set for each user identifier information . this makes it possible to conduct the access control operation at a personal level . additionally , in accordance with the present invention , the unit of access control operation is also applied not only to the referring operation to a document but also to an editing operation of a document . in this regard , the editing operation includes deletion , writing , addition , etc . of texts . as above , in accordance with the present embodiment , for each group to which users registered to the document management system belong , accessible documents are registered as an access control table at document registration . under this condition , when a retriever desires to retrieve a document , information of accessible documents of a group to which the retriever belongs is extracted to accomplish the access control processing . therefore , the access control operation can be achieved at a plurality of levels without dividing the database in accordance with the access control levels . in consequence , it is possible to provide a low - cost document management system having advantages in the operation management and maintenance thereof . additionally , a new access control level ( corresponding to a group number in the embodiment ) can be achieved by registering a new entry to the access control table . consequently , there is provided a document management system having improved expandability when compared with the conventional method in which a new database is to be additionally registered in the document management system . incidentally , in the access control method in accordance with the present embodiment , the access control operation can be completed in the access right determination only by referring to entries ( one megabit ( mbit )= 125 kilobytes ( kb ) for one million document information items ) of the access control table . in consequence , the retrieval response is rarely deteriorated for a large - sized document database . in accordance with the present invention , accessible documents of each group to which users registered to the document management system belong are registered as an access control table at document registration and hence the access control operation can be achieved at a plurality of levels without dividing the database in accordance with the access control levels . moreover , there is provided a low - cost document management system having advantages in the system operation management and maintenance . additionally , since a new access control level can be established by registering a new entry to the access control table , there can be provided a document management system having wider expandability when compared with the conventional method in which a new database is registered in the registration of a new entry . while the present invention has been described with reference to the particular illustrative embodiments , it is not to be restricted by those embodiments but only by the appended claims . it is to be appreciated that those skilled in the art can change or modify the embodiments without departing from the scope and spirit of the present invention . | 8 |
the hydraulic circuit arrangement shown in fig1 includes only the elements essential for the description of the present invention . sensors and the evaluating electronic unit necessary for slip control are not shown . also , only one brake circuit is shown , whose second wheel brake cylinder , which is usually included in the fluid supply , is omitted for the sake of clarity . from master cylinder 1 connected to a pressure fluid reservoir 2 , a brake line 3 extends to a wheel cylinder 6 by way of an electromagnetically operated , normally open separating valve 4 and a normally open inlet valve 5 which is also operated electromagnetically . a return line 7 extends from a wheel cylinder 6 to a low - pressure accumulator 9 by way of an electromagnetically operated , normally closed outlet valve 8 , and further to the suction side of a pump 10 . the pressure side of pump 10 is connected to the brake line 3 between the separating valve 4 and the inlet valve 5 by way of a pressure line 11 and a damping chamber 12 which cushions the pressure pulses of the pump . to aspirate pressure fluid during traction slip control , pump 10 additionally includes a suction line 13 which branches from the brake line 3 between the master cylinder 1 and the separating valve 4 and leads to the suction side of pump 10 . a hydraulically operated , normally open change - over valve 14 and a hydraulically operated , normally open shut - off valve 15 are arranged in the suction line 13 . a non - return valve 16 opening from the suction side of the pump 10 to the master cylinder 1 is connected in parallel to the shut - off valve 15 . the operation of the brake system during normal pedal - operated braking and during brake slip control corresponds to the operation of a state of the art brake system . for traction slip control , pump 10 aspirates fluid from the pressure fluid reservoir 2 by way of suction line 13 , the open change - over valve 14 and the open shut - off valve 15 , and the master cylinder 1 . the separating valve 4 in brake line 3 is then closed . the aspirated pressure fluid is conducted by pump 10 through the pressure line 11 and the damping chamber 12 into the brake line 3 downstream of the separating valve 4 , and into the wheel cylinder 6 by way of the open inlet valve 5 . when the braking pressure in the wheel cylinder 6 is sufficient for traction slip limitation , inlet valve 5 will close , permitting pressure to build up in the brake line 3 only between the separating valve 4 and the inlet valve 5 . the pressure is generally identical to the pressure on the pressure side of the pump 10 . when the pressure in the pressure line 11 has reached a predetermined value which is in excess of the amount of braking pressure necessary for traction slip control , the shut - off valve 15 will be closed hydraulically by the pressure in the pressure line . thus , pump 10 is prevented from aspirating additional pressure fluid from the pressure fluid reservoir 2 . when a new pressure increase phase becomes necessary after pressure reduction in the wheel cylinder 6 due to opening of outlet valve 8 , the inlet valve 5 will re - open , and the pressure in the pressure line 11 decreases . this causes the shut - off valve 15 to re - open so that the pump 10 can conduct a fluid flow into the pressure line again . a pressure - relief valve 17 is connected in parallel to the separating valve 4 . the purpose of the pressure - relief valve 17 ( as shown ) is to decrease pressure fluid towards the master cylinder 1 , which is still discharged from the wheel cylinder 6 to the pump 10 , even when the shut - off valve 15 is closed . the pilot pressure of the pressure - relief valve 17 is in excess of the closing pressure of the shut - off valve 15 to prevent the above - mentioned shortcomings of a permanent pressure fluid delivery . to prevent the self - priming pump 10 from excessively retracting the brake shoes of the wheel brakes and from causing a large lost motion during pedal - operated braking , which is due to an excessive pressure decrease in the return line 7 when the shut - off valve 15 is closed , a non - return valve 18 is inserted into the return line 7 between the low - pressure accumulator 9 and the suction side of the pump 10 for safety reasons . the pilot pressure of non - return valve 18 amounts to roughly 1 bar so that the pressure in the return line 7 will always be at least as high as the atmospheric pressure , even at a major suction rate of the pump . fig2 shows an example of an appropriate shut - off valve 15 . shut - off valve 15 includes three pressure fluid ports 21 , 22 and 23 in a housing 20 . one port 21 is associated with the portion of suction line 13 close to the master cylinder 1 , and the second port 22 leads to the suction side of the pump 10 . the third pressure fluid port 22 is connected to the pressure line 11 . the connection between the pressure fluid ports 21 and 22 is governed by a seat valve having its closure member 24 shaped on a floating piston 25 . the floating piston 25 is axially slidable in a housing bore 26 and is acted upon by a compression spring 27 so as to open the valve . floating piston 25 is sealed in relation to the housing bore 26 and separates a control chamber 28 , connected to the pressure fluid port 23 , from a valve chamber 29 including pressure fluid ports 21 and 22 . thus , the supply pressure of the pump is applied to control chamber 28 , and the respective master cylinder pressure prevails in valve chamber 29 . the supply pressure of the pump acts on the total cross - sectional surface of the floating piston 25 so as to close the valve . the effective surface of the master cylinder pressure is produced from the difference between the piston cross - section and the closing surface of the valve . the pressure on pressure fluid port 22 , which corresponds to the pressure on the suction side of the pump when the change - over valve 14 is open , acts upon the valve closing surface . it is achieved by this construction that the shut - off valve 15 is permanently open during pedal - operated braking and pressure build - up in the master cylinder 1 because the compression spring 27 also acts in the opening direction and , along with the master cylinder pressure , applies a force to the floating piston 25 which is in excess of the supply pressure of the pump 10 . when the master cylinder is not operated , however , the valve chamber 29 is under atmospheric pressure so that the supply pressure of the pump , from the control chamber 28 , displaces the floating piston 25 in the closing direction of the valve , thereby closing the shut - off valve 15 . in this arrangement , the compression spring 27 has a rigid design sufficient to cause displacement of the floating piston 25 only when the pressure in the control chamber 26 exceeds a desired nominal value . as soon as the nominal value is not reached , the shut - off valve 15 re - opens . the brake system of fig3 is largely identical to the brake system of fig1 . therefore , like parts of both figures have like reference numerals , increased by 100 in fig3 . the only difference is the arrangement of the shut - off valve 115 . in fig3 shut - off valve 115 is arranged directly on the suction side of the pump 110 so that both the pressure - fluid supply from master cylinder 101 and the supply line from low - pressure accumulator 109 is closed when the shut - off valve 115 closes . it is important in this respect that the control pressure generated in the master cylinder 101 and acting in the opening direction of the shut - off valve 115 is taken from the suction line 113 at a point disposed between the master cylinder 101 and the change - over valve 114 . the reason is that in a pedal - operated braking operation , the change - over valve 114 is closed so that only low pressure prevails between the change - over valve 114 and the shut - off valve 115 . at a high supply pressure of pump 110 , this low pressure would not be in a position to keep the shut - off valve 115 open . the result would be that the pump 110 could not aspirate pressure fluid from the low - pressure accumulator 109 . fig4 shows a preferred embodiment of the shut - off valve 115 . apart from chamber 128 , i . e . the control chamber that is acted upon by the supply pressure of the pump 110 , and the valve chamber 129 , the shut - off valve 115 still includes another control chamber 130 in which master cylinder pressure is connected . compression spring 127 , which acts in the valve opening direction , is also arranged in the second control chamber 130 . shut - off valve 115 includes a stepped bore 126 in housing 120 . a stepped piston 125 is sealed twice and axially slidable in stepped bore 126 . the large sealed piston cross - section frontally confines a control chamber 130 . valve chamber 128 is arranged between the two sealed piston cross - sections , i . e . in the intermediate axial portion of the stepped piston 125 with the piston step . valve chamber 129 , into which the pressure fluid ports 121 and 122 terminate , is arranged on the piston front face of small cross - section . the connection between the two pressure fluid ports is controlled by a slide valve having its control edge shaped on the stepped piston 125 . the separate control chamber 130 is required because the master cylinder pressure must act so as to open the shut - off valve , although the master cylinder 101 shall be separated from the suction side of pump 110 during traction slip control . because the master cylinder pressure in the control chamber 130 has the largest of all effective surfaces , the shut - off valve 115 will be reliably opened during pedal - operated braking . the supply pressure of the pump 110 , which acts on the surface of the piston step , therefore , can close the shut - off valve 115 only when the master cylinder 101 is unpressurized and the supply pressure is sufficient to compress the compression spring 127 . if this is the case , the stepped piston 125 will displace in opposition to the compression spring 127 so that the control edge overrides the pressure fluid ports 121 and 122 and thereby throttles the pressure fluid supply to the pump i 10 . the result is that the shut - off valve 115 automatically causes a controlled decrease of the fluid flow propagating to the pump 110 . apart from taking into account the corresponding surface ratios , there are no constraints with respect to the construction of the shut - off valve 115 . for example , it is also possible to use a seat valve kept open by a tappet when the stepped piston 125 is in its inactive condition . the inactive condition is determined by the compression spring 127 . | 1 |
the invention relates to an architecture for use in designing optical digital devices including an optical computer in which all logical operations are accomplished in the optical domain with predetermined wavelengths corresponding to predetermined values . the architecture relies on a logic structure different from boolean logic . the logic structure supports an n - ary logic system and is compatible with transfer functions obtainable using presently available optical components . the proposed architecture takes advantage of improved technology in fiber optics that allows the information to be encoded by wavelength and / or by intensity . currently , fiber optic networks can use 40 wavelengths or more . in it &# 39 ; s simplest form , an optical computer might use 2 wavelengths or channels to represent “ 0 ” and “ 1 ” in which only one wavelength is present at a time . alternatively , more wavelengths are used increasing the amount of information that is wavelength encoded . for example , if 40 discrete wavelengths are used then information is represented by the combinations of the 40 - values from 0 to 39 with each of the 40 wavelengths . the proposed architecture allows the data to be encoded in the intensity domain and logic operations in the wavelength domain , which forms a two - dimensional data representation and manipulation system . in a proposed embodiment the architecture is implemented using mach zender interferometers ( mzi ) and semiconductor optical amplifiers ( soa ). the mzi when combined with soas produce a component that can be used as a logic gate . referring to fig1 the mzi 100 and soas 111 a and 111 b work as follows : light enters the mzi 100 through the input port 1 and is split equally . the two beams of light propagate through waveguides 2 and 3 respectively and each enters different soas 111 a and 111 b . the soas 111 a and 111 b are capable of introducing a phase shift on the beams . when a second optical signal is presented at the input port 4 a , it triggers soa 111 a . when soa 111 a is triggered , a phase shift is not induced in light from the corresponding waveguide 2 . when no light is presented to the input port 4 a , then a phase shift is induced in the light signal from waveguide 2 . the two beams are then recombined and exit the mzi 100 through the output port 5 . if one of the beams is phase shifted 180 ° relative to the other beam then a destructive interference condition results . the destructive interference condition causes no light to appear at the output waveguide 5 . when there is no phase difference between the two beams , for example if neither beam has an induced phase shift , then the two beams add constructively resulting in a light signal propagating at output port 5 . as shown herein , when an soa is shown alone it does not behave the way it does when integrated within the mzi 100 . referring to fig2 a continuous light signal enters the soa 200 via input port 6 . when a second light signal is provided via input port 7 the first signal looses energy and is attenuated . when the second light signal provided via input port 7 has minimal intensity , the first optical signal is nominally attenuated and exits the soa 200 via output port 8 . referring to fig3 an o - and optical logic gate is shown for producing the transfer function given in table 1 . 1 . there are numerous ways of achieving this transfer function in an all optical device . fig3 shows a simple embodiment using an mzi with two soas . this device corresponds to the mzi 100 previously described . this gate 10 has two input ports 11 and 14 a and one output port 15 . a first optical logic signal x enters the mzi at the first input port 11 . it will exit the mzi 10 through the output port 15 provided that a second input signal y having a predetermined value is present at the second input port 14 a entering the soa . within a broad range , the wavelength of the signal entering the soa through input port 14 does not affect the operation of the device . when an optical signal exits the gate at the output port 15 it will have the same wavelength as the signal at the first input port 11 , although it has been modulated by light entering at the second input port 14 . referring to fig4 an o - or gate 20 is shown for providing a transfer function in accordance with table 1 . 2 . this gate is implemented in any of a variety of different ways . the o - or gate 20 relies on a continuous input signal provided at input port 21 . the continuous input signal is at a known wavelength that is the same wavelength as a wavelength of a signal provided to input port 26 . light entering port 24 modulates the continuous signal within the device producing an output signal at the output port of the mzi 25 a . this output port 25 a is connected to the input port 25 of the soa 28 . when a light signal is present on the other input port 26 a to the soa 28 then the output signal is substantially attenuated . when light below a predetermined intensity enters the second input port 26 a then light entering from the input port 25 a propagates to the output port 27 with nominal attenuation . referring to fig5 an o - nor gate 30 operates on light signals based on a transfer function given in table 1 . 3 . this gate is implemented in any of a variety of different ways . the o - nor gate shown is formed with a single soa 30 . an optical signal is provided at first input port 31 . when an optical signal having sufficient intensity is presented at a second input port 32 of the soa 30 then light from the first input port 31 is substantially attenuated prior to exiting at the output port 33 . when there is no signal of sufficient intensity at the second input port 32 then the optical signal entering the soa from the first input port 31 exits the soa at the output port 33 with minimal attenuation . referring to fig6 an o - not gate 40 operates on light signals based on a transfer function given in table 1 . 4 . this gate is implemented in any of a variety of different ways . the o - not gate shown is formed with a single soa 40 . a continuous signal is provided at first input port 41 . when an optical signal having sufficient intensity is presented at a second input port 42 of the soa 40 then light from the input port 41 is substantially attenuated prior to exiting at the output port 43 . when there is no signal of sufficient intensity at the second input port 42 then the optical signal entering the soa from the first input port 41 exits the soa at the output port 43 with minimal attenuation . referring to fig7 a bandpass filter 50 operates on light signals based on a transfer function given in table 1 . 5 . it is a common component used in various dwdm applications and is known to those skilled in the art . an optical signal entering the input port 51 will be allowed to exit the bandpass filter at the output port 52 if and only if the wavelength of the input signal corresponds to the predetermined wavelength . referring to fig8 an o - nand gate 60 operates on light signals based on a transfer function given in table 1 . 6 . this gate is implemented in any of a variety of different ways . a first optical signal x is provided at first input port 61 . this optical signal is split into two separate optical signals with a coupler 62 . the coupler causes some of the first input signal to enter a first input port 63 of the soa 64 . the remainder of the optical signal enters the first input port 68 a of the mzi 65 . when a second optical signal y having sufficient intensity is presented at a second input port 66 of the soa 64 then light from the first input port 63 is substantially attenuated prior to exiting at the output port 67 . when there is no signal of sufficient intensity at the second input port 66 then the optical signal entering the soa from the first input port 63 exits the soa at the output port 67 with minimal attenuation . the optical signal at input port 68 a will exit the mzi 65 through the output port 71 provided that a second input signal is present at the second input port 67 a entering the soa 72 . within a broad range , the wavelength of the signal entering the soa through input port 67 a does not affect the operation of the device . when light exits the gate at the output port 71 it will have the same wavelength as the signal at the first input port 61 . as basic optical logic elements the gates can be combined to produce different digital optical circuits . conceptually , this is analogous to the use of boolean logic gates to represent the operation of a digital electrical circuit . however , they are not equivalent because the optical logic gates work with various wavelengths and the boolean electrical logic gates work with only two states (“ on ” or “ off ”). the optical logic gates have been given names that that are consistent with boolean logic gates . an “ o ” has been added as a prefix to the gate &# 39 ; s name to distinguish these optical logic gates from the boolean gates . these gates can be combined to produce optical circuits whose function is analogous to similar electrical circuits . the analogous electrical circuits to these circuits provide the architecture used to design electrical binary computers . the n - valued logic circuits provide the architecture used to design an n - valued based computer and other n - valued optical digital devices . the proposed implementation of the n - valued digital system uses optical signals with different wavelengths to represent different data values however an n - valued computer need not be optical . quantum states , for example , can be used to implement the current n - valued digital system . the design of a complex n - valued device based on the proposed architecture requires a means of describing the mathematical operations algebraically . the algebra is based on a structure which is defined such that ( w , +, −, “, ‘, 0 ) with two binary operators + and −, two unary operators “, and ‘, and one distinguishing element 0 and a set w along with a set of postulates . the postulates include closure , commutative laws , associative laws , distributive laws , identities , subset complements , global complements and conversion . the set w contains n elements where n can be any whole number . we denote w ={ c 0 , c 1 , c 2 . . . c n } with c 0 , c 1 , c 2 . . . c n ε w . the closure postulate states that set w is closed with respect to the unary operators “ and ‘ and binary operators + and −. the commutative laws state that for all a , b ε w , a − b ≠ b − a but a − b = ( a + b )− b = a − ( a − b ) the identity postulate states that the distinctive element 0 ε w is an identity element with respect to binary operators + and − for every a ε w such that , the subset complement postulate states that for any element in a two element subset w ε w with w ={ 0 , a } there corresponds an element of a ′ with w such that the complement or global complement postulate states that for any element a in w there corresponds an element a ″ in w such that the conversion postulate states that for any element a ε w there is a conversion such that while it is known that n - valued logic , also referred to as switching algebra , is not unique , numerous other embodiments may be envisaged without departing from the spirit and scope of the invention . | 6 |
with reference to fig1 and 2 , a brazed structure 10 includes an open - faced honeycomb structure or component 12 and a closure component 14 which are bonded together by a metallic brazing alloy 16 to define a plurality of cells 18 . with reference to fig3 the cells 18 are packed with a wire transport material 20 . the wire transport material fills the cells and may slightly overflow the cells . as used in the instant specification , wire transport material means a packing of metal wires of various sizes and shapes which form capillary passages at the interstitial locations between the wires . the wire transport material comprises a metal material having a melting temperature greater than that of the metallic brazing alloy 16 used to bond the honeycomb structure 12 to the closure component 14 . the wire transport material 20 must also be wettable by the metallic brazing alloy . in accordance with the present invention , the wire transport material may be formed of a metal selected from the group consisting of aluminum , cobalt , copper , iron , nickel , their alloys , carbon steel , stainless steel and mixtures thereof . particularly suitable metals include stainless steels and carbon steels . as noted above , the wire transport material is formed of metal wires of various shapes and sizes . the metal wires have diameters of between 0 . 005 ″ to 0 . 050 ″, a length of up to 0 . 500 ″ and an interstice of between 0 . 0001 ″ to 0 . 015 ″. in the preferred embodiment , the metal has a diameter of between 0 . 010 ″ to 0 . 030 ″, a length of up to 0 . 500 ″ and an interstice of between 0 . 001 ″ to 0 . 007 ″. the interstice or spacing is such that it acts as a capillary passageway for the liquid brazing alloy as will be discussed hereinbelow . located on top of the cell or honeycomb structure 12 is a metal wire fiber material 22 which contacts the wire transport material 20 . the metal wire fiber material 22 , preferably , comprises a commercial grade steel wool material of between # 0000 and # 4 . the steel wool material has a diameter of between 0 . 0006 ″ to 0 . 008 ″. the wire transport material 20 creates a differential pressure between the bottom of the cell ( the metallic brazing alloy 16 ) and the metal wire fiber material 22 wherein the differential pressure is between 2 . 5 psia to 12 . 6 psia . the purpose of the differential pressure will be explained with reference to the process as set forth hereinbelow . the process of the present invention comprises the steps of : locating in a cell a wire transport material , covering the cell with a metal wire fiber material which contacts the wire transport material , heating the cell to sufficient temperature wherein the metallic brazing alloy flows through interstice of the wire transport material and onto the metal wire fiber material where the liquid brazing alloy is solidify . the components are thereafter separated and the metal wire fiber material with the solidified brazing alloy can be removed ( either before or after separation of the component parts ). the process of the present invention is preferably performed in an inert , hydrogen or vacuum furnace atmosphere in order to reduce oxidation and promoting wetting of the wire transport material by the liquid brazing alloy . generally , the debrazing temperature is not substantially higher than the original brazing temperature and is normally between 25 - 50 ° f . above the original brazing temperature . temperatures significantly higher can alter the metallurgical structural properties of the component parts and adversely affect the mechanical properties . it has been found that the total cycle time is generally between 10 - 30 minutes at the debrazing temperature . the preferred materials for the wire transport material are carbon and stainless steel wire . as noted above , the wire transport material is packed into the cell to form interstices of between 0 . 001 ″ to 0 . 015 ″, preferably 0 . 001 ″ to 0 . 007 ″. these interstices act as capillary passageways and are filled in seconds upon melting of the metallic brazing alloy . the metallic brazing alloy flows upward as a result of capillary action . the metal transport material which creates a differential pressure between the cell at the brazing alloy and the wire fiber material above the cells helps draw the liquid brazing alloy onto the metal wire fiber material ( by providing a wicking affect ) where the brazing material is solidified . the brazing material is then removed from the hollow component by simply removing the metal wire fiber material . upon removal of sufficient amounts of the brazing material , the component parts may be disassembled . a fifth stage low pressure , outer air seal honeycomb segment of a pw 4000 jet engine was selected as a candidate component to utilize the thermal brazing process of the present invention . a set of 20 engine run parts were cleaned per ual gn / mm 4 - 0 - 06 process 2n . the air seal segment parent material was ams5536 , the honeycomb was made of hastelloy x and the braze metal was ams4777 . the honeycomb cells of the segment were filled with 510 grams of cut wire . the cut wire was made of carbon steel of 0 . 014 - inch nominal diameter that conformed to ams2431 / 3 . honeycomb cells were filled to the top with some allowed overflow . specific preparation attention was focused on the edges of the segment to insure peripheral cells were filled . loose cut wire was removed from all non - honeycomb regions to prevent unwanted flow locations . the cut wire fill area was sprayed with a standard braze powder binder and allowed to dry for 45 minutes . the air seals were inverted and checked to insure cut wire did not fall out . three commercially available pads of # 0000 steel wool were placed ( lengthwise ) on top of cells containing the cut wire . all cells were covered with steel wool and overhang was trimmed . the air seal segments , with steel wool attached , were placed in a vacuum furnace with honeycomb face down . strips of fiber frax cloth were cut to dimension ( 10 inch length and 3 - ½ inch wide ) and placed over the air seal . fiber frax cloth is used to keep liquid braze metal from flowing in unwanted regions . another air seal , containing cut wire and steel wool , was placed on top followed by another sheet of fiber frax cloth . four stacks of five air seals ( separated by cloth ) were placed in the furnace . weights were placed on top of the sandwich stacks to ensure equal pressure on steel wool . the furnace cycle began by evacuating chamber to 0 . 56 - micron vacuum . the load was heated to 1800 ° f .± 25 ° f . and held for 10 minutes . heating rate was 30 ° f ./ min . the load was then heated to 1950 ° f .± 25 ° f . at 20 ° f ./ min and held for 30 minutes . the load was cooled to 1800 ° f .± 25 ° f . at 15 ° f ./ min and then quench cooled to 300 ° f . honeycomb , cut wire and steel wool with the brazing alloy was easily removed from the air seal segment with pneumatic and hand chisel . the component parts were than separated . the invention will be further described with reference to the following example . it is to be understood that the invention is not limited to the illustrations described and shown herein , which are deemed to be merely illustrative of the best modes of carrying out the invention , and which are susceptible of modification of form , size , arrangement of parts and details of operation . the invention rather is intended to encompass all such modifications which are within its spirit and scope as defined by the claims . | 1 |
throughout the description , identical reference numerals are used to identify like parts . fig1 and 2 illustrate the registration of a multimedia conferencing resource 10 for the provision of a multimedia conferencing service by a network supplier to a network user , using a service broker application 12 and a service broker resource registry 13 according to the invention . in order to make available the multimedia conferencing resource 10 , a multimedia conferencing resource management module 11 , finds and contacts , step 41 , over a network , an application programming interface front - end 121 of the service broker application 12 . in an authentication and authorisation interchange , step 42 , the service broker application 12 and multimedia conferencing resource management module 11 match the facilities of the multimedia conferencing service 10 , e . g . assigning a security protocol , with the needs of the service broker application 12 , to determine , step 43 , agreed facilities to be brokered . the multimedia conferencing resource 10 and the agreed facilities are registered , step 44 , by the multimedia conferencing resource management module 11 in the service broker resource registry 13 associated with the service broker application 12 . that is , a network resource owner registers a network resource with a network and , after passing relevant security procedures , enters details of the network resource into a network repository . the repository is a logical , i . e . virtual , entity and can be located anywhere in the network . the multimedia conferencing resource management module 11 updates , step 46 , a network client such as a soft switch 14 using a policy rule to advertise the availability of the multimedia conferencing resource 10 . the policy rule may , for example , define a time slot during which the service is available . that is , the network is characterised to ensure optimal operation by interaction with a policy management infrastructure by updating access points on the network to indicate that the registered network resource is available . in the embodiment illustrated in fig1 and 2 , the network client 14 activates , step 47 , the service by updating a universal translation module 15 . in this manner the service broker resource registry 13 provides a central registry of network resources 10 available to a network . that is , network resource suppliers register network resources with the service broker resource registry 13 to form a collection of network resources which can be offered to third party users . referring to fig3 and 4 , a third party user 21 , requiring a multimedia conferencing resource 10 , requests a conference call from a network client such as soft switch 14 . the soft switch 14 handles , step 52 , the request by passing the un - interpreted request from the third party user to the universal translation module 15 which interprets the request from look - up tables as a request for conference call service and passes the interpreted request back to the soft switch 14 . the soft switch 14 determines from the service broker resource registry 13 the availability of a multimedia conferencing resource 10 meeting the third party &# 39 ; s requirements , for example least - cost routing or a particular quality of service . the service broker resource registry 13 monitors use of registered network resources so that at any time the registered network resources which are available are known . that is , the interface monitors usage of registered network resources by counting how many of the network resources are in use and allowing no more users access once all the network resources are in use . when a network resource of a particular type is in use , a notification is sent to the service broker service registry to decrement the number of network resources of that type available . the number of network resources available from this pool of network resources is increased only as the pool becomes empty . if a multimedia conferencing resource 10 meeting the third party &# 39 ; s requirements is available , a request for the multimedia conferencing resource 10 is passed , step 53 , by the soft switch 14 to the multimedia conferencing resource 10 and a transmission link bearer path is set up , step 54 , between the third party user 21 and the multimedia conferencing resource 10 meeting the third party &# 39 ; s requirements . the third party user 21 is then able to make , step 55 , conference calls through a real time protocol portal 101 of the multimedia conferencing resource 10 . the soft switch 14 monitors the use of the multimedia conferencing resource 10 by the third party 21 in order to create , step 56 , a bill for use of the network resource by the third party . in this manner , the third party 21 is billed only for actual use of the multimedia conferencing resource 10 , and the network resource can be made available to other potential users when not in use by the third party . more generally , a user requesting a network resource accesses a familiar resource management network entity and once the user has been authenticated by security procedures , the user can access a network resource . the familiar resource management network entity may be an internet web page which provides access to a network portal giving access to the broker . the request for a network , resource may require updating of a service profile associated with the user . that is , a list of services to which the user is allowed access is updated by adding the brokered network resource to the list , so that the network will accept a request for the brokered service from the user . this updating may be handled by interaction with a software resource adaptation layer . the user can then interact with an interface of the network resource to action the user &# 39 ; s request for service . an information flow of a further embodiment of the invention , for providing a menu - driven interactive voice recognition service , is illustrated in fig5 and 6 . a network operator application 31 , requesting , step 61 , an interactive voice recognition service 32 sends a findservicebroker message 71 to a service broker application 12 including a registry 13 . the service broker application 12 requests , step 62 , the creation of an interactive voice recognition service specifying the required service attributes . the service broker application 12 selects , step 63 , an available voice recognition service 32 with the required attributes from the service broker service registry 13 and assigns , step 64 , a resource policy to the request . the request for service is populated , step 65 , from the registry 13 with a location of the interactive voice recognition service 32 and a servicelocationlnfo message 72 is passed to the network operator application 31 . the network operator finds , step 66 , the interactive voice recognition service 32 using the received servicelocationlnfo message , and the network operator accesses an interface of the interactive voice recognition service and begins using , step 67 , the network resource , by exchanging , step 73 , commands between the network operator application 31 and the interactive voice recognition service 32 . it will be understood that the invention is not limited to registering any particular types of network resource for providing any particular type of network service . examples of network resources which may be registered , but to which the invention is not limited , include network resources providing any telecommunication or information technology service , such as teleconferencing , multimedia conferencing , telephone service , call forwarding service , voicemail service , internet telephone service , user validation service , billing service , gaming service , database services and data back - up services . the invention provides an advantage of allowing a network operator to broker network resources to enable a distributed service infrastructure . for example , by providing a platform with an applications programming interface to define a broker capability , network services are made available to third parties , so that a network resource may be allocated on a time basis , for example for the working hours in a particular time zone , and the third party billed based on usage of the network resource . outside the working hours of the particular time zone , the network resource can be made available to other users . moreover , end - users can obtain all their telecommunication and information technology services from a single virtual source . the applications programming interface therefore handles requests for access to the broker , finds a service within the broker registry meeting the service requirements of the request , informs the user making the request of the location of the required network resource , assigns policy information to the request , for example time slots in which the service is to be provided , and records the usage time by the user of the network resource in order to bill the user for the actual usage . the applications programming interface may provide succession brokering where , for example for a gaming service , a first registered network resource from a first vendor provides user validation , a second registered network resource from a second vendor provides secure access to a gambling site and a third registered network resource from a third vendor provides consequential billing . alternative embodiments of the invention can be implemented as a computer program product for use with a computer system , the computer program product being , for example , a series of computer instructions stored on a tangible data recording medium , such as a diskette , cd - rom , rom , or fixed disk , or embodied in a computer data signal , the signal being transmitted over a tangible medium or a wireless medium , for example microwave or infrared . the series of computer instructions can constitute all or part of the functionality described above , and can also be stored in any memory device , volatile or non - volatile , such as semiconductor , magnetic , optical or other memory device . although the present invention has been described with reference to preferred embodiments , workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention . | 7 |
the present invention will now be described by way of embodiments thereof with reference to the drawings . fig1 to 3 show a principal part of a first embodiment of the present invention . since the first embodiment has the same basic structure as the conventional kneader having been described referring to fig1 , common portions are designated by the same reference numbers , and the characterizing portions of the present invention will be described in detail . materials to be kneaded by the kneader of the present invention are rubbers , plastics and the like , which may be admixed with additives such as pigment or reinforcing materials such as glass fiber . the first embodiment comprises a pair of right and left rotors 3 which are rotatably inserted into first and second kneading chambers 6 and 7 defined in a barrel 2 , the rotors 3 having , on the periphery thereof , feed portions 10a and 10b and kneading portions 11a and 11b axially separated by a dam portion 12 having a cylindrical surface with a reduced diameter , the feed portions and the kneading portions having substantially the same outer diameter , the feed portions each comprising a screw tip 19 having a helical angle of 30 °. the barrel 2 defines a vent port 14 extending to the second kneading chamber 7 on the upper side of the second kneading chamber and adjacent the dam portion 12 . the barrel 2 is provided with a pair of upper and lower gating members 16 and 17 at locations corresponding to the outer periphery of the dam portion 12 . the gating members 16 and 17 are movable toward and away from the dam portion 12 so that a channel 21 defined by the clearance around the outer periphery of the dam portion 12 is freely adjusted . the screw tip 19 of the feed portion 10b in the second kneading chamber 7 , at least within a vent zone v , includes a material feed surface 19b comprising a gently outwardly curved surface in section ( the center of the curvature thereof is located inside the rotor 3 or the material feed surface 19b ) and a material feed back surface 19c being flat and upright . the minimum clearance ho ( tip clearance ) between a screw tip flight 19a and the inner diameter d of the barrel 2 is 0 . 03 to 0 . 08 times the inner diameter d of the barrel 2 , so that the material undergoing kneading is ground by the outwardly curved material feed surface 19b and permitted to turn into a continuous viscous flow streaming in the screw groove 19d without any break . preferably , the helical angle θ is 15 ° to 60 °. when the helical angle θ is less than 15 °, the material stays in the vent zone for longer time , resulting in an excessive increase in the amount of the material in the vent zone , though the vent - up ratio ( amount of vent - up / amount of production ) is reduced . when the helical angle θ is greater than 60 °, the feeding speed of the material along the screw tip 19 is lowered . this increases the vent - up ratio , that is , the material is readily vented up . as described above , the ideal minimum clearance ho is 0 . 03 d to 0 . 08 d . when the clearance ho is less than 0 . 03 d , the vent - up ratio is increased because the cutting function of the flight 19a of the screw tip is enhanced to increase cuttings of the material . when the ho is greater than 0 . 08 d , the material feeding function of the screw tip 19 is extremely degraded . as a result , the value θ is desirably set to 15 ° or 30 ° when the value ho is 0 . 03 d , and to 30 ° when the value ho is 0 . 04 d . the advantages of the first embodiment of the present invention are apparent from the test results for comparison with the conventional kneaders as shown in fig4 . the graph in fig4 shows the ratio of the amount of vented - up resin to the amount of production , i . e ., the vent - up ratio (%) of each of the conventional kneader ( test nos . 1 and 2 ) and the first embodiment of the present invention ( test nos . 3 , 4 , 5 and 6 ). the tests were conducted under the conditions : test material = linear low - density polyethylene ( lldpe ); number of revolutions of rotors = 450 rpm ; and production rate = 440 kg / h . as obvious from fig4 the vent - up ratio of the conventional kneader was 0 . 07 % or greater , while the vent - up ratio of the embodiment of the present invention was 0 . 02 % or less and the vent - up ratios in the tests nos . 3 , 4 , and 6 , except no . 5 were not greater than 0 . 01 %, i . e ., not greater than the maximum allowable value . fig5 shows a second embodiment of the present invention which differs from the first invention in that screw tip 19 of feed portion 10b within vent zone v of second chamber 7 is formed in a tapered configuration growing greater in outer diameter as it approaching the discharge outlet side ( in the material feed direction ). this arrangement prevents the material from generating excessive heat . it should be noted that other constituents of the second embodiment are expected to function in the same way as the corresponding constituents of the first embodiment and hence are respectively designated by the same numbers as those used for the first embodiment to omit the description of such constituents . the foregoing embodiments are not limitative of the invention , and may be subjected to any changes . for example , the rotor with a single screw tip 19 as shown in fig7 as well as the rotor with double screw tips 19 as shown in fig6 may be employed in the present invention . further , the kneading portion 11b in the second kneading chamber 7 may be formed into a different configuration from the kneading portion 11a in the first kneading chamber 6 . for example , the kneading portion 11b in the second kneading chamber 7 may have extended screw tip 19 as shown in fig8 . the embodiments of the present invention may be modified in design as a double - rotor kneader ( including a double - rotor kneading extruder ) or a single - rotor kneader ( including a single - rotor kneading extruder ). in the double - rotor kneader , the rotors have engagement portions at their screws , and the rotors may be variously designed such that the rotors rotate in a circumferential direction or in the opposite directions or such that they rotate with complete engagement , with partial engagement or without engagement . fig9 to 11 illustrates an embodiment according to claim 2 of the present invention wherein a screw tip 19 forming a feed portion 10b within a vent zone comprises a material feed surface ( pushing surface ) 19b and a feed back surface ( pulling surface ) 19c both of which comprise respective outwardly curved surfaces in section . other constituents of this embodiment are common to the corresponding parts of the aforementioned embodiments and hence are designated by the same numbers as those used to designate the corresponding parts . the material feed surface 19b and feed back surface 19c both comprise respective outwardly curved surfaces in section so that the amount of resin which passes through a tip clearance ho while flowing round in a screw groove 10d can be increased . this reduces the scattering of melted resin thereby restraining the vent - up of the resin . compared to the aforementioned first embodiment , the increase in the amount of resin passing through the tip clearance ho in this embodiment ensures finer grinding of melted resin between the screw tip and the inner surface of the barrel 2 to eliminate gel , resulting in improved kneading quality . specifically , the outwardly curved surface of the feed back surface 19c presses the material against the inner surface of the barrel at a location adjacent gating device 5 ( outlet of channel 21 ) thereby further facilitating the elimination of gel . accordingly , while the curvature radiuses of the material feed surface 19b and the feed back surface 19c may be equal to each other , it is advantageous that the feed back surface 19c is formed to have a greater curvature radius than the feed surface 19b , in other words , the feed surface 19b is formed to have a smaller curvature radius than the feed back surface 19c . since the material feed surface 19b and the feed back surface 19c both comprise respective outwardly curved surfaces in section , the screw flight 19a substantially is a curved surface . the kneader comprising double rotors with triple screw tips shown in fig9 to 11 may be modified into a kneader comprising rotors with single or double screw tips . this embodiment is applicable to a kneader comprising a single rotor and to the kneaders shown in fig5 and 8 . while the screw tip comprising the outwardly curved material feed surface or comprising both the outwardly curved material feed surface and the outwardly curved material feed back surface is particularly advantageous in the second kneading stage , the screw tip in the first kneading stage may also comprise an outwardly curved surface in section . with the first embodiment of the present invention , the material to be kneaded is possible to stream in a continuous viscous flow without any break . as a result , the generation of cuttings of the material and the clogging of the vent port are avoided , so that the kneader can continuously be operated and efficiently remove volatile contents , such as water , contained in the material through the vent port , thereby ensuring improved kneading quality . with the second embodiment of the present invention , the material feed surface and the material feed back surface of the screw tip both comprising respective outwardly curved surfaces in section enhance the grinding function cooperatively with the inner surface of the barrel to eliminate gel , thereby contributing to a further improvement in kneading quality . the present invention is applicable to kneaders with vent function which are adapted to plasticize and homogeneously knead material containing rubber or resin and admixed therewith additives such as pigment and reinforcing materials such as glass fiber . | 1 |
in the liquid - liquid extraction method of the invention , a plurality of water soluble , mutually immiscible substances are added to water in amounts effective for phase separation upon agitation followed by equilibration and quiescent conditions . extensive studies have been made of water soluble substances useful as phase - forming materials in aqueous systems ( see references cited above ). by way of summary but not limitation , these substances include polymeric materials alone or in combination with salts and other water soluble compounds . while simple liquid - liquid extraction systems are constituted by a pair of such liquid phase - forming substances , more than two such different substances have also been used , resulting in a number of phases equal to the number of different immiscible substances . for each extraction system , the amounts of the extractants are easily selected so that phase separation will occur . representative multiple phase systems are the following wherein the percentage is the concentration of the substance in the aqueous system : two - phase systems : dextran ( 11 . 1 %)- polyethylene glycol ( 8 . 9 %); three - phase systems : dextran ( 6 . 67 %)- non - ionic synthetic sucrose polymer ( 8 %)- polyethylene glycol ( 5 . 33 %); and four - phase systems : dextran ( 5 %)- non - ionic synthetic sucrose polymer ( 6 %)- polyethylene glycol ( 4 %)- polypropylene glycol ( 25 %). ( albertsson , biochemistry , volume 12 , no . 13 , 1973 , page 2526 .) generally , suitable liquid phase - forming substances include polyalcohols , polyethers , polyesters , polyvinyl pyrrolidones and inorganic salts . specific extractants are polyethylene glycol , polypropylene glycol , methoxy polyethylene glycol , trimethyl amino polyethylene glycol , polyethylene glycol sulfonate , polyvinyl alcohol , polyvinyl pyrroldone , methylcellulose , ethylhydroxy ethyl cellulose , deae - cellulose , alkali metal carboxy methylcellulose , dextran , hydroxy propyl dextran , deae - dextran , dextran sulfate , alkali metal carboxy methyldextran , non - ionic synthetic sucrose polymer , and alkali metal sulfates and phosphates such as potassium phosphate . specific phase - forming pairs which have been extensively investigated and preferred for use in the present invention include polyethylene glycoldextran , polyethylene glycol - potassium phosphate , and polyethylene glycol - magnesium sulfate . the patent and other literature disclosing the foregoing and other liquid - liquid aqueous extraction systems useful in the present invention includes u . s . pat . nos . 4 , 144 , 130 - kula et al and 4 , 508 , 825 - kim et al , and the following articles : hustedt et al in biotechnology and bioengineering , volume xx 1989 - 2005 ( 1978 ); edmond et al , biochem . j ., 109 , 569 - 576 ( 1968 ); saeki et al , polymer , volume 18 , 1027 - 1031 ( oct . 1977 ); knoll et al , journal of biological chemistry , volume 258 , no . 9 , issue of may 10 , 1983 , 5710 - 5715 ; fisher et al , biochem . biophys . acta , 801 ( 1984 ) 106 - 110 ; johansson , biochem . biophys . acta , 222 ( 1970 ) 381 - 389 ; alberts , biochemistry , volume vi , no . 8 , aug . 1967 ( 2527 - 2532 ); flanagan et al , the journal of biological chemistry , volume 250 , no . 4 , issue of feb . 25 , 1975 ( 1484 - 1489 ); jizomoto , journal of pharmaceutical sciences , volume 74 , no . 4 , apr . 1985 ( 469 - 472 ); albertsson , biochemistry , volume 12 , no . 13 , 1973 ( 2525 - 2530 ); and the thesis by ramstorp , cited above . all of the foregoing patents and publications are incorporated herein by reference . as is apparent from the patents and literature cited above and examples set forth below , the molecular weight of the phase - forming substance and the ionic environment of the extraction system will have considerable influence on the partitioning effects . concentration of the substances , temperature and ph are additional conditions which influence partition . the particulate polymeric adsorbent to be admixed with the plurality of liquid phase - forming substances in an aqueous medium generally is a known material and may be either charged or uncharged depending upon the biomaterial or other product to be extracted . if the material to be extracted is uncharged , then other binding forces , e . g ., van der waals forces , will govern coupling or complexing with the adsorbent . any water - insoluble polymeric adsorbent material which is compatible with and preferably chemically inert to the phase - forming substances , and which can interact with but not denature the biomaterials or other products to be extracted , can be used . typical of the adsorbents are homopolymers and copolymers formed from vinylidene monomers such as acrylic and methacrylic acids and esters , and other monoethylenically unsaturated monomers or mixtures thereof , such as monocyclic and polycyclic aromatic monomers , e . g ., styrene and substituted styrenes , and the like . the monoethylenically unsaturated monomers may be polymerized without crosslinking or may be crosslinked in situ with a polyethylenically unsaturated monomer such as a polyvinyl aromatic hydrocarbon ( divinyl benzene , divinyl toluene , etc . ), a glycol dimethacrylate such as ethylene glycol dimethacrylate , or a polyvinyl ether of a polyhydric alcohol , such as divinoxyethane and trivinoxypropane . the polymeric adsorbents are prepared in a conventional manner including bulk , solution , suspension and emulsion polymerization . if the polymerization process is an emulsion polymerization , the desired small particle size range can be obtained directly , as shown in u . s . pat . nos . 4 , 359 , 537 and 4 , 380 , 590 to chong , u . s . pat . nos . 4 , 200 , 695 to chong , isacoff and neely , and u . s . pat . no . 4 , 537 , 683 to isacoff and neely , all of such patents being incorporated herein by reference . if the polymerization is suspension or other form , the particulate product polymers can be reduced in size by grinding techniques well known in the art . in the case of polymeric adsorbents having an ion exchange functional group or an affinity group , and useful in the process of the present invention , the particle size is generally 0 . 01 micrometer to 10 micrometers in diameter , preferably 0 . 01 micrometer to 5 micrometers , and even more preferably 0 . 05 to 2 micrometers . unfunctionalized polymers which attach to adsorbed materials by hydrophobic / hydrophilic bonding are useful in the same particle size range but particles in the range to 0 . 05 to 5 micrometers are preferred . irregularly shaped particles ( e . g ., ground resins ) are assumed , for purposes of this invention , to have longest dimensions with the diameter limitations set forth above . as indicated above , the polymeric adsorbents useful in the process to this invention are normally crosslinked and in the case of functionalized polymers , are uniformly functionalized as conventional for materials available heretofore in the ion exchange or affinity chromatography fields . however , water - insoluble , uncrosslinked or partially functionalized materials may also be suitable . for instance , ion exchange polymers functionalized with an ionogenic group near the particle surface , e . g ., a monolayer of ion exchange groups about the periphery of the bead , are useful . lightly crosslinked or surface - crosslinked beads having low water solubility are also effective . generally , the particle size of the polymeric adsorbent should be small enough so that the adsorbents will flow and partition in the aqueous system and feed lines ( the latter when the method is practiced as part to a more general processing sequence , involving feed from other manufacturing steps , possibly with subsequent separation and additional purification , both batch and continuous modes ). however , the particle size must not be so small that the complex cannot be supported on or retained by a filtration medium for separation of the complex from the aqueous medium . generally , for conventional filtration , the particle size should be at least about 1 . 0 micrometer ; for membrane filtration , the particle size may normally range from about 0 . 1 to about 1 . 5 micrometer . on the other hand , the particle size must not be too large ; otherwise , the material will not adsorb effectively on the polymeric particles and the particles will not remain suspended in the aqueous extraction system during partitioning and therefore will not carry adsorbed material efficiently into a phase or to an interface . liquid - liquid aqueous extraction systems for the separation or purification of biomaterials are also influenced by the ph of the aqueous medium , particularly for separation of biomaterials having characteristic isoelectric points . thus , in addition to complexing as a result of electrostatic attraction , complexing can also be controlled by the ph of the extraction medium . for example , a serum globulin having an isoelectric point at ph 4 . 4 will have an enhanced absorption on a positively charged polymeric adsorbent if the ph of the system is modified so that the globulin acquires a negative charge . the globulin thus is not only attracted more effectively to the adsorbent but also will tend to coat the adsorbent . additional enhancement of partitioning is achieved by combining polymeric adsorbents having opposite charges . the result is flocculation of the adsorbents , which in turn in many cases will magnify absorption of a material , thus carrying more of the adsorbed material into one of the phases or interfaces upon partitioning . the oppositely charged adsorbents may be combined either before addition to the extraction system ( such as the resin floc of u . s . pat . no . 200 , 695 ) or in situ upon sequential addition to the system . following partitioning , the liquid phases are separated by decanting , suction or other technique , and the complex is removed from the liquid by filtration ( e . g . ; microfiltration or ultrafiltration ) centrifugation or other suitable means . the product is then recovered from the filtrate or from the complex ( if adsorbed on the polymeric adsorbent ) by one or more conventional desorption treatments such as elution , salting - out , centrifugation or membrane filtration ( ultrafiltration or microfiltration ). in some cases , particularly if the polymeric adsorbent is an ion exchange resin , desorption of product from the complex can be achived by treatment with another ion exchange resin having the same charge as that of the carrier resin of the complex . in some cases , also , adjustment of ph of a liquid environment containing the complex will be sufficient for desorption . after recovery from the extraction system , the product may be further purified by repetition of the liquid - liquid extraction method of the invention or by other treatments known in the art . the following examples will further illustrate the invention but without necessarily limiting the scope thereof , it being understood that those skilled in the art will be able to vary the conditions set forth therein , including the addition of other substances and amounts , without departing from the spirit and scope of the invention as set forth in the appended claims . in the examples , all parts and percentages are by weight unless otherwise specified . this example illustrates the ability of small particle size ion exchange resins to partition in liquid - liquid extraction systems , and the extent separation capacity , c sep ) of partitioning relative to molecular weight of peg ( part b ). ( a ) ten ml of polyethylene glycol 300 ( peg300 ) ( 30 %) potassium phosphate buffer ( ppb ) ( 1 . 5 m ) two - phase system was prepared with peg300 , ph 7 . 2 ppb , and various concentrations of ion exchange resins in 15 ml centrifuge tubes . the mixtures were shaken for 10 minutes and centrifuged for 10 minutes at 700 times gravity ( 700 × g ). the critical level of ion exchange resin concentration for the two - phase system was determined by measuring absorbance of the resin at 600 nm . as shown in table 1a , strongly basic styrene resin and strongly acidic styrene resin partitioned into the bottom and the top phases , respectively . strongly basic acrylic and weakly basic acrylic resins were concentrated at the interface . ( b ) ten ml of a polyethylene glycol molecular weight 8000 ( peg8000 ) ( 6 %)/ dextran molecular weight 40000 ( dex40000 ) ( 10 %) two - phase system were prepared in ph 7 . 2 , 10 mm potassium phosphate buffer ( ppb ) with various concentrations of ion exchange resins in 15 ml centrifuge tubes . the mixtures were shaken for 10 minutes and centrifuged for 10 minutes at 700 × g . the separation capacities of this system were determined as described in part a . as shown in table 1b , the basic resins partitioned into the bottom phase and acid resin partitioned into the top phase . table 1a__________________________________________________________________________ separation capacity , csep ( g resin / 100 ml partitiontype of ion exchange resin of system ) behavior__________________________________________________________________________strongly basic 1 . 0 interfaceacrylic dvb . sup . a ( 0 . 1 micrometer ). sup . bweakly basic 0 . 5 interfaceacrylic - dvb . sup . a ( 0 . 08 micrometer ). sup . bstrongly basic 0 . 5 bottom phasestyrene - dvb . sup . a ( 0 . 27 micrometer ). sup . bstrongly acidic 2 . 5 top phasestyrene - dvb . sup . a ( 0 . 22 micrometer ). sup . b__________________________________________________________________________ . sup . a crosslinked with divinyl benzene ( dvb ) . sup . b mean diameter of ion exchange resin ( prepared as described in u . s . pat . no . 4 , 380 , 590 table 1b__________________________________________________________________________ separation capacity , csep ( g resin / 100 ml partitiontype of ion exchange resin of system ) behavior__________________________________________________________________________strongly basic 1 . 5 bottom phaseacrylic dvb . sup . a ( 0 . 1 micrometer ). sup . bweakly basic 4 . 0 bottom phaseacrylic - dvb . sup . a ( 0 . 08 micrometer ). sup . bstrongly basic 2 . 0 bottom phasestyrene - dvb . sup . a ( 0 . 27 micrometer ). sup . bstrongly acidic 1 . 05 top phasestyrene - dvb . sup . a ( 0 . 22 micrometer ). sup . b__________________________________________________________________________ . sup . a crosslinked with divinyl benzene ( dvb ) . sup . b mean diameter of ion exchange resin ( prepared as described in u . s . pat . no . 4 , 380 , 590 ten ml of peg8000 ( 6 %)/ dex40000 ( 10 %) aqueous two - phase system was prepared by adding peg8000 , dex40000 , bovine serum albumin ( bsa , 0 . 1 %, wt / v ) in ph 7 . 2 potassium phosphate buffer ( ppb , 10 mm ) and various concentrations of strongly basic acrylic ion exchange resin ( mean diameter = 0 . 1 micrometer ) to 15 ml centrifuge tubes , shaking for 10 minutes , and centrifuging for 10 minutes at 700 × g . concentrations of bsa and resin were determined spectrophotometically by measuring the absorbance at 280 nm and 600 nm , respectively . table 2 shows the improvement of bsa partitioning with strongly basic acrylic resin in the peg / dex two - phase system . the peg / dex system partitioned bsa mostly into the dex - rich bottom phase but left some in the peg - rich top phase . when strongly basic acrylic resin was added , the concentration of bsa in the peg - rich top phase decreased with increase in the concentration of resin . strongly basic acrylic resin at a concentration of 0 . 02 % transferred bsa completely from the top to the bottom phase . resin partitioned completely into the bottom phase and sedimented bsa resin flocs were observed on the bottom of the centrifuge tube in the dex - rich bottom phase above strongly basic acrylic resin concentration of 0 . 01 %, indicating that the separation of resin - absorbed bsa was feasible . table 2______________________________________concentration of concentration of bsaion exchange resin partition in peg - rich top phase (%, wt / v ) behavior (%, wt / v ) ______________________________________0 . 000 -- 0 . 01210 . 0005 bottom phase 0 . 00930 . 001 bottom phase 0 . 00730 . 002 bottom phase 0 . 00590 . 005 bottom phase 0 . 00540 . 010 bottom phase 0 . 0012 (+). sup . a0 . 015 bottom phase 0 . 0003 (++). sup . a0 . 020 bottom phase 0 . 0000 (++). sup . a0 . 040 bottom phase 0 . 0000 (+++). sup . a______________________________________ . sup . a + indicates the relative amounts of sedimented flocs on the bottom of the dextranrich bottom phase the procedure of example 2 was repeated except weakly basic acrylic resin ( mean diameter = 0 . 08 micrometer ) was used instead of strongly basic acrylic resin . table 3 shows the improvement of bsa partitioning by weakly basic acrylic resin . weakly basic acrylic resin also improved the partition of bsa in peg / dex two - phase system . the concentration of bsa in the peg - rich top phase decreased with increase in the concentration of resin . with 0 . 01 % weakly basic acrylic resin , the concentration of bsa in the top phase decreased to less than half that in the absence of resin . at the concentration of resin higher than 0 . 02 %, flocs were formed and sedimented on the bottom of the centrifuge tube in the dex - rich phase indicating that protein - resin flocs were easily recoverable . table 3______________________________________concentration of concentration of bsaion exchange resin partition in peg - rich top phase (%, wt / v ) behavior (%, wt / v ) ______________________________________0 . 000 -- 0 . 01210 . 001 bottom phase 0 . 01160 . 002 bottom phase 0 . 01020 . 005 bottom phase 0 . 00820 . 010 bottom phase 0 . 00500 . 020 bottom phase -- (+). sup . a______________________________________ . sup . a formation of flocs on the bottom of the centrifuge tube in the dextranrich bottom phase the procedure of example 2 was repeated except that strongly basic styrene resin ( mean diameter = 0 . 27 micrometer ) was used instead of strongly basic acrylic resin . the partition behavior and improvement of bsa partitioning in peg / dex two - phase system are shown in table 4 , demonstrating that the strongly basic styrene resin improved the partitioning of bsa in the peg 8000 ( 6 %)/ dex40000 ( 6 %) two - phase system . the concentration of bsa in the peg - rich top phase decreased with increase in the concentration of resin . bsa concentration in the top phase decreased by a factor of 13 at 0 . 08 % resin . flocs formed and sedimented at a resin concentration above 0 . 04 %. table 4______________________________________concentration of concentration of bsaion exchange resin partition in peg - rich top phase (%, wt / v ) behavior (%, wt / v ) ______________________________________0 . 000 -- 0 . 01210 . 001 bottom phase 0 . 01130 . 002 bottom phase 0 . 00820 . 005 bottom phase 0 . 00790 . 010 bottom phase 0 . 00930 . 020 bottom phase 0 . 00770 . 040 bottom phase 0 . 0060 (+). sup . a0 . 060 bottom phase 0 . 0037 (++). sup . a0 . 080 bottom phase 0 . 0008 (++). sup . a0 . 100 bottom phase 0 . 0009 (+++). sup . a______________________________________ . sup . a + indicates the relative amounts of sedimented flocs on the bottom of the dextranrich bottom phase this example illustrates partitioning of a positively charged protein ( lysozyme ). ten ml of peg8000 ( 6 %)/ dex40000 ( 10 %) aqueous two - phase system was prepared by adding peg8000 , dex40000 , and lysozyme ( 0 . 1 %, wt / v ) in ph 7 . 2 potassium phosphate buffer ( ppb ) with the various concentrations of strongly acidic styrene resin ( mean diameter = 0 . 2 micrometer ) of example 1 in 15 ml centrifuge tubes . the mixtures were shaken for 10 minutes and centrifuged for 10 minutes at 700 × g . concentrations of lysozyme and resin were determined spectrophotometically by measuring the absorbance at 280 and 600 nm , respectively . table 5 shows the partition behaviors of lysozyme and strongly acidic styrene resin in peg / dex two - phase system . at the optimum concentration ratio to resin to lysozyme ( 1 . 4 g resin / g lysozyme ), lysozyme was concentrated on the interface in peg8000 ( 6 %)/ dex40000 ( 10 %). below the optimum concentration ratio of resin to lysozyme , the resin partitioned into the dex - rich bottom phase . above the optimum concentration ratio of resin to lysozyme , the resin was partitioned into the peg - rich top phase . as also shown in example 1b , all of the acidic resin partitioned into the top phase . lysozyme is a basic protein , pka = 11 . 0 . at ph 7 . 2 lysozyme has net positive charges . in the presence of excess lysozyme , lysozyme - resin flocs are formed and partition into the bottom phase because the flocs have net positive charges , like the strongly basic resins of example 1 . in the presence of excess resin , the lysozyme - resin flocs partition into the top phase ( like strongly acidic resin itself ) because the flocs have a net negative charge . therefore , lysozyme can be concentrated at the interface by controlling the amount of resin added . table 5______________________________________ concen - concentration partition lysozyme trationof ion exchange behavior ( a . sub . 280 ) ier ( a . sub . 600 ) resin (%, wt / v ) of flocs top bottom top bottom______________________________________0 -- 1 . 757 2 . 666 -- -- 0 . 10 bottom phase 0 . 983 -- 0 . 010 -- 0 . 11 bottom phase 0 . 783 -- 0 . 000 -- 0 . 12 bottom phase 0 . 700 -- 0 . 000 -- 0 . 13 interface phase 0 . 698 0 . 869 0 . 000 0 . 0620 . 14 interface phase 0 . 655 0 . 600 0 . 122 0 . 0040 . 15 top phase -- 0 . 589 -- 0 . 0130 . 16 top phase -- 0 . 633 -- 0 . 0000 . 17 top phase -- 0 . 481 -- 0 . 0000 . 18 top phase -- 0 . 493 -- 0 . 0000 . 19 top phase -- 0 . 431 -- 0 . 0020 . 20 top phase -- 0 . 398 -- 0 . 003______________________________________ the experiments of this example were performed substantially as described in examples 2 - 5 . the cell concentration in each of the experiments of this example was 1 g / liter of broth , and the resin concentration was 0 . 5 g / liter of broth . the total volume used in each experiment was 10 ml . in the first experiment , the partitioning of beta - galactosidase from e . coli with the strongly basic styrene - dvb resin of example 1 was studied . the results are given in table 6a from which it will be apparent that most of the beta - galactosidase partitioned into the peg - rich top phases in the various phase systems tested and that peg3350 ( 6 )/ ppb ( 0 . 8m ) gave the highest yield . however , peg1450 ( 15 %)/ ppb ( 1 . 0m ) showed the highest purification fold . it was also observed that cellular debris obtained by centrifugation of the disrupted e . coli cells was concentrated in ppb phase . accordingly , enhanced , selective recovery of beta - galactosidase is evident . in other experiments the resin was added to sonicated e . coli cell suspensions . adsorption was carried out in 10 mm ppb at ph 5 . 6 to increase yield and adsorption of beta - galactosidase on the resin . cell debris / beta - galactosidase / resin flocs were then collected by centrifugation . additional ppb was added to the sedimented flocs and the resulting suspension was shaken for 30 minutes to increase desorption yield . after the desorption , peg was added , and the suspension was shaken for 10 minutes , and centrifuged to form a two - phase system . the highest yield and purification fold of beta - galactosidase was achieved at ph 6 . 1 as shown in table 6b . the partition behavior of beta - galactosidase from asp . niger was found to be different from that from e . coli ( table 6c ). contrary to the beta - galactosidase from e . coli , most of the asp . niger beta - galactosidase partitioned into the ppb - rich bottom phase , and only at high concentrations of low molecular weight peg ( mw 300 and 600 ) did the asp . niger enzyme partition into the top phase ( table 6d ). accordingly , it appears that the beta - galactosidase produced by e . coli and asp . niger are quite different in their surface properties . the enzyme produced by e . coli is more hydrophobic than that from asp . niger . table 6a______________________________________partition of beta - galactosidase from e . coli dh1extract in peg / ppb two - phase system activity puri - composition top bottom yield ficationtwo - phase system phase phase (%) fold______________________________________peg1450 ( 15 %)/ ppb ( 1 . 0m ) 831 32 69 3 . 0peg3350 ( 6 %)/ ppb ( 0 . 8m ) 928 19 77 2 . 2peg3350 ( 15 %)/ ppb ( 1 . 0m ) 839 11 73 2 . 1peg8000 ( 12 %)/ ppb ( 0 . 7m ) 842 23 70 2 . 0______________________________________ activity of cell extract = 5993 units / ml extract volume of cells added to two phase system 0 . 2 ml = 1199 units table 6b______________________________________influence of ph on the partition of beta - galactosidase in a two - phase system activity yield purificationph of ppb recovered (%) fold______________________________________5 . 9 2100 69 3 . 46 . 1 2820 89 4 . 66 . 3 2720 86 4 . 36 . 5 2540 80 4 . 27 . 0 2160 68 3 . 4______________________________________ table 6c______________________________________partition of beta - galactosidase from asp . nigerin peg / ppb systems activitycomposition of bottom partitiontwo phase system top phase phase coefficient______________________________________peg300 ( 20 %)/ ppb ( 1 . 5m ) 290 181 1 . 6peg600 ( 20 %)/ ppb ( 1 . 5m ) 29 300 0 . 097peg1450 ( 15 %)/ ppb ( 1m ) 6 439 0 . 014 ( 20 %)/( 1 . 2m ) 7 425 0 . 016 ( 25 %)/( 1 . 5m ) 24 328 0 . 073peg3350 ( 15 %)/ ppb ( 0 . 8m ) 6 455 0 . 013 ( 20 %)/( 0 . 8m ) 5 432 0 . 012peg8000 ( 12 %)/ ppb ( 0 . 8m ) 6 467 0 . 013 ( 12 %)/( 0 . 7m ) 7 452 0 . 015 ( 15 %)/( 0 . 8m ) 10 445 0 . 022 ( 20 %)/( 0 . 8m ) 21 417 0 . 050 ( 25 %)/( 1 . 0m ) 38 391 0 . 097 ( 25 %)/( 1 . 2m ) 69 528 0 . 13______________________________________ activity of 0 . 1 % betagalactosidase solution = 122 . 7 units / ml total volume of system = 5 ml 613 units table 6d______________________________________partition of beta - galactosidase from asp . nigerin peg / ppb systems activitycomposition of bottom partitiontwo phase system top phase phase coefficient______________________________________peg300 ( 25 %)/ ppb ( 1 . 5m ) 324 12 27peg300 ( 30 %)/ ppb ( 2 . 4m ) 230 5 46peg300 ( 30 %)/ ppb ( 1 . 5m ) 245 6 41peg300 ( 30 %)/ ppb ( 1 . 8m ) 198 3 66peg300 ( 35 %)/ ppb ( 1 . 8m ) 241 5 48peg300 ( 35 %)/ ppb ( 2 . 0m ) 212 6 35peg300 ( 40 %)/ ppb ( 2 . 0m ) 168 7 24peg600 ( 40 %)/ ppb ( 1 . 5m ) 51 41 1peg600 ( 35 %)/ ppb ( 1 . 5m ) 89 5 18peg600 ( 40 %)/ ppb ( 2 . 0m ) 250 6 42______________________________________ activity of 0 . 1 % betagalactosidase solution = 122 . 7 units / ml total volume of system = 5 ml = 613 units the procedure of example 5 was repeated using a ground , weak - acid acrylic ion exchange resin . the partition behavior and improved separation of lysozyme in peg / dex two - phase systems are illustrated in table 7 . the results demonstrate that a weakly acidic acrylic resin improved the partitioning of lysozyme in the peg600 ( 20 %)/ dex40000 ( 15 %) two - phase system . the concentration of lysozyme in the peg - rich top phase decreased with increasing concentration of this weak - acid acrylic resin , which directed the partition of lysozyme into the dex - rich bottom phase . the partition yield of lysozyme increased from 60 % ( in the top phase ) to 100 % ( in the bottom phase ) with resin . table 7______________________________________cation exchange concentration of partition * resin concentration lysozyme in top phase yield ( g resin / g lysozyme ) (%, wt / v ) (%) ______________________________________0 . 0 0 . 086 . sup . t 60 . sup . t 0 . 107 . sup . b . sup . 38 . sup . b0 . 2 0 . 082 470 . 4 0 . 051 670 . 6 0 . 031 800 . 8 0 . 034 781 . 0 0 . 032 801 . 5 0 . 004 972 . 0 0 . 001 1002 . 5 0 . 001 1003 . 0 0 . 001 100______________________________________ * partition yield in the dextranrich bottom phase t top phase ( volume of top phase = 65 % of total system volume ) b bottom phase ( volume of bottom phase = 35 % of total system volume this example illustrates the recovery of enzyme activity ( lysozyme ) from resins in liquid - liquid extraction . ten ml of peg8000 ( 6 %)/ dex40000 ( 10 %) aqueous , two - phase system was prepared by mixing peg8000 , dex40000 and lysozyme ( 0 . 1 %, wt / v ) in ph 7 . 2 potassium phosphate buffer with 0 . 15 % ( wt / v ) weakly acidic acrylic group resin of example 7 in the 15 ml centrifuge tube . the mixture was shaken for 10 minutes and centrifuged for 120 minutes at 700 × g . the peg - rich top phase was replaced with potassium phosphate buffer . the ph of the mixture was adjusted with 2 n naoh , the mixture was shaken for 20 minutes and centrifuged for 5 minutes at 15 , 000 × g . the lysozyme activity of the supernatants was determined spectrophotometrically from their effect upon a micrococcus lysodeiktus lysate : the supernatant was diluted 100 - fold in 0 . 5 molar potassium phosphate buffer solution having a ph of 7 . 0 , 0 . 1 ml of the dilute solution was added to 2 . 9 ml of the lysate at 75 ° c ., and the change in absorbance ( at 450 nm ) with time was measured . this absorbance change , in absorbance units per minute , was multiplied by the dilution of the supernatant to obtain a lysozyme activity value for the original supernatant . table 8 shows the results of these measurements . using 200 mm potassium phosphate at ph 10 . 1 , the recovery yield was as high as 89 % of the total activity of lysozyme initially added into the two - phase systems . table 8______________________________________ total activity recovery recovered yieldph ( a . sub . 450 / minute )* (%) ______________________________________free lysozyme 21 , 500 -- 100 mm potassium phosphate 7 . 3 2 , 000 9 8 . 0 6 , 900 32 9 . 9 13 , 500 6310 . 7 14 , 800 6911 . 6 14 , 500 6712 . 1 13 , 000 61200 mm potassium phosphate 7 . 1 12 , 100 56 8 . 1 16 , 900 7910 . 1 19 , 100 8911 . 3 18 , 400 8611 . 7 18 , 300 85______________________________________ * absorbance units per minute , on basis of original supernatant concentration . | 1 |
referring to fig1 this figure shows a prior art bulkhead 102 . apertures 108 allow liner load / vent tubes 306 ( shown in fig3 ) to pass through the bulkhead . discharge door 106 is located at the base of bulkhead 102 . corner units 104 are attached at lower opposing corners of bulkhead 102 . fig2 is closeup view of an embodiment of the corner units of fig1 . in this embodiment , corners 104 are attached via hinges 202 . fig3 shows a prior art container 302 which has liner 304 installed . bulkhead 102 has discharge door 106 located at its base to allow discharge of cargo from container 302 as it is being tilted . during loading , discharge tube 308 is sealed and load / vent tubes 306 located near the top of the liner 304 are used to provide access for loading the cargo . fig4 illustrates a corner unit 104 attached via hinge 202 to a side wall of container 302 near rear opening 408 . corner unit 104 is held flat against the wall of container 302 by retaining pin 402 which fits into pin holder 404 . those skilled in the art will recognize that any number variations may be used to secure corner unit 104 to the wall of container 302 , including pins , latches , bolts , magnets , etc . the only requirement being that the hinge mechanism be sturdy enough to hold corner unit 104 to the wall of container 302 under load . therefore , the attachment methods shown herein are intended for illustration only . corner unit 104 is shown in the closed position . in this position , corner unit 104 is held against the wall of container 302 and does not interfere with the loading or unloading of non - bulk cargo . further , it allows non - bulk cargo to be transported by container 302 without loss of floor space . an advantage of reusable corner unit 104 is that its location need only be adjusted once during initial installation . thereafter , corner unit 104 can be rapidly placed in the open position by merely removing retaining pin 402 and folding corner unit 104 down into the open position . in this position , the lower edge of corner unit 104 will rest on the floor 406 of container 302 . the preferred embodiment envisions a corner unit 104 fabricated from a high strength durable material , such as steel . however , the invention can be implemented by other materials so long as they are sufficiently sturdy to be allow repeated reuse . by installing corner unit 104 on the wall of container 302 , labor cost is reduced due to the speed an ease with which corner unit 104 is actuated . by manufacturing corner unit 104 from reusable material , shipping cost is reduced due to the elimination of expense heretofore caused by disposable corner units . an additional advantage of corner unit 104 is that it is independent of bulkhead 102 due to the greater strength of corner unit 104 and due to the secured attachment provided by the wall of container 302 and the support provided by container floor 406 . by eliminating the need for support from bulkhead 102 , corner unit 104 can be used in conjunction with bulkheadless liners , thereby increasing the efficiency of these devices without incurring the unnecessary expense of a bulkhead 102 . those skilled in the art will recognize that corner unit 104 can alternatively be located flat against the floor of the container and hinge upward from a floor mounted hinge to rest against a side wall and the bulkhead . in this configuration , when corner unit 104 is closed it can rest flat against the floor or or be located in a recessed opening in the floor . fig5 shows corner unit 104 of fig4 in the open position . retaining pin 402 can be stored in pin holders 404 when not used to hold corner unit 104 . as can be seen , corner unit 104 is supported by container floor 406 and the wall of container 302 via hinge 202 . the third edge of corner unit 104 faces the open end 408 of container 302 . while bulkhead 102 can provide additional support , it is not required . fig6 is an alternative embodiment showing the reusable corner units 104 integrated with a reusable bulkhead 602 . the reusable bulkhead employs the same labor saving technique used by previously discussed corner units 104 in that when not needed , it conveniently folds flat against the side of container 302 . this eliminates interference with non - bulk cargo while at the same time allowing rapid opening for use with bulk cargo . bulkhead 602 is shown with hinges 604 attaching bulkhead 602 to container 302 . those skilled in the art will recognize that any number of variations in the hinge mechanism can be made without departing from the spirit of the invention . optional wheel 612 is shown attached to the base of bulkhead 602 . depending on the weight and the width of bulkhead 602 , wheel 612 may be employed to facilitate control and movement of bulkhead 602 . bulkhead 602 is shown in this figure in the closed position . in this position , it is secured to the wall of container 302 by latch and pin assembly 606 , 608 , 610 . of course , any number of known securing means can be used to retain bulkhead 602 in the closed position . an alternative method of securing bulkhead 602 is to use hinged locking devices 614 which can be inserted into lash pins in the grove of container 302 normally found behind the doors of most intermodal containers . another feature of this embodiment is the placement of reusable corner units 104 on the bulkhead 602 surface . in this embodiment , corner units retain the previously discussed advantage of folding for easy storage and non - interference with non - bulk cargo . those skilled in the art will recognize that while corner units 104 are shown attached to bulkhead 602 , the invention could easily be implemented by attaching corner units 104 to opposite walls of container 302 rather than to bulkhead 602 . fig7 shows the embodiment of fig6 in the open position . this single gate embodiment allows a worker to release bulkhead 602 from its secured position against the wall of container 302 , swing the bulkhead in gate - like fashion to the open position and secure bulkhead 602 to the opposite wall of container 302 via latch means 608 , 610 , 702 . after bulkhead 602 is secured in the open position , corner units 104 are released from retention and moved to the open position ( as shown ). this procedure allows a single worker to rapidly install the reusable bulkhead 602 and corner units 104 without any delay caused by prior art installation methods , or any expense caused by disposable materials . if corner units 104 are attached to the wall of container 302 , then bulkhead 602 would typically be secured first and then corner units 104 would be opened and placed into position against bulkhead 602 . an optional hinged and latched door 704 is shown which can be used to securely hold the product and liner in place until discharge . fig8 illustrates an alternative embodiment in which bulkhead 602 and corner units 104 are stored near the ceiling of container 302 . in this side view , fig8 a through 8c illustrate the bulkhead 602 and corner units 104 moving from the closed to the open position . in fig8 a , support posts 802 are attached at one end to hinges 902 ( shown in fig9 ). bulkhead 602 which is attached to the other end of support posts 802 . in turn , corner units 104 are attached to bulkhead 602 . bulkhead 602 , corner units 104 and support posts 802 are held up in the closed position by cables 804 through pulleys 806 . for ease of illustration , a simple cable / pulley system is shown as the means to raise and lower bulkhead 602 . however , any suitable lifting device can be used to control bulkhead position . in addition , the lifting means can be powered with a motor ( not shown ) or manually . in the closed position of fig8 a , bulkhead 602 and corner units 104 are held above the cargo . this completely eliminates any interference with non - bulk cargo by moving bulkhead 602 out of cargo storage area . fig8 b shows bulkhead 602 at midpoint in change of position . in fig8 c , bulkhead 602 is shown in the open position . in addition , corner units 104 are also shown in the open position . as was the case with the embodiment discussed in fig6 and 7 , corner units 104 can be independently mounted on the wall of container 302 rather than on the bulkhead 602 . fig9 shows the embodiment of fig8 in the open position . while the preferred embodiment envisions support posts 802 attached to hinges 902 at the ceiling of container 302 , any number suitable attachment schemes may be implemented at the ceiling or to the side walls of container 302 . in the open position , bulkhead 602 is secured to the sides of container 302 in the same manner as the embodiment discussed in fig6 and 7 . fig1 illustrates another alternative embodiment in which bulkhead 602 and corner units 104 are stored near the ceiling of container 302 . in this side view , fig1 a through 10c illustrate the bulkhead 602 and corner units 104 moving from the closed to the open position . in fig1 a , track rails 1002 are attached to the ceiling and side walls of container 302 . bulkhead 602 which is slidably mounted on track rails 1002 by wheels 1102 ( shown in fig1 ). bulkhead 602 and corner units 104 are held up in the closed position by a spring mechanism ( not shown ) similar to those commonly used for garage door openers . a strap ( not shown is attached to the base of bulkhead 602 to allow a worker to pull bulkhead 602 from the closed to the open position much like a garage door is closed . in the closed position of fig1 a , bulkhead 602 and corner units 104 are held above the cargo . as was the case in the embodiment discussed in regard to fig8 and 9 , this completely eliminates any interference with non - bulk cargo by moving bulkhead 602 out of cargo storage area . fig1 b shows bulkhead 602 at midpoint in change of position . in fig1 c , bulkhead 602 is shown in the open position . in addition , corner units 104 are also shown in the open position . as was the case with the embodiments discussed in fig6 - 9 , corner units 104 can be independently mounted on the wall of container 302 rather than on the bulkhead 602 . fig1 shows the embodiment of fig1 in the open position . in the open position , bulkhead 602 is secured to the sides of container 302 by track rails 1002 and to the floor 406 of the container 302 by latch means ( not shown ). fig1 illustrates another alternative embodiment . this dual gate embodiment is similar to the single gate embodiment shown in fig6 and 7 . the difference between this embodiment and the embodiment discussed in fig6 and 7 is as follows . in this embodiment , the bulkhead is split into two gates 1202 and 1302 ( shown in fig1 ), each attached to an opposite wall of container 302 . separate hinges 604 are required for each gate 1202 , 1302 , as well as latch and pin assemblies 606 , 608 , 610 . further , gates 1202 , 1302 must be held together by a brace bar ( not shown ) when in the open position . the brace bar is held by brace bar retainers 1204 . while a brace bar is used in the preferred embodiment , any suitable means of holding the gates 1202 , 1302 in the open position may be used . fig1 shows the embodiment of fig1 with one gate 102 in the open position and the other gate 1302 in the closed position . in all of the embodiments discussed above , corner units 104 can be implemented as attached to the wall of container 302 or to bulkhead 602 . an ease of use advantage is achieved by attaching corner units 104 to bulkhead 602 because retaining pin 402 can be more easily reached from outside of container 302 . the advantage of attaching corner units 104 to container 302 is the reduction of weight which must be supported or moved at any one time . in each of the embodiments discussed above , installation of the intended components are more rapidly installed than heretofore possible , worker safety is improved by using sturdier parts which are less likely to fail , and cost savings are achieved due to the elimination of disposable parts . while the invention has been described with respect to a preferred embodiment thereof , it will be understood by those skilled in the art that various changes in detail may be made therein without departing from the spirit , scope , and teaching of the invention . for example , the materials used may vary , corner unit attachment may vary , methods of attaching and moving the bulkhead may vary , etc . accordingly , the invention herein disclosed is to be limited only as specified in the following | 1 |
in describing the preferred embodiments illustrated in the drawings and summarized above , specific terminology will be resorted to for sake of clarity . however , it is not intended to be limited to the specific terms so selected and it is to be understood that each specific term includes all technical equivalents which operate in a similar manner to accomplish a similar purpose . with reference to the basic invention in fig1 ., and also in both fig2 . and fig3 note wrench 50 , with wrench multi - joint handle portion “ s ”, a wrench handle means hereinafter referred to also as comprising ratchet wrench head “ a ,” comprising pawl switch 8 . noting fig5 same said mhp could comprise at least three other wrench heads in use . said mhp could have hinge head - portion 32 that would support , in fig5 b the standard , adjustable wrench head depicted therein as easily as fig5 d and the cam - slipping adjustable wrench head illustrated , or as well , the claw - type adjustable wrench head shown in fig5 c . said mhp is preferred to have only two joints , as depicted in the figures above , however , three or more joints are possible and potentially beneficial on one wrench handle . said hinge head portion 32 connects to a first hinge means , also know as head yoke 54 a , using one of threaded rivets 7 , that nests in first yoke arms 5 by encasing and continually biasing ball bearing 9 and spring 10 against hinge head ratchet teeth 31 . these serve to enable the wrench user to “ detent ” the wrench head in various angular positions so that wrench user may gain access to hard to reach fasteners and this mechanical joint arrangement is known in prior art . however , intermediate handle portion , also known as a double yoke piece 6 comprises at opposite end the novel addition of a second hinge means handle yoke 54 b which hingably joins handle end 20 through handle hinge portion 22 through said rivets 7 , nesting in second yoke arms 4 , encasing and continually biasing ball bearing 12 and spring 11 inside a bore ( not shown ) in said double yoke piece 6 , against handle hinge teeth 24 of said handle hinge portion 22 . this enables the said handle end 20 to be oscillated on said handle yoke 54 b with the same range of freedom that said wrench head “ a ” or any of the said wrench head figures shown in fig5 possess , on said hinge head portion 32 . it is easily understood by one skilled in the art that the hinge and detenting action is identical on both ends of the said double yoke piece 6 , as described to this point . and that it is highly novel and useful to include this said additional handle yoke 54 b at or near the location depicted in the above said figures , since compactness and versatility are enhanced greatly , due to the increased “ flexibility ” of the said mhp . fig4 depicts at least nine major wrench handle positions of the said mhp in fig4 a through fig4 i , but many other positions are possible within the internal ranges of these double - jointed “ right - angle ” fixed position configurations , that are also useful angles in which to ratchet a fastener . two additional features of the said mhp are described which involve the use of an optional , additional biasing or locking component , detent ring 14 a , ( preferably with knurls 60 and with internal compression ring spring 18 ), which comprises biasing surface 30 that biases against detent surfaces 28 on said second yoke arms 4 , as said ring 14 a rotatably nests on handle end shaft portion 47 . the angles of said handle hinge teeth match the said detent surfaces 28 to add the optional double detenting or combined detenting force of both said ring , though either detenting means described could accomplish the forces necessary to fix said mhp in any desired fixed position within the predetermined hinge range . a locking feature , in addition to the biasing capability described in said detent ring 14 a , is included in locking - detent ring 14 b , which comprises indents 3 that mate with yoke prongs 5 that are shown as integral to alternate yoke portion 54 c . as said ring 14 b is twisted and pulled back out of a locked ( mated - said prongs 5 and said indents 3 ) position , toward the mhp end , yoke prong surfaces 15 “ sprag ” on the surfaces 17 of said ring 14 b until it “ click - locks ” again back into a straight handle position , after approximately 180 degrees of ring spin . other angles may by chosen in which to lock the wrench handle by simply changing the angle of the said yoke prongs 5 and their respective mating said ring indents 3 . as well , these said indents 3 can have a variety of shapes , such as v - shape or u - shape , that can serve to adequately supply locking capability to the mechanism purposes described . note also that at section “ x ,” which is approximately the midpoint of said double yoke piece 6 , that a third joint may be included to furnish the structure with even more flexibility , though two joints should be sufficient for most wrench user applications . it is to be understood that the form of the invention herewith shown and described above is to be taken as preferred embodiments . various changes may be made in the shape , size and arrangements of parts , for example : other equivalent elements may be substituted for those illustrated and described herein , parts and elements may be reversed and certain features of the invention may be utilized independently of the use of other features , all without departing from the spirit or scope of the invention , as defined in the subjoining claims . | 1 |
the following description supplies specific details in order to provide a thorough understanding . nevertheless , the skilled artisan would understand that embodiments of crash energy absorbing tables and associated methods of using the tables can be implemented and used without employing these specific details . indeed , exemplary embodiments and associated methods can be placed into practice by modifying the illustrated units and associated methods and can be used in conjunction with any other devices and techniques conventionally used in the industry . for example , while the description below focuses on an embodiment used in a passenger train , the tables and associated methods could be equally applied with other situations , such as counter - tops , cabinets , and other fixtures in a variety of vehicles in addition to trains , such as boats , ships , rvs , camper trailers , ferries , etc . one exemplary crash energy absorbing body in table configuration is illustrated in fig1 - 4 . in the figures , crash energy absorbing table 100 includes table top 110 , leg 150 , and wall mount 170 . table top 110 may include a top skin 112 , bottom skin 114 , edges 116 , 118 , 119 forming a generally planar shape consistent with a table top . the interior of table top 110 may be filled with a filler 120 and may include structural elements such as leg support 122 and wall mount attachment 124 to provide additional strength and attachment points . structural elements 122 , 124 may be formed from a material that allows for sufficient support and to accept fasteners to secure table top 110 to a wall and to leg 150 . filler 120 may be a honeycomb material , as shown in the cutaway window portion of fig4 , or may be corrugated material , or any other suitable material sufficient to provide structural strength to table top 110 and also be crushable to allow for deformation should a body impact with table top 110 with sufficient force . filler 120 may be formed from cardboard , plastic , aluminum , etc ., with the wall thickness between cells and cell size determined by the crushability and deformation of table top 110 in the event of a collision . the exterior surfaces of table top 110 , i . e ., top skin 112 , bottom skin 114 , edges 116 , 118 , 119 , may be formed of any suitable material such as aluminum , plastic , laminate , wood , steel , etc . the thicknesses of the various exterior surfaces may vary depending on material . the thickness may be sufficient to provide a sturdy work and support surface , while also allowing for deformation in the event of a collision with a body with minimum or no injury to the body . in some embodiments , top skin 112 , bottom skin 114 , edges 116 , 118 , 119 may be formed of different materials from each other , as desired . for example , top skin 112 may be aluminum , bottom skin 114 , may be plastic , and edges 116 , 118 , 119 may be wood . filler 120 may be bonded to top skin 112 and bottom skin 114 in a pattern to allow for crushing and / or deformation of table top 110 when impacted with sufficient force . as shown in fig4 , bonding areas 126 may be spaced apart with non - bonded areas 128 in between . in the event of an impact , non - bonded areas 128 may be crushed and / or deformed and top skin 112 and bottom skin 114 may buckle independent of filler 120 or otherwise deform to absorb energy from a collision with table top 110 . the bonding agent used in bonding areas 126 may have a bonding strength such that the bond between top skin 112 and / or bottom skin 114 will fail after non - bonded areas begin to crush , allowing filler 120 in the bonded areas 136 to crush to further absorb energy . the bonding pattern shown in fig4 has stripes orthogonal to edge 119 and parallel to edges 116 , 118 . in this embodiment , crash energy absorbing table 100 provides energy absorbing impact protection from a person impacting side 116 or 118 , or both . depending on the desired use and placement in a particular application , it may be desirable to alter the bonding pattern based on likely impacts . for example , in embodiments where impact may occur from any angle , the bonding pattern may be spaced apart geometric forms , such as circles , squares , etc ., that provide crush areas from any angle . in other embodiments , the pattern for bonded and non - bonded areas may be any desired pattern or configuration . for example , the bonding pattern may be circles as shown in fig5 with crash energy absorbing table 200 , with bonded areas 226 , 222 and non - bonded areas 228 . or the bonding pattern may be zig - zag lines as shown in fig6 with crash energy absorbing table 300 , with bonded areas 326 , 322 and non - bonded areas 328 . in some embodiments , or stripes of bonded areas may be at any desired angle from the various edges 116 , 118 , 119 , depending on the desired crash energy absorbing performance . crash energy absorbing table 100 may be any size or dimension useful to the particular desired application . for example , in some embodiments , crash energy absorbing table 100 may be the size of a twin bed to be used as both a table and a sleeping surface , depending on the configuration of the area in which crash energy absorbing table 100 is deployed . for example , an rv may have a table for eating and working that becomes a sleeping surface by moving cushions or a mattress onto crash energy absorbing table 100 for sleeping . of course , crash energy absorbing table 100 may be used for various other applications , or joint applications as well . leg 150 may include shaft 156 and may be secured to a floor with base 152 and base fasteners 154 . similarly , leg 150 may be secured to table top 110 through attachment 158 , which may be attached to leg support 122 embedded in table top 110 with fasteners 159 . leg 150 may be formed of any suitable material , such as aluminum or other metals , wood , carbon fiber , plastic , a composite of various materials , or any other suitable material . leg 150 may be formed with dimensions sufficient to support table top 110 and to prevent damage to leg 150 from normal and anticipated use and impacts . in some embodiments , two or more legs may be used to support table top 110 . wall mount 170 may be used to provide mounting for crash energy absorbing table 100 to a wall or vertical surface . wall mount 170 may be a formed in a generally “ l ” shaped cross - section and having a length extending along an edge of table top 110 in contact or proximity with the vertical wall or surface . wall mount 170 may be formed from any suitable material such as steel , aluminum , or other metals , carbon fiber , etc ., sufficiently strong to support the weight of table top 110 and any anticipated loads on table top 110 . wall mount 170 maybe secured to the vertical wall or surface with fasteners 174 . a structural support may be provided within the vertical wall or surface to provide sufficient attachment and anchoring for fasteners 174 . wall mount may be secured to table top 110 through fasteners 172 that engage with wall mount attachment 124 . fasteners 172 , 174 , 159 , 154 may be any fastener sufficient to secure the respective portions of crash energy absorbing table 100 to each other and to other surfaces . fasteners may be bolts , screws , lags , rivets , etc ., as desired and suitable for a particular application . similarly , in some embodiments , crash energy absorbing table 100 may be secured together and to surfaces permanently with welding , gluing , bonding , or other desired joining process . in addition to any previously indicated modification , numerous other variations and alternative arrangements may be devised by those skilled in the art without departing from the spirit and scope of this description , and appended claims are intended to cover such modifications and arrangements . thus , while the information has been described above with particularity and detail in connection with what is presently deemed to be the most practical and preferred aspects , it will be apparent to those of ordinary skill in the art that numerous modifications , including , but not limited to , form , function , manner of operation and use may be made without departing from the principles and concepts set forth herein . also , as used herein , examples are meant to be illustrative only and should not be construed to be limiting in any manner . | 1 |
in one embodiment , the present invention is a system that includes means for real - time monitoring of at least one datacenter environmental variable , and a plurality of modules which allow a user to interact with the system and perform at least one of : viewing the real - time status of at least one environmental variable ; forecasting at least one environmental variable in response to a change in the datacenter equipment ; and satisfying queries in connection with physical placement of to - be - installed datacenter network equipment . as used herein , “ real - time ” may be understood as instantaneous or near - instantaneous . the modules can be a part of a computerized system capable of being operated on a server or workstation computer , or any other electronic device which can provide the necessary interaction between the user and the system of the present invention . fig1 illustrates an exemplary datacenter dashboard ( dashboard ) module in accordance with an embodiment of the present invention . the dashboard module can display the real - time status of at least one datacenter environmental variable . the dashboard module illustrated in fig1 is shown displaying five datacenter environmental variables : ( 1 ) power , ( 2 ) thermal , ( 3 ) connectivity , ( 4 ) weight , and ( 5 ) rack space . each of these five readouts shows capacity utilization and availability measurements ( shown in percentages ) for the cabinets in a datacenter . depending on the embodiment , the present invention may monitor any number of cabinets , including a single cabinet , a subset of cabinets located in a portion of a datacenter , an entire datacenter , or a plurality of datacenters . for example , the thermal capacity measurement of fig1 shows the thermal capacity utilization to be about 35 %, which means that about 65 % of the total thermal capacity remains available . the dashboard can also provide a forecast of where the capacities will be in 60 or 90 days . in alternate embodiments , the forecasting displayed on the dashboard can be varied in any desirable manner , including , but not limited to , increasing or decreasing the number of forecasts provided for any of the environmental variables , and increasing or decreasing the number of days for any forecast . in one embodiment , a forecast will be shown if and when the user selects a trigger to view that particular forecast . this can be done by associating a check - box that can be checked on ( to show the forecast ) or off ( to hide the forecast ) by way of a computer and its supporting equipment . in other embodiments , any number of forecasts can be shown automatically upon entry into the dashboard . for environmental variables which may have more than one subset ( such as , for example , the connectivity variable where the datacenter may include 1 gigabit ethernet connectivity and 10 gigabit ethernet connectivity throughout ), the capacity displayed on the dashboard can be configured to show any combination desired by the user . therefore , in the exemplary dashboard of fig1 , the user may select the option to view the connectivity capacity measurements for just the 1 gigabit ethernet connectivity , the connectivity capacity for just the 10 gigabit ethernet connectivity , or a combined connectivity capacity for both the 1 and 10 gigabit ethernet connectivity . in the present embodiment , different levels of capacity availability / utilization ( also referred to as guard bands or bands ) for power , thermal , connectivity , weight , and rack space are represented by three colors . these colors can generally signify a particular level of criticality associated with capacity utilization and availability , and can be defined at the time of a sla ( service - level agreement ) between a service provider and a customer , or any time thereafter . for example , green or gold may be considered low capacity utilization and high capacity availability ; yellow or silver may be considered moderate capacity utilization and moderate capacity availability ; and red or bronze may be considered critical or high capacity utilization and low or no capacity availability . in alternate embodiments , green or gold may be considered high overprovisioning , yellow or silver may be considered moderate overprovisioning , and red or bronze may be considered low overprovisioning , where the more critical resources require a higher level of overprovisioning . furthermore , the band ranges can be defined depending on any particular user &# 39 ; s needs , by setting up the transition points between the various criticality levels at any desired percentage for any particular environmental variable . alternate embodiments of the invention can display specific values of environmental variables rather than percentages . for example , the “ thermal ” environmental variable can be shown as a range from 40 degrees to 100 degrees fahrenheit . referring to the dashboard of fig1 , the power variable ( upper left corner ) shows the power utilization to be about 42 %. this means that the monitored network equipment is taking up about 42 % of the total available power , leaving about 58 % of the total power available . the dashboard of fig1 has been configured such that from 0 to 50 % is marked as low capacity utilization , 50 to 80 % is marked as moderate capacity utilization , and 80 to 100 % is marked as critical capacity utilization . note that fig1 is exemplary and the gauges shown therein can be illustrated in any number of ways while staying within the scope of the present invention . for example , the various capacity levels can be illustrated by any number of analog and / or digital gauges or gauge - like displays . as noted previously , the embodiment illustrated by fig1 includes a forecast for the available rack space , which shows capacity utilization to be estimated at about 52 % in 60 days ( surpassing the minimum level for moderate capacity utilization , which is set to 50 %) and about 82 % in 90 days ( surpassing the minimum level for critical capacity utilization , which is set to 80 %). the user may elect to view a detailed model of this forecast . in one embodiment , a detailed forecast modeled can be accessed by selecting ( clicking ) a respective forecast on the dashboard . an embodiment of a detailed forecast model module is illustrated in fig2 , showing a 90 - day forecast plot of rack space utilization within the datacenter . the in - flight forecast line indicates the estimated rack space utilization for upcoming equipment installations . the y - axis represents the rack space utilization percentage , and the x - axis represents the timeline shown in days . while the detailed model is illustrated as a forecast of the rack space , such a model can be developed for any one or more environmental variables that are monitored by the system of the present invention . alternate embodiments of the invention may utilize actual environmental values rather than percentages on the y - axis . similarly , the timeline may be represented in any desirable fashion , including , but not limited to , hours , weeks , and months . note that the graph of fig2 is exemplary , and the projection of the capacity over a certain amount of time can be illustrated in any number of graphical , tabular , or other detailed ways while staying within the scope of the present invention . based on the model shown in fig2 , the user can observe that there are 12 days until the estimated rack space capacity utilization reaches the moderate threshold , and 85 days until the estimated capacity utilization reaches the critical threshold . as mentioned previously , the rack space guard bands have been defined as follows : 0 to 50 % is low capacity utilization , 50 to 80 % is moderate capacity utilization , and 80 to 100 % is critical capacity utilization . at day 12 , the in - flight forecast line reaches the moderate capacity utilization level of 50 %. this can be illustrated by a vertical line extending along the y - axis and crossing the forecast line at day 12 . at day 85 , the in - flight forecast line reaches the critical capacity utilization of 80 %. similarly , this occurrence can be illustrated by a vertical line extending along the y - axis and crossing the forecast line at day 85 . the vertical lines may be of the same color as the corresponding guard bands for various capacities . this model can offer the user the ability to view detailed datacenter capacity utilization / availability forecasts based on previously saved and / or real - time requests made in infrastructure management software such as panduit &# 39 ; s physical infrastructure manager ( pim ). real - time ( or also known as in - flight ) requests can include work order requests entered by a user and assigned to a technician or another party for execution . fig3 illustrates a task manager module according to one embodiment of the system of the present invention . in this module , the user can see the pending and executed service requests ( also referred to as tasks ). in one embodiment , these service requests originate via entries made in infrastructure management software by a user such as a datacenter manager or a technician . directly from this module , the user can also perform search operations to help fulfill a service request . one example of such a search would be a capacity search which may help determine the availability of space within a datacenter for networking equipment based on one or more criteria . the requested task selected in fig3 is to add 100 cloud application servers to the datacenter . the user can select the task ( left - clicking the task to generate a menu ) and search the datacenter to determine physical locations that can satisfy the service request . after a search option is selected , information related to the task request can be automatically populated into a capacity search module , as illustrated in fig4 . alternatively , information needed to satisfy the search query can be entered manually . when searching for available physical locations , it may be desirable to narrow the search down to locations that are within a certain capacity utilization level . the present invention can provide the user with two options for achieving this . for the first option , the user may individually specify the desired guard band levels for the capacity utilization of each environmental variable . for example , setting the “ power ” variable at “ gold ” and the “ space ” variable at “ bronze ,” the search results will be limited to physical locations having a real - time status of low capacity utilization for the “ power ” variable , and low , moderate , or critical capacity utilization for the “ space ” variable . in essence , the guard band level selected during the search acts as an upper limit , restricting the search results to any locations having the selected or better capacity utilization ( with low capacity utilization being better than moderate capacity utilization , and moderate capacity utilization being better than critical capacity utilization ). for the second option , the user may select an overall guard band level where only physical locations having the selected guard band levels or better are returned in the search results . for example , a search with a general guard band level of moderate ( silver ) capacity utilization will return results for physical locations where every monitored environmental variable has a real - time status of low or moderate capacity utilization . if any one of the monitored variables for a particular physical location has a capacity utilization status which is considered worse than specified in the search request ( which in the present example would be critical ( bronze ) capacity utilization ) that physical location will not be returned in the search results . in response to an inquiry submitted through the capacity search module , the user receives a list of datacenter racks that meet the search criteria in a search - results module . an exemplary search - results module is shown in fig5 where four racks meeting the search criteria are highlighted silver : rack - 06 , rack - 07 , rack - 13 , and rack - 14 . although most of the rack attribute fields are highlighted gold , in the present embodiment , the rack level is determined by the lowest attribute rating , where bronze is the lowest rating and gold is the highest . for example , the 10 g port column is highlighted silver and the rest of the attribute columns are highlighted gold , hence the racks are highlighting silver . if one of the rack &# 39 ; s capacity attributes is rated bronze , then the rack is also rated bronze . after receiving the results , the user can select the rack ( by clicking it ) and virtually insert therein devices and the required connectivity . fig5 shows an embodiment of the menu that is brought up if a user chooses to install devices into rack - 14 . as the user inserts various devices , the rack &# 39 ; s capacity attributes are updated within the system of the present invention . the results of the virtual additions can be shown on a “ what - if ? planning ” module , an example of which is shown in fig6 . here , we can see that the user inserted two devices into rack - 06 and two devices into rack - 14 and correspondingly reserved one 10 g port for every device inserted into the respective rack . prior to the additions , rack - 06 had a total of two available 10 g ports and rack - 13 had one available 10 g port . after the device additions , the user can see that the port numbers have been updated , and that the 10 g port attribute for rack - 13 is highlighted bronze as a result of going below a pre - defined limit for a silver guard band range . this dynamic update feature may be helpful in that guard band violations can be easily visualized and therefore the undesirable features of a planned upgrade or downgrade can be worked out virtually , prior to physical implementation . for example , a user faced with the virtual projections illustrated in fig6 may determine that there is a need to avoid a guard band violation associated with the 10 g port . he can then make further virtual changes , adding or removing various devices from various racks until a satisfactory result is reached . an example of this is shown in fig7 , where after having noticed the guard band violation on rack - 13 , the user virtually removes one device from that rack and installs it in rack - 07 . since rack - 07 had one available 10 g port , and only one 10 g port is necessary for the one device virtually installed , no guard band violations , which would cause a rack to appear bronze , are caused . additionally , the power and thermal capacity availability levels are also automatically updated . the “ what - if ? planning ” module of the currently described embodiment also includes a slide - out forecast tool . this feature allows the user to slide a marker to a particular number of days and view how the virtual changes will impact the capacity levels of the shown racks based on forecasting models previously described . for example , if a change , which will bring the available number of 10 g ports in rack - 06 from two ( originally shown in fig5 ) to zero , is planned in five days from the day that the user making the virtual changes , the user may not realize that installing any additional devices in rack - 06 with 10 g connectivity would cause a guard band violation after the planned change takes effect . this can be avoided by forecasting the guard band violations past five days . in alternate embodiments , the search results can immediately take into account any planned equipment installations ( additions ), limiting the returned physical locations to those which have not yet been reserved . in this embodiment , the slide - out forecast tool will change the search results based on future equipment removals but not on equipment additions . for example , if a separate service request , which will bring the available number of 10 g ports in rack - 06 from two ( originally shown in fig5 ) to zero , has been scheduled to take place five days from the day that the user making the virtual changes , rack - 06 will not be visible in the search results ( presuming that the sla during the search request was set to silver and the bronze guard band has been pre - defined to include any location where the number of 100 ports that is less than two ). on the other hand , if the same rack ( rack - 06 ) has a planned service request to remove equipment which will result in two 10 g ports becoming available ten days from the day that the user is making the virtual changes , rack - 06 will become visible in the search results if the user slides the slide - out forecast tool past the ten - day mark . when the virtual additions of all necessary equipment are complete , the user can generate a work order , reserving selected racks for the service request , as shown in fig7 . as noted earlier , the user has virtually inserted all the necessary network equipment into the rack without causing any undesired guard band violations ; all racks are highlighted silver , which fulfills the search criteria indicated in the capacity search . the generated work order can be received by a technician , who can then proceed to physically install the required network equipment into the corresponding physical locations . after completing the tasks , the user can return to the dashboard to see how the changes have impacted the datacenter . similarly , the user can return to the task manager to proceed working on the remaining tasks . the present invention can also be extended to provision racks as well . this means that in certain embodiments , the present invention can be used for capacity planning of complete racks already populated with network equipment . typically , when a datacenter is designed , rack locations are included in the blueprints in order to identify where key components such as cooling , power , and connectivity are to be installed . each rack position in the datacenter can include an associated capacity for power , weight , cooling , cabling , floor space , and other characteristics that can be entered into the system and stored / used for provisioning these racks . information regarding these blueprints and the associated capacities can be entered into the system of the present invention . in one embodiment , shown in fig8 , the user can view a blueprint of the datacenter with all available rack locations . the user can then select any of these locations to view , enter , or modify the corresponding capacity information for that location . this information is later used in provisioning of racks . at the same , the user can set up virtual models of racks that need to be provisioned . this can be done by virtually assembling a rack in a virtual rack model module . an example of such a module is illustrated in fig9 . here , a user can input all the necessary information / characteristics regarding the rack being provisioned . this information can include , but is not limited to , cooling , power , weight , connectivity , rack size , floor space , and particular networking equipment . furthermore , the present invention may be linked to a database which provides at least some of the information necessary for provisioning based on the make / model of the equipment being installed . in this embodiment , the user can obtain the necessary consumption information by entering the make and model of the network equipment being virtually installed . once a rack has been virtually modeled , it appears in the infrastructure manager module of the present invention . this module can provide a list of racks that have been completed and are ready to be provisioned , racks which have successfully been provisioned and have had associated physical locations already reserved , and / or racks which have already been physically installed in the datacenter . an example of such module is shown in fig1 which shown a list of racks by way of a location tree . the user can select any particular rack to view and modify its associated characteristics . from the infrastructure manager module , the user can initiate rack provisioning , as illustrated in fig1 . this can be done by selecting any one or more of the racks and requesting that the system begin the required operations . the present invention allows the user to provision for racks through at least two separate modules . the first provisioning module , illustrated in fig1 , outputs a blueprint - like view of a datacenter with various physical locations allocated for racks . physical locations which are already occupied by equipment can be shaded , or identified by any suitable means , to warn the user that these locations are unavailable for new rack installations . similarly , locations which have been reserved , but have not had any equipment installed therein , can also be identified by shading , patterning , or any other suitable means . the first provisioning module further outputs a series of racks that the user has virtually built and is provisioning . these can be in a form of rack - icons aligned along the periphery of the blueprint - like view of the datacenter . the user can proceed to drag any one of the rack - like icons ( each representing a virtual rack ) and drop it into the desired physical rack location shown on the blueprint - like view . the first provisioning module can then compare the requirements of the virtual rack to the capacity characteristics of the selected physical rack location to determine whether the selected location can support a rack corresponding to the virtual rack that is being provisioned . the capacity characteristics can be calculated or obtained from a variety of sources , including information entered earlier by the user ( as illustrated and discussed in fig8 ), real - time sensing equipment such as a power distribution unit ( pdu ) that is capable of determining current and remaining power capacities for a given power line , and forecasting data obtained from forecasting models discussed previously . if an allocated rack location can support a virtual rack that was drag - and - dropped therein without any guard band violations or other potential concerns , the user can be notified of this and that particular physical location can be further reserved for future installation of the rack . similarly , the user can be notified of any potential concerns or guard band violations if the selected location does not or may not have sufficient available capacity to satisfy the capacity requirements of a virtual rack or to stay within a certain guard band level . an instance of a potential concern is illustrated in fig1 where after attempting to drag - and - drop rack 3 into physical location a 1 the first provisioning module determines that the pdu may no longer be able to support the series of racks that is would be providing power to . this potential problem is made known to the user . the first provisioning module can further indicate ( by highlighting , or otherwise suitably identifying ) the component that lacks or may lack the required available capacity . in the present embodiment , because the pdu may not have sufficient capacity , it is highlighted for easier identification . the user may also chose to employ a second provisioning module . this module can perform a search of the available datacenter locations and output only those locations which will satisfy a particular search request . such a search request can be similar in nature to the search request shown and described in fig4 , in that the user can specify a specific guard band level needed to fulfill the request and as a result obtain physical locations having only that particular level or better . furthermore , a slide - out forecast tool can also be used to eliminate or include physical locations which would fall under the required guard band level at some future date . note that while this invention has been described in terms of one or more embodiment ( s ), these embodiment ( s ) are non - limiting , and there are alterations , permutations , and equivalents , which fall within the scope of this invention . it should also be noted that there are many alternative ways of implementing the systems , methods , and apparatuses of the present invention . it is therefore intended that claims that may follow be interpreted as including all such alterations , permutations , and equivalents as fall within the true spirit and scope of the present invention . | 7 |
examples of suitable hydrocarbon oil charge stocks for the process of this invention are those naphthenic crudes which typically boil in the range of 250 ° to 500 ° c and have viscosities in the range of 50 to 650 sus , preferably 70 to 500 sus at 100 ° f . it is also possible to obtain refrigeration oils from crudes with viscosities as low as 30 and as high as 750 sus at 100 ° f . the refrigeration oil stocks are initially obtained from the distillation of crude naphthenic petroleum . the stock may be obtained as overhead from a vacuum distillation or may be obtained from the residue of vacuum distillation by deasphalting the residue by contact , for example , with a deasphalting agent such as propane , butane and the like or mixtures thereof . there are present in unprocessed lubricating oils molecular structural types which are particularly susceptible to oxidation and thermal and chemical degradation . these types include olefins , nitrogenous compounds , other compounds containing heteroatoms , certain types of aromatics and others . if allowed to remain in refrigeration oils , oxidation products of these species are polar or acidic in nature and tend to degrade the properties of refrigeration oils . sulfuric acid treating has in the past removed such oxidizable species . this invention will show that oxidizing conditions , not involving the use of sulfuric acid , can oxidize susceptible molecular types . the oxidates thus formed can then be removed or rendered innocuous by other processing steps to be pointed out herebelow . the oxidation step is carried out catalytically with an alkali or alkaline earth metal permanganate being the preferred catalyst . especially preferred is potassium permanganate . operable concentration range of the catalyst is from 0 . 01 to 5 . 0 weight percent basis oil . catalysts may be used in solid form in which case the optimum range is from 0 . 5 to 5 weight percent . the catalyst may be added as a dilute aqueous solution in which case the preferred concentration is from 0 . 01 to 0 . 5 weight percent . alternatively , other alkali or alkaline earth metal salts or permanganate may be used , as may alkali or alkaline earth metal salts of other multivalent metals ( particularly dichromate ) provided that the metal is in a higher oxidation state . the temperature at which the oxidation step should be performed is from ambient temperature to about 275 ° f . the preferred range is from about 150 ° to 275 ° f . this temperature may vary depending on the rate at which air is fed into the reactant mixture . however , the oxidation termperature is a function of the exothermic temperature of the reaction and generally does not require external heating . it is preferred to adjust the air dosage rates so that the heat generated by the oxidation is just sufficient to maintain the required mild reaction temperature . the operable pressure for the oxidation reaction is up to about 300 psi . it is preferred to operate at about atmospheric pressure if possible . the dosage rate of oxidizing gas ( oxygen ) is from about 0 . 01 to 5 . 0 scf per minute per kilogram of oil . however , this dosage rate will depend on the concentration of inert diluent in the oxidizing gas , and the desired operating temperature as well as other operating variables . it is preferred to use from about 0 . 01 to 3 . 0 scf per minute per kilogram of oil when possible . the oxidizing gas may be chosen from the group consisting of air , oxygen , ozone , nitrogen oxides and combinations of these with addition of inert diluents such as nitrogen . it is preferred to use air and oxygen - nitrogen mixtures whenever possible . adsorbent fractionation is a completely different process than the better known clay percolation . clay percolation of course , comprises contacting clay or other adsorbent with the oil to be treated at a rapid rate . that is , the oil passes through the adsorbent rapidly . no solvent for the oil is used so the product directly from the clay percolation column is ready for testing and use without further processing . the yield is about 98 + percent . adsorbent fractionation , however , results in chromatographic separation of the bulk of the oil into large fractions based on the relative polarity ( absorbtivity ) of the major components of the oil , i . e ., aromatics versus naphthenes and paraffin . clay percolation also involves some chromatographic separation but because of the high ratio of oil to charge used , only small quantities of the most polar materials , i . e ., impurities such as nitrogen , oxygen and sulfur containing compounds are removed . in a typical adsorbent fractionation process , a column is filled with a solvent such as cyclohexane . then , for example , reburnt porocel ( bauxite ) which has been calcined at about 900 ° f and sieved to 30 - 60 mesh is slowly added to the column and allowed to soak in the cyclohexane so that the clay will be saturated with cyclohexane . the clay fills the column to the base of the reservoir . excess cyclohexane is then drawn from the column and discarded but the clay is kept covered with cyclohexane . the column is then ready for the fractionation process . in a typical fractionation process , one part of oil would be dissolved in about one and one half parts of cyclohexane and the solution would be placed in a column reservoir and a liquid level drawn down to the top of the clay . the solution drawn off in this step would be retained as the first eluate fraction . at this stage of the process a major portion of the oil is adsorbed onto the clay . the reservoir is then filled with cyclohexane and liquid is drawn off the bottom of the column . as the liquid drops , more cyclohexane is added to the reservoir until the desired fraction of charge oil is eluted . the reservoir is never allowed to run dry . the solvent , cyclohexane for example , is then separated by known processes such as vacuum distillation from the oil . in a typical adsorbent fractionation process , a yield of about 60 - 90 percent oil is obtained with about 80 percent being more typical . residual oil in the column may be removed by passing a stringent solvent such as methyl ethyl ketone through the column . the adsorbents used in adsorbent fractionation may be bauxite and other clays as well as calcined bauxite , alumina oxide , silicon oxide , clay , bentonite , diatomaceous earth , fuller &# 39 ; s earth , bone char , charcoal , magnesium silicate , activated kaolin , silica - alumina and zeolites . it is preferred to use calcined bauxite , a commercial version sold under the trade name &# 34 ; porocel .&# 34 ; the adsorbent will normally have a mesh size ( u . s . standard ) of between about 20 and 200 . the temperature during adsorbent fractionation should range between 50 ° and 300 ° f . the weight ratio of adsorbent to charge oil is between about 10 : 1 to 1 : 1 . the weight ratio of solvent to oil should be between about 50 : 1 to 1 : 1 . a description of adsorbent fractionation is embodied in u . s . pat . no . 3 , 830 , 730 which is incorporated herein by reference . in conventional processing of refrigeration oils , a dewaxing step ( either complex or solvent dewaxing ) is ordinarily incorporated in the processing sequence . the enumeration of the new steps of oxidation and adsorbent fractionation does not preclude the necessity of conventional dewaxing . thus , an example of the overall process for the preparation of refrigeration oils is : oxidation , adsorbent fractionation , complex dewaxing , and clay straining to remove &# 34 ; fines &# 34 ; from urea dewaxing . another example is : oxidation , complex dewaxing , and adsorbent fractionation . since conventional steps are old in the art they will not be discussed further . a naphthenic distillate of 80 sus 100 ° f viscosity ( 1000 g ), solid potassium permanganate ( 25 g ) and sulfuric acid ( 1 ml ) were blown with air ( 0 . 45 scf / min ) for 3 hours at 200 ° f at atmospheric pressure . reaction product was washed twice with 500 ml portions of water ; washings were discarded . product oil ( 871 g ; 87 . 1 wt % yield ) was filtered from traces of inorganic residue . the oxidized product above ( 500 g ) was dissolved in sufficient cyclohexane to make up 1000 ml of solution . oxidate - cyclohexane solution was placed on a column one meter in height containing one kilogram of 30 - 60 mesh bauxite ( commercial product &# 34 ; porocel &# 34 ;). the solution was removed from the column bottom at a rate of 10 ml / min ( 3 . 42 bpt / hr ); a total of 1700 ml of eluate solution was collected in this manner , fresh cyclohexane being added to the column top reservoir at appropriate intervals . solvent cyclohexane was removed under reduced pressure to afford 423 g product . this corresponds to an 84 . 3 weight percent yield across the clay fractionation step and a 74 . 3 weight percent yield across both steps of the process . residual oil was stripped from the porocel column by flushing the column with one liter of methyl ethyl ketone ; both residual oil and ketone were recovered via distillation of ketone . after a second wash with one liter of methyl ethyl ketone , the porocel column was allowed to air dry ; it was then ready for reuse . one generally recognized method of determining the chemical stability of refrigeration oils is by means of the &# 34 ; elsey &# 34 ; test . in this method , equal volumes of oil and freon ® r - 12 are placed in a sealed tube in the presence of iron and copper . the tubes are heated to 347 ° f for extended periods ( 14 days in the present example ) and rate of color formation observed ; a color scale of 0 - 10 is used with 0 representing a water - white oil and 10 a black oil . at the conclusion of a 14 - day test period freon - 12 may be analyzed for freon 22 . the presence of significant quantities of freon 22 is taken as evidence that the lubricant , by virtue of its chemical instability , is contributing to the instability of the refrigerant . that is , low freon 22 analyses are indicative of a good refrigeration oil , with reference to chemical stability . two samples each of the naphthenic stock , conventionally processed ( i . e ., solvent refined - acid treated ) refrigeration oil , and the experimental oil prepared as described in the preceding section were submitted for &# 34 ; elsey &# 34 ; testing . rate of color formation and results of freon - 22 analysis are indicated in table i . table i______________________________________stability testing of conventionaland experimental refrigeration oils untreated 80 sus acid - treated ( at 100 ° f ) naphthene refrigeration experimentaloil oil oil . sup . 1 oil______________________________________sample # 1 2 1 2 1 2color afterday 1 6 7 1 1 0 0 2 7 8 1 1 0 0 3 8 8 1 1 0 0 4 ( not further tested ) 1 1 0 0 10 -- -- 1 1 1 1 14 -- -- 1 1 1 2after14 daysfreon 12 , wt % 99 . 79 99 . 64 99 . 90 99 . 82freon 22 , 0 . 21 0 . 36 0 . 10 0 . 18wt % ______________________________________ . sup . 1 sulfur dioxide refined at 85 vol % dosage and 60 ° f ; sulfuric acid treated at 50 barrels per ton , caustic washed , brightened , complex dewaxed and clay strained . | 2 |
fig1 provides an overview of one embodiment of the present invention . in fig1 , a system 10 is shown . the system includes a wireless device 12 which may be a cellular phone or other type of mobile device . the wireless device 12 is equipped with at least one camera so that the wireless device 12 can take photos . upon taking or viewing a photo a photo print icon 16 is displayed . the photo print icon 16 may displayed on or proximate the photo 14 . the photo print icon may , but need not , include a trademark associated with a known photofinisher . the user may select the photo print icon to indicate that the user wishes to obtain one or more photo prints corresponding with the digital photo 14 displayed on the wireless device 12 . upon such selection or other indication by the user of a desire to receive prints , the digital photo is communicated to the wireless service provider 20 over the wireless network . it is contemplated that due to bandwidth limitations or other concerns that the photo need not necessarily be immediately transferred . for example , if there is no wireless signal present the transfer could be delayed until one was present . once in receipt of the photo , the wireless service provider 20 communicates the digital photo 14 to a photofinishing service 22 . the photofinishing service 22 may be a part of , related to , or independent of the wireless service provider 20 . the photofinishing service then creates one or more photo prints 24 , 26 from the digital photo 14 . these prints may then be mailed to an address associated with the user 30 of the wireless device 12 ( or other address designated by the user ). it is to be understood that the present invention contemplates variations in the manner of delivery . for example , the photos could be picked up instead if that is the preference of the user . the wireless service provider 20 maintains an accounting associated with the number of digital photos which are printed . the wireless service provider 20 may then bill the user 30 in their normal billing statement 32 , regardless of whether billing is via paper or electronically . although it may be preferable for the wireless service to maintain the accounting and providing the billing so as to reduce the number of bills the user receives , the present invention contemplates that a user may pay in a separate transaction instead . it is further contemplated that a separate account may be used , banking information may be separately obtained , or the financial transaction may be otherwise performed . another type of alternative financial arrangement would be that for a fixed period fee the user 30 receives a set number or possibly an unlimited number of photo prints instead of being charged on a per photo basis . it is to be further appreciated that the present invention contemplates that to reduce mailing charges , or possibly to reduce a number of financial transactions , photos may be queued until a particular number of photo print requests have been made . alternatively , the photos may be mailed periodically ( e . g . once a week , or not more than once a day ). thus , in this manner , the wireless service provider provides a valuable service to their subscribers . users are able to easily obtain printed versions of their digital photos in a convenient and seamless way . in addition , a wireless service provider may generate a new stream of income , there by benefiting from the transfer of photos across their network . it is to be further appreciated that the present invention contemplates numerous additional options , variations , and alternatives . for example , because the wireless service provider may know the make and model of the particular phone used to take a picture , the wireless service provider may communicate such information or related information to the photofinishing service 22 . knowledge of such information may be used by the photofinishing service to assist in selecting optimum settings for the photofinishing process to thereby provide the user with as high of quality of photo prints as possible . thus , subscribers to the wireless service provider may have an additional incentive to use the photofinishing service associated with the wireless service provider as opposed to any alternatives . fig2 is a block diagram illustrating one configuration of a wireless device 12 having a housing . the wireless device 12 , which may be a cellular phone , includes a display 40 , a camera 42 , an intelligent control 44 , a wireless transceiver 46 , and a memory 50 . a photo print software component 48 may be stored in the memory 50 and executed by the intelligent control 44 . alternatively a photo print component may be implemented in hardware . the intelligent control 44 may include an application processor or other type of processor . the photo print software component 48 may be a portion of photo or camera software associated with the wireless device 12 . the photo print software component 48 may provide for displaying the icon or otherwise providing a user interface for a user to interact with to indicate whether a digital photo should be printed . the photo print software component 48 may be integrated into an operating environment or operating system of the wireless device 12 . the photo print software component 48 may also provide for initiating transfer of one or more digital photos over a communication network so that the digital photos may be communicated to the photofinishing service . although a representative device is shown in fig2 , it should be appreciated that the present invention contemplates numerous variations in the type of and form of the wireless device , its components , and functions . fig3 illustrates another example of a block diagram of a representative device . fig3 illustrates a wireless device 60 . the wireless device 60 has an application processor 62 and a baseband processor 64 operatively connected to the application processor 62 . an rf transceiver 66 is operatively connected to the baseband processor 64 . an rf power amplifier 68 is operatively connected to the rf transceiver 66 . an antenna 70 is operatively connected to the rf power amplifier 68 . a sim card 72 is shown which is operatively connected to the baseband processor 64 . although a sim card is shown , other types of identifier modules may be used instead as would be appropriate for a particular type of network . a memory 80 is operatively connected to the application processor 62 . a power management circuit 82 is also operatively connected to the application processor 62 and to a charging circuit 84 . a keypad 86 , usb port 88 , removable memory storage connection 90 , and display ( s ) 92 are all operatively connected to the application processor 62 . an audio codec 94 is operatively connected to the application processor 62 . a speaker 96 , microphone 98 , and headset jack 100 are all operatively connected to the audio codec . a wi - fi transceiver 102 is operatively connected to the application processor 62 . a power amplifier 104 is operatively connected to the wi - fi transceiver 102 . an antenna 106 is operatively connected to the power amplifier 104 . as shown in fig3 , the application processor 62 includes an embedded photo - finishing component 108 . the photo - finishing component 108 as shown includes a hardware component which may be implemented within the application processor 62 or may otherwise be included within an integrated circuit or “ chip .” fig4 is a block diagram illustrating one embodiment of a system 120 which may be used for billing . as shown in fig4 , there is a first transaction database 122 and a second transaction database 124 . the first transaction database 122 contains data describing photo - finishing transactions 126 . the photo - finishing transactions may include a periodic ( e . g . monthly charge ), a charge for an individual photoprint , a charge for a set of photoprints , and / or other charges associated with photo - prints . the second transaction database 124 contains data describing wireless service transactions 128 . the transactions include charges for phone service , charges for text messaging , charges for data services , or other charges associated with the offering of wireless services . although shown as two separate databases in fig4 , it is to be understood that instead of database 122 , the photo - finishing transactions may be contained within transaction database 124 . or alternatively , wireless services transactions may be contained in the transaction database 122 . a billing computer system 130 is shown . the billing computer system 130 may include one or more computers operatively connected to the first transaction database 122 and the second transaction database 124 . the billing computer system 130 collects at least one photo - finishing transaction 126 such as from the first transaction database 122 and at least one wireless service transaction 128 such as from the second transaction database 124 . the billing computer system 130 then generates a billing statement or invoice which includes the at least one photo - finishing transaction and the at least one wireless service transaction . the billing statement may be an electronic billing statement or a paper billing statement or may take other forms . fig5 illustrates one example of a screen display from a wireless device . the screen display 150 allows a user to set photofinishing settings . the user can , for example , select a mail option 152 which would allow for mailing photo prints to a physical address 154 of the user &# 39 ; s choice . the physical address may be the billing address used for wireless service , it may be a home address of the user , a business address of the user , or any address the user would like the photo prints to be delivered to . in addition , or alternatively , the user can specify that the photo prints be picked up at a pickup location 158 . the pickup location can be any location chosen by the user . the pickup location thus may be a photo shop , a drugstore , retail store or other location which provides photo finishing services . the pickup location may also be a retail store of a wireless service provider location . the user can also specify the number of copies 160 and the size of the photo prints . it is to be further understood that the user may otherwise specify photo print parameters or delivery options . in addition , it is contemplated that the photo finish settings may be used as default setting so that a user of the wireless device only needs to access the photo finishing settings when the user wants to change the settings from their default settings . | 7 |
fig1 is a sectional view showing a gto 100 according to a preferred embodiment of the present invention , where reference numerals are provided to corresponding components of the gto 100 in fig1 and the gto 200 in fig9 . a component which is characteristic in the gto 100 is an external cathode electrode 30 , and details of the external cathode electrode 30 will be explained later . the external cathode electrode 30 is an electrode block formed of copper , including a cylindrical convex portion 31 and an annular groove ( concave portion ) 35 surrounding the convex portion 31 . as shown in an enlarged view of fig2 one of inner walls of the groove 35 is defined by an insulating sheet 12 covering a side surface 31a of the convex portion 31 , while the other inner wall is defined by a surface 34a of an annular wall 34 . the wall 34 is formed as a unity together with a circumferential portion 32 contiguous to the convex portion 31 . an upper surface 33 of the external cathode electrode 30 has a 3 - level step configuration . fig2 shows an enlarged view of the step configuration , and fig3 shows perspective view of the external cathode electrode 30 . with the step configuration , a first area 33a in the center portion is the highest , a second area 33b surrounding the first area 33a is the second highest and a third area 33c in the outermost part is the lowest . preferably , the difference δh ab between the respective levels of the first and second areas 33a and 33b ( fig2 ) is approximately 0 . 1 mm , while the difference δh bc between the respective levels of the second and third areas 33b and 33c is approximately 0 . 5 mm . the areas 33a to 33c have their respective flat top surfaces . as will be understood from fig1 the first area 33a is opposed to a convex portion 31 , while the second area 33b is opposed to the groove 35 . the third area 33c is opposed to the wall 34 and a lower surface portion 36 extending from the same . the boundary b ab between the first and second areas 33a and 33b ( fig2 ) is aligned with the side surface 31a of the convex portion 31 , while the boundary b bc between the second and third areas 33b and 33c is aligned with the side surface 34a of the wall 34 . corresponding to a cylindrical shape of the convex portion 31 and an annular shape of each of the groove 35 and the wall 34 , the first area 33a is circular in shape , and the second and third areas 33b and 33c are annular in shape . the external cathode electrode 30 can be obtained by cutting a cylindrical copper block . the gto 100 , when mounted in an external equipment , is inserted between the cathode member 51 and the anode member 52 ( fig1 ) of the external equipment . surfaces 51a , 52a of the members 51 and 52 are flat , and therefore the surface 51a of the cathode member 51 comes in contact only with the first area 33a . thus , the first area 33a corresponds to a post electrode surface of the external cathode electrode 30 . on the other hand , the bottom surface 3a of the external anode electrode 3 is not formed as such a 3 - level step configuration , and the entire bottom surface 3a functions as a post electrode face . similar to the prior art gto 200 in fig9 the gto 100 is used with a large pressure applied through the members 51 and 52 . at this time , as schematically shown in fig4 the member 51 itself is deformed in its outer circumferential portion , but the deformation is never propagated to the groove 35 , because the second and third areas 33b and 33c are not in contact with the member 51 . hence the urging force of the conical spring 42 to the gate conductor 13 in fig2 is not changed , and a gate characteristic of the semiconductor element 1 keeps stable . a pressure distribution between the convex portion 31 and the cathode electrode 10k through the temperature compensating plate 11 is spatially uniform . thus , a contact resistance in the interface between them is also spatially uniform , and the breakdown of the semiconductor element 1 is hardly caused by a generation of heat due to an uneven current distribution . thus , with the gto 100 of the preferred embodiment , a configuration of the external cathode electrode 30 is improved so that the troubles caused in the conventional gto 200 can be effectively avoided . in the preferred embodiment in fig1 the upper surface 33 of the external cathode electrode 30 is formed not as a 2 - level step configuration but as the 3 - level step configuration for the following reason : the lower the levels of the areas other than the first area 33a in the upper surface 33 of the external electrode 30 are , the better in order to prevent the cathode member 51 of the external equipment from coming into contact with the second area 33b . however , making the level of the second area 33b excessively low , the thickness of a region 37b ( fig2 ) between the groove 35 and the second area 33b considerably decreases . the region 37b is an important part to retain the strength and prevent the deformation around the groove 35 , and hence , it is desirable to avoid excessive decrease in the thickness of the region 37b . for the purpose , preferably , the level of the second area 33b is not significantly low , and the level difference δh ab should be the lower limit or around enough to prevent the member 51 from coming into contact with the second area 33b . below the third area 33c the groove 35 does not exist . thus , it is possible that the third area 33c is lower in level than the second area 33b . moreover , as shown in fig4 since the member 51 is deformed more greatly as it is closer to its outer circumferential portion , it is especially effective for preventing the contact with the member 51 to make the third area 33c lower in level than the second area 33b . for these reasons , the 3 - level step configuration of the preferred embodiment especially suits for an aspect of the present invention . other preferred embodiments according to the present invention will be now described . an external cathode electrode 60 shown in a partial enlarged sectional view in fig5 includes a circumferential portion 32 of which entire top surface corresponds to the second area 33b . when deformation of the cathode member 51 of the external equipment is relatively small , such a 2 - level step configuration also makes it possible to prevent the circumferential portion 32 from coming into contact with the cathode member 51 . also , even if the cathode member 51 is in contact with the circumferential portion 32 in some part , this results in a very little bending moment being applied to the circumferential portion 32 . in an external cathode electrode 70 in fig6 the boundary b ab between the first and second areas 33a and 33b is deviated from the position of the side face 31a of the convex portion 31 , while the second area 33b is opposed to a part of the groove 35 . with such a configuration , a bending moment to the groove 35 is caused , but the degree is smaller compared with the conventional external electrode 20 ( fig9 ). the boundary b ab is desirably aligned with the side face 31a , but the modification as shown in fig6 is also in the scope of the present invention . in an external cathode electrode 80 in fig7 an area 63c lower than the first area 33a by a level difference δh lies around the first area 33a through a sloping face 63b . in external cathode electrodes according to the present invention , not only a step configuration but also a configuration including a slope are usable . fig8 is a sectional view showing an external cathode electrode 90 of still another preferred embodiment . the external cathode electrode 90 is used as a combination with a semiconductor element 1a which is different in type from the semiconductor element 1 in fig1 . in the semiconductor element 1a , a cathode electrode 10k 1 is provided in the center portion of the top surface of a semiconductor substrate 2 and additionally another cathode electrode 10k 2 is provided on the outer side of the gate electrode 10g . correspondingly , an external cathode electrode 90 is configured as a unity which includes a convex portion 92 in the center portion and an annular outer circumferential portion 94 connected by a connecting portion 93 . below the connecting portion 93 an annular groove 45 is formed , and insulating sheets 12 and 12a are attached to inner walls of the groove 45 . a conical spring 42 is held in the groove 45 , and an annular gate conductor 43 is urged downwards by the conical spring 42 . onto the lower surface of an outer circumferential portion 94 a temperature compensating plate 11a is attached . moreover , an external gate electrode 6 inserted in a notch ( not shown ) formed in a part of the outer circumferential portion 94 is brazed to the gate conductor 13 . the lower surfaces of the convex portion 92 and circumferential portion 94 are positioned opposed to the cathode electrode 10k 1 and 10k 2 on the semiconductor substrate 2 , while the lower surface of the gate conductor 13 is positioned opposed to the gate electrode 10g . the external cathode electrode 90 is mounted on the semiconductor element 1a as shown by an arrow of a broken line and comes into contact with the semiconductor element 1a by external force . in the external cathode electrode 90 of this type , its upper surface 91 is formed as a step configuration composed of first to third areas 91a to 91c . the first area 91a is opposed to the convex portion 92 , while the second area 91b is opposed to the groove 45 . the third area 91c covers the top surface of the outer circumferential portion 94 . the first and third areas 91a and 91c are at a same level , but the second area 91b is lower than them . thus , in the external cathode electrode 90 , since the outer circumferential portion 94 must be pressed against the cathode electrode 10k 2 to come into contact with it through the temperature compensating plate 11a , the third area 91c is shaped to be able to come into contact with the cathode members of the external equipment , but the second area 91b alone is not in contact with the cathode members . as will be recognized , the present invention is applicable in various arrangements of the cathode electrode and the gate electrode on the semiconductor substrate . moreover , the present invention can be applied not only to gtos but to all semiconductor devices having their respective control electrodes , such as other thyristors , transistors , etc . although the present invention has been described and illustrated in detail , it is clearly understood that the same is by way of illustration and example only and is not to be taken by way of limitation , the spirit and scope of the present invention being limited only by the terms of the appended claims . | 7 |
as seen in fig1 an audio - visual display unit or tv 11 has multiple signal source input jacks represented by a first signal source input 13 and second signal source input 15 , which are often labeled in the industry as rf1 and rf2 , respectively . the tv 11 is controlled by its microprocessor 14 while the on - screen program guide feature is controlled by its own microprocessor 16 . the artisan will realize that the description of these microprocessors as functionally separate does not necessarily mean the components are discrete . attached to the first signal source input 13 is an antenna 17 for receiving a broadcast channel with on - screen program guide information contained in the vertical blanking interval ( vbi ). attached to the second signal source input 15 is a videocassette recorder , or vcr 19 . it will be appreciated by the artisan that any number of signal sources can be fed to the multiplicity of signal source inputs . the tv 11 also has a visual display screen 21 and audio output means or speaker 23 as well as a photodetector 25 for receiving command codes from the remote control transmitter ( fig2 ) in order to affect operation of the tv 11 , such as selecting from an on - screen menu 27 which input source to display , as further explained below . as seen in fig2 the remote control transmitter 29 contains switches including : first mode selection switch 31 and second mode selection switch 33 ; a source select switch 35 allowing the operator to select which signal source he would like to have displayed ; the so - called &# 34 ; function keys &# 34 ; including channel / day up and down 39 , 41 , respectively , and the volume / page up and down 43 , 45 , respectively . a great many keys have not been illustrated on the remote control transmitter in order to simplify the drawing . importantly , for a discussion of the present invention there is also a menu key 47 and its concomitant menu adjustment keys 49 . the menu key 47 is necessary to bring up the menus for control of both the operating parameters of the display unit , e . g ., ref . no . 27 of fig1 and the menus of the on - screen programming guide 53 as seen in fig3 . operating the menu key 47 on the remote control transmitter 29 will send a different pulse code depending on whether the remote control transmitter 29 is in the first mode for on - screen program guide control or the second mode for display unit control . the transmitter modes are selected by pressing buttons 31 and 33 respectively . as seen in fig3 a first display type 51 consists of an on - screen program guide 53 superimposed over substantially all of the regular , or entertainment , programming display 55 . the on - screen program guide 53 is broadcast during the vbi by the signal source which is picked - up by antenna 17 ( fig1 ). the on - screen program guide signal must be attached to the first signal source input 13 ( fig1 ), or other dedicated signal source input , so that the display unit 11 &# 34 ; knows &# 34 ; which source the on - screen program guide is on . the first display type 51 is made to show the program guide 53 by operating the remote control 29 to select the first signal source input 13 from the on - screen menu 27 ( fig1 ). the transmitter 29 is then put into its first operating mode by pressing button 31 , whereby the transmitter will issue the pulse code 57 ( fig3 a ) to activate the on - screen program guide 53 when the menu button 47 is pressed . the on - screen program guide 53 may then be manipulated by the menu adjustment keys 49 . as seen in fig4 the second display type 58 consists of the entertainment programming 59 of the second signal source , 19 of fig1 with a tv operating parameter menu 61 , in this case audio , superimposed thereon . as further explained below , according to the present invention , this tv operating parameter menu is called up by the first remote control operation code 57 , fig3 a , which also activated the first display type 51 ( fig3 ). as seen in fig5 a third display type 62 consists of the regular entertainment display 55 from the first signal source input 13 . fig5 is shown as necessary for an explanation of the dual functioning of the function keys 37 ( fig2 ), according to a second aspect of the present invention . referring to the flow chart of fig6 when the remote control transmitter 29 is in its first mode for commanding the operation of the on - screen program guide 53 ( fig3 ), a press of the menu key 47 will transmit the first remote control operation code 57 ( fig3 a ) to the display unit 11 , as at ref . no . 63 . the tv will store the command . the microprocessor of the tv will ask if the tv source selection is set for the first signal source input , as at ref . no . 65 . it will be recalled that the first signal source , here rf1 , is the only signal source which can support the on - screen program guide . if the answer is yes , the tv microprocessor will send the menu command 57 to the on - screen programming guide microprocessor which will then operate , as at ref . no . 67 , to display the on - screen program guide menu 53 as per the first display type of fig3 . if the inquiry finds that the tv is not currently operating on the first signal source , but with the second signal source 15 , i . e . rf2 , the television microprocessor will hold the inoperative on - screen program guide menu command 57 and treat it as a command to display the tv operating parameter menu 61 , i . e ., the second display type of fig4 ; as at ref . no . 69 . as seen in fig7 when the remote control transmitter is in its second , or tv controlling , mode designed to issue pulse code commands for selection of the tv parameters , a press of the menu button 47 will send a command ( not shown ) to display the operating parameter menu ( s ) of the tv , as at ref . no . 71 . this command will be received and sent to the tv microprocessor and the operating parameter menus of the tv will be displayed , as at ref . no . 73 . this is the second display type 58 as seen in fig4 . in either case where the operator has selected a tv signal source not containing the on - screen program guide information , the remote control transmitter menu key will produce a proper tv operating parameter menu regardless of the operating mode of the transmitter . according to a second aspect of the present invention , as seen in the flow chart of fig8 the function keys 37 ( fig2 ) can be made to do double duty without switching the remote control transmitter operating mode . in the first remote control operating mode the channel up and down keys , 39 and 41 , also control paging through the on - screen program guide as well as channel selection for individual channel program listings . the volume up / down keys , 43 and 45 , also control page forward and back within each day of the program guide . in the second mode , as noted , these function keys are used to adjust the operating parameters , i . e ., volume and channel , of the tv . by instituting the recognition subroutine of fig8 the tv microprocessor can learn when the on - screen program guide is active and receive these commands back from the on - screen program guide microprocessor when they are not recognized as commands to manipulate the on - screen program guide . fig8 shows the logic for the channel / day pair . depression of the channel / day up arrow key 39 ( fig2 ), with the remote control transmitter in its first mode , causes the remote control transmitter to send its on - screen program guide code command , as at ref . no . 75 . upon receiving this command the tv microprocessor will inquire if the signal source selection is that of rf1 , as at ref . no . 77 . if not , the tv microprocessor acts to increment the tv channel , as at ref . no . 79 . if in rf1 , the tv microprocessor sends the command on to the on - screen program guide microprocessor , as at 80 . the on - screen program guide microprocessor then inquires whether an on - screen program guide menu is currently displayed , as at ref . no . 81 . if not , the command is handed back to the tv microprocessor at 82 and the tv channel is incremented , as at ref . no . 79 . if an on - screen program guide menu is being displayed , the command is forwarded to the on - screen program guide microprocessor where the type of menu displayed is determined as at 84 . if the menu type contains listings by days , the command is recognized to increment the menu to the next day &# 39 ; s program listings , as at ref . no . 83 . if the menu is that of an individual channel , the channel listing is incremented , as at 85 . as seen in fig9 the logic for the volume / page function keys is similar to that of the channel / day pair . when the on - screen program guide &# 34 ; page up &# 34 ; command is transmitted 87 the tv microprocessor receives the command and inquires 89 if the signal source is rf1 . if yes , the command is passed 91 to the on - screen program guide microprocessor , if no , the tv volume is incremented 93 . the on - screen program guide microprocessor then determines 95 whether an on - screen program guide menu is being displayed . if yes , the menu page is incremented 97 . if no , the command is passed back 99 to the tv microprocessor and the tv volume is incremented 93 . fig1 shows the logic for the menu adjustment keys 49 ( fig2 ) operation which is similar to that of the volume / page pair . when the on - screen program guide menu adjustment command is transmitted 101 the tv microprocessor receives the command and inquires 103 if the signal source is rf1 . if yes , the command is transmitted 105 to the on - screen program guide microprocessor . if no , the tv microprocessor inquires 107 if a tv menu is displayed . if yes , the tv menu adjustment is carried out 109 . if no , the command is ignored 111 . when the on - screen program guide microprocessor receives the menu adjustment command it inquires 113 whether an on - screen program guide menu is being displayed . if yes , the on - screen program guide menu is adjusted 115 . if no , the menu adjustment command is passed back 117 to the tv microprocessor for further processing . while the present invention has been illustrated and described in connection with the preferred embodiments , it is not to be limited to the particular structure shown , because many variations thereof will be evident to one skilled in the art and are intended to be encompassed in the present invention as set forth in the following claims : | 7 |
the present invention safeguards access to resources on the internet against malicious code that accompanies many of those resources . in particular the present invention ensures that a user can safely access web resources because no malicious code will be allowed to execute in the user &# 39 ; s browser . the invention does not depend on the ability to identify malicious code in order to block it . the invention also restores much of the functionality that would be lost by disallowing the execution of any executable ( potentially dangerous ) code in the client browser . lastly the invention will generally provide the client a version of the resource to view without the delay associated with prior art serial type systems that run security protection mechanisms prior to the client receiving the resource . simply explained , the core method the present invention uses to protect a user from malicious code involves using parallel rendering of the initial version of a web resource — one browser executing the potentially dangerous code in the page and one browser not processing that code . changes to the dom structure caused by the executable code on one browser are then echoed in the dom on the other browser . thus only the benign results ( i . e . changes in page layout ) of the executable code are transferred to the user &# 39 ; s browser where security is maintained . this enables the client browser to benefit from the outputs of executable code on a separate machine without ever having to host or run the executable code . the present invention provides a method and apparatus for parallel processing of two versions of a web resource for the purpose of providing a safe , functional version of the web resource to the client in a timely manner . one of the parallel processors is the client and the other is identified here as a rendering processor . the client processor will initially execute a limited version of the resource with only known good code . the functionality that is lost by stripping off any potentially dangerous code will be restored by processing that code on a separate machine and sending the benign outputs of that code to the client browser . the present invention does this 1 .) while minimizing the delay associated with code analysis , 2 .) without significant loss of functionality associated with disabling all executable scripts , and 3 .) without the loss of access to web resources that result from security policies that restricts access to segments of the internet . the code that makes up a web resource can be categorized into three types , that which is known to be safe ( benign ), that which is indeterminate as to its safety , and that which is known to be malicious . the present invention will only allow the client browser to execute code of the first type ( known benign ). code of the second type ( indeterminate ) will only be executed at an isolated rendering processor and only its benign outputs will be passed on to the client browser . code of the third type , that which is known to be malicious , can be stripped off without being processed at either processor . the preferred method for creating safe versions of web resources comprises a method for separation of computer code that makes up a web resource according to its potential to be malicious and treating each resultant type of code according to a different rule set . it also involves dispersing the processing of the different types of code at two separate processors . the object of the present invention is to supply to the client browser completely safe versions of requested web resources in a timely manner and without significant degrading of either the availability of those web resources or the functionality of the web resources . the bulk of the web consists of html based pages ( web pages ) but there are many other file formats that are accessed through the web . differences exist between these many types of resources . web pages are primarily built of html , css and javascript code and varied image types . the bulk of the malware is contained in the javascript code . much of the discussion to this point has been directed toward thwarting the attacks that come through web pages . however , the other types of web resources can also carry malware and must be protected against . these other resources have a fundamentally different file structure than web pages . there is no dom that can act as an intermediary between the client and the rendering processor with these other resources . document formats like portable document format ( pdf ), ms word or others will require different techniques to ensure that they cannot infect the client through their browser . the techniques that can provide security against these types of resources include remote viewing of the resource through a window in the browser , conversion of the resource from one type to another , or manipulating portions of the resource before it reaches the client browser such that the sections of the resource that can hold malicious content are fully disabled . in a pdf document , for example , the potentially malicious code must be contained in the document at certain locations only . the connection between the client and rendering processor can be direct peer to peer ( p2p ) or it can be facilitated through an intermediary . a relatively new browser technology called webrtc enables the direct peer to peer browser connections . this technology would allow faster connections between the client and the browser on the rendering processor . other methods for communications between the client the renderer include going through the proxy as an intermediary for passing data or having the client directly addressing the rendering processor in a client - server type of configuration . when the browser is configured to automatically go through the proxy , the browser controls such as the forward and back buttons , history and favorite records should be able to be used as normal . if the browser is not configured to automatically go through the proxy , additional controls may need to be added to the page to handle these normal browser functions and also to alter links and forms to point to the desired location . the rendering processor will typically be on a virtual machine that can be refreshed frequently , possibly after every browsing session . separate rendering processors might be invoked for every browser tab the client opens . the rendering capability should be hosted on a secure operating system and should use as secure a browser as possible . the rendering processor &# 39 ; s operating system and browser will also be “ locked down ” such that the minimum numbers of services are running . this will greatly reduce the attack space for the rendering processor as compared to the client processor . signature analysis methods and other code checking can be used at the rendering processor to decrease the potential for attack against the rendering processor . code safety can be generalized into three categories — that with is known to be safe , that which is known to be unsafe , and that which is of unknown safety . the rendering processor will receive all three types . it is advisable to disable any code that is known to be malicious ( unsafe ) before it is executed on the rendering processor . this will further reduce the chance that the rendering processor will be compromised . referring to fig1 , the process flow for the preferred embodiment of the present invention is shown and can be described as follows . note that the bulk of the processing at the rendering processor and at the client processor is accomplished in their respective browsers . this description will reference the client and rendering browsers rather than the computer processor ( s ) on which they depend since most of the actions are accomplished by software that runs the browser or runs in the browser . the first action is for the client to initiate a resource request 100 for a web resource . this page request can come in multiple forms . it could come from typing the url in the address bar , from clicking on a link or from the browser going to the designated “ home ” page . it could also come from accessing a url from the browser history or favorites menu . the url for the requested resource is sent to a proxy computer processor ( proxy ). the client browser can be configured such that the requests for new resources go to the proxy automatically . if the browser is not configured to send all requests to the proxy then software controls could be added to the incoming page to direct requests to the proxy . the proxy receives the resource request and requests and retrieves the resource from the resource providers on the internet 110 . the proxy must then determine if the resource is a web page 120 . if the resource is a web , page the proxy sends the page to both the rendering browser and the client browser and passes details for opening a connection between the two entities 130 . if the resource is a different document type than a web page then the client version would primarily consist of a “ window ” through which it could view the resource as rendered in the rendering browser . ( handling of non - web pages is shown in fig2 and will be addressed later in this section ). the remainder of the process flow shown in fig1 addresses this invention only as it applies to web pages . the client browser ( cb ) displays the web page , using only code that is known to be benign ( generally only the html and css code ) 200 . this will immediately give the user a version of the page to view while the rendering processor processes the entire page . the document object model ( dom ) created in the client browser will act as an intermediary through which changes made to a parallel version of the page ( by executable code ) on the rendering processor can be passed , and made visible , in the client browser . a connection needs to be opened between the client browser and the rendering browser ( rb ) using the credentials supplied to both parties 210 , 150 . when that connection is open the client browser will then commence listening for updates 220 to the page that are passed 160 to it from the rendering processor . through this connection the client browser also passes certain mouse , keyboard and form actions to the rendering processor along with page scroll position 240 . simultaneously with the aforementioned client browser actions 200 through 240 , the rendering browser renders the page using the original code set for the page 140 . the rendering browser then tracks the changes to the page that accrue due to execution of the code that was not allowed to execute in the client browser . the rendering browser directly passes to the client those page changes 160 through the connection that has been established 150 . if the page code called for a new resource to be loaded then that new request is sent to the proxy 170 , 110 . the rendering browser continually listens for further input from the client actions such as mouse movements and scrolling 180 . the rendering browser implements the client actions 190 . these client actions often initiate code in the rendering browser &# 39 ; s version of the web page . the code will cause changes to the page in the rendering browser and the resultant page changes will be passed from the rendering browser to the client 160 ( per the feedback loop shown in fig1 ). new page requests can be passed from either the rendering browser 170 to the proxy , which in turn request and receives resources from the internet 110 or from the client browser 250 to the proxy , which in turn request and receives resources from the internet 110 depending on whether these page changes were the result of executable code or not . when new requests are received at the proxy , the process repeats itself . referring to fig2 shows the process flow for resource requests when it is determined that the resource is not a web page 120 . if there are tools available to convert the file to a secure format ( i . e . pdf to jpg ) 300 and if this new format is acceptable to the client 310 a determination will be made about how to present the document to the client in a secure form . two options are as follows : option 1 ) if the document can be converted to a secure type 300 and that type is acceptable to the client 310 then the document will be converted 320 and it will be transferred directly to the client 330 . note that steps 300 , 310 , 320 and 330 could be accomplished at the proxy or at the rendering processor . option 2 ) if the document cannot be converted to a secure type 300 or the new format would not be acceptable to the client 310 then the following steps are necessary 340 : 1 ) send the resource to the rendering browser ( if steps 300 and 310 are accomplished at the rendering browser then this step would already have been accomplished ), 2 ) send a framework to the client browser for remotely viewing the resource as it is rendered on the rendering browser 3 ) ensure that both browsers have the connection information to enable them to open a secure communication channel . at this point the rendering browser can provide a remote view of the resource to the client 350 . the client will then pass back actions to the rendering browser ( ie scroll position ) 360 . based on the client actions , the rendering browser will then make changes to the view of the resource 370 and , per a feedback loop in the flow chart , provide this revised view to the client . referring to fig3 shows the general placement and interaction of the processors involved in this invention . for this description the term “ computer processor ” will also include multicore processor computers or multiprocessor computers . they could also be “ virtual ” processors , meaning that they are composed entirely of software that runs on another machine . the proxy computer processor 400 is situated between the resource providers 430 and the computer processors that secure the resource ( rendering computer processor ) 410 and display the resource ( client computer processor ) 420 . within the rendering computer processor the bulk of the work is being done in the rendering browser that is referenced in fig1 and fig2 . similarly , within the client computer processor the bulk of the work is being done within the client browser that is referenced in fig1 and fig2 . the proxy computer processor is just referred to as “ proxy ” in fig1 and fig2 . interaction shown in fig3 is as follows : in response to a request from either the client computer processor 420 or the rendering computer processor 410 , the proxy computer processor 400 will retrieve a web resource from the resource providers 430 through an internet connection . the proxy 400 will then interact with both the rendering processor 410 and the client processor 420 to give them some form of the resource , or in a limited case described in fig2 , give the client 420 a framework for remotely viewing the resource on the rendering processor browser 410 . interaction between the client processor and the rendering processor is required to allow the client to see changes to the resource that accrue over time and to pass client actions back to the rendering processor . in some cases this interaction is necessary for the client to remotely view potentially dangerous file types . this interaction can be conducted in one of three ways ; 1 ) on a direct peer to peer basis between the client 420 and the renderer 410 , 2 ) it can be facilitated by the proxy 400 , or 3 ) it can be accomplished by using the rendering processor 410 as a server and the client 420 can access dynamic content through a traditional client - server relationship . note that any or all of the items depicted in this figure can be real physical assets or virtual assets created by virtual machine software technology . virtual computer processors will behave identically to physical computer processors but they have an advantage in that they are easily refreshed and set back to a known state . thus the use of virtual assets will make recovery a simple process if either the proxy processor 400 or the rendering processor 410 are compromised by malicious code . also note that the placement of the proxy 400 and the rendering processor 410 is flexible . either or both of them could be located remotely from the client 420 and accessed through the internet , or they could be located in proximity to the client 420 , possibly behind an enterprise firewall . the resource providers 430 could represent any content provider on the internet and would be the source of the malicious code that this invention seeks to block . | 6 |
reference will now be made to the drawings , wherein , to the extent possible , like reference numerals are utilized to designate like components throughout the various views . referring to fig1 it is seen that a vehicle 10 may include a seating structure 12 that supports an occupant 14 positioned in generally opposing relation to a dashboard panel 16 . an inflatable air bag cushion 20 may be positioned partially or wholly within the dashboard panel 16 for outward deployment towards the occupant 14 in the event of a collision or the like . while the air bag cushion 20 is illustrated for descriptive purposes in relation to a vehicle passenger , it is to be understood that the present invention is in no way intended to be limited to a passenger - side configuration . on the contrary , it is contemplated that the present invention may have equal applicability to air bag deployment in opposing relation to a vehicle operator ( not shown ) from a steering column ( not shown ), as well as in relation to air bags deployed from other regions within the interior of the vehicle 10 , including , by way of example , side - impact air bags and inflatable curtain structures . it is contemplated that the interior of the vehicle 10 may include a seat position sensor 22 operable for detecting the position of the seating structure 12 and the occupant 14 relative to the dashboard panel 16 . it is also contemplated that the interior of the vehicle 10 may include additional position sensors , such as an optical sensor 24 or the like , operable for measuring the volume and / or position of the occupant 14 to be protected . it is further contemplated that the interior of the vehicle 10 may include a scale 26 disposed within the seating structure 12 operable for providing additional data regarding the mass of the occupant 14 and thus the load to which the inflatable air bag cushion 20 may be subjected . the seating structure 12 may also include one or more sensors ( not shown ) operable for measuring the degree to which the seating structure 12 is reclined . the interior of the vehicle 10 may still further include one or more sensors ( not shown ) operable for determining and communicating whether or not the occupant 14 is utilizing recommended seatbelt structures 28 . the data so collected may be communicated to a controller 27 to determine desirable expanded profile and venting characteristics for the air bag cushion 20 . according to one embodiment of the present invention , the air bag cushion 20 has at least a first expanded profile and a second expanded profile that is characterized by relatively greater depth and volume than the first expanded profile . one or more extendible tethering elements 30 ( fig2 ) in the form of straps , cords or webs may be utilized to control the inflated profile of the air bag cushion 20 . referring to fig2 the air bag cushion 20 is housed in fluid communication with a gas emitting inflator 40 such that upon expulsion of inflation gas by the inflator 40 , the air bag cushion 30 inflates to an expanded cushioning condition . in order to contour the shape of the air bag cushion 30 , one or more extendible tethering elements 30 are disposed across the interior of the air bag cushion 20 and may extend in a travel path between one or more fixed points of connection 25 at the surface of the air bag cushion 20 . the tethering elements 30 may also be connected to the surface of the air bag cushion 20 at one or more predetermined positions along the travel path by one or more guide elements 29 , such as at an impact face portion 31 of the air bag cushion 20 . as illustrated in fig2 the operative length of the tethering elements 30 may be shortened by drawing a portion of the tethering elements 30 intermediate the fixed points of connection 25 towards an anchoring structure 80 normally held at a supported fixed position remote from the air bag cushion 20 . the anchoring structure 80 may be selectively released or retained at its normal supported fixed position at the time of deployment of the air bag cushion 20 based upon the preferred profile of the air bag cushion 20 in light of the measured occupant and vehicle conditions . that is , if the physical character and position of the occupant 14 in combination with the nature of the impact are such that a deep profile is desired , then the anchoring structure 80 and attached tethering elements 30 are released from their supported fixed position thereby permitting the air bag cushion 20 to assume an expanded profile of increased depth ( fig2 a ). conversely , if the physical character and position of the occupant 14 in combination with the nature of the impact are such that a shallow profile is desired , then the anchoring structure 80 and attached tethering elements remain in a static anchored position thereby restraining the air bag cushion 20 to a final profile of decreased depth ( fig2 ). as indicated , the selective enabling / disabling of the increased and decreased profiles is preferably carried out taking into account steady - state inputs such as vehicle velocity , occupant size , occupant mass , seating position , and seat - belt use . according to the potentially preferred practice , it is contemplated that the tethering elements 30 may remain connected to the one more points of connection 25 across the surface of the air bag cushion 20 . likewise , the anchoring structure 80 may be held by a mooring line 35 secured to a fixed position of attachment remote from the anchoring structure . such connections provide for the continued restraint of the air bag cushion 20 by the tethering elements 30 even if the anchoring structure 80 is released . that is , even with an increased operating depth , the tethering elements 30 may continue to contour the profile of the air bag cushion 20 . in addition , the anchoring structure is also prevented from moving into contact with the face portion 31 . referring simultaneously to fig3 and 4 , in one embodiment of the present invention , a tethering element 30 is connected to an anchoring structure 80 including a first plate 82 , a second plate 84 , and a third plate 86 . the first plate 82 , the second plate 84 , and the third plate 86 may be made of , for example , a metal , a plastic , rubber , a composite material , or the like . the first plate 82 is positioned adjacent to a slot 88 ( fig3 ) disposed within the side portion 90 of a module housing 92 . the second plate 84 is disposed within a fold in the tethering element 30 and the third plate 86 is positioned adjacent to the tethering element 30 distal to the inner surface 94 of the module housing 92 ( fig4 ). the first plate 82 , the second plate 84 , and the third plate 86 are connected via one or more fasteners 96 such as pins or the like inserted through the three structures and , optionally , through the tethering element 30 . in the illustrated arrangement , a portion of the tethering element extends away from the anchoring structure 80 to define a mooring line 35 held at a fixed position remote from the anchoring structure 80 . of course , a separate element such as a strap , cord , wire or the like operatively secured to the tethering element and / or the anchoring structure may likewise be used to form the mooring line 35 if desired . as will be appreciated , while one exemplary attachment arrangement has been shown , any arrangement suitable for anchoring the tethering element 30 may be used . according to the illustrated exemplary configuration , the anchoring structure 80 includes an outwardly projecting planar release bracket 98 normally protruding through the slot 88 disposed within the side portion 90 of the module housing . as best seen in fig5 in the illustrated embodiment the release bracket 98 is connected to the first plate 82 in a substantially “ t ” shaped geometric arrangement . the release bracket 98 may be made of a structural material such as plastic , metal or the like . the release bracket 98 preferably includes a plurality of holes 100 , 104 suitable for receiving one or more pins , as described in greater detail hereinafter . by way of example only , in the exemplary embodiment illustrated , the release bracket 98 includes a primary pin hole 100 suitable for receiving a selectively extendible and retractable primary pin 102 and one or more shear pin holes 104 suitable for receiving one or more shear pins 106 . preferably , the release bracket 98 is shaped such that it may freely pass in sliding relation through the slot 88 disposed within the side portion 90 of the module housing 92 . as best seen in fig3 and 5 , the slot 88 is adapted to accept the release bracket 98 between a first retention bracket 108 and a second retention bracket 10 fixedly attached to the side portion 90 of the module housing 92 . the first retention bracket 108 and the second retention bracket 110 may be , for example , l - shaped brackets , each including a plurality of holes arranged for substantial alignment with the pin holes in the release bracket 98 such that the extendible and retractable primary pin 102 and the shear pins 106 may pass through the first retention bracket 110 , the release bracket 98 and the second retention bracket 110 . as previously indicated , the primary pin 102 is preferably selectively retractable from an extended position engaging the release bracket and retention brackets to a withdrawn position which is out of engagement with the release bracket and retention brackets . the primary pin 102 may also be selectively reinserted through the release bracket and retention brackets . the insertion or retraction of the primary pin 102 may be achieved by the actuation of a solenoid or step motor 112 fixedly attached to the surface of the module housing 92 or at such other location as may be convenient . this actuation may be controlled by a controller 27 ( fig1 ) such as an onboard computer or the like based upon steady - state inputs such as vehicle velocity , occupant size , occupant mass , seating position , and seat - belt use acquired during driving conditions . in operation , the presence or absence of the primary pin 102 through the release bracket 98 may be used to selectively control whether or not the anchoring structure 80 ( and the associated tethering element 30 ) is held in place or is carried through the slot 88 and away from the housing wall . by way of example only , in the event that the measurements taken of vehicle speed , occupant size / mass , seating position , and seat - belt use characteristics dictate that a decreased air bag profile configuration is warranted , the controller 27 directs the solenoid or step motor 112 to insert the primary pin 102 through the first retention bracket 108 , the release bracket 98 , and the second retention bracket 110 . the inserted condition of the primary pin 102 causes the anchoring structure 80 , and the tethering element 30 to be held secure , and in a restrained configuration as shown in fig2 despite the application of a tensioning force through the tethering element 30 as the air bag cushion 20 is inflated . in the event that the measurements of vehicle speed , occupant size / mass , seating position , and seat - belt use characteristics dictate that an increased air bag profile configuration is warranted , the controller 27 directs the solenoid or step motor 112 to withdraw the primary pin 102 from the release bracket 98 . with the primary pin 102 in the withdrawn position , the anchoring structure is supported by the shear pins 106 . under normal conditions , the support provided by the shear pins 106 is adequate to hold the release bracket 98 in place . however , in the event that the air bag cushion 20 is inflated , the tension generated through the tethering elements 30 causes the shear pins 106 to break thereby permitting the release bracket 98 to be carried away from its initial position ( fig2 a ). due to the simplicity of insertion and withdrawal of the primary pin 102 it is contemplated that variations in occupant and / or vehicle conditions may be subject to substantially constant monitoring with insertion or withdrawal taking place as changing conditions dictate during operation over the life of the vehicle 14 . such monitoring and associated adjustment permits the air bag deployment parameters to be set and reset numerous times as conditions change in anticipation of cushion deployment thereby ensuring proper deployment character at such time as cushion deployment may be required . it is contemplated that the present invention may be adaptable to a wide variety of alternative constructions . by way of example only , one alternative construction is illustrated in fig6 and 7 wherein elements corresponding to those previously illustrated and described are designated by like reference numerals with a prime . as shown , in this construction the primary pin 102 ′ is operatively connected to a sliding vent 120 ′ so as to adjust gas venting through the module housing 92 ′. as illustrated , the sliding vent 120 ′ includes a multiplicity of vent openings 122 ′ which are alignable with corresponding openings 123 ′ in the module housing 92 ′. however , as best seen in fig7 upon retraction of the primary pin 102 ′, the vent openings 122 ′ are shifted out of alignment with the openings 123 ′ in the module housing thereby reducing venting capacity and directing an increased amount of inflation gas into the air bag cushion . of course , it is also contemplated that the vent openings 122 ′ may be initially out of alignment with the openings 123 ′ in the module housing such that upon retraction of the primary pin 102 ′ alignment is achieved and venting is increased . thus , it is contemplated that venting capacity may be substantially matched to desired deployment characteristics based upon measured operational and occupant conditions . it is to be understood that while the present invention has been illustrated and described in relation to potentially preferred embodiments , constructions and procedures , such embodiments , constructions and procedures are illustrative only and that the present invention is in no event to be limited thereto . rather , it is contemplated that modifications and variations embodying the principles of the present invention will no doubt occur to those of ordinary skill in the art . in particular , it is to be understood that the present invention is in no way limited to any particular mechanism for the retention and / or release of extendible tethering elements and that all description of such mechanisms is exemplary and explanatory only . it is therefore contemplated and intended that the present invention shall extend to all such modifications and variations as may incorporate the broad aspects of the present invention within the true scope and spirit thereof . | 1 |
the invention will now be further described by referring to exemplary embodiments of the invention , as shown in the accompanying drawings . in the drawings : [ 0047 ] fig1 is a ( diagrammatic ) cross - section of a sulphide tailings deposit situated within a naturally occurring basin and where there is no free standing water above the tailings . [ 0048 ] fig2 is a ( diagrammatic ) cross - section of a sulphide tailings deposit situated within a naturally occurring basin pond of water that has free standing water above the tailings surface . [ 0050 ] fig4 is a ( diagrammatic ) cross - section of an elevated sulphide tailings deposit or a typical sulphide waste rock pile . [ 0051 ] fig5 is a ( diagrammatic ) cross - section of an elevated sulphide tailings deposit , in which precautions have been taken to deoxygenated water entering from the sides . [ 0052 ] fig6 is a close - up of a portion of the cross - section of fig5 . the apparatus shown in the accompanying drawings and described below is an example which embodies the invention . it should be noted that the scope of the invention is defined by the accompanying claims , and not necessarily by specific features of exemplary embodiments . in fig1 un - oxidized ( fresh ) tailings 12 are shown overlain by a layer 14 of oxidized tailings . the layer 14 may be of sediment comprised of clay , silt , till , or desulphurized tailings . the cathode material 18 is placed on top of the layer 14 . a layer 20 of sediment ( which will contain the electrolyte ) is placed over the cathode 18 . a block of magnesium 22 , being the anode , is placed within the electrolyte layer 20 . an electrically conducting cable 24 connects the cathode 18 and the anode 22 . the cable 24 may be made of steel , on cost grounds , although steel is rather unsatisfactory as an electrical conductor , from which standpoint aluminum or copper are preferred . the water table in the tailings 12 and in the surrounding ground 28 is shown at 26 . the water table rises and falls with the seasons , and for other reasons . the cathode 18 , the anode 22 , and the associated layer 20 of clay , silt , etc , comprise an engineered electrochemical barrier . the engineered barrier serves as a physical cover , which protects the tailings from direct exposure to the atmosphere ; since the barrier is in the form of an electrolytic cell , it also protects the mass of tailings 12 from exposure to oxygenated water , by de - oxygenating precipitation water 32 before the water enters the mass of tailings . the anode 22 comprises several blocks of magnesium , spaced over the electrolytic layer 20 . the blocks are wired together for electrical contact , whereby all the anode blocks are at substantially the same electrical potential . the blocks may be welded together , or wired together , in such a manner as will ensure their permanent electrical continuity . the electrolytic layer 20 is of such a resistivity to enable the transfer of ions freely , to ensure good electrolytic contact between anode and cathode and to minimize power consumption . ideally , the cathode should be of such design as to ensure complete coverage of the tailings . that is to say : water should not be able to by - pass the cathode , i . e substantially all water that enters the mass of tailings is water that has been de - oxygenated by passing through the cathode . the anode 22 is of such form as to optimize current distribution ; the designer should provide the anode , not as a few large blocks , but as many smaller blocks , well distributed over the whole barrier . preferably , all the anodes should be connected together . however , for the purpose of evaluating the effectiveness of the electrochemical barrier , one or more isolated cells may be included in the barrier , within specified areas . by periodically measuring the current in the isolated cell , an engineer can determine the oxygen flux through the barrier within the area of influence of that cell . the cable 24 is secured , in electrical conducting fashion , to the cathode 18 and the anode 22 . an electrical cell is therefore established between the electrodes 18 , 22 , current flowing one way through the cable 24 , and returning through the electrolyte in the layer 20 . in the case of a galvanic cell , the anode 22 is electro - chemically more active than the cathode 18 , creating a potential difference , which causes electrons naturally to flow from the anode to the cathode . at the cathode , oxygen gas in the water is reduced to hydroxyl ions . this creates alkalinity , and results in a substantial increase in ph . furthermore , hydrogen ions and other cations and water molecules migrate , through the electrolyte , towards the cathode . at the cathode , hydrogen ions are turned into gaseous hydrogen , or interact with oxygen to form water . as hydrogen ions are used up at the cathode in this way , a substantial raising of the ph of the electrolyte gradually takes place . preferably , as shown , the cathode 18 is located at the bottom of the electrolytic layer . water tends to flow down more quickly through the upper regions of the layer , and then to settle more slowly in the lower regions , around the cathode . the electrolytic layer does not have to be totally saturated throughout with water in order to maintain electrolytic continuity between the anode and the cathode , but of course the layer tends to be more saturated in the lower than in the upper regions . to maximize the effectiveness of the cathode , in its function of reducing dissolved oxygen to hydroxyl ions , the cathode is placed where the electrolyte is most saturated . the electrolyte layer 20 , being of clay , silt , etc , acts to soak up water and retain water within itself by capillary action , and the designer should engineer the barrier such that the electrolytic layer 20 will not dry out normal during periods between falls of rain . however , if there should be a prolonged drought , the layer might dry out , to the extent that there is no longer electrolytic continuity between the anode and the cathode . this does not matter actually during the drought , when of course there is no water infiltrating into the tailings . but sudden heavy rain , falling onto a dried - out electrolytic layer , might lead to water passing through into the tailings before the electrolytic cell can become re - established , whereby the infiltrating water would not have been de - oxygenated . if this happens only very occasionally , the overall effect on acid drainage is small . however , the designer of the system should aim to minimise the number of occasions in which the electrolytic layer dries out . the capillary properties of the layer , and the thickness of the layer , are important in this regard . the designer should also take steps to prevent damage to the cell , and unwanted infiltration of oxygenated water into the sulphide mass , due to flooding . another point is that , if the water in the cell should freeze , electrolytic activity will cease , and the designer should ensure that the cell resumes activity smoothly when the water melts , bearing in mind that this is a time when flooding tends to occur . the anode is a conductor that is electro - chemically more active than the cathode , and , since the metal of the anode will gradually dissolve , the dissolved metal should be environmentally - friendly . magnesium is preferred for the anode for these reasons . at the anode , the magnesium , being the source of the electrons flowing along the cable 24 , oxidizes and dissolves into the electrolyte , forming magnesium ions , mg ++. if the ph of the water remains below about ph - 9 , the magnesium will remain dissolved in the water as it passes through the layer 20 and into , and eventually through , the tailings . should the ph of the electrolyte pore water exceed ph - 9 , the magnesium ions produced by the oxidation of the anodic material will begin to precipitate , as a gelatinous hydroxy - carbonate compound . the magnesium of the anode becomes depleted , in a sacrificial - anode type of electrolytic reaction . it should be understood that a more or less optimal electrical energy flux is automatically maintained in the cell . if the infiltrating water is rich in dissolved oxygen , the electrolytic reactions drive the voltage of the cell upwards , which increases the rate of production of hydrogen at the cathode , and the rate of reduction of oxygen at the cathode , and consequently to a more rapid rate of de - oxygenation of the water infiltrating into the underlying sulphide . the alkalinity passing into the tailings mass serves to flush whatever acidity might be present in the porewater of the tailings mass , although the level of acidity in the tailings porewater does not affect the rate at which the electrolytic reactions take place in the cell . it has been described that the electrochemical cell treatment system acts to prevent the breakdown of acid - generating minerals by preventing oxygen from entering the sulphide wastes or sulphide bedrock . alkalinity , the by - product of the cathodic reactions , seeps into the underlying sulphide wastes , flushing out and reacting with the acidic porewater and leading to the formation of secondary products such as iron hydroxide minerals . these minerals in many cases will precipitate on the surface of the acid - generating minerals , and in cracks and voids . when this happens , the precipitates act as a filler or sealer material . this results in a diminished permeability to oxygen diffusion and infiltrating oxygenated waters , which in turn inhibits the acid - generating characteristics of the system . it will be understood that , when such sealing of a mass of tailings happens , due to the precipitation of these iron hydroxides , the mass becomes much less of a threat , because new precipitation water then tends to by - pass the mass , and to enter the groundwater ( and streams and ponds , etc ) by other routes . also , because the oxygen supply to the now - sealed mass is inhibited , such water as does pass through the mass can be expected to pick up correspondingly little acidity . the action of the iron hydroxide precipitates in sealing up the cracks can be especially beneficial when the sulphide is in rocks , and has become exposed due to cracks occurring in the rocks . it will also be understood that if , in future decades , the electrolytic layer should , for some reason , fail structurally , or be washed away , the sealing of the sulphide mass that has already taken place can render the now - re - exposed sulphide mass less infiltrate - able . the various effects that may be expected to take place when the electrochemical cover system as described herein is used , may be summarized as : ( 3 ) hydrogen is reduced at the cathode to hydrogen gas ( and it will be appreciated that as the hydrogen gas diffuses upwards , it further inhibits the ingress of oxygen by displacing oxygen occupying the pore spaces within the electrolyte ); ( 4 ) the precipitates that form in the sulphide wastes as a result of the downward migration of alkalinity from the cathode region of the electrochemical cover into the underlying sulphide wastes serve to physically seal the sulphide minerals against future oxidation . the electro - chemical cell treatment system based on the electrochemical barrier , or cover , as described , is relatively simple to service and maintain over the long term , with minimal costs . this is especially true when the cell can be engineered to operate galvanically , but even when the cell is operated in an impressed - current mode , service and maintenance are undemanding . the electrochemical cover system has been described as it relates to mining activities and waste materials . but , as mentioned , other kinds of activity can give rise to acidity in groundwater . for example , it is known that the mere movement of heavy machinery over sulphide - rich shale can cause the shale to crack , allowing acid - causing minerals to leach out or to become exposed ; thereafter , precipitation passing through the exposed minerals picks up acidity . an electrochemical barrier as described herein can be used to de - oxygenate water infiltrating into the exposed cracks . under normal operating conditions the anodes are wired or welded together . since the magnesium anode is sacrificial , and gradually used up , the quantity or amount of the sacrificial anode should be large enough to maintain the operation of the cell over a long period . a galvanic potential of 1 to 2 volts will result . the cable 24 should be of such dimensions and materials as not to cause any significant voltage losses , and the material should not be corrosive . [ 0079 ] fig2 shows a modification of the invention , in which the electrolyte layer covering the mass of sulphide comprises a layer of water 44 . this may be contrasted with the system depicted in fig1 in which the electrolyte layer comprised the fine - grained sediment 20 . of course , a very deep layer of water provides an excellent barrier for preventing ingress of oxygen into sulphide underneath the deep water , and if the mass of sulphide could be placed under very deep water ( i . e several meters deep ), there would be little need for the invention . the fig2 system should be considered in cases where a depth of water can be provided over the mass of tailings , but where the depth of the water that can be provided is , in itself , too shallow ; that is to say , where the water is so shallow that the amount of oxygen reaching the underlying un - oxidized sulphide creates an unacceptable level of oxidation of the contained sulphide minerals and consequently an unacceptable level of production of acidity . in fig2 the ( magnesium ) anode 46 is suspended in the water electrolyte and the ( steel ) wire mesh cathode 48 is placed at the bottom of the pond immediately overlying the oxidized tailings 50 . if there is no oxidized tailings layer 50 , the cathode 48 is placed immediately overlying the un - oxidized tailings 52 . an electrically conducting cable 54 connects the cathode and anode 22 . [ 0081 ] fig3 shows another modification of the invention , in which the electrochemical cover is placed over fractured / permeable sulphide bedrock which is the source of acidity . ( in fact , in most of the situations where the electrochemical barrier is depicted as being placed over a mass of sulphide tailings , the same barrier could be placed over a mass of fractured / permeable sulphide bedrock .) [ 0082 ] fig4 shows another modification of the invention in which the electrochemical cover is placed over a mass of sulphide tailings . in this case , despite the presence of the engineered dams or berms 60 , the mass may be classed as a “ raised stack ”, and as such might have a greater tendency to be more permeable to oxygenated water and oxygen diffusion . such raised deposits represent a greater acidity hazard , as they are even more liable to oxygen infiltration . again , as shown in fig4 the electrolytic cell system , engineered to form a barrier or cover , can be applied to the raised mass . when the mass is raised , or perched , the designer may have to pay attention to the possible difficulties of engineering the cell so that electrical and electrolytic continuity can be maintained between anode and cathode . in each case , whether the mass of sulphide is perched , or at ground level , or in a depression in the ground , the designer must see to it that the structure of the engineered cell , as to its thickness , accommodation to slopes , etc , is physically adequate for the situation , and especially must ensure that the electrolyte - layer will not be washed away , or otherwise disturbed . one way of enhancing the structural coherence of the electrolyte layer , when the layer is of particulate material , is to establish plants and vegetation thereon . in addition to its function as a component of the electrolytic cell , the electrolyte layer provides a physical cover for the mass of sulphide , for inhibiting the physical penetration of oxygen down into mass . this downward penetration can be derived from oxygen gas from the atmosphere , or from oxygen dissolved in the water , or from the infiltration of substances in an oxidation state that can transform readily to a reduced state . theoretically , what is needed to prevent a mass of sulphide from generating acidity in water passing through it is a cover that keeps oxygen from penetrating into the sulphide . if the sulphide lies underneath several meters of water , for example , oxygen can be effectively excluded . if the sulphide lies underneath ( even more ) meters of soil or the like , again oxygen can be effectively excluded . however , providing a simple cover , which is thick enough , over the large area of a tailings mass , can be prohibitively expensive . the cost can be very large of building a dam around a mass of dumped tailings , to provide a deep enough layer of water . the cost of a bringing in a thick enough layer of soil is hardly less . but , if the lie of the land is favourable , as it sometimes is , an effectively - deep cover can be provided inexpensively enough , and in that case of course that can be done . but there are in existence many masses of sulphide tailings , where a full - thickness cover is out of the question on cost grounds , but where a thinner cover might be feasible . it is an aim of the present invention to enable adequate oxygen exclusion by the use of a thin cover . in the invention , as described , the cover , i . e the electrolyte layer , may be of water , or of soil . the actual thickness dimension of a granular - solid electrolyte layer , to be adequate for use in the invention , depends on the type of soil or other material being used to provide the layer , on the expected level of precipitation and the possibility for droughts , and so on . in a typical case , where the layer is of clay or fine silt , which retains water for long periods , it is possible that an effective electrolyte layer may be no more than 30 cm thick . where the layer is of coarser till or sand , to be effective the layer should be 100 cm thick or more . if the electrolyte cover is of water , the minimum depth of the water should be not less than 30 cm . these thicknesses should be contrasted with the corresponding needed thicknesses of the same materials which are required , as mentioned , when the cover is a purely physical one . [ 0088 ] fig5 a shows a mass 70 of sulphide tailings , in which the mass is so placed , in relation to the ground 72 , as to be vulnerable to infiltration of oxygen - laden water into the pile laterally , i . e from the sides . fig5 b shows how the electrochemical barrier apparatus can be engineered so as to protect the mass from the side - infiltrating water . in fig5 b , a steel - mesh cathode 73 has been placed over the mass 70 . a covering layer 74 of soil ( clay , silt , sand , etc , as previously described ) is placed over the cathode 73 . the layer 74 holds enough moisture that the layer can serve as the electrolytic layer , in the manner as described . a magnesium anode 75 is provided , and the resulting electrolytic cell operates galvanically , as described . in the fig5 b case , however , a trench 76 has been provided in the ground surrounding the mass , and the steel - mesh cathode has been extended down into the trench , to form an apron - portion 78 of the cathode . the trench has been back - filled with a granular conductive material , such as graphite . this ensures that the water , as it passes through the cathode , remains in electrolytic contact with the cathode for an adequate residence time . unless it can be determined that , at a particular sector of the mass 70 , inwards - infiltration is precluded by , for example , the lie of the land , whereby an apron would not be needed at that sector , the apron - portion 78 should be provided all around the perched mass . it might well happen that , in some places , or at some times , water will pass outwards from the tailings mass , i . e outwards through the apron - portion of the cathode . assuming the electrolytic treatment cell has performed its task , such water will be already de - oxygenated , and will contain little or no acidity ; if the eh - voltage level of such water should undergo a further fall , in passing through the apron , that would not pose a problem . in suitable cases , the barrier may be made more effective by the inclusion of a second electrolytic cell , so placed that the oxygenated water infiltrates down in series through two cells , and two cathodes . this can be useful , for example , in a case where the electrolyte layer has been damaged , or is too thin . the systematic placement of the cell at the tailings or waste rock surface during the construction of conventional engineered covers would provide a direct non - invasive method of measuring the effectiveness of the said engineered cover . the electrolytic cell systems as described herein are aimed at preventing the oxidation of sulphide minerals and the associated production of acidity . the engineered cell serves as a cover , to physically inhibit atmospheric oxygen from penetrating downwards into the mass of sulphide ; the cell also operates electro - chemically , to de - oxygenate the water reaching the mass of tailings . the engineered cell systems can be relatively inexpensive to construct , even in respect of a tailings heap that has lain totally abandoned for years , and can be satisfactory from the standpoint of maintenance , in that the procedure can be made to function , if desired , substantially without any regularly scheduled maintenance at all . preferably , the electrochemical barrier apparatus , or cover , should be insulated from the sulphide mass . in the case where the uppermost layer of sulphide has become oxidised , the oxidised layer can serve as the insulation . if there is no already - oxidised layer , or if it is desired to supplement the oxidised layer , a layer of sand or other insulative material can be introduced , and placed on top of the sulphide - mass , and then the electrochemical cover is put in place over the layer of sand . the electrochemical cover may be regarded as functionally and structurally separate from the sulphide mass . this may be contrasted with the prior art technique , in which the cathode has been formed actually by the sulphide - mass . however , this technique required that the sulphide - mass not only be highly conductive , but that it be so homogeneously over the whole body of sulphide . thus , the technique had limited applicability . the present engineered electrochemical barrier is useful even when the sulphide - mass is not especially conductive or homogenous . in the context of the present invention , the sulphide - mass is oxygen sensitive in the sense that the redox state of the sulphide is such that exposure to oxygen - containing water makes the sulphide liable to oxidise , leading to the acidity - producing reactions as described above . | 1 |
a first embodiment of the present invention will be described with reference to fig1 to 3 . referring to fig1 a canister comprises a casing 10 including a cylindrical body 11 , an upper lid 12aand a bottom lid 12b . the diameter of the bottom of the cylindrical body 11 is reduced such that a stepped portion 11a is formed on the inner periphery thereof , as shown in fig2 . a cylindrical portion 11b is formed to protrude from a central bottom of the cylindrical body 11 . the height of the cylindrical portion 11b corresponds to that of the stepped portion 11a . a drainboard - like lattice member 13 is placed on the stepped portion 11a . the lattice member 13 has a cylindrical rib 13a protruding from the central underside thereof . the rib 13a is inserted into an annular groove 11b l formed in the upper end of the cylindrical portion 11bl so that the lattice member 13 is secured in position . two filter pads 14 each having gas permeability and elasticity are provided on the top and the underside of the lattice member 13 respectively . the outer periphery of the casing body 11 is formed with a suction pipe 11c located between the stepped portion 11a and the bottom . the suction pipe 11c communicates between the interior and exterior of the cylindrical body 11 . the bottom lid 12b is formed into the shape of a dish having an upper opening the periphery of which is hermetically bonded to the underside periphery of the cylindrical body 11 . an exhaust pipe 12bl communicating between the interior and exterior of the dish - shaped bottom lid 12b is also formed on the peripheral wall of the same . the filter pad 14 is placed on the top of the lattice member 13 as described above . a predetermined amount of activated carbon is put into the casing body 10 until it reaches the level equal to about a half of the whole height of the cylindrical body 11 , thereby constituting a lower activated carbon layer 21 . a partition member 30 having an external diameter approximately equal to an inner diameter of the cyclindrical body 11 is placed on the upper surface of the lower activated carbon layer 21 . the partition member 30 is formed into the shape of a thin hollow column . a cross rib 33 is formed inside the partition member 30 , as shown in fig3 . the cross rib 33 interconnects upper and lower wall members 31 and 32 . the cross rib 33 serves as a communicating wall or a radial wall , as will be described later . three of four pieces of the rib 33 are not adjacent to the inner peripheral wall of the partition member 30 and accordingly , a gap is defined between the end of each piece and the inner peripheral wall of the partition member 30 . the other piece of the rib 33 is adjacent to the inner peripheral wall of the partition member 30 . the interior of the partition member 30 is divided into four chambers 34a , 34b , 34c and 34d by the cross rib 33 . the first chamber 34a has in the underside thereof three openings 35a each communicating with the outside of the partition member 30 in the cylindrical body 11 . the fourth chamber 34d has in the top three openings 35b each communicating with the outside of the partition member 30 in the cylindrical body 11 . two filter pads 36 each having gas permeability and elasticity are provided on the top and the underside of the partition member 30 . a predetermined amount of activated carbon is put over the filter pad 36 on the top of the partition member 30 until it reaches the upper end of the cylindrical body 11 , thereby constituting an upper activated carbon layer 22 . a drainboard - like lattice member 16 is placed on the upper surface of the upper activated carbon layer 22 . the lattice member 16 has a peripheral portion formed into the shape of a short circular cylinder so that the peripheral portion is closely fitted with the inner peripheral wall of the cylindrical body 11 . two filter pads 15 each having gas permeability and elasticity are disposed on the top and the underside thereof respectively . the upper lid 12a is formed into the shape of a dish having a lower opening . the upper lid 12a has a flat flange 12a1 formed on the peripheral edge thereof . the flange 12a1 has a presser wall 12a2 forming into the shape of a short cylinder and extending downwardly from the inner peripheral underside thereof . the outer diameter of the presser wall 12a2 is smaller than the inner diameter of the peripheral edge of the lattice member 1b . accordingly , the upper lid 12a is bonded at its flange 12a1 to the upper end of the cylindrical body 11 to be thereby secured , pressing the presser wall 12a2 from above the lattice member 16 . an atmosphere pipe 12a3 is formed on the upper face of the upper 1id 12a to communicate between the interior and exterior of the upper lid 12a . the operation of the canister will now be described . the suction pipe 11c is connected to one of two ends of a pipe which is further connected at the other end to an intake system of an engine . the exhaust pipe 12b1 is connected to one of two ends of a pipe which is further connected at the other end to a fuel tank . fuel in the fuel tank is vaporized when the atmospheric temperature rises in the stopped state of the engine . the resultant fuel vapor enters the dish - shaped bottom lid 125 through the exhaust pipe 12b1 . the fuel vapor further enters the lower activated carbon layer 21 through the cylindrical portion lib . the fuel vapor flows upwardly in the lower activated carbon layer 21 with the fuel component being adsorbed by the activated carbon . reaching the upper end of the lower activated carbon layer 21 , the fuel vapor enters the first chamber 34a inside the partition member 30 through the openings 35a formed in the underside of the partition member 30 . the fuel vapor passes through the first to fourth chambers 34a - 34d , entering the upper activated carbon layer 22 through the openings 35b of the fourth chamber 34d , as shown by arrows - a in fig4 . when passing through the chambers 34a - 34d , the fuel vapor passes through the narrow gaps between the ends of the respective three pieces of the cross rib 33 and the inner peripheral wall of the partition member 30 . the fuel vapor is well mixed with the air when entering a larger space or each of each of the second to fourth chambers 34b - 34d out of the narrow gaps and when entering each of the narrow gaps out of each of the chambers 34a - 34d . the fuel vapor is sufficiently captured by the activated carbon in the lower activated carbon layer 21 and is again captured by the activated carbon when passing through the upper activated carbon layer 22 . the fuel vapor containing less amount of fuel component enters the interior of the dish - shaped upper lid 12a , exiting out of the casing body 11 through the atmosphere pipe 12a3 . according to the above - described embodiment , the partition member 30 provides , between the lower and upper activated carbon layers 21 , 22 , a flow path or a labyrinth through which the fuel vapor turns about 360 degrees . thus , the path of the fuel vapor passing through the cylindrical body 11 can be rendered longer . consequently , since the fuel vapor is sufficiently mixed with the air , the fuel component adsorbing efficiency can be improved when the fuel vapor passes through the upper activated carbon layer 22 . upon start of the engine , the negative pressure is produced in the intake system . the negative pressure is supplied to the suction pipe 11c of the cylindrical 10 of the canister . since only the atmosphere pipe 12a3 of the cylindrical 10 communicates with the atmosphere , the air is drawn through the atmosphere pipe 12a3 into the dish - shaped upper lid 12a . the air passes through the upper activated carbon layer 22 , the fourth to first chambers 34d , 34c , 34b , 34a defined in the partition member 30 and the lower activated carbon layer 21 . since the air passing through the activated carbon layers has low fuel concentration , the fuel component captured by the activated carbon is evaporated by the air and released from the activated carbon . thus , the air containing the fuel component in high concentration is supplied to the intake system of the engine through the intake pipe 11c . since the air containing the fuel vapor flows round in the partition member 30 , its flow path is increased and the fuel vapor is sufficiently mixed with the air . this enhances evaporation of the fuel component in the lower activated carbon layer 21 . the above - described suction path is shown by arrows b in fig4 . in the foregoing embodiment , the partition member 30 is provided with the cross rib 33 partially interconnecting the upper and lower wall members 31 , 32 thereof so that the flow path is lengthened . to achieve the same object , a plurality of parallel ribs may be connected alternately to one half of the inner peripheral wall of the partition member 30 and the other half thereof so that the fuel vapor zigzags in the partition member 30 . furthermore , various types of baffle plates may be disposed in the partition member 30 so that the flow path of the fuel vapor can be lengthened . the interior of the partition member 30 may be divided vertically into a plurality of chambers for the same purpose . additionally , integral or separate ducts may be formed in the partition member 30 . fig5 and 6 illustrate a second embodiment of the present invention . a fuel intake cylinder 13b similar to the rib 13a is formed on the side of the lattice member 13 opposite the side on which the rib 13a is formed . when the rib 13a is connected to the upper end of the cylindrical portion 11b . the cylindrical portion 11b is contiguous with the fuel intake cylinder 13b . in the above - described construction the fuel vapor produced by vaporization of fuel in the fuel tank enters the bottom lid 12b . the fuel vapor then enters the lower activated carbon layer 21 through the cylindrical portion 11b and the fuel intake cylinder 12b in turn . the fuel vapor flows upwardly in the lower activated carbon layer 21 , diffusing transversely . in this regard , the fuel vapor would reach the partition member 30 with insufficient transverse diffusion if the fuel intake cylinder 13b should not have a sufficiently low height . in the embodiment , however , the fuel vapor enters the lower activated carbon layer 21 through an opening of the fuel intake cylinder 13b even when the height of the fuel intake cylinder is low . accordingly , the fuel vapor produced in the fuel tank upon start of the engine exits out of the opening of the fuel intake cylinder 13b and then passes through the activated carbon layer , whereupon the fuel vapor is supplied to the intake system of the engine . without the fuel intake cylinder 13b , the fuel vapor having entered the casing 1 through the opening 1a would sometimes be supplied into the suction pipe 5 through the opening 1b without passing through the activated carbon layer 2a , as shown in fig7 . in this case the concentration of the fuel supplied to the engine becomes uneven , which renders the operation of the engine unstable . in the second embodiment , however , the fuel vapor is supplied through the adsorbent layer to the suction system of the engine and accordingly , the operation of the engine can be stabilized . the foregoing description and drawings are merely illustrative of the principles of the present invention and are not to be construed in a limiting sense . various changes and modifications will become apparent to those of ordinary skill in the art . all such changes and modifications are seen to fall within the true spirit and scope of the invent ion as defined by the appended claims . | 1 |
fig1 . is a functional block diagram of a voice response unit 100 for providing telephone directory information to a caller and for providing related services including call completion to the named party . vru 100 includes a processor 102 connected to , controlling , and receiving a recognized speech output from a speech recognition engine 116 . processor 102 is also connected to a sound card 118 for playing and / or synthesizing voice messages to a caller . telephone line interface card 120 , under control of processor 102 , supplies an audio output from telephone equipment represented by telco switch 130 to speech recognition engine 116 . sound card 118 , in turn , provides a speech audio output to telephone line interface card 120 for transmission to telco switch 130 . processor 102 further has access to mass storage , conventionally in the form of a hard disk memory , including stored voice messages 122 and telephone directory 124 . processor 102 includes and runs several software systems including a supervisory operating system 104 ( including pseudorandom number generator 108 ), delay timer 106 , speech recognition client 110 , telephony module 112 , and voice dialing application and interface 114 . conventionally , pseudorandom number generator 108 may be implemented in software as an operating system supplied function , although specialized applications and even hardware implementations are also possible . also depicted in fig1 , for purposes of illustration of the vru , are calling party 132 connected to telco switch 130 and a called party 134 , likewise connected to telco switch 130 . processor 102 may be a dedicated , specialized central processing unit ( cpu ) board running specialized software , or may be a general purpose personal computer or workstation running an appropriate operating system such as windows nt or unix . other suitable platforms include the sun sparc20 , pentium 200 , periphonics vas , ibm rs6000 with direct talk , or the dialogic antares card utilizing digital signal processing ( dsp ) technology . delay timer 106 may be a standard operating system - supplied timer or clock function . in one implementation , a call is made to the system clock upon start of the delay , and a program loop continues to read the clock time until ( i ) a predetermined time has elapsed or ( ii ) an alternative processing command is received and the loop is exited . alternatively , a series of nested loops may be used to provide a desired time delay during which an alternative processing command may be received . delay timer 106 provides a predetermined silent period between announcement of the name or telephone number identified by the system and default dialing of the number . during the silent period the system listens for an alternative command from the user , either in the form of a dtmf signal or , more preferably , by speaking the alternative action requested , such as “ stop ”, “ listing ”, “ voice mail ”, etc . the selection of an appropriate silent delay period has been found to be critical to user acceptance of the system . delay periods of less than 1 . 2 to 1 . 5 second have been found to be inadequate to signal a user that the system is available to receive an input and provide sufficient reaction time for the user to initiate the request , i . e ., speak the alternate command word or words . on the other hand , silences of greater then 2 . 0 to 2 . 3 seconds are perceived as processing delays and are unacceptable , particularly to users who are not requesting alternate processing . accordingly , a silent delay period should be in the range of 1 . 2 to 2 . 3 seconds and preferably in the range of 1 . 5 to 2 . 0 seconds , the optimal delay being 1 . 8 seconds . use of a silent delay in these time ranges results in no perceptible or at least an acceptable delay while providing sufficient opportunity for those users requiring alternative processing to initiate the appropriate actions . pseudorandom number generator 108 may be a standard operating system - supplied random number function such as supported by ansi c . depending on the particular random function generator supported by the system , the result might need to be scaled to correspond to the number of messages comprising a particular group . for example , if the maximum value provided by the pseudorandom number function call rand were equal to randmax and the number of prompts in a group were equal to n , then a pseudorandom integer j between 1 and n could be obtained using the following code : alternatively , other random number generators may be used , although quality of the randomness is not a major factor in the present embodiment . in addition to the operating system and pseudorandom number generator , processor 102 runs software applications and modules written , for example , in “ c ” code for implementing a particular service , such as a voice dialing application . in this configuration , speech recognition client 110 receives a speech signal from telephone line interface card 120 and performs preprocessing of the speech signal including gross end - pointing and speech buffer management . the speech recognition client 110 further manages the results provided by speech recognition engine 116 to match the phonetic strings with the appropriate names and telephone numbers stored in telephone directory 122 . telephone directory 122 includes three flat database files associated with matching including a names - file , nicknames - files and a phone book . telephony application 112 performs call answering , caller id capture , speech capture , billing information processing and call transfer . the latter function , call transfer , may be provided by using the three - way calling feature of telco switch 130 . using this feature , after an incoming call has been terminated at telephone line interface card 120 and the telephone number of a requested party has been identified , telephone line interface card 120 is instructed by telephony module 112 to perform a switchhook operation to obtain a second dial tone from telco switch 130 . the telephone number of the identified called party 134 is then outdialed to initiate a call to that party . upon ring detection , telephone line interface card 120 performs a second flashhook operation to signal telco switch 130 to bridge calling party 132 and , subsequently , telephone line interface card 120 goes back on hook to drop out of the bridge and wait for the next user to call . voice dialing application and interface 114 provides system prompts , call error handling , call handling features ( i . e ., “ call completion ,” “ listing ,” “ sent to mailbox ,” etc .) and manages the speech client recognition results to determine the appropriate response or prompt group of messages . stored voice messages 122 are arranged in groups of content equivalent prompts or messages . all of the prompts within a group are interchangeable , conveying substantially the same substance but with variations in wording and / or phraseology and sentence structure to mimic normal variations in human speech . for example , a message group may include five suitable system greetings that might be played to a user when a call is first answered . one prompt may include “ bell atlantic , who would you like to call ?”; a second prompt might be “ this is bell atlantic , who would you like to call ?”; a third prompt “ corporate dialing , who would you like to call ?”; a fourth prompt “ this is the corporate dialer , who would you like to call ?”; and a fifth “ bell atlantic here , who would you like to call ?”. similarly , other message groups would include appropriate messages or prompts to be used in a particular situation , each of the prompts within a particular group being interchangeable with substantially the same content , i . e ., content equivalent prompts . telephone directory 124 may be a flat file of names , organizations , functions , etc ., with their respective telephone numbers or other handling or routing information as appropriate or as required by the particular application . speech recognition engine 116 is preferably speaker independent so that there is no requirement for users to train the system to respond to their voices . the basic speech recognition technology is commercially available through several sources including nuance communications , inc . although shown apart from processor 102 , speech recognition engine 116 may be implemented as an application running on processor 102 . upon receipt of a speech signal from telephone line interface card 120 , speech recognition client 110 performs preprocessing of the speech signal for speech recognition engine 112 including gross end - pointing and speech buffer management . the buffered speech is processed to extract the phonetic components , match them with the appropriate speech models and return the highest probability string . the matching string is derived from a grammar file . the matching string is then associated with name files forming part of the telephone directory by a speech recognition client 110 . fig2 is a flow diagram for a voice response unit ( vru ) implementing a voice activated dialer . entering the process at terminal 202 , an initialization routine 204 sets an interrupt flag to false . the process includes a loop at decision 206 which is exited upon detection of a ring signal . upon detecting an incoming call , the call is answered at 208 and an appropriate greeting is played to the caller at 210 . the caller is then prompted at process 212 to provide the name of a party to be called . a speech input from the caller is looked for at decision 214 and , if none is found , appropriate error processing is performed at 216 . the error processing detail could include prompting the caller to speak louder or to try again . if speech is received at 214 , the content of the speech segment is recognized at 218 and a match is attempted at 220 between the recognized speech segment and names present in a telephone directory . if no match is found at decision 222 , error processing 224 is performed . conversely , if a match is found , the name is read back to the caller and a delay segment of code starting at process 228 and ending at decision 240 is entered . specifically , the time upon entry of the delay is obtained at 228 . this time can be obtained from the system under most operating systems and languages . for example , the c library includes the standard time and date functions library & lt ; time . h & gt ;. using these functions , a call to time will return the current calender time which is used as the start time upon entry into the subsequent “ while ” loop . another variable such as “ timenow ” may be used to get the time during loop execution with the function “ double difftime ( time_t timenow time_t starttime )” used to compute the elapsed time in the loop . processing continues in the while loop until the delay has expired or an alternative processing command is recognized . upon entry into the loop , the decision block 230 is encountered to decide if a speech segment has been received . if not , processing skips down to continue at “ get timenow ” process 238 . a check is then performed at the bottom of the “ while ” loop to see if either ( i ) the elapsed time in the loop is equal to or exceeds the predetermined time “ delay period ” or ( ii ) if the interrupt flag has been set equal to “ true ,” ( i . e ., an alternative processing command has been recognized ). conversely , if a speech segment has been received , it is recognized at 232 and the resulting content is examined at decision box 234 to determine if alternate processing has been requested . if alternate processing has been recognized , then the interrupt flag is sent to true at 236 . otherwise , the interrupt flag is not altered . processing then continues at 238 to get the current time . decision box 240 then decides if the predetermined delay period (“ delay period ”) has been achieved or if the interrupt flag is true indicating that alternative processing has been requested , either of which condition causes the process to exit the “ while ” loop and continue at decision box 242 . alternatively , if the time in the loop has not reached the predetermined “ delay period ” and alternative processing has not been identified , the process loops back to continue at the top of the “ while ” loop at decision box 230 . since the loop can be exited by either of two conditions , decision box 242 is necessary to determine if the exit is due to a timeout condition or because alternative processing has been requested . if the exit from the loop is in response to a timeout , then the lefthand branch is taken out of decision box 242 and the telephone number is dialed at 244 . otherwise , alternative processing is initiated at 246 . a flow diagram of another automated dialer according to the invention is shown in fig3 a - 3 d . fig3 a shows call processing for call answer and provision of a welcome prompt . speech recognition processing is further detailed in fig3 b . processing for providing a second guess is shown in fig3 c . finally , normal and special handling processing is shown in fig3 d . referring to fig3 a , at system start - up normal system configuration files are read and initialization of the speech server , client and telecom applications is performed . the program then enters a wait state until an incoming call is received . on detecting ringing , the call is answered by the telephone line interface card 120 . a pseudorandom number between 1 and 5 inclusive is generated and used to randomly select one of five content equivalent greetings to be played to the caller . the content equivalent greetings are substantively the same , but vary slightly in wording and phraseology . if no speech is detected within a predetermined period after the greeting has completed , the system will prompt the caller to speak a name of the party to be called . again , the prompt is selected from among five content equivalent messages in response to a newly generated random number . if , after a second period following this prompt no speech is detected from the calling party , one of five error messages is selected in response to another random number informing the caller that he or she is being transferred to a trouble line . if speech is detected after the initial greeting or after the caller is prompted , processing continues as shown in the call flow of fig3 b . first , the system attempts to identify phonemes from the speech signal of the calling party . the phonemes are then compared to names and nicknames contained in the telephone directory and , if a name is found , the system proceeds to retrieve the associated telephone number . if the telephone number is invalid or is otherwise recognized to require special handling , processing continues as shown at connector c in the lower left of fig3 d . for example , if the associated telephone number is all 9 &# 39 ; s , the wav file associated with the name is played , but no telephone number is dialed and processing loops back near the beginning of the call flow to play a new greeting and give the caller an opportunity to try another name . alternatively , if the telephone number is all 7 &# 39 ; s , the caller is informed that the person named is no longer in the directory served by the system and , again , processing continues back to give the caller the opportunity to lookup another name . referring back to fig3 b , if the name is found and no special handling is indicated , the system will attempt to open a wav format audio file associated with the name . if such a wav file corresponding to the called party &# 39 ; s name is found , then the name is played back to the caller as confirmation that the correct directory listing has been identified by the system . alternatively , if the system is unable to identify a wav file associated with the found name , the corresponding telephone number is read back to the caller using a synthesized voice . in either case , the system waits for a predetermined time of between one and two and one - half seconds , and preferably within the range of 1 . 2 seconds to 2 . 3 seconds , an optimal time being 1 . 8 seconds , before proceeding to initiate default processing by dialing the telephone number as shown at the top of fig3 d . if , during the silent delay period , the system recognizes the caller speak an exception processing command , such as “ cancel ,” “ listing ,” “ leave a message ,” or “ voice mail ,” a flag indicating the appropriate alternative processing is set . if the caller commands the system to cancel dialing by speaking the word “ cancel ” or any equivalent phrase ( e . g ., “ stop ,” “ no ,” “ wait ,” “ whoa ,”, etc .) and the system has made less than six attempts toward dialing a number , then processing continues at the top of fig3 c . there , if the system recognizer has a second guess ( i . e ., there as another close match ), then a new pseudorandom number is obtained to select one of five error messages to be played to the caller indicating that the system has a second best guess that it will attempt to use . processing then continues at the entry point shown by connector h in fig3 b to check for any special handling requirements as might be indicated by an invalid telephone number for the second guess . if no special handling is required , then the name of the second guess is played ( or the corresponding telephone number is no wav file is found ). the system waits for 1 . 2 to 2 . 3 seconds for any alternative verbal instructions or processing interruption requests from the caller and , if none is received , dials the number . if the calling party has indicated that the name or telephone number played is incorrect but the system does not have a second guess , then processing continues at entry point shown by connector a in fig3 a , affording the caller a chance to repeat the name or input another name . if a name has been recognized and the caller has not indicated that the name or telephone number is incorrect , then processing continues at the top of fig3 d at connector f . if the caller has spoken the word “ listing ,” or any equivalent recognized by the system ( e . g ., “ number ,” etc .) during the silent prompt period , then the telephone number corresponding to the found name is played and processing loops back to connector d in fig3 a . special processing is also indicated by the caller speaking “ leave a message ” during the silent prompt period so that the voice mail telephone number of the called party is substituted for their direct dial number . the calling party is notified by the system they will be “ leaving a message ,” one of five randomly selected closing messages is played , and the call is transferred to the called party &# 39 ; s voice mail platform . if the called party has spoken the phrase “ voice mail ” during the silent prompt period indicating that they would like to access their own voice mail , then the calling party &# 39 ; s voice mail access number is substituted , the message “ voice mail ” is played and processing continues as before . if a name and valid telephone number have been identified , and no special processing has been requested , call flow continues in the middle of fig3 d to generate a random number used to select one of five closing messages and the call is transferred to the telephone number identified . in the case of a caller having requested his or her own or the voice mail of the called party , the system delays release of the line until it can provide the voice mail platform with the appropriate voice mailbox identification using in - band dtmf signaling or equivalent as shown at the bottom of fig3 d . the silent prompt provides a user friendly interface mimicking human speech modalities . while automated systems have traditionally stepped a user through seemingly endless menus of voice prompts and options , the present invention allows the user to interact much as if talking with a human operator or attendant . the majority of callers allow the system to proceed and process according to its default programming . if the process needs to be interrupted , the user need only so indicate during a short delay period and without accessing further menus . although several embodiments of the invention have been described in detail above , it should be clear that the present invention is capable of numerous modifications as would be apparent to one of ordinary skill in the art . such modifications fall within the purview of the appended claims . it will be readily seen by one of ordinary skill in the art that the present invention fulfills all of the objects set forth above . after reading the foregoing specification , one of ordinary skill will be able to effect various changes , substitutions of equivalents , and various other aspects of the invention as broadly disclosed herein . it is therefore intended that the protection granted herein be limited only by the definition contained in the appended claims and equivalents thereof . | 7 |
a bidirectional signaling scheme is described with implicit termination . the invented bidirectional approach allows data transmission simultaneously in two directions over one wire . this doubles the effective bandwidth per pin over a point - to - point unidirectional scheme operating at the same frequency . the line termination is provided by the driver , eliminating discrete terminations from the board . when the drivers at both ends of the line are in the same state , no power is consumed during input / output ( i / o ) operations . this can result in significant power savings . a conceptual version of the bidirectional signaling scheme using a single wire 21 is shown in fig2 . coa , cob and cia , cib are signals from and to the core of two components ( core a and core b ) in the system respectively . refa and refb are reference generators for core a and core b respectively used to dynamically set the threshold of the receivers according to the present state of the outgoing data . refa and refb subtract the outputs from core a and core b respectively so that only the output from core b is seen by the input to core a and only the output from core a is seen by the input to core b . diffa and diffb are differential amplifiers driving to core a and core b respectively . drva and drvb , which are drivers from core a and core b respectively , form a voltage divider that creates the states shown in table 1 : table 1______________________________________possible statescoa cob refa refb line 21______________________________________0 0 1 / 4 v . sub . cc 1 / 4 v . sub . cc v . sub . ss0 1 1 / 4 v . sub . cc 3 / 4 v . sub . cc 1 / 2 v . sub . cc1 0 3 / 4 v . sub . cc 1 / 4 v . sub . cc 1 / 2 v . sub . cc1 1 3 / 4 v . sub . cc 3 / 4 v . sub . cc v . sub . cc______________________________________ this is a ternary encoding in which there is a one - to - one correspondence between two of the binary states ( i . e ., coa , cob = 0 , 0 or coa , cob = 1 , 1 ) and two of the ternary states ( i . e ., v ss and v cc ). the remaining two binary states ( i . e ., coa , cob = 0 , 1 or coa , cob = 1 , 0 ) are mapped to a single ternary state ( i . e ., 1 / 2 v cc ). it is this state that creates the need for the adjustable references in order to decode the line voltage . the state of the signal being sent by the local driver is the information used to do the decode . as an example , assume that cob is in the low state . as coa switches between the high and low states , the line voltage moves between 1 / 2v cc and v ss respectively . refa alternates between 3 / 4v cc and 1 / 4v cc , while refb is a constant 1 / 4v cc . note that the line voltage is always lower than refa , while diffb sees a signal with a 1 / 2v cc swing centered on a 1 / 4v cc reference . cia is , therefore , a constant zero , which reflects the state of cob , while cib follows coa . refa switching is used to keep cia constant as the line voltage switches . with cob high , the results are analogous , except that the line alternates between v cc and 1 / 2v cc , and refb is 3 / 4v cc . the case where both drivers are switching is a direct extension of the above example with both refa and refb switching to correctly decode the line voltage at the receivers , i . e ., diffa for driver drvb and diffb for driver drva . in the ideal case ( a lossless line , both drivers matched to the line , and step function input signals at nodes n1 and n2 ), the presence of the transmission line 21 does not affect the decoding since the line is correctly terminated for signals traveling in both directions . the only effect of the line is a time shifting of the edges from and to nodes n1 and n2 . in this ideal system , the only voltages seen on the line and at nodes n1 and n2 will be those shown in table 1 . the peak - to - peak swing for the bidirectional case with a single driver switching is the same as for the unidirectional link case , 1 / 2v cc . in the unidirectional case , this swing is between 1 / 4v cc and 3 / 4v cc . this means that the on chip power in the driver is in the bidirectional case , when the line is at either v cc or v ss , no power is dissipated . when the line is at 1 / 2v cc , the power consumed by the driver is if it is assumed that all states are equally likely , the power would be half this amount , since two out of four states dissipate no power . the total on chip power is then which is double the power of the unidirectional case . the bidirectional case , however , dissipates no off chip termination power , while the thevenin terminated , unidirectional case dissipates the total system power saved per pin in the bidirectional case is of additional on chip power dissipation . the total system power for the unidirectional case is double the power for the bidirectional case . the savings would be half the amount shown above if the unidirectional link were terminated to a rail , rather than a thevenin termination , but still quite significant . the signal swing of 1 / 2v cc with 1 / 4v cc noise margin is the same for both the unidirectional and bidirectional cases . this is significant , since it means that the ternary encoding has cost nothing in terms of noise margin with respect to the unidirectional links . with an effective swing of 1 / 2v cc , this also means that the noise generated on the links will , to first order , be equal . the signal to noise ratio has , therefore not been changed . this also means that the swing at the input receiver is unchanged , so that the receiver &# 39 ; s gain does not need to be increased for the bidirectional case . the ideal bidirectional scheme of fig2 is conceptually simple to implement . however , in actually implementing such a scheme , there are several circuit challenges to overcome . the discussion to this point has assumed that the drivers drva and drvb and the reference generators refa and refb have equal delays . any deviation from this assumption will result in jitter on cia and cib with respect to the clock used in the core of the component , since the inputs to the differential amplifiers diffa and diffb will not switch simultaneously when the local driver switches . if the delay difference is extreme ( e . g ., greater than 1 / 2 ns ), glitches will appear on these nodes . one approach that may be used to attempt to alleviate this problem is to avoid switching the local driver and reference as incoming data edges arrive at the receiver . however , it has been determined that if the total jitter and skew of incoming data with respect to clock is greater than 1 / 4 bit cell , switching of the drivers and references coincident with incoming edges can not be avoided on both ends of the wire simultaneously . it is unlikely that at the speeds being targeted ( 200 mhz +), the jitter and skew can be kept under 1 / 4 bit cell . this being the case , the problem must be reduced to a minimum with careful circuit design and layout . an approach which addresses these issues will now be described with reference to fig3 in which a reference control signal 23 or 25 from the pre - driver 27 or 29 of the output cell is used to control a multiplexor ( 31 and 33 ), which switches between reference levels input to each multiplexor based on the reference control signal ( 23 or 25 ). the reference control signals are each 0 or 1 and are equal to the value of the signal from their respective core , i . e . core a or core b . to implement refa and refb , the circuit portions indicated by reference numbers 35 and 37 are utilized where , z 1 and z 2 are chosen so that : ## equ1 ## where z u is the upper resistor of the pair and z l is the lower resistor of the pair . it should be noted that the use of two separate differential amplifiers per incoming pin , with one of the reference levels going to each , then multiplexing their outputs is not feasible due to problems in matching the two differential amplifiers and timing the multiplexor select . the references 39 and 41 are generated on chip as follows . two reference signals 39 and 41 ( per data port consisting of several data signals ) are generated on the chip and are connected between the two communicating ports . the logic state of the outgoing data dynamically selects which reference is used by the input amplifier . if the outgoing data is a logic low , then the ( 1 / 4 ) vcc reference is selected , if the data is a logic high , then the ( 3 / 4 ) vcc reference is used . conceptually this technique subtracts outgoing data from the incoming data digitally , rather than in analog mode , reducing sensitivity to noise . generating reference signals on the chip reduces common mode noise , and allows the reference levels to track any variations in driver impedance . in order to track most of the common mode noise between the two ports , the output impedance of the reference generator is closely matched to that of the driver . in fact , the reference is constructed using the driver , with both p and n transistors conducting to closely match the line impedance as described below with reference to fig5 . when switching the reference and local driver , it is important to match the paths from the pad and the predriver to the differential amplifier . any mismatch between these paths adds to the jitter of the input signal relative to clock , and could cause glitches at the output of the differential amplifier . the references 39 and 41 are connected bidirectionally in order to couple as much common mode noise as possible to the inputs of the differential amplifiers diffa and diffb , and to allow any variation in line voltage due to process variation to be tracked by the reference 39 and 41 ( refa and refb ). in order for this scheme to be effective , the impedance of the references 39 and 41 must be as close to that of the i / o buffers of the core as possible . the references 39 and 41 are built using an output driver with both the pmos and nmos devices on . the impedance of each of these devices is set such that the thevenin equivalent circuit is a resistance of z o to a power supply equal to the desired reference voltage . although fig3 shows two references and a single data wire 21 , it should be noted that only two references are needed ( one for output logic low and one for output logic high ) notwithstanding that there are multiple data wires , typically 16 , connecting the two component cores . in this connection , it should be noted that only two references are needed regardless of the number of data wires . however , for electrical performance reasons , more than two references may be employed for wider ( 32 bit or 64 bit ) data paths . multiplexors 31 and 33 are each built as a pass gate structure . the parasitic diodes ( not shown ) associated with the multiplexor transistors ( not shown ) are also used for electrostatic discharge ( esd ) protection . multiplexors 32 and 34 are also inserted into the data path from n1 and n2 to the differential amplifiers diffa and diffb to ensure that the data and reference paths are matched as closely as possible . fig4 shows an alternate embodiment of a circuit implementing drva to subtract the outgoing wave from the line voltage using a differential amplifier . the circuit for drvb would be identical . as shown in fig4 the subtraction may be implemented using differential amplifier 43 as is well known in the art . for unidirectional links , the impedance of the driver should be matched to the line carrying the signal to the other component so that reflections from discontinuities , and crosstalk from adjacent lines are correctly terminated . since these terms are expected to be small , relatively large deviations from absolute matching can be tolerated . in the bidirectional scheme , the driver drva and drvb must still perform these functions , but the driver is also used as the line termination . matching driver impedance to the line 11 is much more critical in this case . the driver used is of the binary weighted , multi - leg variety as described below with reference to fig5 . the driver must be larger than in the unidirectional scheme since the impedance of the line must be matched at 1 / 2v cc rather than 1 / 4v cc and the impedance of an mos driver is non - linear . this style of driver allows the impedance to be varied to match that of the line . impedance adjustment may be performed using a scan mechanism as is well known in the art . fig5 is a circuit diagram of a driver with termination which may be utilized in the present invention . the nand gate , nor gate and transistor gate arrays function as the termination set to an impedance of z 0 . the precise termination value is determined by the settings of en0 , en1 , en2 , en3 and their inverses which are set when the board on which the chip utilizing the driver is being built so that the p and n transistors are conducting so as to closely match the line impedance . one way this can be accomplished is to use a chip scan chain using external scan data and control signals to set en0 , en1 , en2 , en3 and their inverses to enable the correct number of legs of the transistors within box 61 as is well known in the art . this operation is performed one time and accounts for process variations but not voltage and temperature variations which may exist when the part is being used . also , if scan is not needed for other purposes , the external pins needed for the scan data and control signals are wasted since they are used for only this one function . an alternate approach is to use an external resistor which is input to a state machine which provides the en0 , en1 , en2 , en3 signals and their inverses this approach uses just one external pin and a well behaved resistor which allows for temperature and voltage variations to be compensated for . the specifics for implementing a suitable state machine and resistor should be readily apparent to persons skilled in the art . a major consideration for the input differential amplifiers ( diffa and diffb ) is the common mode range . while the amount of signal swing for both bidirectional and unidirectional links is equivalent , the common mode levels are quite different . in the unidirectional case , with no noise , the common mode level is 1 / 2v cc . in the bidirectional case , the common mode level varies between 1 / 8v cc and 7 / 8v cc . once noise is factored in , the differential amplifier must have rail to rail common mode range . it must also be a relatively simple , low power structure , since there will be about 120 inputs on a typical routing component utilizing the technology . the circuit chosen to implement the differential amplifier diffa and diffb is of the self biased , large common mode range variety described in m . bazes , &# 34 ; two novel fully complementary self - biased cmos differential amplifiers &# 34 ;, ieee journal of solid - state circuits , vol . 26 , february 1991 and u . s . pat . no . 4 , 958 , 133 which issued sep . 18 , 1990 entitled &# 34 ; cmos complementary self - biased differential amplifier with rail - to - rail common mode input voltage range .&# 34 ; this circuit is symmetric , requires no separate bias generator , and the negative feedback built into the self biasing scheme helps make the amplifier insensitive to process , temperature , and v cc variations . the circuit is shown in fig6 . a bidirectional signaling scheme has been described which allows simultaneous transmission of data in two directions on the same wire . the scheme is self terminating , so that no explicit terminations are required to properly terminate a transmission line . this scheme implements a ternary encoding with signal swings and signal to noise ratios equal to those which could be achieved on a double terminated unidirectional link . since no external termination resistors are required , and no power is dissipated when the drivers on both ends of the wire are in the same state , the system i / o power requirement is 1 / 2 that of a thevenin terminated , unidirectional link . use of this scheme with no modification of the component clock frequency would reduce the required number of i / o pins to half the number required for unidirectional links . the scheme is generally applicable to any chip - to - chip link that can be implemented in a point - to - point fashion . although the description references two component cores communicating with each other , persons skilled in the art will recognize that the inventive principles has application to systems with more than two component cores where each core is one element of an n by m matrix , with core communicating to an adjacent core over a single wire for each signal such that each core can have up to an arbitrary number of adjacent cores . of course , an entire system of multiple components communicating with each other as described herein can be a subsystem of larger computer system as shown in fig7 which includes in addition to communications network 71 of the type described herein , a data entry device such as a keyboard 73 , internal memory such as ram 75 , cpu 76 , external memory such as disk 77 and display device such as monitor 79 , all interconnected by bus 81 . the details for implementing a system of the type shown in fig7 are well known to persons skilled in the art . | 7 |
referring now specifically to the drawings , in which identical or similar parts are designated by the same reference numerals throughout , and first referring to fig1 a convertible automobile seat in accordance with the present invention is generally designated by the reference numeral 10 . the seat 10 provides for the seating of two adults , each of the adult seats being shown to be convertible into an infant seat . it will be clear , however , from the discussion that follows , that the seat 10 can be provided with only one child seat and , therefore , accommodate only one child on one or the other side of the seat 10 . since each of the two seats of the seat 10 are identically constructed , only one will be described in detail , it being understood that the other seat has like construction . the convertible automobile seat 10 in fig1 shows one of the infant seats extended to receive a child , while the other infant seat is in the retracted position to accommodate an adult , as will be more fully described below . each convertible automobile seat in accordance with the present invention includes a back rest section 12 which includes a fixed portion 13 which generally consists of fixed side or lateral portions , and a central movable portion 14 . a conventional seat section 16 is provided which may be fixed relative to the automobile , although the back rest section 12 and the seat section 16 may be adjustably moved relative to each other to accommodate the comfort of a passenger in accordance with well known techniques . the present invention does not relate to the means used to adjust the general positions or orientations of the back rest section 12 and / or the seat section 16 . similarly , while the fixed portion 13 is shown as a smooth surface while the movable and seat portions 14 , 16 are shown tufted , the specific materials or upholstering methods used for the adult seat sections is not critical for purposes of the present invention . an important feature of the present invention is the provision of a head rest 18 which is pivotally mounted for movements between an upper position generally above the back rest section 12 when the seat is to be used by an adult as shown at the right - hand or far view of fig1 and in a lower position generally in front of the back rest section 12 when the seat is to be used by a child as shown at the left - hand or near view of fig1 . when in the upper position , the surface of the head rest 18 facing the seat section 16 is advantageously suitably padded so as to provide a soft surface for the head of the adult . the entire head rest 18 is advantageously padded so as to provide soft surfaces for the child when used in the lower position as a restraint . however , the specific design or material used for the head rest 18 is not critical , except as hereinbelow noted . the head rest 18 is connected at each end or side thereof to two levers or arms 20 which extend between the head rest 18 and pivot pins 22 for pivotally mounting the head rest 18 between the aforementioned positions as shown in fig1 . the arms 20 have substantially equal lengths selected to clear the back rest section 12 when the seat 10 is used by an adult and to engage a child seat 24 , to be described , and restrain a child received in the child seat when the seat is used by a child . the child seat 24 , in the embodiment being described , is of unitary construction and includes side restraining walls 26 which are pivotally mounted on pivot pins 28 . the restraining walls 26 include an upper wall portion 30 , at the rear of the restraining wall 26 , and a lower wall portion 32 at the front of the restraining wall 26 in the extended position of the child seat 24 . in the child seat 24 , being of unitary construction , the back rest 33 and lower seat section 34 are rigidly connected to each other and move together as a single unit between the extended and retracted positions . referring to fig2 and 4 , there is provided a space or storage compartment c behind the back rest section 12 , in the retracted position of the child seat 24 , which receives same as shown in fig4 when the seat 10 is used by an adult . the compartment c may be a space within the seat 10 or may , when the seat 10 is a rear passenger seat , extend into the trunk space . referring to fig5 a head rest lock 35 is provided which includes a loop or retainer 36 which defines an opening for receiving a latch or pin 38 mounted on the head rest 18 for movement between a locking position wherein the head rest is locked in the lower position as shown in fig2 and an unlocked position which permits the head rest to be moved to the upper position shown in fig4 . according to one possible arrangement , the latch 38 consists of a pin mounted for slideable movement into and out of the loop or retainer 36 . advantageously , biasing means in the nature of a spring 40 is provided to resiliently urge the latch or pin 38 to the locking position of the lock 34 . a release member 42 ( as shown in fig1 ) is provided which is attached to the pin 38 which permits the application of an external force to the pin to move same to the unlocked position against the action of the spring 40 . the spring 40 may be in the nature of a compression or a tension spring , depending on which side of the pin 38 or release member 42 it is situated . once the head rest 18 is locked to the lower wall portions 32 , the head rest provides the desired restraint on the child and advantageously cannot be inadvertently unlocked by the child . since the child seat 24 is pivotally mounted , it is important to fix its positions in either the extended or retracted positions thereof . although this can be accomplished in a number of different ways , including a design which maintains the desired positions due to forces of gravity and / or friction , the approach shown in the drawings includes the use of a seat belt 46 which is attached to the forward end of the child seat 24 provided with a male buckle 48 . attached to the top of the seats 10 is a belt 50 provided with a female buckle 52 adapted to receive the male buckle 48 in the retracted position of the seat 24 , as shown in fig4 . when the child seat 24 is in the extended or open position , it may be retained in that position by engaging the male buckle 48 to a female buckle 56 attached to a belt 54 connected to the seat section 16 . connection of the buckle 48 , therefore , to the buckle 52 will maintain the child seat 24 in the closed or retracted position , while connection with the buckle 56 will maintain the child seat 24 in the open or extended position . within the child seat 24 , there is advantageously provided a conventional seat belt restraint 58 of the type commonly used in infant seats , although the nature or construction of the restraint 58 is not critical and any such restraint may be used . another embodiment 10 &# 39 ; of the invention is illustrated in fig6 . here , while the central movable portion 14 &# 39 ; forms part of a child seat 24 &# 39 ;, only the lower seat section 34 is pivotally mounted together with modified side restraining walls 26 &# 39 ;. the child seat 24 &# 39 ; is not of unitary construction as the previously described seat 10 , and the back rest 33 &# 39 ; remains fixed in all positions of the seat 10 &# 39 ;. the lowering of the seat section 34 converts the seat 10 &# 39 ; to a children &# 39 ; s seat and exposes the back rest 33 &# 39 ;. there is no need , therefore , to provide a separate storage compartment similar to the compartment c shown in fig2 and 4 . while the invention is described with reference to specific embodiments thereof and with respect to the incorporation therein of certain combinations of features , it is to be understood that the invention may be embodied in other forms , many of which do not incorporate all of the features present in this specific embodiment of this invention which has been described . for this reason , the invention is to be taken and limited only as defined by the claims that follow . | 1 |
reference now will be made in detail to presently preferred embodiments of the invention , one or more examples of which are illustrated in the accompanying drawings . each example is provided by way of explanation of the invention , not limitation of the invention . in fact , it will be apparent to those skilled in the art that various modifications , combination , additions , deletions and variations can be made in the present invention without departing from the scope or spirit of the invention . for instance , features illustrated or described as part of one embodiment can be used in another embodiment to yield a still further embodiment . it is intended that the present invention covers such modifications , combinations , additions , deletions and variations as come within the scope of the appended claims and their equivalents . the injection delivery devices and systems according to the present invention are useful to deliver substantially simultaneously multiple fluid doses to a recipient such as small birds . the devices and systems of the present invention are particularly useful for delivering fluids that cannot be stably stored or mixed together . the injection delivery systems of the present invention also allow the co - delivery of vaccines such as herpes virus of turkey ( hvt ) vaccine with compositions such as antibiotics that may otherwise reduce the therapeutic efficacy of a live virus vaccine . referring now to fig1 the present invention provides an injection needle support 10 adapted to receive at least two injection needles 14 , 15 . the injection needle support 10 comprises a base 38 having a base plate 30 and an end plate 11 disposed thereon . the base 38 may be any geometric shape , such as square , rectangular , circular or the like , that will rigidly hold the base plate 30 and the end plate 11 in a fixed spatial relationship . the base 38 may be a solid plate or a frame defining a hole as shown , for example , in fig1 . in preferred embodiments , the base 38 is triangular or trapezoidal , with the end of the base 38 having the end plate 11 thereon being narrower than the end having the base plate 30 , as shown in fig1 . the end plate 11 has at least two substantially parallel bores 21 , 22 , each bore capable of receiving a shank 23 , 24 of one of the injection needles 14 , 15 . suitable injection needles 14 , 15 for use in the system of the present invention each generally will comprise a hub or distal end 17 , 18 and an injection or proximal end 25 , 26 disposed at the opposite end of the shank 23 , 24 . preferably , the injection end 25 , 26 of each needle is sharpened to ease penetration of the skin of a recipient bird , and further is typically beveled . the injection needle support 10 of the present invention further comprises recesses 27 , 28 in the base plate 30 . the recesses 27 , 28 are configured to receive the hubs 17 , 18 of the injection needles 14 , 15 and which may be held in position in the recesses 27 , 28 by a releasable or backing plate clamp 12 . the claim generally will be secured with a set screw or similar fastener 13 to prevent the needle hubs 17 , 18 from disengaging from the recesses 27 , 28 . fluid connections 19 , 20 provided , and generally are mounted in communication with the recesses 27 , 28 and are also able to engage with the hubs 17 , 18 held in the recesses 27 , 28 , thereby allowing fluids to pass into the injection needles 14 , 15 from a fluid supply source ( not shown ). the injection needles 14 , 15 may be attached to the injection needle support 10 by passing the injection end 25 , 26 of a injection needle 14 , 15 through a bore 21 , 22 and placing a hub 17 , 18 in a recess 27 , 28 of the base plate 30 . the clamp 12 is then positioned on the base plate 30 and secured over the needle hubs to prevent the hubs 17 , 18 from being displaced from the recesses 27 , 28 and the injection needle support 10 . in one embodiment of the present invention , the clamp 12 is a detachable plate . in another embodiment , the clamp 12 can be connected to the injection needle support 10 along a hinge mechanism that allows the clamp to the be displaced , but not removed from , the injection needle support 10 . exemplary fasteners for securing the clamp 12 in a closed configuration and which can be easily released to allow the injection needles 14 , 15 to be easily replaced when blunted , blocked or otherwise becomes unsuitable for injecting birds include , but are not limited to , a screw means or opposed polarity magnets , and the like . the injection needles 14 , 15 can be replaced by releasing fasteners 13 of the clamp 12 , lifting the hub 17 , 18 from the recess 27 , 28 , disconnecting the needles 14 , 15 from fluid connectors 19 , 20 , and extracting the respective needle 14 , 15 from the end plate 11 of the needle support . substitute injection needles 14 , 15 may then be introduced to the injection needle support 10 by reversing this order of operation . in one embodiment of the present invention , the distance separating the recesses 27 , 28 from one another exceeds the distance between the bores 21 , 22 . in such an embodiment , the injection ends 25 , 26 of injection needles 14 , 15 , once placed into position in the injection needle holder 10 , generally will remain substantially parallel while the shanks 23 , 24 between the hubs 17 , 18 and the end plate 11 are curved . however , the shanks 23 , 24 preferably are not bent , so as to thus maintain unimpeded fluid flows through the cannula of the needles 14 , 15 . alternatively , the distance separating the recesses 27 , 28 can be about , or substantially the same as the distance between the bores 21 , 22 of the plate 11 so that the needle shanks 23 , 24 are substantially parallel . in the various embodiments of the injection delivery systems of the present invention , the injection ends 25 , 26 of the injection needles 14 , 15 , when inserted into the injection needle support 10 , will project beyond the end plate 11 . the extent to which the injection ends 25 , 26 project beyond the end plate 11 may be selected manually or automatically according to the type or size of the recipient birds . the selected length of the injection ends 25 , 26 of the needles and the degree of the extension movement of the carrier 4 imparted by the actuator 6 also determines whether the injection of fluid ( s ) into the recipient bird is subcutaneous or intramuscularly by affecting the depth of penetration of the needles . injection needles 14 , 15 suitable for use in the present invention may be from 2 - 20 gauge . preferably , the injection ends 25 , 26 are sharpened and beveled . for example , beveled injection ends 25 , 26 orientated in substantially opposite directions are shown in fig1 . this substantially opposed orientation of beveled injection ends 25 , 26 can direct injected fluids in divergent directions to reduce potential co - mingling of incompatible fluids within the tissues of the recipient bird . as illustrated in fig2 a and 3 , the present invention provides an injection needle support 10 connected to a carrier 4 slidably disposed in a guide 5 . the carrier 4 is operably connected to an actuator 6 configured to reciprocally move the carrier 4 and injection needle support 10 from a retracted position to an extended injection position . suitable actuators 6 include , but are not limited to , a solenoid , electric motor or driver , or a hydraulic actuator , the selected actuator 6 further comprising a power source . the actuator 6 is also operably connected to a switch 35 that may include , but is not limited to , a manually activated switch , or an automatic switch such as a pressure switch or sensor , or a photoelectric switch . it is contemplated that the switch will be reversible so that in a first position the carrier 4 and injection needle support 10 are extended by the actuator 6 , and in a second position the carrier 4 and the injection needle support 10 may be retracted away from the injected recipient bird . it is further contemplated that the carrier 4 and the injection needle support 10 may be automatically retracted , for example , by a spring - biased device , for example , once the actuator 6 is deactivated . the injection delivery system of the present invention further comprises one or more dose distributors 31 , 32 communicating with the fluid connectors 19 , 20 for the needles 14 , 15 . suitable fluid distributors 31 , 32 for use in the present invention include , but are not limited to , pumps or syringes , such as a multi - dose syringe and the like that are capable of receiving a fluid dose from fluid containers or supplies 33 , 34 and delivering the fluid dose to an injection needle 14 , 15 . each fluid container 33 , 34 is preferably connected to a dose distributor 31 , 32 by a two - way valve 36 , 37 that allows a fluid dose to be withdrawn from the fluid container 33 , 34 and delivered to the injection needle 14 , 15 without back - flow to the fluid container 33 , 34 . in one embodiment of the injection delivery system of the present invention , each dose distributor 31 , 32 is attached to the carrier 4 or to injection needle support 10 such that the dose distributor 31 , 32 will move with the carrier 4 and injection needle support 10 . in another embodiment , dose distributors 31 , 32 may be separate from the carrier 4 and the injection needle support 10 and connected to the fluid connectors 19 , 20 by flexible fluid ducts or lines 8 , 9 . in these embodiments of the present invention , the fluid container 33 , 34 also may be optionally attached to the carrier 4 or injection needles support 10 , or attached to a fixed structure such as a housing ( fig3 ). the fluid container 33 , 34 likewise can communicate with the dose distributor 31 , 32 by a flexible or rigid fluid duct 8 , 9 . the injection delivery system further generally includes a control means and power source to activate the dose distributors 31 , 32 to deliver at least two fluid doses to a bird maintained against the retaining plate 2 , and cause movement of the needle support to its operative injection position . the needle injection device of the present invention further generally includes a retaining plate 2 having an aperture 3 therein . the retaining plate 2 and the aperture 3 are positioned so that when the carrier 4 and the injection needle support 10 are in an extended position , the injection ends 25 , 26 project through and beyond the aperture 3 to a selected distance that allows injection of a fluid dose into a recipient bird . the chick or other small bird can be slightly pressed against the retaining plate 2 by the operator or otherwise restrained in a desired position for injection . the retention means also may be sloped with regard to the travel axis of the needles . in operation of the injection delivery systems of the present invention , a chick or other small bird is maintained against the retaining plate 2 with the area of the bird to receive the fluid dose ( s ) positioned over the aperture 3 in the retaining plate 2 . generally , the neck of the bird is the targeted area , but any other areas of the bird , including the breast , thigh , wing and the like may be selected to receive the delivered fluid dose . an optional restraint may be used to prevent escape of the bird . pressure of the bird against the retaining plate 2 can engage and actuate a switch to activate the actuator 6 to move the carrier 4 and the injection needle support 10 attached thereto , to a predetermined extended operative injection position . the injection ends 25 , 26 of the needles 14 , 15 project through the retaining plate 2 and the aperture 3 therein , to penetrate the skin overlying the selected injection point of the bird . when the carrier 10 and the needles 14 , 15 thereon are in the extended position with the injection 25 , 26 ends , in the bird , the dose distributors 31 , 32 are actuated by a switch means activated automatically , as described in u . s . patent ser . no . 5 , 312 , 353 incorporated herein by reference in its entirety , or by a system operator to deliver the fluid doses through their respective needles 14 , 15 . the volumes for the delivered doses are selected depending on the treatment protocol administered to the birds . a suitable adjustment means , for example , as taught in u . s . pat . no . 5 , 312 , 353 can administer doses from 0 . 05 to 4 ml per dose . the volumes can be identical or different between needles . it is contemplated to be within the scope of the present invention for the fluid doses delivered to a recipient bird to be the same therapeutic fluids or different . the delivery systems of the present invention can deliver the same fluid to two different positions in the bird or two different fluids that may be incompatible or unstable when mixed . | 0 |
the entire disclosure of u . s . patent application ser . no . 09 / 912 , 024 filed on jul . 24 , 2001 is expressly incorporated by reference herein referring to fig1 a perspective view of an exemplary embodiment of the present invention is shown . the system is included in wire bonding machine 100 , and employs a cornercube 106 , having a plurality of internal reflection surfaces ( best shown in fig6 ), located at or below image plane 112 of bonding tool 104 . in an exemplary embodiment , cornercube offset alignment tool 109 ( comprising cornercube 106 and lens elements 108 , 110 ), has a total of three internal reflection surfaces , 218 , 220 , and 221 ( best shown in fig6 and described below ). in another exemplary embodiment , cornercube 106 may have a plurality of total internal reflective surfaces . in one exemplary embodiment , cornercube 106 is formed from fused silica , sapphire , diamond , calcium fluoride or other optical glass . note , optical quality glass , such as bk7 made by schott glass technologies of duryea , pa ., may also be used . note also that materials for cornercube 106 can be selected for maximum transmission with respect to the desired operating wavelength . optical imaging unit 102 , such as a ccd imager , cmos imager or a camera , for example , is mounted above image plane 112 in order to receive an indirect image of bonding tool 104 through cornercube offset alignment tool 109 . in another exemplary embodiment , a position sensitive detector ( psd ), such as that manufactured by ionwerks inc ., of houston , tex ., may also be used as optical imaging unit 102 . in such an embodiment , when the hole in bonding tool 104 is illuminated , such as by using an optical fiber for example , the psd can be utilized to record the position of the spot of light exiting bonding tool 104 . it is also contemplated that the psd may be quad cell or bi - cell detector , as desired . in the exemplary embodiment , the focal point of the vision system ( coincident with imaginary plane 211 shown in fig2 a ) is located above bottom surface 223 ( shown in fig2 a ) of cornercube 106 . in addition , the exemplary embodiment includes two preferably identical lens elements 108 , 110 located at or below image plane 112 . another embodiment , shown in fig2 b , includes a single lens element 205 located below image plane 112 and in line with optical axes 114 , 116 . hereinafter , the combination of cornercube offset tool 106 , and lens elements 108 , 110 ( or lens element 205 ) will be referred to as assembly 109 . image plane 112 of cornercube 106 , including lens elements 108 , 110 , is positioned at the object plane of optical imaging unit 102 . in other words , the object plane of cornercube 106 and lens elements 108 , 110 are aligned to bonding tool 104 which also lies in image plane 112 . in the exemplary embodiment , lens elements 108 , 110 ( or 205 ) preferably have a unitary magnification factor . first lens element 108 is positioned in a first optical axis 114 between bonding tool 104 and cornercube 106 . second lens element 110 is substantially in the same plane as that of first lens element 108 and is positioned in a second optical axis 116 between optical imaging unit 102 and cornercube 106 . in one exemplary embodiment , first and second optical axes 114 and 116 are substantially parallel to one another , and are spaced apart from on another based on specific design considerations of bonding machine 100 . in one exemplary embodiment the distance 118 between first optical axis 114 and second optical axis 116 is about 0 . 400 in . ( 10 . 160 mm .) although distance 118 may be as small as about 0 . 100 in . ( 2 . 54 mm ) depending on design considerations related to the bonding machine . fig2 a is a detailed side view of image ray traces and illustrates the general imaging concept of an exemplary embodiment of the present invention . in fig2 a , exemplary ray traces 210 , 214 are separated for clarity to illustrate the relative immunity of the resultant image due to positional changes . the same distance also separates the image points because lens elements 108 , 110 serve as unitary magnification relays . fig2 a also demonstrates how changes in the bonding tool 104 position are compensated for . for example , once conventional methods have been used to accurately measure the distance between imaging unit 102 and bonding tool 104 ( shown in fig1 ), the present invention is able to compensate for changes in the bonding tool 104 offset position 222 due to changes in the system . the location of bonding tool 104 can be accurately measured because cornercube offset tool 106 images bonding tool 104 onto image plane 112 of the optical system . the reference position of bonding tool 104 is shown as a reflected ray which travels from first position 202 along first optical axis 114 ( shown in fig1 ), as direct image ray bundle 210 from first position 202 through first lens element 108 . direct image ray bundle 210 continues along first optical axis 114 where it then passes through top surface 226 of cornercube 106 onto first internal reflection surface 218 . direct image ray bundle 210 is then reflected onto second internal reflection surface 220 , which in turn directs it onto third internal reflective surface 221 ( best shown in fig3 ). next , direct image ray bundle 210 travels back through top surface 226 of cornercube 106 as reflected image ray bundle 212 along the second optical axis 116 ( shown in fig1 ) and through second lens element 110 to image plane 112 . it is reflected image ray bundle 212 that is detected by imaging unit 102 as image 204 . consider now that the position of bonding tool 104 is displaced by a distance 222 due to a variation in system temperature , for example . as shown in fig2 a , the displaced image of bonding tool 104 is shown as position 206 and imaged along the path of second position ray trace 214 . as shown in fig2 a , direct image ray bundle 214 travels along a path similar to that of direct image ray bundle 210 from first position 202 . second position 206 image travels as a direct image ray bundle 214 , through first lens element 108 . direct image ray bundle 214 then passes through top surface 226 of cornercube 106 onto first internal reflection surface 218 . direct image ray bundle 214 is then reflected onto second internal reflection surface 220 , which in turn directs it onto third internal reflection surface 221 ( best shown in fig3 ). next , direct image ray bundle 214 travels through top surface 226 of cornercube 106 as reflected image ray bundle 216 and through second lens element 110 to image plane 112 . reflected image ray bundle 216 is viewed as a reflected image by imaging unit 102 as being in second position 208 . although the above example was described based on positional changes along the x axis , it is equally applicable to changes along the y axis . as illustrated , the original displacement of bonding tool 104 , shown as offset position 222 , is evidenced by the difference 224 in the measured location of bonding tool 104 at second position 208 with respect to reference location 204 . as evidenced by the above illustration , a positional shift in assembly 109 does not affect the reflected image as viewed by imaging unit 102 . in other words , assembly 109 of the present invention may be translated along one or both the x and y axes such that the image of the bonding tool 104 appears relatively stationary to imaging unit 102 . there will be some minimal degree of error , however , in the measured position of bonding tool 104 due to distortion in the lens system ( discussed in detail below ). referring again to fig2 a , vertex 228 ( shown in phantom ) of cornercube offset alignment tool 109 is located at a position approximately midway between first optical axis 114 and second optical axis 116 . to facilitate mounting of cornercube 106 , a lower portion 235 of the cornercube may be removed providing bottom surface 223 , which may be substantially parallel to top surface 226 . removal of lower portion 235 does not affect the reflection of image rays since the image rays emanating from image plane 112 do not impinge upon bottom surface 223 . exemplary cornercube 106 comprises top surface 226 , first reflective surface 218 , bottom surface 223 , second reflective surface 220 , and third reflective surface 221 . if top surface 226 is set such that optical axes 114 , 116 are normal to top surface 226 , first reflective surface 218 will have a first angle 230 of about 45 ° relative to top surface 226 , and a second angle 234 of about 135 ° relative to bottom surface 223 . likewise , ridgeline 225 ( formed by the intersection of second and third reflective surfaces 220 and 221 ) has similar angles 232 and 236 relative to top surface 226 and bottom surface 223 , respectively . in addition , second and third reflective surfaces 220 and 221 are orthogonal to one another along ridgeline 225 . in the exemplary embodiment , bottom surface 223 of cornercube 106 may be used as a mounting surface if desired . it should be noted , however , that it is not necessary to form top surface 226 so that the image and reflected rays are normal thereto . as such , the corner cube will redirect the incident light or transmit image of bonding tool 104 parallel to itself with an offset equal to 118 . the present invention can be used with light in the visible , uv and ir spectrum , and preferably with light having a wavelength that exhibits total internal reflection based on the material from which cornercube 106 is fabricated . the material selected to fabricate cornercube offset alignment tool 109 is based on the desired wavelength of light which the tool will pass . it is contemplated that cornercube offset alignment tool 109 may be fabricated to handle a predetermined range of light wavelengths between the uv ( 1 nm ) to the near ir ( 3000 nm ). in a preferred embodiment , the range of wavelength of light may be selected from between about i ) 1 and 400 nm , ii ) 630 and 690 nm , and iii ) 750 and 3000 nm . illumination may also be provided by ambient light or by the use of an artificial light source ( not shown ). in one exemplary embodiment , typical optical glass , having an index of refraction of 1 . 5 to 1 . 7 , may be used to fabricate cornercube 106 . note , the index of refraction is based upon the material chosen for maximum transmission at the desired operating wavelength . in one embodiment , cornercube offset alignment tool 109 has an index of refraction of about 1 . 517 . fig3 is a perspective view of image ray traces according to an exemplary embodiment of the present invention translated in a direction perpendicular to the separation of lens elements 108 , 110 . the same image properties shown in fig2 a are also evident in fig3 . for example , the reference position of bonding tool 104 is represented by first position 302 and its image 304 is viewed as a first direct image ray 310 which travels along first optical axis 114 through first lens element 108 ; passes through top surface 226 of cornercube 106 ; strikes first reflective surface 218 of cornercube 106 ; travels through cornercube 106 in a path parallel to top surface 226 ; strikes second reflective surface 220 ; strikes third reflective surface 221 before exiting the cornercube 106 through top surface 226 and travels along second optical axis 116 through second lens element 110 onto image plane 112 and viewed by imaging unit 102 at position 304 . positional displacement of bonding tool 104 is also shown in fig3 and is illustrated by the path of the ray traces 314 , 316 from second position 306 to second viewed position 308 . fig4 a - 4b are perspective and side views , respectively , of an exemplary embodiment of the present invention illustrating lens elements 108 , 110 and cornercube 106 . the two lens elements 108 , 110 ( or 205 ) are preferably doublets located above the cornercube 106 based on their focal distance from image plane 112 and imaginary plane 211 . doublets are preferred based on their superior optical qualities . as illustrated in fig4 a - 4b , an exemplary embodiment of cornercube 106 has three internal reflective surfaces , 218 , 220 and 221 . as shown in fig4 b , the exterior edges of lens elements 108 , 110 and cornercube 106 are coincident with one another . fig5 illustrates the telecentricity of an exemplary embodiment of the image system of the present invention . as shown in fig5 lens elements 108 , 110 produce a unitary magnification and are arranged relative to cornercube 106 such that the telecentricity of the machine vision system is maintained . note that front focal length 502 from lens element 108 to vertex 228 of cornercube 106 is equal to front focal 502 from lens element 110 to vertex 228 of cornercube 106 . note also , that back focal length 504 from lens element 108 to image plane 112 is equal to back focal length 504 from lens element 110 to image plane 112 . fig6 is a detailed view of an exemplary cornercube 106 of the present invention . note that internal reflection surface , 218 and ridgeline 225 allow an image of bonding tool 104 to be translated in the x and y directions . note also , that the surfaces of cornercube 106 are preferably ground so that a reflected beam is parallel to the incident beam to within 5 arc seconds . as shown in fig6 surfaces 220 and 221 are orthogonal to one another along ridgeline 225 . in addition , the angle between ridgeline 225 and surface 218 is about 90 °. furthermore , surface 218 and ridgeline form an angle of 45 ° relative to top surface 226 and bottom surface 223 . note also , that surfaces , 218 , 220 , and 221 meet to form triangular shaped bottom surface 223 , which may be used to facilitate mounting of cornercube 106 . fig7 a - 7c illustrate the effect of tilt about the orthogonal of cornercube offset alignment tool 109 in an exemplary vision system . fig7 a is an overhead view of lens elements 108 , 110 and cornercube 106 . exemplary image origins , 702 , 704 , 706 , and 708 correspond to the position of image ray traces 210 , 214 ( shown in fig2 a ). note that optic axis position 710 corresponds to the position where the image of bonding tool 104 ( shown in fig1 ) would be if cornercube 106 was not tilted along the z axis . fig7 b - 7c are graphs of the effect of tilt around the z axis in terms of tilt in arc minutes vs . error in microns . fig7 b shows the effect of tilt around the z axis versus error and image location along the y axis . fig7 c shows the effect of tilt around the z axis versus error and image location along the x axis . fig8 a - 8c illustrate the effect of tilt about the x and y axis of the exemplary vision system . fig8 a is an additional side view of exemplary image ray traces 210 , 212 , 214 , 216 . in fig8 a , arrow 804 and dot 802 are used to depict the x and y axes , respectively . fig8 b - 8c are graphs of the effect of tilt around the x and y axes in terms of tilt in arc minutes vs . error in microns . fig8 b shows the effect of tilt around the x axis versus error and image location along the y axis . fig8 c shows the effect of tilt around the y axis versus error and image location along the x axis . fig9 is a detailed side view of image ray traces according to a third exemplary embodiment of the present invention . in fig9 the reference position of bonding tool 104 is shown as a reflected ray which travels from first position 914 ( on image plane 112 ) along first optical axis 114 ( shown in fig1 ), as direct image ray bundle 922 from first position 914 through lens element 902 . note that in this exemplary embodiment , lens element 902 has a relatively planar , upper surface 904 and a convex lower surface 906 . direct image ray bundle 922 continues along first optical axis 114 where it then passes through upper surface 904 of lens element 902 , and in turn through convex surface 906 . direct image ray bundle 922 is then reflected onto total reflective surface 908 . in a preferred embodiment , total reflective surface 908 is a mirror . next , direct image ray bundle 922 travels back through lens element 902 as reflected image ray bundle 920 along second optical axis 116 ( shown in fig1 ) and onto image plane 112 . it is reflected image ray bundle 920 that is detected by imaging unit 102 ( shown in fig1 ) as image 912 . similarly , positional displacement of bonding tool 104 is also shown in fig9 and is illustrated by the path of direct image ray bundles 918 , 924 from second position 910 to second viewed position 916 . fig1 a - 10e illustrate a further embodiment of the present invention . in this exemplary embodiment , a cornercube alignment tool is used to improve the accuracy of alignment of fibers , such as optical fibers 1008 and 1009 . as in the previous exemplary embodiment , the use of a corner cube offset tool allows for the use of a single optical detector instead of the conventional multiple detector systems . referring to fig1 a , the exemplary embodiment includes cornercube 1014 , lenses 1016 , 1018 , dark field illumination systems 1020 , 1021 ( which are well known to those practicing the art ) to illuminate the fiber cladding edge 1010 , 1011 of fiber cores 1012 , 1013 , respectively ( which in turn produces reflections 1024 , 1025 to outline cladding edges 1010 , 1011 ), and optical detector 1002 . in this exemplary embodiment , downward facing fiber 1008 is viewed by downward looking optical detector 1002 , such as a camera ( i . e ., a substrate camera ). downward looking optical detector 1002 detects the emission of light 1022 from fiber core 1012 and is then be able to determine the proper offset 1027 between the optical fiber centerline 1023 and central ray 1029 of downward looking optical detector 1002 . as is further shown in fig1 a , downward facing fiber 1008 and optical detector 1002 are offset from one another by predetermined distance 1006 . fig1 b is a plan view of the exemplary embodiment illustrated in fig1 a illustrating the relative positions of lenses 1016 and 1018 , and cornercube 1014 . in fig1 c , downward looking optical detector 1002 and downward facing fiber 1008 are then repositioned such that central ray 1029 of downward looking optical detector 1002 is aligned with fiber centerline 1031 of upward facing fiber 1009 . once again dark field illumination system 1021 is used to illuminate upward facing fiber 1009 for recognition by the vision system to ensure proper alignment with optical detector 1002 . next , and as shown in fig1 d , optical detector 1002 and downward facing fiber 1008 are again repositioned based on the offset 1027 determined during the process discussed above with respect to fig1 a . as a result downward facing fiber 1008 and upward facing fiber 1009 are aligned with one another . as shown in fig1 e , optical fibers 1008 and 1009 are then joined using conventional techniques , such as fusing the fibers together using radiation ( not shown ), or mechanical means , for example . fig1 illustrates yet a further embodiment of the present invention . in this exemplary embodiment , a cornercube alignment tool is used to align individual fibers ( sub - fibers ) 1202 a of a fiber optic splitter 1200 with respective individual optical fibers 1008 , etc . as in the previous exemplary embodiment , the use of a corner cube offset tool allows for the use of a single optical detector instead of the conventional multiple detector systems . as the steps leading up to alignment and coupling of optical fiber 1008 and sub - fiber 1202 are similar to the above exemplary embodiment , they are not repeated here . once the first sub - fiber is aligned with single fiber 1008 , the process is repeated for a further sub - fiber , such as 1202 b , and another single fiber ( not shown ). of course the exemplary embodiment is not limited to the fiber optic bundle of a fiber optic splitter being below optical detector 1002 . the embodiment also contemplates that the relative positions of fiber optic bundle 1200 and optical fiber 1008 are reversed , such that fiber optic bundle 1200 is positioned above cornercube 1014 . fig1 a - 13d illustrate a further embodiment of the present invention . in this exemplary embodiment , a cornercube alignment tool is used to improve the accuracy of alignment of an optical fiber 1008 with a circuit element , such as a detector 1302 . in fig1 a , exemplary detector 1302 is part of an array 1300 , although the invention is not so limited . it is also contemplated that circuit element 1302 may be a diode , such as a photodiode or an emitter of optical radiation . as in the previous exemplary embodiments , the use of a corner cube offset tool allows for the use of a single optical detector instead of the conventional multiple detector systems . referring to fig1 a , the exemplary embodiment includes cornercube 1014 , lenses 1016 , 1018 , dark field illumination system 1020 ( which is well known to those practicing the art ) to illuminate the fiber cladding edge 1010 of fiber core 1012 ( which in turn produces reflections 1024 to outline cladding edge 1010 ), and optical detector 1002 . in this exemplary embodiment , downward facing fiber 1008 is viewed by downward looking optical detector 1002 , such as a camera ( i . e ., a substrate camera ). downward looking optical detector 1002 detects the emission of light 1022 from fiber core 1012 and is then be able to determine the proper offset 1027 between the optical fiber centerline 1023 and central ray 1029 of downward looking optical detector 1002 . as is further shown in fig1 a , downward facing fiber 1008 and optical detector 1002 are offset from one another by predetermined distance 1006 . in fig1 b , downward looking optical detector 1002 and downward facing fiber 1008 are then repositioned such that central ray 1029 of downward looking optical detector 1002 is aligned with optical centerline 1304 of detector 1302 . it is understood that optical centerline 1304 , may not necessarily coincide with the physical center of detector 1302 , but rather is dependant on the layout of the particular detector 1302 . in this case the determination of optical centerline 1304 may be accomplished by the location of the center of the active sensing area of the detector . next , and as shown in fig1 c , optical detector 1002 and downward facing fiber 1008 are again repositioned based on the offset 1027 determined during the process discussed above with respect to fig1 a . as a result downward facing fiber 1008 and detector 1302 are aligned with one another . as shown in fig1 d , optical fiber 1008 and detector 1302 are then kept in aligned position using conventional techniques , such as optical epoxies , uv epoxies , for example . although the invention has been described with reference to exemplary embodiments , it is not limited thereto . rather , the appended claims should be construed to include other variants and embodiments of the invention , which may be made by those skilled in the art without departing from the true spirit and scope of the present invention . | 7 |
the structure and operation of the present invention is dependent upon the partitioning of one of the multiplying factors into a plurality of k bit - wide pieces . thus , instead of representing a binary number a as ∑ i = 0 n - 1 a i 2 i , a i 2 i , one of the multiplying factors in the present invention is represented instead in the form a m − 1 r m − 1 +. . . + a 2 r 2 + a 1 r + a 0 = ∑ j = 0 m - 1 a j r i , a j r i , where r = 2 k . in this representation , the number a is represented in block form where each of the m blocks includes k bits . that is , each a i represents an integer having k bits . in the present system , multiplication modulo an odd number n is a significant object . also , for purposes of understanding the present invention , the symbol n is used to denote the number of bits in the binary representation for n . also , for present purposes , it is assumed that the number a , as stored in register a ( reference numeral 10 in fig1 ), is the number that is partitioned into m blocks . in general , the number of blocks m is selected to be the smallest integer for which mk ≧ n + 2 . additionally , it is understood that n 0 represents the least significant k bits of the number n . likewise , the constant s is equal to the negative reciprocal of n 0 taken modulo r ( that is , − 1 / n 0 mod r ). from a mathematical point of view , the present applicants have employed an algorithm for which the input variables are the two numbers being multiplied , namely , a and b , the modulo number n , the constant s associated with n , and the parameters m , k and r = 2 k . the output of the function provided by the present invention z is given by z = ƒ ( a , b )= ab 2 − mk mod n . the procedure specified by applicants &# 39 ; method initializes the value z 0 to be zero and , for the integer i ranging from 0 to m − 1 , calculations are carried out to produce x i and y i and z i + 1 . the values for x i and y i are computed during a first operational phase of each one of m cycles . the value z i is computed during a second phase of each cycle . the adders and multipliers used to calculate x i are “ time shared ” to also carry out the calculation needed to produce z i . in particular , at each stage i , x i is given by z i + a i b . at this stage , the value of y i is also computed as the constants times the least significant k bits of x i modulo r . if one represents the least significant k bits of x i as x i , 0 then y i = s x i , 0 . this completes the operations that are carried out in a first phase ( x - phase ) during one of the cycles of the present process . in the second phase ( z - phase ), an updated value for z register ( 50 in fig1 ) is computed as ( x i + y i n )/ r . at the last stage of processing , the desired value of z is present in the z register . in particular , at this stage , z m = ab 2 − mk mod n . at each stage ( cycle ), values for x i , y i , and z i are stored for purposes of computation in subsequent steps . it is noted that if both input variables a and b have n + 1 bits , the output of the function provided by the present invention z = ƒ ( a , b )= ab 2 − mk mod n , for n being an n - bit odd number , has no more than n + 1 significant bits . that is , the output is less than 2 n + 1 . the hardware circuit described herein takes as inputs a and b of n + 1 bits each and generates as output z of n + 1 bits . a hardware circuit for carrying out this process is illustrated in fig1 . in particular , the factor a of n + 1 bits , which is the factor which is treated as being in partitioned form , is stored in a register ( 10 ). multiplexor 11 supplies sequential blocks of k bits from register 10 to multiplexor 31 , with k = 32 bits for illustration . multiplexors 31 , 21 , and 52 operate in conjunction with one another selecting one of two possible input values depending upon whether or not the circuit is operating in the x - phase or the z - phase . accordingly , during the first phase of its operation , multiplexor 11 provides the k bits in a 0 . in the first phase of the second cycle , the next k bits a i in a are supplied via multiplexor 11 . a sub - block of k bits from a is provided during the initial or x phase portion of each cycle . in the third cycle , multiplexor 11 , therefore , provides the next k bits in a , namely , the bits denoted above and herein as a 2 . accordingly , multiplexor 11 is seen to operate selectively as a function of the cycle number ( namely , cycles 0 through m − 1 ). during the x - phase of each cycle , the value a i is selected from the a register ( 10 ) via multiplexor 11 and correspondingly multiplexor 21 selects the contents of the b register ( 20 ). thus , in accordance with the present invention , the numbers to be multiplied are stored in registers 10 and 20 . it does not matter which number is stored in which register . it is also noted that , whether or not the circuit is operating in the initial x - phase or in the final z - phase in each cycle , multiplexors 31 and 21 supply k bits and n + 1 bits , respectively , to multiplier array 70 in each phase . it is thus seen that , during the x - phase , multiplexors 31 and 21 select contents from the b register and part of the a register . it is also noted that , in typical situations , the value of n is often around 512 or more and the value of k is approximately 32 . accordingly , it is seen that multiplier array 70 strikes a balance between 1 bit × n bit multiplication and full n bit × n bit multiplication . it is also noted that increases in the value of n are almost always , in practice , an increase by a factor of at least a power of 2 . as with any binary multiplier with inputs that are n + 1 bits wide and k bits wide respectively , multiplier array 70 produces an output which is n + 1 + k bits wide . the lower order k bits from multiplier array 70 are supplied to adder 65 which is designed to add two k bit addends at a time . in this regard , it is noted that adder 65 is present in the circuit for computing y i . as such , and given that the value of y i is dependent upon the last k bits of the value x i which is a sum which has not yet been fully computed , it is necessary to perform this addition which is essentially the addition for the low order k bits of x i . the first addend comes from the rightmost k bits in the z register as selected by multiplexor 52 . these bits are added to the k bits in the rightmost portion of the product a i b . the output of adder 65 is x i , 0 which is the least significant k bits of x i = z i + a i b . this output is stored in register 55 and is also supplied to multiplier 80 which multiplies two k bit numbers together . this is not , however , a multiplication modulo n . the other factor supplied to multiplier 80 is the number s from the s register ( 60 ). since this result is required modulo r , only the rightmost k bits from multiplier 80 are supplied back to the y register ( 30 ) in this x - phase . the value stored in this register is used during the calculation carried out in the z - phase as discussed below . the rest of the x - phase calculation is devoted to calculation of the high order n + 1 bits of the sum z i + a i b . multiplier 70 is configured as a circuit for multiplying together the bits from the b register ( 20 ) and a sequence of m blocks of k bits each from selected k bit blocks a i from the a register . multiplication of two k bit numbers generally produces a number having 2k bits and , in particular , this is the situation with respect to applicants &# 39 ; multiplier 80 . however , it is noted that the calculation of y i is computed modulo r . the modulo requirement of the computation is easily accomplished simply by returning only the rightmost k bits from the output of multiplier 80 to the input of the y register ( 30 ). as pointed out above , multiplication of numbers generally produces outputs having bit lengths greater than either of the two input number bit lengths . in particular , with respect to multiplier 70 , the output is considered to be n + 1 + k bits in length . the low order ( rightmost ) k bit output is supplied from multiplier 70 to adder 65 . however , each k bit block multiplication carried out in multiplier array 70 produces 2k bits formed as a k bit “ result ” and a k bit “ carry ” into the next position . the summation to produce the desired intermediate output a i is carried out in adder 75 which adds together two portions , the first portion which is n + 1 bits long and the second portion which is only n + 1 − k bits long . the n + 1 − k bits represent the “ carry ” portion of the multiplication . accordingly , the output of adder array 75 is the result of the high order n + 1 bits of a i b . this result is supplied directly to adder array 85 which adds to it a shifted value of z i from z register 50 . and appropriately , this high order n + 1 bits of x i = z i + a i b is stored in z register 50 in preparation for the z - phase calculation . the low order k bits of x i are stored in register 55 as described above . in the z - phase of an operation cycle , multiplier array 70 and adders 75 and 85 are again employed except that now the inputs to multiplier array 70 are the contents of they register ( 30 ) as selected by multiplexor 31 . the other factor supplied to multiplier array 70 is the contents of the n register ( 40 ) which is selected during the z - phase of an operation cycle by means of multiplexor 21 . as before , multiplier array 70 computes the product of an n + 1 bit number and a k bit number . adder array 75 performs the natural addition operation associated with multiplication in which there is an effective carry - like operation from one k bit subfield to the next k bit subfield . accordingly , the output of adder array 75 during the z - phase of operation is the high order n + 1 bits of the product y i n . the addition of y i n and the value x i together with its division by r in the present method is accomplished by discarding the low order k bits from the output of adder 65 and storing only the high order n + 1 bits from adder 85 to register 50 . the differences in the x - phases and z - phases of operation are more fully appreciated from an inspection of the differences between fig2 and 3 . in particular , fig2 illustrates the active data flow paths that are present in the first or x phase of each operational cycle . likewise , fig3 illustrates the data flow paths which are active during the second or a z - phase of each operational cycle . the calculations that are carried out in the x - phases and z - phases are repeated a total of m times with the final result z m , being one of the desired results at the end of m cycles of operation with each cycle including an x - phase and a z - phase . at this stage of operation , the value present in z register 50 is ab 2 − mk mod n the circuit illustrated in fig1 - 3 is also capable of producing the multiplicative result ab mod n . this is accomplished by first using the circuit shown to compute ab 2 − mk mod n and then by using the circuit again with either the a or b register being provided with the output from the first operational stage and multiplying this value by 2 2mk mod n . since each operation of the circuit ( through m cycles ) introduces the factor of 2 − mk , the multiplication by 2 2mk cancels the first factor 2 − mk introduced during the first stage of operation of the circuit and also cancels the other factor of 2 − mk introduced during the second multiplicative stage of operation . thus , using two passes ( two stages ) with m cycles each through the circuit of fig1 - 3 , the result ab mod n is computed . for purposes of clarity and ease of understanding and description as used herein , an operational stage of the process of the present invention refers to m cycles of circuit operation following the loading of the factors into the a and b registers . the operation of the above circuit is perhaps more easily understood by means of the following example in which k = 3 , r = 2 3 , n = 107 = r 2 + 5r + 3 =( 1 , 5 , 3 )=( n 2 , n 1 , n 0 ), n 0 = 3 , m = 3 , s =− 1 / n 0 mod r = 5 , a = 83 = r 2 + 2r + 3 =( 1 , 2 , 3 ), b = 70 = r 2 + 0r + 6 =( 1 , 0 , 6 ). decimal digits are employed here merely for the sake of example and for an easier understanding of the process . for a more detailed illustration , the decimal numbers may be represented as blocks containing 3 bits each . the process carried out by the circuit disclosed above occurs in three steps as follows ( i = 0 , i = 1 , and i = 2 ): x 0 = z 0 + a 0 b =( 3 , 2 , 2 ), y 0 = 2s mod r = 2 although it is the objective to compute ab mod n where ab and n are all n bits long , for convenience , the process herein employs a , b , and z registers that are n + 1 bits or mk bits long . this avoids the necessity for checking the final and intermediate results to determine whether or not they are in fact greater than n . this aspect , for example , shows up in step 2 in the example provided above . the present inventors have also recognized that , at least partly due to the typically large difference between the size of n and k , there is a certain disparity in processing that occurs in the construction of an n by k multiplier . accordingly , it is possible to partition the calculation carried out in the circuit shown in fig1 - 3 . in particular , the circuit shown in fig1 is in fact constructable in the form a plurality , d + 1 , of processor elements ( pe ) which are connected together in a chained or cascaded fashion . each of the processing elements is constructed in the same way . however , the processing element for the rightmost portion of the data , herein referred to as pe 0 , has a somewhat more complicated structure , as shown in fig4 . a simpler circuit is employed for processing elements 1 through d . however , in preferred embodiments , the leftmost or last processor element pe d can in fact be constructed much more simply as shown in fig6 . accordingly , fig4 shows a structure for a processing element circuit for the rightmost portion of the data . fig5 illustrates a circuit for a processing element which is usable in a repeated fashion which utilizes as many individual processing elements as necessary and thus , illustrating the scalability aspects of the present invention . lastly , fig6 illustrates a preferred , simplified embodiment for the last or leftmost processing element . for purposes of understanding and appreciating the present invention , the registers r 0 through r d , as illustrated in fig4 , and 6 , are not considered as a part of the processing elements per se but rather are best understood as part of a separate , partitioned register structure . it is these registers that contain the desired results of the modulo n multiplication operation . these registers thus serve the same function as the z register in fig1 . with specific reference to fig4 it is seen that multiplexor 193 operates during the x - phase to supply a 2k bit augend to adder 185 . during the first or x - phase of operation , multiplexor 193 supplies a 2k bit number which has leftmost bits from register r 2 ( reference numeral 192 ) and rightmost bits from register r 1 ( reference numeral 191 ). during the second or z - phase of prosecution , multiplexor 193 supplies a different 2k bits of data to adder 185 . in particular , during the z - phase multiplexor 193 supplies as its leftmost k bits the contents of register r 1 , and as its rightmost k bits the contents of register r 0 ( reference numeral 190 ). in contrast to the full - width registers 10 , 20 , 40 , and 50 in fig1 the corresponding registers in a partitioned system have fewer bits . in particular , the corresponding b and n variable registers in a general processing element pe preferably employs a width equal to 2k bits . however , for the rightmost processing element , a larger number of bits is desired . in particular , in the case in which n equals 512 , registers 120 and 140 in fig4 preferably have a width of 96 bits . multiplexor 121 selects the contents of register b ( reference numeral 120 ) during the x - phase of computation and likewise selects the contents of register n ( reference numeral 140 ) during the z - phase of computation . in general , the overall n - bit wide series of computations is broken down into partitions of any convenient size . it is not even necessary that all of the processor elements are the same size or process the same data width . however , for conveniences of circuit design and circuit layout , it is preferable that each of the individual processing elements ( except for the rightmost element , pe 0 ) have the same data processing capability in terms of data width . therefore , in general , for purposes of consideration and discussion herein , it is assumed that there are a total of d + 1 processing elements labeled from pe 0 through pe d . processing element pe 0 preferably has a structure such as that shown in fig4 pe d has the preferred structure illustrated in fig6 although it is noted that a more generic structure , such as that shown in fig5 may be employed for the leftmost processor element pe d though it is not necessary that this leftmost processing element be any more complicated than that shown in fig6 . also , for purposes of convenience of circuit design , layout , and packaging efficiency , it is generally desirable that the data width , w . of each processing element be an integer multiple of k . in the designs presented herein for a value of n = 512 , processor elements pe 1 through pe d − 1 , each process data in 2k bit wide chunks . thus , in this example , w = 2k , where w is the width of the data in each of the typical or generic forms of processing element , as illustrated in fig5 and 5a . it is noted that processor element pe 0 as shown in fig4 possesses an extra k bit processing capability , as is more particularly described below . thus , if each typical processing element pe 1 processes data in w bit wide chunks and if there are d + 1 processing elements with the rightmost processing element processing an extra k bits , then it is the preferred case that n = wd + k . thus , in general , the output of multiplexor 121 preferably comprises w + k bits . the leftmost third of these bits are supplied to multiplier 173 , the middle third of the bits in register bn ( reference numeral 198 ) are supplied to multiplier 172 , and the rightmost third bits are supplied to multiplier 171 . multipliers 171 , 172 , and 173 are thus each k bit by k bit multipliers . in this regard , it is noted that the original relatively large multiplier array 70 in fig1 employs an n by k multiplier . however , it is noted that the partitioning of the computation into a system employing a plurality of nearly identical processing elements results in the construction of circuits which now utilize multipliers which operate much more quickly since each multiplier now is typically only k bits by k bits . and clearly , since k is typically much less than n , processing takes place significantly faster . the leftmost of the 2k bits output from multiplier 173 are supplied as a partial product out ( ppo ) to the next unit in the chain . in particular , it should be appreciated that in the discussions herein , that the natural order of processing is from the rightmost on through to the leftmost processing element in the chain ( see fig7 ). thus , data is passed from one processing element to the processing element on its immediate left . however , it should be noted that left and right are relative terms useful essentially only for descriptive and understanding purposes . the rightmost k bits from multiplier 173 are supplied as the leftmost k bits of a 2k bit augend supplied to adder 175 . the rightmost k bits of this 2k bit augend are supplied from the lower or rightmost k bits of multiplier 172 . thus , the rightmost k bits of multipliers 173 and 172 , respectively , are combined , as shown in fig4 to supply a 2k bit wide augend to adder 175 . adder 175 also has as its other input a 2k bit augend which is supplied from the leftmost k bits of multiplier 172 and 171 , respectively , with multiplier 172 supplying the leftmost k bits of the 2k bit augend and with multiplier 171 supplying the rightmost k bits of the 2k bit augend supplied to adder 175 . thus , adder 175 is a 2k bit wide adder . an equivalent but alternate connection arrangement is shown in fig4 a . multiplexor 152 operates to select , during the x - phase of computation , k bits from register r 0 ( reference numeral 190 ). during the z - phase , multiplexor 152 selects as its input the contents of temporary register 150 containing the variable xo . the output of multiplexor 152 is supplied to adder 165 which is k bits in width . adder 165 receives two augends , namely , the rightmost k bits from multiplier 171 and the k bits supplied from multiplexor 152 . the output of adder 165 is stored in temporary register 150 and is also supplied to multiplier 180 which is also a k bit by k bit multiplier . the other factor supplied to multiplier 180 is the contents of register 160 which contains the variable s . ( the calculation of s as − 1 / n 0 mod r is efficiently carried out in the circuit shown in fig1 which is discussed in detail below .) the output of multiplier 180 is supplied to register 130 which thus contains the value y as defined by the algorithm set out above . the output of register 130 is supplied to multiplexor 131 and is also supplied to the next processing element pe 1 ( see fig5 ). multiplexor 131 operates to select a portion of the variable a which is one of the factors in the multiplication operation . ( other k bit wide portions of variable a are selected by their respective processing elements .) in particular , register 110 contains the rightmost k bits of the variable a . thus , during the x - phase of operation , multiplexor 131 operates to select the contents of register 110 to be supplied to multipliers 173 , 172 , and 171 , as shown . likewise , during the z - phase of computation , multiplexor 131 operates to select the variable from register 130 to be supplied to this same set of multipliers as the other factor . a carry - out signal line from adder 165 is also supplied as a carry input to the lowest order position in adder 185 , as shown . additionally , adder 175 supplies a first carry - out signal line to the next processing element in the chain ; similarly , adder 185 also supplies a second carry - out signal line to the next processing element in the chain . in particular , since fig4 illustrates processing element pe 0 , carry - out signal line 1 and carry - out signal line 2 are both provided to processing element pe 1 . the connections between pe 0 and pe 1 are readily apparent simply by placing fig4 to the right of fig5 . in particular , processing element pe 0 supplies the variable y , the partial product out , and the two carry - out signal lines to the inputs shown in pe 1 of fig5 . in particular , it is also noted that the variable y ( that is , the contents of register 130 ) is supplied to each one of the individual processing elements . and lastly , with respect to fig4 it is noted that the output of adder 185 is supplied to registers r 0 and r 1 shown at the top of fig4 . as indicated above , it is the register set ( containing r 1 and r 0 on the right ) which ultimately contains the desired calculation result . accordingly , reference numeral 100 in fig4 describing processing element pe 0 does not include this register set . this register set is discussed separately below in terms of some of the other variations and structures that are employed in the present invention . attention is now directed to a discussion of fig5 which illustrates a more typical processor element and , in particular , which illustrates the form of a processor element which may be repeated in a circuit / system chain which is as long as is required to process factors which are n bits wide . with specific reference to fig5 it is noted that it is similar to fig4 except that the part of the processing dealing with k bit wide operations involving s and n 0 need not be present in any processing elements except the rightmost one , namely , pe 0 . in particular , fig5 indicates that the generic form of a processing element pe p bearing reference numeral 200 specifically does include register bn ( reference numeral 298 ) but does not include the other registers shown . one of the significant differences between fig4 and 5 is that register 220 contains only a portion of the bits for the second factor b . in particular , register 220 contains 2k bit wide chunks designated as b 2p + 2 and b 2p + 1 , where ranges from 1 to d − 1 . again , as above , multiplexor 221 selects either the 2k bits from register 220 or the 2k bits from register 240 which has corresponding portions ( here 2k bits chunks ) of the variable n . accordingly , register bn is 2k bits wide . unlike register 198 in fig4 register 298 ( bn ) in fig5 is only 2k bits wide . in one preferred embodiment of the present invention when n = 512 , register bn is 64 bits wide . from an overall perspective , general processing element pe 1 ( reference numeral 200 as shown in fig5 ) accepts , as input from the right , the value of y , the partial product in , carry - in 1 and carry - in 2 . processor element pe 1 also has as an input the corresponding portion of the k bits of the multiplier factor a from register 210 . the register involvement for registers , 292 , 291 , and 290 is substantially as shown in fig4 except now shown in the generic version of a processor element . it is these registers that store intermediate values between phases and ultimately store the completed product , ab mod n . also , from an overall perspective , processor element 200 produces , as an output , a k bit partial product out which is supplied to the processor element on its left together with carry out signals 1 and 2 which are supplied to the corresponding adders 275 and 285 in the processor element on the left . the output of adder 285 is supplied back to registers r 2p + 1 and r 2p . accordingly , other than the connections to the register sets for r , b , n , and a , the processing elements are connected simply by matching partial products in and out and carries in and out 1 and 2 . accordingly , in systems constructed in accordance with those aspects of the present invention which employ a plurality of similar processing units , the overall system is constructed by starting with the circuit shown in fig4 or 4 a as a rightmost position and placing , in adjacent positions , processing elements similar to those shown in fig5 or 5 a . the overall configuration , therefore , is seen in fig7 . however , before proceeding , it is useful to consider the fact that the leftmost processor element pe d does not have to be as complicated as the processing elements to its right such as these shown in fig5 or 5 a . in particular , the leftmost processing element only needs to process k bits . in the x - phase of operation , the circuit shown in fig6 acts to add carry - in 1 to the partial product input to the leftmost processing element via increment - carry circuit 375 . likewise , adder 385 adds carry - in 2 to the other input to adder 385 to produce an output which is supplied to register r 2d in the immediate preceding processor element . in the z - phase of operation as controlled by and - gate 399 , the contents of register r 2i ( reference numeral 390 ) are added to the output of increment carry circuit 375 and this is also supplied to register r 2i in the feedback configuration as shown . accordingly , it is seen that in partitioned embodiments of the present invention , it is preferable to employ a leftmost processing element which is simpler than that which is generally required in one of the generic processing elements between the rightmost and leftmost elements . however , while preferable , this substitution is not mandatory . the partitioning of the computational problem as provided in one embodiment of the present invention into a solution having a plurality of nearly identical processing elements provides significant advantages in terms of design , efficiency , layout , and structure . concomitantly , these advantages also lead to advantages in circuit speed and throughput . however , it is also very important to note that the partitioning into a plurality of processing elements also provides significant advantages in terms of the fact that a pipelined operation is now possible . in particular , while pipelined operations generally introduce a small initial delay , the total throughput , as measured in terms of modulo n multiplications per time unit is significantly improved . accordingly , a significant portion of the description below is devoted to a discussion of the use of the described partitioned processing element structure in conjunction with a pipelined method for operating the circuits shown in fig4 , and 6 , and variations thereof . however , before embarking on a discussion regarding the pipelining aspects of the present invention , it is also useful to note that the circuits shown in fig4 - 7 are perfectly capable of operation in a non - pipelined fashion . such a mode of operation is illustrated in fig8 . in particular , it is noted that fig8 is a logical time - sequence diagram illustrating the use of the register set r 0 through r 33 as a final and temporary storage medium for passing information between the x - phase of computation and the z - phase of computation . fig8 also more particularly illustrates the distinction pointed out above between the register set and the individual processing elements . this figure also illustrates the unique positions for the rightmost and leftmost processing elements wherein the rightmost element is supplied with information from three registers and wherein the leftmost processing element receives direct information only from the leftmost portion of the register set , namely , r 33 since , in this particular case , n is assumed to be 1 , 024 and k is assumed to be 32 . not shown in fig8 are the signal connections between the processing elements . rather , fig8 is meant to be illustrative of time sequencing and the utilization of the register set . in particular , it should also be noted that , in fig8 the processor elements in the upper half of the illustration are all operating in the x - phase at the same time , and likewise , all of the processing elements in the lower portion are operating in the z - phase . variations of this operational modality are more particularly described below with respect to fig9 and considerations relating to pipelining of the information into and out of the circuit . in the case of no pipelining , such as shown in fig8 all of the processing elements start to process data at the same time and finish at the same time . in any given clock cycle , all of the processing elements are either all in the x - phase or are all in the z - phase of calculation . in this node , each processing element updates a fixed slice of the complete partial result register ( two r i registers ). since all of the partial product registers are updated at the same time , everything works smoothly in accordance with the algorithm described above . attention is now directed to that aspect of the present invention in which the processing elements are operated in a pipelined fashion . in order to achieve this result , certain hardware modifications are made to the circuits shown in fig4 and 5 . these modifications are more particularly illustrated in fig1 and 11 , respectively , to be discussed more particularly below . however , for purposes of better understanding the utilization of the processing elements in a pipelined fashion , attention is specifically directed to fig9 . in the pipelined approach , it is the case that , in a given clock cycle , any two adjacent processing elements are always in different phases with the processing element processing the less significant slice of data always being one clock cycle ahead . as seen by the circular arrows in fig9 it is unfortunately the case that , while a given processing element is in the x - phase , it requires , as input , a 32 - bit value from the z - phase that is being calculated at the same time by the next processing element in the chain that is still in the previous z - phase . for example , as shown in fig8 the rightmost processing element pe 0 on the top right is in the x - phase . this requires , as an input , the value in r 2 from processing element pe 1 which is one clock cycle behind in the z - phase . this problem is solved by adding a feedback paths from the next processing element in the chain , which links to a k - bit adder ( see reference numeral 235 in fig1 and reference numeral 135 in fig1 ). this solution creates additional delay due to the presence of a new k - bit adder . however , the maximum working frequency is not significantly affected since a k - bit adder is a relatively fast circuit . additionally , it is noted that the previous signal path , before this change , was not a critical path . the original critical path occurred in the rightmost processing element pe 0 due to the calculation of the constant y . the advantage to this particular solution is that there is no need to modify the formulas in the algorithm ; however , on the other hand , the maximum frequency is nonetheless slightly effected . additional variations , to be considered more particularly below , consider this minor problem and provide yet another solution which eliminates the delay introduced by adder 235 and 135 . in any event , either of the two pipelining solutions presented is an improved solution over that provided by the purely parallel approach illustrated in fig8 . as pointed out above , fig1 is similar to fig5 but more particularly illustrates the inclusion of extra hardware elements that are used to achieve smooth operation in a pipelined fashion . in particular , latches 232 , 233 , and 234 are added as temporary storage mechanisms between processors elements for holding the k bit wide partial products out ( ppo ), and the single bit carry - out lines 1 ( from adder 275 ) and 2 ( from adder 285 ). additionally , it is noted that latch 231 stores either the selected k bit wide portion of multiplier factor a i or the constant y . this is provided in an alternating fashion from multiplexor 131 ( as shown in fig1 ). additionally , it is noted that the lower k bits from the output of adder 285 are supplied to the adjacent adder 235 which is actually present in the preceding processing element , namely the one to the right . in a similar fashion , the lower k bits from the next ( that is , the left ) processing element are supplied to adder 235 . additionally , there is a feedback connection ( not shown for reasons of drawing congestion ) from the output of adder 235 to the corresponding segment of the register “ set ,” namely , to r 2p + 1 . similar changes in the circuit are made to the rightmost processing element pe 0 , as shown in fig1 . in particular , latches 131 , 132 , 133 , and 134 are added to serve a function that is the same as that provided by latches 231 , 232 , 233 , and 234 in fig1 . and as in fig1 , adder 135 is now included to incorporate the extra addition step for pipelined operations . it is also noted that latch 131 ′ in fig1 is supplied from multiplexor 131 . it is from this latch that values of a 1 and y are supplied to subsequent processing elements in the chain . in this regard , it is also noted that register 110 containing the value a 1 is illustrated in fig1 as a k bit register , while in fact the preferred embodiment is the one illustrated in fig1 in which a long a register with n + 1 bits provides information to a multiplexor which selects subsequent k bit wide chunks from the contents of the a register . accordingly , register 110 in fig1 is preferably constructed as illustrated from register 10 and multiplexor 11 in fig1 . the simplification shown in fig1 is only for clarity and for ease of understanding . also , as is seen in the corresponding portion of fig4 the output of multiplexor 121 is preferably w + k bits wide where w is the width of the data chunks processed by each of the generic processing elements . before proceeding to a discussion of yet another preferred embodiment of the present invention , it is worthwhile to consider the development described so far so in order to provide some overall perspective . in particular , a first preferred embodiment of the present invention provides a circuit such as that shown in fig1 which employs relatively large multiplier and adder arrays . in a second preferred embodiment , the adder and multiplier arrays are partitioned so as to be deployed in a chained sequence of individual processing elements with each one possessing the same structure and passing information from the rightmost to the leftmost processing elements in a system which efficiently carries out the same operations as shown in fig1 . in a third preferred embodiment of the present invention , the processing elements are further provided with an additional adder and latches which enable the processing elements to be operated in a pipelined fashion , such as illustrated in fig9 . in the next preferred embodiment of the present invention which is now considered in detail below , additional adders 135 and 235 are repositioned in the circuit so as not to negatively impact critical data flow paths . it is now this embodiment which is described . in particular , in this embodiment , the processing elements and register sets are configured as shown in fig1 . in particular , it is noted that , in fig1 , the register connections to the individual processing elements are in fact different . this difference is due to the repositioning of the adder . in particular , fig1 illustrates the repositioning of adder 135 from fig1 and likewise , fig1 illustrates the repositioning of adder 235 from fig1 to the position shown as adder 435 ′ as shown in fig1 . accordingly , the design illustrated in fig1 and 11 for pipelined operations is improved even further by moving the indicated adder to the input stage of the processing elements which is facilitated by eliminating certain feedback paths between the processing elements , as shown . the adder is moved from the output of the processing element to the partial product input ( r register path ) and works in parallel with the slower multiplier function blocks . this eliminates an adder from a critical path . from fig9 it can be seen that when processor element pe p is in the x - phase , it requires an input from both register portions r 2p + 2 and r 2p + 1 . the r 2p + 1 value is actually updated by the p th processor element during its previous clock cycle . the “ problem ” is that the value in r 2p + 2 , which is supposed to be contain the value of z 2p + 2 is updated in the same clock cycle by processor element p + 1 ( pe p + 1 ). it is noted that during the x - phase , processor element pe p adds the value z 2p + 2 contained in r 2p + 2 to the upper k bits of its output and loads the result into r 2p + 1 ( this is the x 2p + 1 value ). given that the contents of register r 2p + 1 are used and updated exclusively by pe p , one can proceed as follows : ( 1 ) during the x - phase , processor element pe p does not add the value of r 2p + 2 to its output before loading r 2p + 1 ; and ( 2 ) during the z - phase pe p receives as an extra input , the value in register r 2p + 2 ( which at this time has been updated by pe p + 1 with z 2p + 2 and adds this immediately to the r 2p + 1 input before any further processing ). the modifications to the circuit shown in fig1 , which are illustrated in the circuit of fig1 , are designed to accomplish these goals . the consequence of step ( 1 ) recited in the previous paragraph is that at this point the value generated by the processing elements during the x - phase is not any more the same as described in the algorithm set forth above . in order to compensate for this difference , another term is added during the z - phase . the benefit of this change is an increase in the maximum frequency of operation and a reduction in the power of the needed by the circuit . additionally , there are also advantages in terms of a reduced need for silicon area ( that is , chip “ real estate ”) together with advantages in having a more uniform and repeatable circuit design . accordingly , fig1 illustrates the new flow of data between the r register “ set ” and the processing elements . likewise , fig1 and 14 illustrate the presence of additional circuitry to accomplish the objectives stated above . the specific changes to the rightmost processing element for the improved pipelining version of the present invention are now specifically set forth . as above , a partial product out from multiplier 173 is latched up into k - bit wide register 432 . additionally , the variable m from multiplexor 131 is latched up into latch 437 . repositioned adder 435 is an adder having a width of 2k bits . it also receives a carry input signal ( carry - in 3 ) and includes two input signal lines . a 2k bit wide signal comes from a combination of the output from and - gate 402 which is supplied from register r 1 ( reference numeral 191 ). register 191 also supplies multiplexor 193 which has as its other input the k bit output signal from register r 0 ( reference numeral 190 ). the output of multiplexor 193 under the control of the “ x / z select ” signal line which causes the supply of either the output of register r 1 or register r 0 as the rightmost k bits for the right input to adder 435 . ( note though that adders and multipliers are symmetric with respect to the use of left and right inputs since the desired operations are commutative .) the first ( rightmost ) 2k bit input to adder 435 is either ( r 1 , r 0 ) or ( 000 . . . 0 , r 1 ) depending on the “ x / z select ” signal being 1 or 0 , respectively . the “ x / z select ” signal configures the circuits for x - phase or for z - phase operation . during the x - phase , adder 435 executes the following operation : ( 00 . . . 0 , r 1 )+ 0 which result is sent to adder 135 . in comparison with fig1 , it is seen that adder circuit 185 in fig1 receives ( r 1 , r 0 ) but can also receive the additional signal input ( r 2 , 00 . . . 0 ). the reason for this option is based on pipelining operations because in such a mode the processing element ( pe ) on the left is always behind one clock cycle . for example , since pe i in fig1 is responsible for updating the r 2 register with the z value , this means that during the x - phase pe 0 needs the z value stored in r 2 in pe 1 which is still generating it . thus , in fig1 , adder 135 is used to transform the x value in r 2 to the successive z value . however , in contrast in fig1 , the value in r 2 is added later in the next phase ( a z phase ) via adder 435 which is not in a critical path . the signal “ select r 2 ” is always ‘ zero ’ while the signal “ x / z select ” controls the x and z phase during modular multiplication . this signal , when set to ‘ one ’ provides the capability of performing regular multiplication as opposed to modular multiplication as needed , or as desired . for regular multiplication , the “ x / z select ” signal line is always “ zero ” while the “ select r 2 ” signal line is always “ one .” the other input to adder 435 is a 2k bit wide signal whose rightmost k bits , driven by the and - gate 401 , are all zeros during a modular multiplication or equal to the register r 2 value during a standard multiplication as determined by the signal “ select r 2 ”. the output of and - gate 401 is connected now to the lower k bits of the leftmost 2k bit input to adder 435 . the leftmost k bits of this second input comes from register r 2 ( reference numeral 192 ) under the control of the “ x / z select ” signal line which controls and - gate 403 . and - gate 403 is , like multiplexor 193 , also under control of the “ x / z select ” signal line , as shown . the reconfiguration of the adder &# 39 ; s input signals is necessitated by the repositioning of adder 135 to a position which is not in a time - critical path . the functioning of signal line “ select pe 0 ” is now more particularly described . the inclusion and functioning of this control line is not related to the repositioning of adder 435 . when signal line “ select pe 0 ” is “ one ” the hardware in the processing element becomes equivalent to the generic hardware processor element p i ( 1 ≦ i & lt ; d ). when the “ select pe 0 ” signal line is set to “ one ,” multiplier 406 selects the “ previous p ” input signal bus and provides it to adder 175 ( which is equivalent to adder 275 in pe i ). the output of and - gate 405 changes from “ zero ” ( in the case of pe 0 functioning ) to the value driven by the carry input signal line for adder 175 ( or 275 in pe i functioning ). multiplexor 404 selects the “ carry in 2 ” signal line and provides it as a carry input to adder 185 or 285 in pe i functioning ). accordingly , the “ select pe 0 ” signal line is used to “ disable ” the following devices so that the processing element operates as a generic pe i rather than as pe 0 : multiplier 171 , adder 165 , multiplexor 152 , multiplier 180 , register 150 and register 160 . there are two cases in which it is desired that the “ select pe 0 ” signal line should be driven into the “ one ” state . this means that the pe behaves specifically like a generic pe i as opposed to the rightmost pe 0 . the first case is when the system is designed comprising two separate chains of processing elements . for example , each of the two chains is made up of a concatenation of one pe 0 together with seven pe i &# 39 ; s ( that is , with eight processing elements per chain ). these two chains ( with eight pe &# 39 ; s each ) are particularly useful in carrying out operations of modular multiplication involving public key cryptography algorithms such as the rsa algorithm using the chinese remainder theorem ( crt ). in such cases , each of the two chains operates independently to perform two modular multiplications . in the case of modular multiplication as described above , there is thus provided a command which effectuates this operation together with an exponentiation function which is described in more detail below . in this case , the two chains of processing elements are concatenated to form a longer chain that is thus able to process more data in the same amount of time . in this case , the “ pe 0 ” on the rightmost position of the left chain behaves as a pe i and receives the inputs from pe 7 ( here “ 7 ” is used as an example which is in harmony with the exemplary chain size of eight , as recited above ) from the right chain . this is accomplished by setting the “ select pe 0 ” signal to “ one .” these two chains may be represented diagrammatically as follows : pe 7b pe 6b . . . pe 1b pe 0b ⇄ pe 7a pe 6a . . . pe 1a pe 0a in the event that the hardware herein is not being operated in the chinese remainder theorem mode ( to be discussed in more detail below ), pe 0b acts as a pe i and its “ select pe 0 ” signal input line is set to “ one .” there is also one other input control signal that is set to “ one ” in order to have pe 0b act as a pe i . in particular , this signal line is labeled “ auxiliary select ” in fig1 . more particularly , control line “ select pe 0 ” controls the operation of multiplexors 404 and 406 and and - gate 405 . in the pe 0 mode of operation , the carry - in 1 signal line is supplied to adder 175 together with the signal from the previous pe signal line coming in to the modified rightmost processing element shown in fig1 . if it is not in “ pe 0 mode ,” no carry input is supplied to adder 175 . likewise , based upon the state of the “ select pe 0 ” signal line , multiplexor 404 operates to select , as a carry input to the low order position of adder 175 , either the usual carry - out signal from adder 165 or , in the event of non - pe 0 mode operation , the signal supplied to the carry input of adder 185 is the carry - in 2 signal . apart from these variations , the rest of the circuits shown in fig1 operate in substantially the same manner as their counterparts in fig1 . [ 0154 ] fig1 also introduces several other signal lines for proper operation in various hardware modes . as described above the “ auxiliary select ” signal line is a 2 bit signal taking on the values “ 00 ,” “ 01 ”, or “ 10 .” the “ auxiliary select ” line has the value “ 10 ” to pe 0b above to concatenate pe 0b with pe 7a on its right in the case of non - crt operation . this is the only time that the “ auxiliary select ” signal bus is set to this value . in the other cases , this signal line is set to “ 01 ” during the z - phase ( select x / z = 1 ). the “ 00 ” value of “ auxiliary select ” selects the a i input used for the x - phase while the “ 01 ” value for this signal line selects the y input for the z - phase of operation . with respect to the other signal lines present in fig1 , the “ select r or x ” signal line is equivalent to “ select x / z ”; and the “ select r 2 ” signal line is driven independently when the processing elements are used to perform standard multiplication operations as opposed to modular multiplication . the “ select b or n ” signal line assumes the value given by “ select x / z ” during the next clock cycle ( that is , the anticipated version of “ select x / z ”). the reason for this is that the output of multiplexor 121 is used to select what is stored in bn register 198 which contains b during an x - phase and n during a z - phase . [ 0156 ] fig1 illustrates modifications made to the circuit shown in fig1 to accommodate repositioning adder 235 in fig1 to a position in the signal flow path which reduces time criticality with respect to addition operations . with respect to the specific differences between fig1 and 14 , it is noted that , in fig1 , it is no longer necessary to supply the low order k bit output from adder 285 to the processing element to the right . additionally , it is noted that instead of the signal line being labeled a i / y , the input signal line is labeled m to reflect the fact that multiplexor 131 in fig1 now has three possible inputs to select from rather than just a i or y . the third input of multiplexor 131 ( that is , the “ previous m ” signal line ) is used to concatenate pe 0b to pe 7a ( as per the example given above ) during non - crt operations . this allows on - the - fly construction of a long chain of processing elements ( sixteen in the example ) versus two independent chains of half as many ( that is , eight in the example ) processing elements . additionally , adder 435 ′ which is 2k bits wide is now interposed between its corresponding register set segment and adder 285 . in particular , the output of adder 435 ′ is supplied as the second input to adder 285 and the carry out of adder 435 ′ is supplied to latch c 3 ( reference numeral 436 ) which supplies the carry - out 3 signal line . the contents of register r 2p + 2 ( reference numeral 292 ′) which is k bits in width is supplied as the lower k - bit portion of the left adder input under control of and - gate array 401 which is in turn controlled by the signal line “ select r 2p + 2 .” the contents of register r 2p + 2 are also supplied as the upper k - bit portion of the left adder input under control of and - gate array 403 which is in turn controlled by the “ x / z select ” signal line . the right input to adder 435 ′ is also 2k bits in width and is supplied from and - gate array 402 and from multiplexor 493 . under control of the “ x / z select ” signal line , multiplexor 493 provides either the contents of register r 2p + 1 ( reference numeral 291 ′) or the contents of register r 2p from the processing element on the right . the 2k - bit data portion supplied to the left input of adder 435 ′ is controlled by and - gate 401 and by and - gate 403 . the right 2k - bit input to adder 435 ′ includes two portions one of which is a high order k bit wide portion which is either zero or the k - bit data portion coming from register r 2p + 2 ( reference numeral 292 ′ ) control of and - gate array 401 which is also under control of the “ select r 2 ” signal line . the lower order k bit wide portion of the right input to adder 435 ′ is selected by multiplexor 493 to be either the contents of register 291 ′ ( that is , r 2p + 1 ) or the contents of the 292 ′ register ( that is , r 2p ) in the processing element to the right . the operation of the circuits described produces the result that adder 285 ( fig1 ) accumulates the results of the multiplication operations performed by multipliers 272 and 273 together with the output of adder 275 . the left input of adder 285 is dependent on the phase of the operation for the processor element containing adder 285 . for example , during the x - phase , the result is ( 00 . . . 0 , r 2i + 1 ) while during the z - phase , the result is the binary sum ( r 2i + 1 , r 2i ,)+( r 2i + 2 , 00 . . . 0 ), where “ 00 . . . 0 ” is k bits wide . the term including r 2i + 1 is added only during the z - phase since , during the x - phase , this register value is still being updated by the processing element to the left . this aspect is best seen in fig1 . additionally , it is noted that if one desires to employ a simplified leftmost processing element such as one that is similar to that shown in fig6 modifications are made to this circuit to accommodate the improved pipelining version associated with fig1 and 14 . in particular , this is accomplished by the inclusion of an increment - carry circuit 439 between previously employed and - gate array 399 and k bit wide adder 385 . the other signals supplied to increment carry circuit 439 is a carry input c m which comes from latch 436 in the processing element to the immediate right of the circuit shown in fig1 . in particular , this signal line is designated as carry - out 3 in fig1 . as above , the use of a simplified leftmost processing element ( pe d ) is optional but is clearly desired for purposes of circuit simplification , speed , and cost . the processing element pe end or pe d includes the function of adding the previous ppo ( partial product out ) from the pe to its right to the potential carry out signal from adder 435 ′ which signal is temporarily stored in latch c 3 ( 436 ). this result is stored in register r 2p . during the z - phase , the result of this operation is accumulated in register r 2p , as shown . it is noted that it is also possible to utilize the pipelined version of the present invention to process operands that are actually in fact wider than the hardware present in the processing element chain width ( n & gt ;& gt ; wd or equivalently n & gt ;& gt ; mk ). the method for carrying out this extra wide operation processing is illustrated in fig1 . in particular , each horizontal line in fig1 represents a single clock cycle and each vertical column represents a slice of the data that is to be processed . assuming that each processing element processes 64 bits of data ( 2k bits typically ), the first column indicates that the lower two k bits of the data are always processed by processing element pe 0 . during the first clock cycle , only processing element pe 0 is active . all of the other processing elements are activated sequentially , clock cycle after clock cycle . this provides sufficient time to the previous processor element to generate the pipelined data for the next processing element . in fact , it is possible that the width of the operand is larger than the processing element chain itself . for example , in the discussions herein , the situation in which n = 512 bits has been considered . however , in accordance with this aspect of the present invention , it is possible to process operands that are longer than 512 bits using a pipelined hardware structure which is designed for 512 bits . in such circumstances the clock cycle after the first processing element is activated , the entire processing element chain is shifted left by 2k bits ( see fig1 ) leaving the lower two k bits unprocessed . this shifting continues until the upper processing element ( in this case , pe 8 ) is capable of processing the upper 2k bits of the operand . following this , the processing element chain , instead of shifting back to the home position , stays in place with the exception of the rightmost processing element pe 0 . the lower processing element , after the others go into a home position , continues processing the lower two k - bit slice of the operand . when all of the processor elements are back in their home positions , the entire chain starts a shift left as before . this mechanism allows all of the processing elements to be busy all of the time and , accordingly , achieves a maximum performance level . additionally , a new operation can start before the previous operation is finished . the approach described herein provides maximal performance in the sense that all of the processing elements are always busy . additionally , the next operation can be started immediately without any delay and without idling any of the processor elements . furthermore , these operations are fully compatible with the pipelined approach as described above . as indicated very early above in the description for the present algorithm for computing ab mod n , it is desirable to begin the calculation with a value s which is equal to the negative inverse of the value n 0 where the inverse is now taken modulo r where r = 2 k . that is to say , in the initial presentation of the algorithm employed herein , the availability of the value s =− 1 / n 0 mod r was assumed . a circuit for carrying out this calculation is illustrated in fig1 which shows , in its upper portion , a circuit for calculating successive values of the variable q and correspondingly illustrates a circuit in its lower portion for calculating a companion variable s which ultimately becomes the desired s =− 1 / n 0 mod 2 k . in this regard , it is noted that the circuit shown in fig1 actually performs two operations . firstly , it computes a multiplicative inverse modulo , a number which is a power of 2 , and also at the same time computes the additive inverse of the multiplicative inverse . in ordinary , non - modular arithmetic , the computation of an additive inverse is a relatively simple operation requiring either the addition or change of a single bit at the leftmost portion of a representative number or at most the addition of a 1 to the low order position depending upon the format in which the numbers are stored . however , in the case of modular addition , it is noted that the operation cannot be carried out as simply as it is for ordinary , non - modular arithmetic . accordingly , it is noted that the circuit shown in fig1 actually carries out simultaneously two nontrivial operations modulo r . in particular , it computes a multiplicative inverse while at the same time ensures that the final result is the negative additive inverse modulo r = 2 k . in the context of the present invention , the algorithm set forth above for computing ab mod n employs the variable s =− 1 / n 0 modulo r . however , the circuit shown in fig1 is capable of generating the negative multiplicative inverse of any k - bit number a initially stored in the n 0 register ( reference numeral 501 ). the method employed for carrying out the formation of the desired negative multiplicative inverse is set forth below . the inputs to the process are the values k and the number whose negative multiplicative is desired , namely , a which is expressible as an ordered k - tuple of the form ( a k − 1 , . . . a 1 , a 0 ). the desired output of this process is a variable s =− 1 / a modulo 2 k . in the process described below , the variable s is initially set equal to the value 2 k − 1 . the variable a is also initially loaded into the q register ( reference numeral 504 ) at the start of the process . accordingly , if the “ start ” signal line is “ 1 ,” then multiplexor 505 selects as its output the contents of register 501 which contain the value n 0 or , more generally , a variable a whose negative multiple inverse is to be generated . multiplexor 505 also receives as an input the output of k bit adder 503 . this adder has two inputs , namely , the leftmost k − 1 bits from q register 504 and a k bit input the value of a as stored in register 501 . adder 503 also effectively performs a shift right operation under circumstances to be described more particularly below , and accordingly , a zero high - order bit is added as appropriate to effect this shift operation with zeros being shifted into the high - order position . the process for carrying out the desired calculation resulting in the variable s being transformed to − 1 / a mod 2 k is set forth below : accordingly , it is seen that the process in this embodiment of the present invention occurs in k − 1 steps . at the last step , the contents of the s register are equal to the desired negative multiplicative inverse of a ( or n 0 for the specific purposes of the present invention ). it is also seen that the process for calculating the negative multiplicative inverse employs the concomitant calculation and updating of two variables , s and q . the upper portion of fig1 illustrates the updating and calculation of the variable q . in particular , it is noted that if the rightmost bit of q ( that is , q 1 ) is i then , via the utilization of and - gate array 502 , the contents of register 501 are added to the current value of q from q register 504 with the output being stored back in the q register via multiplexor 505 . it is noted that , at this stage of operation , the “ start ” signal line is not equal to “ 1 ” and , accordingly , multiplexor 505 selects as its input the output of adder 503 . otherwise , the initialization q = a is carried out . the circuit in the lower portion of fig1 calculates the companion variable s which is also the desired output at the end of the process . it is noted that in the updating of the variable s , in accordance with the process indicated above , one performs a subtraction from the current value of s by an amount which is equal to a power of 2 ( s = s − 2 i ). to effect the desired process , s register 560 is initially loaded with a value which is “ all ones ” representing the integer 2 k − 1 . and - gate array 561 controls the writing of particular bits into the s register . in particular as seen in fig1 , a k bit wide vector from and - gate array 561 is available for writing into register 560 . and - gate array 561 permits , during each clock cycle if necessary , the writing of a k bit vector into s register 560 . the selection of which vector is controlled by the current value in counter 563 which counts upwards from 0 to k − 1 , and then immediately back to zero again in a rollover fashion . in the examples of the present invention described above , k is typically equal to 32 bits . as such , counter 563 need contain only 5 bits . in general , counter 563 contains k ′= log 2 k . thus , decoder ring 562 receives k ′= 5 bits and produces as an output a k bit vector , only one of whose entries is 1 . this is the essential operational feature of a decoder circuit . counter 563 also supplies a signal line “ zerocount ” which is a “ 1 ” when the counter is all zeros . this signal line is also supplied to and - gate array 561 which triggers a write - enable bit when q ( 1 ) is “ 1 ” and the zerocount signal line is false and the start signal line is false . accordingly , under these circumstances , and - gate array 561 , in accordance with the algorithm described above , then permits the writing of a 0 bit into the corresponding portion of s register 560 as determined by the current value in register 563 which , in effect , contains the variable i recited in the algorithm listed above for negative multiplicative inverse calculation . it is in this fashion that the value of s is updated to s = s − 2 i . finally , at the end of the calculation , the value in the s register , which is initially set equal to all ones , is now equal to the negative multiplicative inverse modulo r of the value that was stored in the n 0 register 501 . if instead of (− 1 / a ) mod n , one wishes to calculate ( 1 / a ) mod n , one can employ the following algorithm : accordingly , there is provided a circuit and a process for producing in a single set of operations not only the multiplicative inverse modulo r of a given number , but also , its arithmetic negative value modulo the same value r . for purposes of the multiplication algorithm of ab mod n described above , it is noted that it is the circuits shown in fig1 which are preferably employed for the calculation of the variable s =− 1 / n 0 mod r which is stored in registers 60 in fig1 in fig4 and 4a , 160 in fig1 , and 160 in fig1 . as discussed above , a primary purpose of the present invention is the multiplication of large integers modulo n for cryptographic purposes . since cryptography often involves the exponentiation operation , the use of the present hardware to perform exponentiation is now described . the relevant circuits and materials described above can be considered as implementing a specific function , f with the following properties : in the above , the problem has been partitioned into m “ words ” of k bits each where mk ≧ n + 2 where n is the number of bits in the binary representation of n . and as above , n 0 is the least significant k bits of n . and n is , of course , odd . in the discussion above , it was pointed out that multiplication modulo n would normally be carried out in a two step process : step 1 : result 1 = ƒ ( a , b )= a b 2 − mk mod n step 2 : result 2 = ƒ ( result 1 , 2 2mk )= a b mod n . from the above properties of f , it is seen that premultiplication of either a or b by 2 mk produces the same result in one step : this is clearly the preferred approach for performing modular multiplication in one shot situation since premultiplication by 2 mk is easily performed via a shift operation . however , in the case of exponentiation , one uses the modular multiplication function , as implemented in the hardware described above , in a repeated fashion . in the present case then , exponentiation is carried out in a repeated fashion , but now one must deal with the fact hat there is a factor of 2 − mk present in the output of each iteration of the function , f ; that is to say , ƒ ( a , b )= a b 2 − mk mod n . accordingly , in the present invention , the hardware implemented function f is used but with the factor 2 mk being “ preapplied ” to both of the multiplicands , a and b , as follows : ƒ ( a 2 mk , b 2 mk )= a b 2 + mk mod n . this way , since the function f introduces a factor of 2 − mk at each step , repeated iterations using preapplication of the 2 mk factor to both operands keeps a constant factor of 2 mk as part of the result . as a last step this factor is removed using the function f as implemented by the present hardware in the following manner : ƒ ( a 2 mk , 1 )= a mod n . therefore , at the last iteration in an exponentiation operation , a is the output from previous repeated applications of the function ƒ . in order to see that this value of a going into the f function hardware at this stage is constructed as an appropriate exponential , consider the general case of constructing the value a e mod n where e is an integer and in particular is an integer represented by the t + 1 bit binary value e t 2 t + e t − 1 2 t − 1 +. . . + e 2 2 2 + e 1 2 + e 0 = ∑ i = 0 t e i 2 i , e i 2 i , where e i is either “ 1 ” or “ 0 .” here advantage is taken of the fact that a sum in an exponent becomes a product ( a x + y = a x a y ) so that : a e = ∏ i = 0 t a 2 ′ e i = ∏ i = 0 t ( a 2 ′ ) e i = ∏ i = 0 t ( a 2 ) ie i . based upon this expression for a e in terms of the binary integer e , it is seen that the following algorithm provides a method for using the hardware for the function f herein to produce the result a e mod n , a result which is very important for cryptographic operations and particularly important for public key cryptographic systems . here , n , k , m , n 0 and s (=− 1 / n 0 mod r where r = 2 k ) are as given above . the inputs to the method are the values a and e with e being a t + 1 bit binary integer . the method is summarized in the following outline : if e t − 1 = 1 , then z = ƒ ( z , z 0 ), else continue thus , at the end of this method the value stored in the z register is a e mod n , as desired . this procedure is also summarized in the flow chart shown as fig1 . a slightly different form of the exponentiation algorithm is implemented in fig1 . it is also described in the pseudo code provided below : if e i = 1 , then z = ƒ ( z , z 0 ), else continue in constructing circuits for implementing either of these methods for modular exponentiation , it should be noted that f is a symmetric function so that ƒ ( a , b )= ƒ ( b , a ). if f is instead viewed as an operator , this condition is referred to as commutivity . thus , circuits implementing ƒ can have their inputs switched with no change in operation . one also notes in the algorithm set forth immediately above that e 0 is the lowest order bit in the binary representation for the exponent e . as such , for the cryptographic purposes described herein , one notes that n is an odd number . thus , it &# 39 ; s lowest order bit position is always 1 . thus , for cryptographic purposes the step which tests to see if e 0 = 0 can be eliminated . as an example , a circuit which can implement either one of the algorithms for exponentiation is shown in fig2 . the core of this exponentiation circuit is provided by an engine which implements the ƒ ( a , b )= a b 2 − mk mod n function . thus , engine 600 may be implemented by means of any of the hardware components described above which performs this function . the output from multiplication modulo n engine 600 is provided to decoder 603 which operates under control of finite state machine ( fsm ) 607 to store this output either in z register 604 or in z 0 register 605 , or in both ( to provide the z = z 0 step in the algorithm of fig1 ), as needed . thus , decoder 603 does not always function in accordance within the standard operational definition of a “ decoder ” which would normally have only one set of output lines carrying information . if the circuit of fig2 is intended to implement either of the exponentiation algorithms herein , then the outputs of registers 604 and 605 ( z and z 0 ) are both provided as inputs to multiplexors 601 ( for input a ) and 602 ( for input b ). these multiplexors are also provided with constants 1 and c = 2 + 2mk mod n . it is noted , however , that the constant “ 1 ” could also have been provided instead as an input to multiplexor 601 . however , the constant c and the input a ( which is used for computing a e mod n ) need to be provided to different ones of multiplexors 601 and 602 for the purpose of calculating the value z 0 = ƒ ( a , c ). multiplexors 601 and 602 and decoder 603 all operate under control of controller 607 which is preferably implemented as a finite state machine which can have as few as 6 states which depend only on the contents of index counter 608 ( which counts from 0 to t and then resets back to 0 ) and on the i th selected bit e i from register 606 which contains the exponent e in binary form . for example , in implementing the algorithm illustrated in fig1 , when counter 608 is at 0 , controller 607 selects the a input for multiplexor 601 and the c input for multiplexor 602 . it is also noted that , for both algorithms , the initialization and repetition aspects both involve two steps . accordingly , fsm 607 also includes one - bit register 609 ( step state register ) which is indicative of this step state . having used multiplexors 601 and 602 to select a and c as inputs to engine 600 , fsm 607 also controls decoder ( or router , if you will ) 603 to store the outputƒ ( a , c ) = a c 2 − mk mod n into z 0 register 605 . the design of fsm &# 39 ; s for such purposes is standard and is well known and is , for example , described in the text “ digital logic and computer design ” by m . morris mano , copyright 1979 by prentice - hall . in the use of the crt as described above it is seen that one requires the constant c defined as 2 + 2mk mod n . while the constant 2 2mk is generally easy to determine and construct , the inclusion of the need for this to be modulo n is a complicating factor . note here too that it is the case that mk ≧ n + 2 where n is the number of bits in n and that m is picked to be the smallest integer satisfying this relationship . thus 2 + 2mk is always going to be greater than n and hence the modulo n form is needed . however , this constant is readily calculable using the ƒ engine described above . one first calculates t = 2 mk + 1 for a small value of t . the f engine is then used repeatedly as follows : f ( t , t ) = 2 mk + t 2 mk + t 2 - mk mod n , = 2 mk + 2 t mod n f ( 2 mk + 2 t , 2 mk + 2 t ) = 2 mk + 4 t mod n , f ( 2 mk + 4 t , 2 mk + 4 t ) = 2 mk + 8 t mod n , etc . this process is repeated until the first time that the result is greater than n . in public key cryptographic systems someone who wants to receive information picks two ( large ) prime numbers n p and n q and publishes only their product n = n p n q . the potential receiver then generates ( or otherwise creates , often randomly ) a public key e which is also published . before publication , however , the receiver - to - be checks to make sure that e is relatively prime with the respect to the product ( n p − 1 ) ( n q − 1 ). this is easily done since the receiver knows both n p and n q . with n and e thus known to the public , anyone wishing to transmit a message a destined for the receiver can form the encrypted version c of the message by computing c = a e mod n . thus , encryption is an exponentiation operation modulo n . it is the “ modulo n ” aspect which makes this a nonstandard arithmetic problem . however , the systems provided herein are particularly capable of performing the a e mod n operation . at the receiving end the message is decrypted as a = c d mod n , where , as above , c is the received / encrypted message and where d is a private key known only to the receiver and which is calculated as d = e − 1 mod [( n p − 1 ) ( n q − 1 )]. this is something which can be computed by the receiver since the receiver ( and only the receiver ) knows the values n q and n p . ( since n = n p n q is a large number , typically with thousands of bits , even though n be known , its factors , the prime numbers n q and n p are very hard to determine . this fact lies at the heart of public key cryptography .) the receiver also computes , actually precomputes , several other values that are useful in efficient decryption . in particular , the receiver computes two values u , d p and d q as follows : these values render it possible to more efficiently construct the desired result which is c d mod n . this process is more particularly illustrated in fig2 . ( coded message c is not to be confused with the constant c = 2 + 2mk used above .) advantage is now taken of the fact that the receiver , knowing n p and n q is able to calculate u , d p and d q so that advantage maybe taken of the chinese remainder theorem . the coded message c is an integer between 0 and n = n p n q where gcd ( n p , n q )= 1 end where “ gcd ” stands for “ greatest common denominator .” if c p = c mod n p and c q = c mod n q then the crt implies that c may be computed as follows : c = c q +( n q ( ( c p − c q ) mod n p ) u ) mod n p , where u is as defined above . this result is now more particularly applied to the computation of c d mod n , one first considers ( c d ) p which is defined as c d mod n p . likewise , one also considers ( c d ) q which is similarly defined as c d mod n q . note that ( c mod n p ) d mod n p =( cmodn p ) d p where d p = d mod ( n p − 1 ). similarly , ( c mod n q ) d mod n q =( c modn q ) d q where , similarly d q = d mod ( n q − 1 ). thus , given c , d p , d q , n p , n q and u the exponential c d mod n can be calculated in three steps : step 2 . ( c p ) d =( c p ) d p mod n p ; ( c q ) d =( c q ) d q mod n q . step 3 . c d mod n =( c q ) d +[ n q ((( c p ) d −( c q ) d ) mod n p ) u ] mod n p . step 2 above is readily carried out using the methods set forth in fig1 and 19 . step 3 is a straightforward calculation not involving exponentiation . furthermore , as indicated above it is possible to split the sequence of processing elements into two chains which together calculate ( c p ) d and ( c q ) d simultaneously . attention is now directed to a method for further simplifying the computation shown in step 1 immediately above . since the input to the process is a relatively large number , perhaps being represented by as many as 2 , 048 bits , the calculation can be time consuming . however , the modular reduction is based on numbers n p and n q which are often roughly only half that size . suppose then that , phrased more generally , one wishes to compute a p = a mod n p and likewise a q = a mod n q . without loss in generality one may assume that n p & gt ; n q . suppose further that n p and n q are the number of bits in the binary representations for n p and n q , respectively . suppose even further that one picks values m p and m q such that these are the smallest integers for which : where k is the word size in the circuits described above for modular multiplication . with these parameters one may now write a in either of the two forms : depending on whether one wishes to compute either a p or a q , both of which are employable in the application of the crt as described above . if a is of the order of 2 , 048 bits , then : n p + n q ≧ 2048 ; and in general : 0 ≦ a 0p ≦, 2 m p k ; 0 ≦ a 0q ≦ 2 m q k ; 0 a 1p & lt ; n p ; and 0 ≦ a 1q & lt ; n p . one further defines two constants c p = 2 + 2m p k mod n p and c q = 2 + 2m q k mod n q . these constants have substantially the same role as the constant c = 2 + 2mk mod n discussed above , but now these new constants are employed to facilitate computation on a smaller scale problem in accordance with the representation of a as having two parts ( a 1p and a 0p for the mod n p calculation and a 1q and a 0q for the mod n q computation .) as indicated above the present inventors have provided circuits for construction of an engine which implements the function ƒ ( a , b )= a b 2 − mk mod n . this engine / circuit is also fully capable of implementing different functions in dependence on the m and n parameters . accordingly , the functions ƒ p and ƒ q are defined as follows : ƒ p ( a , b )= a b 2 − m p k mod n p , ƒ q ( a , b )= a b 2 − m q k mod n q . consider first the use of ƒ p in the calculation of a p based on the use of the two part representation of a as a 1p 2 m p k + a 0p : a = f p ( a 0 p , 1 ) = a 0 p 2 - m p k mod n p b = f p ( a lp 2 m p k , 1 ) = a lp mod n p g = a + b = a lp + a 0 p 2 - m p k mod n p f p ( g , c p ) = g2 - m p k 2 + 2 m p k mod n p , = g2 m p k mod n p , = a lp 2 m p k + a 0 p mod n p = a mod n p = a p in the same manner one uses the circuits herein to compute a q using the parameters m q and n q to produced ƒ q as defined above . the overall structure for a preferred embodiment of cryptographic engine 700 employing the circuit and operational principles set forth above is shown in fig2 . the main feature of cryptographic engine 700 is the inclusion of modulo n multiplier 600 as described above . it is noted that , as implemented herein as a sequence of independent processing elements ( pe &# 39 ; s ), multiplier engine 600 is dividable into two pieces by the operation of electrically controlling a processing element so as to cause it to operate as a “ pe 0 ” element . this is particularly useful during decryption operations since in this circumstance the receiver knows both n p and n q , whereas during encryption the sender knows only the product n = n p n q . for the calculation of a b mod n , register set 658 contains registers for holding the following values : a , b p , b p , n p , n q and u , where b p = b mod ( n p − 1 ) and b q = b mod ( n q − 1 ). register set 658 also preferably includes at least two utility registers for holding temporary and / or intermediate results . in particular two such utility registers are preferably employed to contain the values a 1q and a 0q as described above , with a 0p and a 1p being thus stored in the ah and al registers respectively . clearly , the roles of these two utility registers are interchangeable . register set 658 also includes an output register which contains output results from multiplier engine 600 . cryptographic engine 700 also includes modular reduction unit 653 ( also described herein as auxiliary computation circuit in fig2 ) which performs addition and subtraction operations and performs single shot modular reductions . the flow of signals across databus 670 between register set 658 to and from multiplier engine 600 and modular reduction unit 653 is carried out under control of finite state machine ( fsm ) command control unit 660 in accordance with the methods , algorithms , and protocols set forth above for carrying out any or all of the following : modular multiplication , constant c generation , exponentiation and the use of the chinese remainder theorem ( crt ) for calculating modular numbers and for efficient exponentiation . i / o control unit 665 , besides implementing the decoding and control function necessary to supply values such as a , b , n , b p , b q , n p , n q and u to the registers set 658 through databus 670 , provides two important functions in the case of modular exponentiation with crt : the first important function is that it dynamically calculates the value of m or m p and m q and it also calculates the lengths of the exponents b or b p and b q . each value of the m &# 39 ; s is a function of the length of a modulus ( position of the leading 1 ) and is a key parameter used throughout the operations . the length of an exponent is simply used to determine when to stop the exponentiation process . the traditional solution is the use of a length detector that monitor the value of each bit in this large registers . this approach has disadvantages in terms of requiring more silicon area and also in terms of electrical loading on the output of the registers . the approach used in the i / o control logic is much less wasteful and is based on the detection of the leading ‘ 1 ’ in the k bit word being written and the associated address . every time a non - zero k bit word is written , a small piece of logic is used to calculate the location of the most significant ‘ 1 ’ which is being written , based on the address of the word itself , and is compared with a value stored in a register that is the result of the loading of the previous k bit word . if the new value calculated is larger than the value stored in the register , the register is updated accordingly . the calculation of the m parameter follows a similar approach and thus saves the need for a lookup table and another large leading ‘ 1 ’ detector . the second important function is that in preparation for performing modular exponentiation with the crt , the values of a 1p , a 0p , a 1q , and a 0q , as described previously , are calculated and loaded into separate registers under control of i / o control unit 665 . commands which externally govern the operation of engine 700 are also supplied via i / o control unit 665 . attention is now directed to a checking system and method which takes the fullest advantage of the modular multiplication circuits described above . in general , there are several ways to provide checking for the results of the hardware operations carried out by the system of the present invention . however , most of the standard approaches to checking are negatively impacted by size , economies of chip real estate and / or by the fact that the arithmetic operations carried out are modulo n operations . for example , result checking based on a straight forward duplication of hardware is very expensive in terms of “ silicon real estate .” error checking for the various function blocks employed ( multipliers , adders , controls , etc .) is also very expensive and complicated . lastly , the use of residue arithmetic check sum methods is not directly applicable to checksums for the modular multiplication hardware that implements the z = ƒ ( a , b )= ab 2 − mk mod n function described above . for example , if z ′, a ′, and b ′ are the check sums of z , a , and b , respectively , then it is still unfortunately the case that z ′ is not necessarily equal to ƒ ( a ′, b ′). accordingly , driven by the inappropriateness of standard approaches to hardware operation checking , there is provided herein a method and system which is closely tied to the architecture described above and which is particularly tied to the fact that the systems herein perform modulo n multiplication using x and z phases of operation and employ a plurality of processing elements based on the notion of partitioning the operands involved into a plurality , m , of k bit words . for an easier understanding of the checking method and system herein , one starts with an understanding of the process described above : k = number of bits in a word ( i . e ., in each chunk processed by one of the processing elements . a = ∑ i = 0 m - 1 a i r i y i + 1 = s x i , 0 mod r ( where x i , 0 = least significant k bits of x i ) based on the above algorithm , structure , and process , the following equations lie at the heart of the model employed herein for checking the operation of the modulo n multiplication circuits : a = ∑ i = 0 m - 1 a i r i b = ∑ i = 0 m - 1 b i r i n = ∑ i = 0 m - 1 n i r i z = ∑ i = 0 m - 1 z i r i f ( a , b ) = ( a b ) / r m + n ∑ i = 0 m - 1 y i / r m - i z mod ( r - 1 ) = ∑ i = 0 m - 1 z i mod ( r - 1 ) = ab + n ∑ i = 0 m - 1 y i mod ( r - 1 ) = [ ( ∑ i = 0 m - 1 a i mod ( r - 1 ) ) ( ∑ i = 0 m - 1 b i mod ( r - 1 ) ) + ( ∑ i = 0 m - 1 n i mod ( r - 1 ) ) ( ∑ i = 0 m - 1 y i mod ( r - 1 ) ) ] mod ( r - 1 ) the hardware which calculates the function ƒ ( a , b ) is therefore checkable through the use of the following relationship ( referred to below as equation ( 1 )): ∑ i = 0 m - 1 z i mod ( r - 1 ) = [ ( ∑ i = 0 m - 1 a i mod ( r - 1 ) ) ( ∑ i = 0 m - 1 b i mod ( r - 1 ) ) + ( ∑ i = 0 m - 1 n i mod ( r - 1 ) ) ( ∑ i = 0 m - 1 y i mod ( r - 1 ) ) ] mod ( r - 1 ) ( 1 ) the fortunate part of this checksum calculation is that it is computed on the fly . for example , the circuitry necessary for the calculation of ∑ i = 0 m - 1 y i mod ( r - 1 ) is shown in fig2 . it is noted , however , that the circuit ( s ) shown in fig2 are provided for the specific case of the use of the chinese remainder theorem where n p and n q are known and the processing elements are split into two independent chains , one for calculating multiplication modulo n p and the other for calculating multiplication modulo n q . in the case of modulo n , calculations , accumulating register y ( reference numeral 652 . 3 a ; not to be confused with the y i variable used above to describe the algorithm ) is initially set to zero with its output being used as an input to adder 652 . 2 a along with the input y i , p from the corresponding portion of register for the processing element partition which generates they values . the input from register 652 . 1 a is added to the current y p value to produce a running accumulation which is stored between cycles in register y ( reference numeral 652 . 3 a ). at the end of m cycles the contents of this register is the value y p ′ = ∑ i = 0 m - 1 y i , p mod ( r - 1 ) . likewise , the corresponding circuit shown in the lower portion of fig2 operates in an identical fashion to compute y q ′ = ∑ i = 0 m - 1 y i , q mod ( r - 1 ) . in the case of both the y ′ p and the y ′ q computations , adders 652 . 2 a and 652 . 2 b respectively are each k bit integer binary adders with carries out of the high order position being fed back as carry inputs to the low order positions . in this way addition modulo ( r − 1 ) is carried out . thus , the circuits shown in fig2 supply check sum values y ′ p and y ′ q to check sum predictor circuit 800 of fig2 . it is noted that circuits ( not shown ) very similar to those of fig2 are likewise provided for the generation of checksum values a ′ p and a ′ q from accumulated sums ( modulo ( r − 1 )) of the values a i , p and a i , q respectively for i = 0 , 1 , . . . , m − 1 . similarly , checksum values b ′ p and b ′ p are generated from similar circuits ( also not shown ). similar circuits also generate the values n ′ p and n ′ q from the n i , p and n i , q values . since these circuits are identical in structure and operation and differ only in the naming of the signal components , like the circuits mentioned just above they are also not shown herein . the addition operation indicated in equation ( 1 ) is carried out by adder 820 which performs addition modulo ( r − 1 ) and accordingly , like the other adders in the checksum system , includes a high order carry out signal output which is fed back as a low order carry input , as shown . multiplexors 824 , 825 , 826 , and 827 are operated under control of two signal lines . a first signal control line ( p / q ) controls multiplexors 824 and 826 to select between the two independent processor element chains for n p and n q processing . a second signal control line ( select add ) controls multiplexors 825 and 827 to effect the cumulative addition operation indicated by the summation from i = 0 to ( m − 1 ) in equation ( 1 ). in order to calculate the intermediate checksum values a ′ p b ′ p and a ′ q and b ′ q a final addition operation is performed which adds together the contents of the p 0 and p 1 registers ( reference numerals 821 and 822 , respectively ) via operation of the select add control line . adder 820 is also responsible for the final addition which generates ( ab )′ p and ( ab )′ q by adding together the previous checksum values , stored in registers 831 and 832 , with the cumulative checksums ( ny )′ p and ( ny )′ q . this results in the generation of the p checksum and q checksum values from registers 831 and 832 respectively . these signal lines are supplied to main checksum generation block 670 ( in fig2 ). in particular , the p checksum and q checksum signal lines are supplied to comparators 657 a and 657 b , respectively , as shown in fig2 . accordingly , attention is now focused on the structure and operation of fig2 . the main function of block 670 is the calculation of the left hand side of equation ( 1 ). as above , this circuit has two parts devoted to split calculations based on n p and n q operations as when the processor elements in fig7 are split by controlling a middle processing element so as to force it into operating in the pe 0 mode . each processing element chain ( the n p chain or the n q chain ) outputs results of the modular multiplication operation 2k bits at a time . accordingly , the circuit for generating the checksum value z ′ for the z variable is implemented as two adders with k bits each . additionally , because of the splitting , there are actually a total of four adders shown in fig2 . for the n p chain , for example , adder 656 a , processes the high order bits output from the multiplication operation that produces each high order k bit output from the chain working on the modulo n p multiplication . after all of the 2k bit portions have been added together , multiplexor 656 a 2 is operated to add together the sums in the high order register z ′ p , h and the low order register z ′ p , l . this resulting sum is compared with the p checksum value by comparator 657 a to produce an error indication error 2a , if there is no match . it is also noted that the adders in fig2 all perform addition modulo ( r − 1 ) and include a carry feedback out of the high order position into the low order position . the bottom circuit shown in fig2 is structured and operates in the same way as the upper circuits . however , as is clearly evident the bottom circuit is associated with and operates on signals generated during calculations modulo n q based on the splitting of the processor element chain as described . accordingly , the lower circuit in fig2 generates the z ′ q checksum signal from the modulo n q calculations , which resultant value is compared in comparator 657 b to generate error signal error 2b , if there is no match . thus , the output of block 670 is describable as : error 2a or error 2b . thus , at the end of each modular multiplication operation , an error signal is available which functions to provide an indication that all hardware elements have worked as designed to produce the intended result . additionally , fig2 also shows the inclusion of auxiliary computation circuit 653 . this circuit is used to perform auxiliary operations such as z = j + k , z = j − k and z = j mod n . checksum operations for these calculations are optional but preferable . the calculations carried out by auxiliary computation circuit 653 are relatively simple in comparison with the modular multiplication features . residue checking for these calculations are also relatively simple . for the addition operation z = j + k , the checking mechanism is to make sure that the value of z mod ( r − 1 ) is the same as the value of the modulo ( r − 1 ) sum of ( j mod r − 1 ) and ( k mod r − 1 ), where r is an even integer . similarly , to check the operation of z = j − k , one is to check if the value of z mod ( r − 1 ) is the same as the value of the modulo ( r − 1 ) difference of ( j mod r − 1 ) and ( k mod r − 1 ). as for the operation of the modular reduction z = j mod n that is implemented by a long division , z is the remainder of j divided by n . one has the expression j = qn + z , where q is the quotient . the error checking for this modular reduction operation can be carried out by comparing the value of j mod ( r − 1 ) and the modulo sum of ( q mod ( r − 1 ))( n mod ( r − 1 )) and ( z mod ( r − 1 )). while many of the concepts presented above have been couched in terms of what are seemingly purely mathematical algorithms , the applications involved are really directed to the encryption , transmission and decryption of messages in whatever form these messages may be represented , as long as they are in digital form , or its equivalent ( octal , binary coded decimal or hexadecimal ). in these methods for encryption , transmission and decryption , messages are represented by large integers expressed in binary form so that for purposes explaining the theory , operation and value of the methods and devices presented herein , the description is necessarily of a mathematical nature . nonetheless , the devices and methods describes herein provide practical methods for ensuring secure communications . as such the devices and methods described herein represent practical implementations of mathematical concepts . it is also noted that the operation of the circuits described herein are meant to occur over a repeated number of cycles . the description herein sets forth the ideal number of cycles generally required for proper operation in the most general situations . however , neither the specification nor claims should be interpreted as being limited to the most general cases . in particular , it is noted that suboptimal control methods can sometimes lead to operation of the circuits for more cycles than is absolutely necessary , either by accident or by design . the scope of the claims herein should not be so narrowly construed as to forego this inclusion . likewise , for certain input situations , the full number of cycles normally required for the most general cases is not required . accordingly , some of the claims herein recite the operation for at most t cycles . clearly , for its intended use in encryption and decryption , the circuits herein have been designed to handle the most general cases . the claims , however , should not be construed to be so narrow as to exclude either the simpler cases or the cases of deliberate operation over more than the necessary number of cycles . accordingly , from the above , it is seen that all of the objectives indicated are achieved by the circuits and processes described herein . in particular , it is seen that there is provided a circuit and process for carrying out multiplication of relatively large numbers modulo n using either multiplier and adder arrays or a plurality of nearly identical processing elements . it is also seen that these same circuits can be used not only to implement modular exponentiation but can also be employed as part of hardware circuits for implementing solutions to problems based on the chinese remainder theorem . it is even further noted that the objective of providing pipelined operations for a series of connected processing elements is achieved in a manner in which all of the processing elements are functioning at all times to produce desired final or intermediate results . and it is also seen that circuits are provided for carrying out functions which are ancillary to the processes described above and , in particular , circuits and processes for producing negative multiplicative inverses . while such inverses are providable in a data processing system via software or by means of prior ( and perhaps separate ) computation , the processes and circuits shown herein are capable of providing this function in a short period of time with relatively simple hardware which takes advantage of already existing circuit registers and other elements . from the above , it is clear that the circuits shown in applicants &# 39 ; figures fulfill all of the objects indicated . additionally , it is noted that the circuit is easy to construct and takes full advantage of the parallelism brought about by structuring one of the operands in the multiplication process as m blocks of k bits each . in particular , it is seen that the circuit shown herein carries out a two - phase operation , one of which computes x i and y i , with the second phase computing a value for z i which eventually , at the last step , becomes a desired result . in particular , it is seen that the circuit shown in applicants &# 39 ; figures provides a desired trade off between multipliers which have to be n bits by n bits in size and between serial circuits which operate with only one bit of a factor being considered at each step . while the invention has been described in detail herein in accordance with certain preferred embodiments thereof , many modifications and changes therein may be effected by those skilled in the art . accordingly , it is intended by the appended claims to cover all such modifications and changes as fall within the true spirit and scope of the invention . | 6 |
referring now to the drawings and more particularly to the fig1 and 2 , the wire clamp of this invention is shown to advantage and generally identified by the numeral 10 . the clamp 10 comprises a casing 11 having a cone - shaped cavity 11 &# 39 ; and jaws 12 operable to engage walls of the cavity 11 &# 39 ; about a wire 13 . the jaws 12 may have a transversely curved and longitudinally tapered configuration which together forms a cone , which contiguously engages cone - shaped walls of the cavity 11 &# 39 ;. the interior walls at which the jaws 12 mate are each provided with a central rectilinear groove 12 &# 39 ; which together are nominally smaller than the diameter of the wire 13 . it has been found to advantage to fabricate the jaws 12 by forming a cone - shaped member , drilling the member rectilinearly to form the grooves 12 &# 39 ;, and then to cut the cone rectilinearly in half . of course , three jaws 12 may be formed by rectilinearly cutting a cone - shaped section into three portions . in operation , the wire 13 is threaded through the casing 11 with the apex thereof in the direction of loads ( as shown by the vector line ). the jaw grooves 12 &# 39 ; may be provided with knurling 12 &# 34 ; operable to conform to the wire - like rope wire 13 . the casing 11 may be disposed in the hole 14 of a flange 15 which is secured to a deadman ( not shown ). the hole 14 may be of any size or configuration sufficient to retain outer walls of the casing 11 . it may also be seen that a casing 11 may be provided in a structural member by providing the cone - shaped cavity 11 &# 39 ; in the structural member itself . the clamp 10 may secure cable , wire , sheathed wire , and the like . referring to the fig3 a further embodiment of the clamp 10 comprises a casing 11 identical to that described above , and a plurality of ball - jaws 17 . the jaws 17 are of a size suitable to be inserted into the cavity 11 &# 39 ; about the wire 13 . it has been found to advantage to fabricate the ball - jaws 17 of a semiductible material such as copper , aluminum , zinc or the like , to insure that the jaws 17 will grip with the wire 13 . the ball - jaws 17 may also be provided with suitable knurling ( not shown ). in operation , the wire 13 is threaded as set out above . a pair or more usually three , ball - jaws 17 are inserted into the cavity 11 &# 39 ; without the wire 13 , and the wire 13 is caused to draw the casing 11 and jaws 17 together . it is to be understood that the present wire clamp 10 is operable in various electrical applications , such as tie downs , tie down terminals , and the like . elements of the wire clamp 10 may be insulated or not according to requirements of the particular application . referring to the fig4 the wire clamp 10 may be employed in a wire guide kit 18 for securing a mast 19 . the kit 18 comprises a mast strap 20 , crosstree 21 secured to the mast strap 20 by a turnbuckle 22 and the clamps 10 . the strap 20 may be a strip having a pair of overlapping holes 20 &# 39 ;. the crosstree 21 is a plate - like member having a central turnbuckle receiving hole 21 &# 39 ; and a pair of clamp receiving holes 21 &# 34 ; disposed distally from each of the terminal ends of the crosstree 21 . the bolt 22 is a substantially j - shaped member having a threaded shaft portion 22 &# 39 ;. the kit 18 is assembled by disposing a suitably sized strap 20 about a mast 19 and securing it with the hook or &# 34 ; j &# 34 ; portion of the bolt 22 . the crosstree 21 is then engaged through the hole 21 &# 39 ; and secured thereto to a nut 23 . cables 13 may be threaded through the holes 21 &# 34 ; of the crosstree 21 , and the clamps 10 may be engaged distally from their rearwardmost terminal ends engaged through the crosstree 21 , and the casings 11 engaged with the holes 21 &# 34 ;. the cables 13 may then be tightened at the crosstree 21 by tightening the nut 23 on the turnbuckle 22 . having thus described in detail a preferred apparatus which embodies the concepts and principles of the invention and which accomplishes the various objects , purposes and aims thereof , it is to be appreciated and will be apparent to those skilled in the art that many physical changes could be made in the apparatus without altering the inventive concepts and principles embodied therein . hence , it is intended that the scope of the invention be limited only to the extent indicated in the appended claims . | 5 |
referring now to fig1 and 2 , a dewar assembly is shown having a readout integrated circuit ( roic ) substrate 2 of a semiconductor material , preferably silicon . an ir detector array 4 is positioned on the substrate 2 and includes a plurality of individual detector elements , also called pixels , 6 . although fig2 shows only a 5 × 6 rectangular array of detector pixels 6 , it is understood that a typical ir integrated circuit generally includes a planar ir detector array with up to several hundred by several hundred pixels 6 . in most commercial applications , ir detectors are usually uncooled and detect the intensity of ir radiation by sensing increases in temperature which result from the heat imparted to the detectors by the ir radiation . a typical example of an uncooled ir detector is a vanadium oxide ( vox ) microbolometer ( mb ), in which a plurality of individual detectors are usually formed in an array on the roic substrate 2 by conventional semiconductor manufacturing processes . the mb array detects ir radiation by sensing the ir - generated heat , and is also called a focal plane array ( fpa ) or a sensor chip assembly ( sca ). the substrate 2 is an integrated circuit used to process the signal produced by the bolometers . in this case the bolometer is a microbridge resistor that changes its resistance when it is heated up . the incoming radiation causes a change in the temperature of the microbridge . although other semiconductor materials such as si may be used , vox is a commonly available and cost effective material that is used in most commercial ir detection applications . the vacuum - sealed dewar assembly includes a seal 8 ( fig4 ) surrounding the ir detector array to seal off the detector array from the atmosphere . the seal 8 can be , for example , an indium , gold - tin , or lead solder , with the height of the seal precisely controlled when it is deposited on the substrate 2 or preferably wafer 10 . the seal 8 supports a second substrate , here an ir transparent window 10 , here for example , silicon so that with wafer level packaging the window wafer 10 must have compatible thermal expansion coefficient with the fpa wafer which is also silicon . the wafer 10 includes : a plurality of trenches formed in a surface of the wafer 10 to form protrusions 16 having sidewalls to form , here for example , column - like protrusions 16 ( fig3 b ) separated by gaps 18 ( fig3 a ) and getter material members 19 on the sidewalls , shown more clearly in fig5 a . the protrusions 16 are preferably rectangular columns for ease of manufacture , but other shapes can also be used . the getter material members 19 may grow as , for example , noodle - like members , rod - like members , cone - shaped members or lumpy globs of getter material . more particularly , the getter material 19 grows on individual sites of the sidewalls of the trenches so that a plurality of getter material members project outwardly from the sidewall of the protrusion . a detailed perspective view of the ir window 10 is shown in fig3 a , which illustrates a preferred embodiment of an etched center portion of the ir window 10 surface facing the detector array ( the array portion ( i . e ., the ir transmissive part of the window ) 21 , ( fig3 a and 5 ) and the protrusions 16 ( i . e ., the getter grating portion 23 ) in another portion of the same surface adjacent the edges of the ir window 10 . the width of the trenches is by design narrow enough restrict the arriving angle of the depositing atoms of getter material to a very small angle , typically less than about 3 degrees . a range of the ratio of depth to width may be between about 5 to 1 to 10 or greater to 1 . although it is preferred that the getter grating portion 23 surround the array portion 21 so that the getter traps residual gas molecules inside the dewar body , the getter portion 23 can be implemented at other locations inside the dewar body as long as it does not block ir radiation from striking the detector array . silicon is the preferred material for the second substrate , i . e ., the ir window , because it has the same thermal expansion coefficient as the si fpa wafer . germanium is more widely used as an ir window in conventional metal or ceramic packages as it has a wide transmittance spectrum with a usable wavelength range of about 2 - 50 micrometers . however its expansion rate is much higher than si . ge could be used in this application if the wafer dimensions were small enough , and bonding temperature was compatible . the surface on which the ir window portion and the getter portion are etched at the same time into the face the substrate and is positioned inside the dewar assembly when it is sealed . the column - like protrusions forming the protrusions 16 and the recesses providing the array portion 21 are both preferably etched into the surface of the ir window 10 using a conventional etching method for silicon , and can be etched in a single step or in two separate steps . the getter material 19 ( fig5 a ) is preferably metals deposited by vacuum evaporation onto the surface of the second substrate , i . e ., the ir window surface , at a very oblique angle ( grazing angle , less than 2 or 3 degrees ). the metal atoms will initially nucleate in points on the sidewalls of the column - like protrusions . further deposition will grow from these points into the depositing direction . as each grain grows , it shadows the area immediately behind it , forcing the growth to form the getter material 19 ( fig5 a ) growing into the direction of the arriving atoms . if the trench structure of the above - described u . s . pat . no . 5 , 701 , 008 is etched into a silicon ( si ) lid wafer using very narrow trenches , a getter material from a source 30 ( fig5 ) deposited ˜ vertically ( 90 degrees to the plane of the lid wafer 10 ) will form such getter material 19 on the walls of the protrusions 16 , as well as conformally coat the top surface of the protrusions 16 . the array portion ( ir window ) 21 and hermetic seal area 8 are masked during this deposition by a shadow mask , a technique commonly used in the coating industry . the resulting surface area of the deposited getter material will be greater than the geometrical area of the surfaces of the sidewalls of the projections plus the top surface of the protrusions 16 . the getter material ( i . e ., source 30 ) may be , for example , titanium , which reacts with gas molecules to form metal oxides , carbides , hydrides and nitrides . these compounds are highly stable and relatively permanent at room temperature once they are formed , and therefore the risk of future gas release from these compounds is nearly nonexistent . species of residual gas molecules that are usually found in an outgassed vacuum - sealed dewar assembly include oxygen , nitrogen , hydrogen , methane , carbon monoxide and carbon dioxide . an effective getter metal is titanium . the getter material ( an unoxidized metal , such as titanium ) is deposited in a way that causes it to form a very non - dense structure with a large surface area ( like scales on a butterfly wing ). the metal is preferably vacuum evaporated into narrow trenches between the column - like protrusions 16 etched into the surface of the wafer level package ( wlp ) cap wafer 10 ( i . e ., the afore - described second substrate 10 ) at a grazing angle of incidence with respect to the sidewalls of the protrusions 16 the getter material will nucleate at random points on the sidewalls of the protrusions and subsequent arriving atoms will collect on the nuclei and grow the getter material 19 into the direction of the depositing source 30 . self - shadowing enhances the growth of the getter material 19 growth . the structure will have a greater effective area than the geometric area of the trench . metal deposited on the wafer surface will have only the geometric area . the whole dewar assembly can be fabricated in a vacuum chamber using a conventional process such as that described in u . s . pat . no . 5 , 433 , 639 . contaminants are removed from the substrate and the ir window as well as the solder and getter materials . the substrate and the ir window are then baked in the vacuum chamber at a temperature of about 250 degrees c . to further remove the contaminants . to fabricate the solder seal , a film of solder is preferably deposited onto narrow metalized strips of the window wafer substrate surface surrounding the getter and window ( detector array ) areas . the two wafers are then soldered or hybridized together in the vacuum chamber . the dewar assembly is then cooled and the solder seal solidifies . the hermetically sealed dewar assembly is thereby produced in the vacuum chamber , and can be removed from the chamber thereafter . it should be understood that the formation of the getter material 19 on the sidewalls of the trenches may also be applied to single dewar assemblies as well as to wafer level packaging ) a number of embodiments of the disclosure have been described . nevertheless , it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure . for example , the column - like protrusions may be tapered by the etch chemical and / or crystallographic structure to provide an optimal deposition angle with respect to a deposition at 90 degrees to the wafer surface . accordingly , other embodiments are within the scope of the following claims . | 8 |
the following description and examples illustrate a preferred embodiment of the present invention in detail . those of skill in the art will recognize that there are numerous variations and modifications of this invention that are encompassed by its scope . accordingly , the description of a preferred embodiment should not be deemed to limit the scope of the present invention . a sensor strip is provided that contains two chambers : a reaction chamber and a detection chamber . a sample is received in the reaction chamber , wherein components of the sample undergo an immuno - reaction . one or more products of the immuno - reaction are detected in the detection chamber in order to quantitate the antigen present in the sample . the reaction chamber and detection chamber are arranged such that sample may flow from the reaction chamber into the detection chamber . after the immuno - reaction has taken place in the reaction chamber , at least some of the reacted sample is transferred to the detection chamber , where the presence of a probe is detected and analyzed to obtain a result . it is preferred that sufficient sample is transferred such that the detection chamber is sufficiently filled , namely , that sufficient sample is transferred to the detection chamber such that the presence of a probe may be detected and analyzed by the detection method employed . the reaction chamber contains antibodies to the antigen of interest immobilized within it . the antibodies can be immobilized on a wall of the chamber itself . alternatively the antibodies may be immobilized on a support contained within the reaction chamber . suitable supports include , but are not limited to , fibrous materials , macroporous materials , powdered materials , or , in particularly preferred embodiments , beads of a material such as are commonly known in the art for supporting antibodies . in the preferred embodiments , the immobilized antibodies are bound to what is referred to as a “ pseudo - antigen ” linked to a probe . the pseudo - antigen - probe binds to the immobilized antibody , but not as strongly as the antigen of interest . if , for example , the antigen to be detected is a human protein , then a suitable pseudo - antigen - probe may include an animal version of the same protein , such as a dog protein or a pig protein , linked to the probe . in this example , antibodies to the human version of the protein are immobilized in the reaction chamber and the animal version of the protein , linked to a suitable probe , is bound to the immobilized antibody to form an antibody - pseudo - antigen - probe complex . when sample fills the reaction chamber , a small fraction of the pseudo - antigen - probe dissociates into solution , since it is relatively weakly bound to the antibody . a dynamic equilibrium will exist between bound pseudo - antigen - probe and free pseudo - antigen - probe , leaving some free antibody binding sites . if there is antigen in the solution , then it will strongly bind to the free antibody binding sites in preference to the pseudo - antigen - probe and so leave the pseudo - antigen - probe in solution . this process will continue until substantially all of the antigen in the sample has bound to the antibodies and there is an equal amount of pseudo - antigen - probe free in the solution . thus each antigen that binds to an immobilized antibody will displace one pseudo - antigen - probe into solution . when all , or a pre - determined fraction , of the antigen in the sample is bound to the immobilized antibodies , the concentration of pseudo - antigen - probe in solution reflects the original concentration of antigen in the sample . in the preferred embodiments , the equilibrium between free and bound pseudo - antigen - probe is relied upon to ensure that antigen in solution ends up bound to the antibody in preference to the pseudo - antigen - probe . hence , a pseudo - antigen - probe is employed that binds more weakly to the antibody than the target antigen , but there is no need to physically remove the pseudo - antigen - probe from the antibody prior to sample introduction , as in certain prior art methods . after the immuno - reactions have taken place , the liquid sample containing any pseudo - antigen - probe liberated from the antibodies is transferred to the detection chamber . in the detection chamber , the concentration of pseudo - antigen - probe present in the sample is measured and a result obtained . a small amount of the pseudo - antigen - probe may dissociate into solution even in the absence of antigen in the sample , as a result of the bound and free pseudo - antigen - probe reaching equilibrium in solution . if this occurs , then the signal generated in the detection chamber due to this free pseudo - antigen - probe is treated as a background signal , which is subtracted from the antigen concentration result as part of the analysis procedure . in copending application ser . no . 09 / 616 , 433 filed jul . 14 , 2000 , incorporated herein by reference in its entirety , an immunoassay strip with a linked immuno - reaction and detection chamber is described . unlike the sensor described herein , which employs a pseudo - antigen - probe initially complexed with an antibody immobilized on a surface within the reaction chamber , in the sensor of application ser . no . 09 / 616 , 433 , prior to the introduction of sample into the reaction chamber , antibodies are immobilized on one surface and antigen - probe is immobilized on another surface of the reaction chamber . when sample is introduced into the reaction chamber , the antigen - probe dissolves into the solution and competes with antigen in the sample for the antibody sites . the method of using the sensor of application ser . no . 09 / 616 , 433 relies primarily on kinetic factors to ensure that the antigen binds to the antibody ( by getting there first ) in preference to the antigen - probe . hence , there is a need to spatially remove the antigen - probe from the antibody in the reaction chamber , and the sensor can function when the antigen and the antigen - probe bind with equal strength to the antibody . in preferred embodiments , the sensor is a single step , no - wash immunosensor . the sensor is a single use , disposable device that employs a reaction chamber and a detection chamber . any suitable detection method can be utilized . suitable detection methods include , for example , visual detection wherein the development of a color is observed , or spectroscopic detection wherein reflected or transmitted light is used to measure changes in light absorbance . in a preferred embodiment , the detection method is electrochemical , wherein the electrical current or potential related to the products of immuno - reactions is measured . methods and devices for obtaining electrochemical measurements of fluid samples are discussed further in copending u . s . patent application ser . no . 09 / 616 , 556 , filed on jul . 14 , 2000 , which is incorporated herein by reference in its entirety . the timing of the various test stages , i . e ., the reaction stage and the detection stage , may be done manually . alternatively , timing may be done automatically in response to a trigger signal generated when the reaction chamber and / or detection chamber is filled . embodiments of sensors suitable for use with electrochemical detection are illustrated in fig1 and 2 and in fig3 and 4 . fig1 is a top view of a first embodiment of a sensor strip and fig2 is a cross - sectional view , showing details of the reaction chamber and the detection chamber . fig3 is a top view of a second embodiment of a sensor strip and fig4 is a cross - sectional view , showing details of the reaction chamber and the detection chamber . the immunosensors of the present invention may be prepared using well - known thin layer device fabrication techniques as are used in preparing electrochemical glucose sensing devices ( see , e . g ., u . s . pat . no . 5 , 942 , 102 , incorporated herein by reference in its entirety ). such techniques , with certain modifications , may also used to prepare immunosensors utilizing non - electrochemical detection methods . in the preferred embodiments of the immunosensors illustrated in fig1 and 2 and in fig3 and 4 , the detection chamber comprises an electrochemical cell . the immunosensors may be prepared by assembling various thin layers of suitably shaped materials according to thin layer sensor fabrication methods as are well known in the art . typically , the fabrication process involves sandwiching one or more spacer layers between a top layer and a bottom layer . in a preferred embodiment , the sensor 20 is an electrochemical cell 28 utilizing an enzyme , e . g ., glucose oxidase or glucose dehydrogenase , as the probe , as illustrated in fig1 a top view of such a sensor 20 , and fig2 a cross section of the sensor through line a - a ′. the reaction chamber 22 and detection chamber 28 are prepared by forming an aperture extending through a sheet of electrically resistive material 36 . the aperture is shaped such that it defines a sidewall of both the reaction chamber 22 and the detection chamber 28 , as well as the sample passageway 38 between the two chambers 22 and 28 . by extending the aperture from the proximal end 24 of the reaction chamber 22 through to the edge of the sheet 37 , the sample ingress 24 is also formed . in one embodiment , the thickness of the sheet 36 defines the entire height of the reaction chamber 22 and detection chamber 28 , which are the same . in another embodiment , the height of the reaction chamber 22 is greater than that of the detection chamber 28 . a reaction chamber 22 of greater height than the detection chamber 28 is prepared by layering multiple sheets 32 , 34 , and 36 together . the middle sheet 36 of the layer has an aperture defining the sidewalls 74 and 76 of both the reaction chamber 22 and detection chamber 28 as described above . this middle layer 36 is sandwiched between two or more additional layers 32 and 34 , the additional layers 32 and 34 having an aperture defining the side wall 74 of the reaction chamber 22 only , the layers 32 and 34 thereby defining end walls 60 and 62 of the detection chamber 28 . in this embodiment , the end walls 60 and 62 of the detection chamber comprise electrodes 52 and 54 , which may be prepared as described below . as illustrated in fig2 antibodies 44 are tethered to the bottom 40 of the reaction chamber 22 . the pseudo - antigen - probe 50 is complexed to the antibodies 44 . the antibody may be tethered to any suitable surface within the reaction chamber , e . g . tethered to a wall or on a surface of a support within the reaction chamber 22 . a first thin electrode layer 52 is mounted or formed on one side 70 of the sheet of electrically resistive material 36 , extending over the aperture forming the detection chamber 28 and forming an end wall 60 . the layer 52 may be adhered to the sheet 36 , e . g ., by an adhesive . suitable adhesives include , for example , heat activated adhesives , pressure sensitive adhesives , heat cured adhesives , chemically cured adhesives , hot melt adhesives , hot flow adhesives , and the like . the electrode layer 52 may be prepared by coating ( e . g ., by sputter coating as disclosed in wo97 / 18464 , by screen printing , or by any other suitable method ) a sheet of electrically resistive material 32 with a suitable material , for example , aluminum , copper , nickel , chromium , steel , stainless steel , platinum , palladium , carbon , carbon mixed with a binder , indium oxide , tin oxide , mixed indium / tin oxides , gold , silver , iridium , mixtures thereof , conducting polymers such as polypyrrole or polyacetylene , and the like . if electrode 52 is to be used as a cathode in the electrochemical cell , then suitable materials include , for example , aluminum , copper , nickel , chromium , steel , stainless steel , platinum , palladium , carbon , carbon mixed with a binder , indium oxide , tin oxide , mixed indium / tin oxides , gold , silver , iridium , mixtures thereof , conducting polymers such as polypyrrole or polyacetylene , and the like . if electrode 52 is to be used as an anode in the electrochemical cell or is to come into contact with oxidizing substances during sensor manufacture or storage , then suitable materials include , for example , platinum , palladium , carbon , carbon mixed with a binder , indium oxide , tin oxide , mixed indium / tin oxides , gold , silver , iridium , mixtures thereof , conducting polymers such as polypyrrole or polyacetylene , and the like . materials suitable for use as electrodes 52 and 54 are compatible with the reagents present in the sensor 20 , namely , they do not react chemically with reagents at the potential of choice or during sensor fabrication and storage . a second thin electrode layer 54 is mounted on the opposite side 72 of the electrically resistive material 36 , also extending over the aperture forming the detection chamber 28 , so as to form a second end wall 62 . in this embodiment , the inert , electrically insulating layer 36 separates the electrode - bearing substrates 32 and 34 . preferably , insulating layer 36 keeps layers 32 and 34 at a predetermined separation . provided this separation is small enough , e . g ., less than or equal to about 500 microns , the current flowing between the electrodes 52 and 54 will be directly proportional to the concentration of reduced mediator after a suitably short time relative to the detection time employed . in this embodiment , the rate of current rise is directly related to the rate of the enzyme reaction and therefore the amount of enzyme present . in certain embodiments , an electrode configuration other than an opposing relationship may be preferred , for example , a side - by - side relationship , or a parallel but offset relationship . the electrodes may be identical or substantially similar in size , or may be of different sizes and / or different shapes . the electrodes may comprise the same conductive material , or different materials . other variations in electrode configuration , spacing , and construction or fabrication will be apparent to those of skill in the art . in a preferred embodiment , the electrode layers 52 and 54 are mounted in a parallel opposing relationship at a distance of less than or equal to 500 , 450 , 400 , 350 , 300 , 250 , or 200 microns , and more preferably from about 5 , 10 , 15 , 20 , 25 , 30 , 35 , 40 , 45 , or 50 microns to about 75 , 100 , 125 , 150 , or 175 microns . in certain embodiments , however , it may be preferred that the electrode spacing is greater than 500 microns , for example , 600 , 700 , 800 , 900 , or 1000 microns , or even greater than 1 , 2 , 3 , 4 , or 5 millimeters . the volume of the detection chamber or the reaction chamber is typically about 0 . 3 microliters or less to about 100 microliters or more , preferably about 0 . 5 , 0 . 6 , 0 . 7 , 0 . 8 , or 0 . 9 microliters to about 20 , 30 , 40 , 50 , 60 , 70 , 80 , or 90 microliters , and most preferably about 1 . 5 , 2 , 2 . 5 , 3 , 3 . 5 , 4 , 4 . 5 , or 5 microliters to about 6 , 7 , 8 , 9 , 10 , 12 , 14 , 16 , or 18 microliters . however , in certain embodiments , larger or smaller volumes may be preferred for one or both of the reaction chamber and the detection chamber . the electrodes 54 and 52 in the detection chamber 28 can be placed in electrical connection with a meter ( not shown ) through the connection end 66 . the connectors ( not shown ) are in electrical connection with the electrodes 54 and 56 in the detection chamber 28 via conducting tracks ( not shown ). in the preferred embodiment illustrated in fig1 these conducting tracks consist of extensions of the films of conductor 52 and 54 coated onto the internal surfaces of 32 and 34 . the meter in connection with the connection area 66 is capable of applying a potential between the electrodes 52 and 54 in the detection chamber 28 , analyzing the electrical signals generated , displaying a response , optionally storing the response in memory , and optionally transmitting stored responses to an external device such as a printer or computer . in other embodiments utilizing electrochemical detection , stripes of conducting material on one or both internal faces of the detection chamber are typically used , with at least two electrodes present , namely , a sensing electrode and a counter / reference electrode . optionally , a third electrode , serving as a separate reference electrode , may be present . when utilizing potentiometric detection methods , the meter is capable of measuring the potential difference between a sensing electrode and a reference electrode , but need not be capable of applying a potential between the electrodes . in embodiments wherein visual detection or reflectance spectroscopy is the detection method used , the layers 32 and 46 and / or layers 34 and 42 are transparent to the wavelength of radiation that is to be observed . in the case of visual detection , a simple color change in the detection chamber 28 is observed . in the case of reflectance spectroscopy , detection radiation is shone through layers 32 and 46 and / or layers 34 and 42 , and radiation reflected from the solution in the detection chamber 28 is analyzed . in the case of transmission spectroscopy as the detection method , layers 32 , 46 , 34 , and 42 are transparent to radiation at the wavelength of choice . radiation is shone through the sample in the detection chamber 28 and the attenuation of the beam is measured . in a preferred embodiment , layer 36 comprises a substrate with a layer of adhesive ( not shown ) coated on its upper surface 70 and lower surface 72 . examples of materials suitable for the substrate of layer 36 include polyester , polystyrene , polycarbonate , polyolefins , and , preferably , polyethylene terephthalate . these may be native materials or may be filled with suitable fillers to confer desirable optical or mechanical properties . examples of materials suitable as fillers include , but are not limited to , titanium dioxide , carbon , silica , and glass . examples of suitable adhesives are pressure sensitive adhesives , heat and chemically curing adhesives and hot melt and hot flow adhesives . alternatively , the spacer layers themselves may consist of a suitable adhesive . if a sample ingress 24 has not already been formed earlier in the fabrication process , then one is provided , for example , by forming a notch ( not illustrated ) in the edge 37 of the device 20 that intersects the reaction chamber 22 . the dashed circle in fig1 denotes an aperture 30 piercing layers 32 , 34 , and 36 but not layers 42 and 46 , the aperture in layer 34 opening into the detection chamber 28 . since layers 42 and 46 are not pierced initially , the only opening to the atmosphere of the detection chamber 28 is the sample passageway 38 opening into the reaction chamber 22 . thus , when the reaction chamber 22 fills with sample , the sample passageway 38 to the detection chamber 28 is blocked . this traps air in the detection chamber 28 and substantially prevents it from filling with sample . a small amount of sample will enter the detection chamber 28 during the time between when the sample first contacts the opening 38 to the detection chamber 28 and when the sample contacts the far side of the opening 38 . however , once the sample has wet totally across the opening 38 to the detection chamber 28 , no more filling of the detection chamber 28 will take place . the volume of the reaction chamber 22 is typically chosen so as to be at least equal to and preferably larger than the volume of the detection chamber 28 . by opening the vent 30 to the atmosphere , sample is transferred to fill the detection chamber 28 . the vent may be opened by means of a needle connected to a solenoid in the meter . an immunosensor 100 of another embodiment , as depicted in fig3 and 4 , may be prepared as follows . a first shaped layer 112 and a second shaped spacer 114 layer of similar thickness are each situated atop a bottom layer 116 . the first spacer layer 112 is rectangular in shape , and is situated at the proximal edge 118 of the bottom layer 116 . the second spacer layer 114 is also rectangular in shape , and is situated on the bottom layer 116 at a distance apart from the first spacer layer 112 . the distal edge 120 of the first spacer layer 116 and the proximal edge 122 of the second spacer layer 114 form portions 120 , 122 of the side walls of the reaction chamber 124 . the bottom layer 116 forms the bottom wall 126 of the reaction chamber 124 . antibodies 164 are tethered to the bottom 126 of the reaction chamber 124 . the antigen - probe or pseudo - antigen - probe 162 is bound to the tethered antibodies 164 . a third shaped spacer layer 128 , similar in shape to the first shaped spacer layer 112 , is situated atop the first shaped spacer layer 112 . a fourth spacer layer 130 has a slit 132 extending through the proximal end 134 of the spacer layer 130 towards the center of the spacer layer 130 . the fourth spacer layer is 130 situated atop the second shaped spacer layer 114 with the proximal ends 122 , 134 aligned . the slit 132 in the fourth spacer layer forms the sidewalls ( not illustrated ) of the detection chamber 132 . the portion 138 of the second spacer layer exposed by the slit 132 in the fourth spacer layer 130 forms the bottom 138 of the detection chamber 132 . the proximal end 140 of the slit 132 forms the passageway 140 between the reaction chamber 124 and the detection chamber 132 . the proximal end 134 of the fourth spacer layer 130 forms a portion 134 of the sidewall of the reaction chamber 124 . a fifth shaped spacer 142 , similar in shape to the first shaped spacer layer 112 and third shaped spacer layer 128 , is situated atop the third spacer layer 128 . a sixth shaped spacer layer 144 , similar in shape to the second shaped spacer layer 114 , is placed atop the fourth shaped spacer layer 130 , with the proximal ends 146 , 122 aligned . the portion 170 of the sixth spacer layer exposed by the slit 132 in the fourth spacer layer 130 forms the top 170 of the detection chamber 132 . an aperture 148 extends through the sixth shaped spacer layer 144 . the distal end 150 of the aperture 148 and the distal end 152 of the slit 132 are aligned . the aperture 148 forms a portion 150 of a sidewall of a vent 154 , allowing displacement of air from the detection chamber 132 as it fills with sample . a top layer 156 is fitted over the fifth spacer layer 142 and sixth spacer layer 144 . the top layer 156 also includes an aperture 158 of similar size and shape and in alignment with the aperture 148 in the sixth shaped layer 144 . in certain embodiments , it may be preferred to delay the filling of the detection chamber 132 to some time after sample has filled the reaction chamber 124 , to allow time for the immuno - reactions to proceed in the reaction chamber 124 . in these embodiments , this is achieved by forming a vent hole 158 in layer 116 and / or 156 after completion of the immuno - reactions . when the reaction chamber 124 fills with sample , air is trapped in the detection chamber 132 , which prevents it from being filled with sample . at a suitable time after sample has filled the reaction chamber 124 , at least one of the top layer 156 and the bottom layer 116 can be punctured above the vent hole 148 or below the vent hole 154 by a suitable device , such as a needle or blade . when this occurs , the air in the detection chamber 132 can vent through the hole 148 or hole 154 formed in layer 116 and / or 156 via aperture 148 or 154 , thus allowing sample to be drawn into the detection chamber 132 from the reaction chamber 124 by capillary action and the displaced air to be vented . the height of the detection chamber 132 is typically selected to be less than the height of the reaction chamber 124 such that , in combination with the surface energies of the faces of chambers 132 and 124 , the capillary force in the detection chamber 132 will be greater than that in the reaction chamber 124 . the stronger capillary force in the detection chamber 132 serves to draw sample into the detection chamber 132 while emptying the reaction chamber 124 . this method of using differentials in capillary force to fill a chamber is described in detail in copending application ser . no . 09 / 536 , 234 filed on mar . 27 , 2000 . in preferred embodiments , the height of the reaction chamber is typically greater than the height of the detection chamber . the height of the detection chamber is typically about 500 microns or less , preferably about 450 , 400 , 350 , 300 , 250 microns or less , and more preferably about 5 , 10 , 15 , 20 , 25 , 30 , 35 , 40 , 45 , or 50 microns to about 75 , 100 , 125 , 150 , 175 , or 200 microns . these detection chamber heights are particularly well suited to applications wherein the top and bottom walls of the detection chamber comprise electrode layers . however , there may be certain embodiments wherein electrochemical detection is employed wherein cell heights greater than about 500 microns may be preferred . these detection chamber heights may also be suitable when detection methods other than electrochemical detection are employed . when another detection method is employed , for example , an optical detection method , different cell heights may be preferred . in such embodiments , a cell height of about 600 , 700 , 800 , or 900 microns or more , or even about 1 , 1 . 5 , 2 , 2 . 5 , 3 , 3 . 5 , 4 , 4 . 5 , or 5 mm or more may be preferred . the height of the reaction chamber is typically greater than that of the detection chamber . however , in certain embodiments it may be preferred to employ a reaction chamber having the same or a similar height as the detection chamber , or even a smaller height than the detection chamber . the detection chamber height is typically from about 5 microns or less to about 1 , 1 . 5 , 2 , 2 . 5 , 3 , 3 . 5 , 4 , 4 . 5 , or 5 mm or more , preferably about 900 , 800 , 700 , 600 , or 500 microns or less , more preferably about 450 , 400 , 350 , 300 , or 250 microns or less , and most preferably from about 5 , 10 , 15 , 20 , 25 , 30 , 35 , 40 , 45 , or 50 microns to about 75 , 100 , 125 , 150 , 175 , 200 , or 250 microns . when the immunosensor 100 is an electrochemical sensor 100 , the top surface of the second spacer layer 138 and the bottom surface 160 of the sixth spacer layer 144 which are exposed by the slit 132 in the fourth spacer layer 130 may be partially or completely coated with a conducting material . alternatively , layers 114 and 144 may themselves be made of electrically conductive materials . electrical connection between the two conducting layers ( not illustrated ) and a meter ( not illustrated ) enable electrochemical measurements to be conducted within the detection chamber . for purposes of illustration , details of the fabrication of sensors of preferred embodiments are discussed with reference to the sensor depicted in fig3 and 4 . the sensor strip 100 is typically constructed of layers of material laminated together . one or more spacer layers 128 , 130 are used to space layers 112 and 114 apart from layers 142 and 144 . the spacer layers have adhesive faces to allow layers 112 , 128 , and 142 and layers 114 , 130 , and 144 to be held together . alternatively , the spacer layers themselves may consist of an adhesive , or may comprise a material capable of adhering to adjacent layers by the application of heat and / or pressure in a lamination method . the detection chamber 132 is a capillary space where layers 114 and 144 form the end walls of the space and the thickness of layers 128 , 130 define the height . layers 114 and 144 can also serve as substrates for electrode coatings ( not illustrated ) that form the electrodes of an electrochemical cell or may act as the electrodes themselves by virtue of being constructed of electrically conductive materials . in construction , detection chamber 132 is typically formed by punching out , or otherwise removing a portion of layer 130 . this cutout portion of layer 130 can also serve to define the electrode area of the electrochemical cell . the reaction chamber 124 can be formed by punching or otherwise removing a portion of the spacer layers , with the areas removed such that the reaction chamber overlaps with the detection chamber 132 , thus causing the detection chamber 132 to open into the reaction chamber 124 . layers 116 and 156 can then be laminated to the external face of layers 112 , 114 and layers 142 , 144 , respectively , to form the end walls 126 , 174 of reaction chamber 124 . the immuno - chemicals 164 and 162 can be coated onto an internal face 126 and / or 174 of layers 116 and / or 156 prior to or following the lamination of 116 and 156 onto layers 112 , 114 and layers 142 , 144 , respectively . layers 116 and 156 can be adhered to layers 112 , 114 and layers 142 , 144 , respectively , by an adhesive layer on the external face of layers 112 , 114 and layers 142 , 144 , respectively , or on the internal face of layers 116 and 156 . the vent 148 and / or 154 can advantageously be formed by punching a hole through layers 114 , 130 , and 144 . from the point of view of simplifying the strip fabrication process , it is particularly advantageous to form vent 148 and / or 154 at the same time as the cut - out portion for the reaction chamber 124 and / or the detection chamber 132 is formed , as this makes it easier to achieve a reproducible spatial relationship between the chamber ( s ) and the vent , and also reduces the number of process steps . in a different embodiment , the vent 148 , 154 , 158 , can be formed by punching through layers 114 , 116 , 130 , 144 , and 156 and additional tape layers ( not illustrated ) laminated over both ends of the hole thus formed . this has the advantage of permitting optimization of the properties of layers 116 and 156 and the vent hole covering tape layers ( not illustrated ) separately . alternatively , vent hole 148 , 154 , 158 can be formed by punching through layers 114 , 130 , 144 and 116 or 156 prior to the lamination of layers 116 or 156 , respectively . this leaves an opening of 158 to only one face of the strip 100 and thus only one covering tape is used . in a further embodiment , the layers 116 and 156 can be formed and laminated to layers 114 and 144 such that layers 116 and 156 do not extend to cover the area where the vent 158 is formed . then it is only necessary to punch through layers 114 , 130 and 144 to form the vent 148 , 154 , 158 and additional tape layers ( not illustrated ) laminated over both ends of the hole thus formed . the layers may be adhered to each other by any suitable method , for example , pressure sensitive adhesive , curable adhesives , hot melt adhesives , lamination by application of heat and / or pressure , mechanical fasteners , and the like . the above - described configurations for the sensor are but two of many possible configurations for the sensor , as will be appreciated by one of skill in the art . for example , the vent may be provided through the top of the strip , the bottom of the strip , both the top and bottom of the strip , or through one or more sides of the strip . the vent may be of any suitable configuration , and may extend directly into a portion of the detection chamber , or may follow a circuitous path into the detection chamber . the detection chamber may be of any suitable shape , for example , rectangular , square , circular , or irregular . the detection chamber may abut the reaction chamber , or a separate sample passageway between the reaction chamber and the detection chamber may be provided . sample may be admitted to the reaction chamber on either side of the strip , as in the sensor of fig4 and 3 , or only through one side of the strip with the opposite side blocked by a spacer , as in fig1 and 2 . the detection chamber may be of any suitable shape , for example , rectangular , square , circular , or irregular . the detection chamber may be contained within the body of the strip , and access to the detection chamber may be provided by one or more sample ingresses through the top , bottom , or sides of the strip . typically , a particular configuration is selected such that the fabrication method may be simplified , e . g ., by performing fewer steps or by using fewer components . when the sensor is an electrochemical cell , the electrode layers , for example , layers 52 and 54 of the sensor of fig1 and 2 , are provided with an electrical connector allowing the sensor 20 to be placed in a measuring circuit . at least one of the electrodes 52 or 54 in the cell 28 is a sensing electrode , i . e ., an electrode sensitive to the amount of oxidized or reduced form of an analyte in the sample . in the case of a potentiometric sensor 20 wherein the potential of the sensing electrode 52 or 54 is indicative of the level of analyte present , a second electrode 54 or 52 , acting as reference electrode is present which acts to provide a reference potential . in the case of an amperometric sensor 20 wherein the sensing electrode current is indicative of the level of analyte in the sample , at least one other electrode 54 or 52 is present which functions as a counter electrode to complete the electrical circuit . this second electrode 54 or 52 may also function as a reference electrode . alternatively , a separate electrode ( not shown ) may perform the function of a reference electrode . if the immunosensor 20 is operated as an electrochemical cell 28 , then the sheet 36 containing the apertures defining the reaction chamber 22 and / or detection chamber 28 comprises an electrically resistive material . in a preferred embodiment , sheets 32 and 34 also comprise an electrically resistive material . suitable electrically resistive materials include , for example , polyesters , polystyrenes , polycarbonates , polyolefins , mixtures thereof , and the like . preferred polyester is polyethylene terephthalate . in the sensor depicted in fig1 and 2 , the layers 32 and 34 are substrates coated with electrically conductive material 52 and 54 . the electrically conductive material 52 or 54 is coated on the surface 60 or 62 facing the detection chamber 28 and an adhesive layer ( not shown ) is coated on the surface 33 or 35 facing layer 42 or 46 , respectively . in the embodiment depicted in fig3 and 4 , the detection chamber 132 has electrically conductive coatings ( not illustrated ) on the internal face of 138 and 170 which are suitable for use as electrodes in an electrochemical sensor cell . also contained in the detection chamber 132 is a dry reagent layer 172 comprising a substrate for the probe enzyme and , if necessary , a redox species capable of cycling the enzyme between its oxidized and reduced forms and capable of being oxidized or reduced at the cell electrodes . a buffer may also be present to control ph in the detection chamber 132 . when the immunosensor is in use , the electrodes are connected to an external electronic meter device ( not illustrated ) through external connectors ( not illustrated ), for example , tongue plugs , as are known in the art . suitable connectors are disclosed in copending application ser . no . 09 / 399 , 512 filed on sep . 20 , 1999 and copending application no . 60 / 345 , 743 filed on jan . 4 , 2002 . if the immunosensor 20 , 100 is operated using a detection method other than an electrochemical detection method , then the materials from which the sensor is constructed need not be electrically resistive . however , the polymeric materials described above are preferred for use in constructing the immunosensors of preferred embodiments because of their ease of processing , low cost , and lack of reactivity to reagents and samples . in an alternative embodiment , an optical rather than an electrochemical detection system are used . according to this alternative embodiment , electrodes are not necessary and an external light source and photocell are used to analyze light transmitted through , or reflected from the solution in detection chamber . in one embodiment , it is preferred to shine the light through the top surface of the sensor then through the sample , where it is reflected off the lower sensor layer and then back up through the sample and the top layer , where it is detected . in another embodiment , light is shone in through the side of the detection chamber and totally internally reflected between the end faces of the detection chamber until it passes out through the other side of the detection chamber , where it is detected . in these embodiments , the layers above , to the side , and / or below the detection chamber are substantially transparent to the analyzing light that is passed through the layer or layers . the techniques described in copending application ser . no . 09 / 404 , 119 filed on sep . 23 , 1999 may be adapted for use with the immunosensors of preferred embodiments utilizing optical detection systems . alternatively , in certain embodiments it may be preferred to use a combination of electrochemical detection and optical detection methods , which is also described in application ser . no . 09 / 404 , 119 . reagents for use in the reaction chamber , e . g ., immobilized antibody , pseudo - antigen - probe , buffer , mediator , and the like , may be supported on the walls of the reaction chamber or on the walls of the detection chamber , on an independent support contained within chambers , within a matrix , or may be self supporting . if the reagents are to be supported on the chamber walls or electrodes , the chemicals may be applied by use of printing techniques well known in the art , e . g ., ink jet printing , screen printing , slot coating , lithography , and the like . in a preferred embodiment , a solution containing the reagent is applied to a surface within a chamber and allowed to dry . rather than immobilize or dry the reagents or other chemicals onto the surfaces of the reaction chamber or detection chamber , it may be advantageous to support them on or contain them within one or more independent supports , which are then placed into a chamber . suitable independent supports include , but are not limited to , mesh materials , nonwoven sheet materials , fibrous filling materials , macroporous membranes , sintered powders , gels , or beads . the advantages of independent supports include an increased surface area , thus allowing more antibody and pseudo - antigen - probe to be included in the reaction chamber , if desired . in such an embodiment , the antibody bound to the pseudo - antigen - probe is dried onto a piece of porous material , which is then placed in the reaction chamber . it is also easier during fabrication to wash unbound protein from independent supports , such as beads , compared to washing unbound protein off of the surface of the reaction chamber . in a particularly preferred embodiment , the antibody bound to the pseudo - antigen - probe is supported on beads . such beads may comprise a polymeric material , e . g ., latex or agarose , optionally encasing a magnetic material ( such as gamma fe 2 o 3 and fe 3 o 4 ). the bead material is selected such that suitable support for the antibody is provided . suitable beads may include those marketed as dynabeads ® by dynal biotech of oslo , norway . optionally , a magnet may be included in the meter to hold the magnetic beads in the reaction chamber and to stop them from moving to the detection chamber . in yet another embodiment , the walls of the reaction chamber are porous , with the antibody bound to the pseudo - antigen - probe incorporated into the pores . in this embodiment , the liquid sample is able to wick into the porous wall , but not leak out of the defined area . this is accomplished by using a macroporous membrane to form the reaction chamber wall and compressing the membrane around the reaction chamber to prevent leakage of sample out of the desired area , as described in u . s . pat . no . 5 , 980 , 709 to hodges , et al . suitable independent supports such as beads , mesh materials , nonwoven sheet materials , and fibrous fill materials include , polyolefins , polyesters , nylons , cellulose , polystyrenes , polycarbonates , polysulfones , mixtures thereof , and the like . suitable macroporous membranes may be prepared from polymeric materials including polysulfones , polyvinylidene difluorides , nylons , cellulose acetates , polymethacrylates , polyacrylates , mixtures thereof , and the like . the antibody bound to the pseudo - antigen - probe may be contained within a matrix , e . g ., polyvinyl acetate . by varying the solubility characteristics of the matrix in the sample , controlled release of the protein or antibody into the sample may be achieved . as illustrated in fig2 dried reagents 64 may optionally be disposed in the detection chamber 28 . these reagents may include an enzyme substrate ( used as a probe ) and a mediator , capable of reacting with the enzyme part of the pseudo - antigen - enzyme probe 50 to produce a detectable signal . the enzyme substrate and mediator , if present , are to be of sufficient amount such that the rate of reaction of any enzyme present with the enzyme substrate 64 is determined by the amount of enzyme present . for instance , if the enzyme is glucose oxidase or glucose dehydrogenase , a suitable enzyme mediator 64 and glucose ( if not already present in the sample ) is disposed into the detection chamber 28 . in an embodiment wherein an electrochemical detection system is used , ferricyanide is a suitable mediator . other suitable mediators include dichlorophenolindophenol and complexes between transition metals and nitrogen - containing heteroatomic species . buffer may also be included to adjust the ph of the sample in the detection chamber 28 , if necessary . the glucose , mediator , and buffer reagents 64 are present in sufficient quantities such that the rate of reaction of the enzyme with the enzyme substrate 64 is limited by the concentration of the enzyme present . the internal surface 40 of the substrate 42 , which forms the base of the reaction chamber 22 , is coated with pseudo - antigen - probe 50 bound to antibodies 44 to the antigen to be detected in the sample . the antibodies 44 are adsorbed or otherwise immobilized on the surface 40 of the substrate 42 such that they are not removed from the substrate 42 during a test . optionally , during or after application of the antibodies 44 to the internal surface 40 of the substrate 42 , an agent designed to prevent non - specific binding of proteins to this surface can be applied ( not shown ). an example of such an agent well known in the art is bovine serum albumin ( bsa ). a nonionic surfactant may also be used as such an agent , e . g ., triton ® × 100 surfactant manufactured by rohm & amp ; haas of philadelphia , pa ., or tween ® surfactants manufactured by ici americas of wilmington , del . the nonionic surfactant selected does not denature proteins . the coating 44 on the internal surface 40 of the substrate 42 is in the dry state when ready to be used in a test . in preferred embodiments wherein electrochemical detection is employed , enzymes may be used as the probe . examples of suitable enzymes include , but are not limited to , horseradish peroxidase , glucose oxidase , and glucose dehydrogenase , for example , pqq dependent glucose dehydrogenase or nad dependent glucose dehydrogenase . the probe can also be an enzyme co - factor . examples of suitable cofactors include , but are not limited to , flavin mononucleotide , flavin adenine dinucleotide , nicotinamide adenine dinucleotide , and pyrroloquinoline quinone . the co - factor is preferably linked to the antigen by a flexible spacer to allow the co - factor to bind to the apoenzyme . when the probe is a co - factor , the apoenzyme may optionally be co - dried with the enzyme substrate and mediator in the reaction chamber . the probe can also be a regulator of enzyme activity . examples of suitable enzyme regulators include , but are not limited to , kinases or phosphorylases . enzyme regulators may alter the activity of the enzyme by changing the state of phosphorylation , methylation , adenylation , uridylation or adenosine diphosphate ribosylation of the enzyme . enzyme regulators may also alter the activity of the enzyme by cleaving a peptide off the enzyme . when the probe is an enzyme regulator , the enzyme is co - dried with the enzyme substrate and mediator in the reaction chamber . the probe can be a protein subunit which is part of a multi - subunit complex . an example of such a protein subunit is one of the subunits in the multi - subunit enzyme cytochrome oxidase . the antibody and pseudo - antigen - probe can be complexed together before being dried into the reaction chamber . complexation conditions are chosen to minimize the amount of free ( uncomplexed ) pseudo - antigen - probe , as this species will increase the background signal in the assay . the amount of free antibody is also minimized as this species will bind antigen and stop it from displacing the pseudo - antigen - probe , thus reducing the sensitivity of the assay . for example , it is possible to optimize the complexation of pseudo - antigen - probes with antibodies by “ crowding ” the solutions with inert macromolecules , such as polyethylene glycol , which excludes volume to the proteins and thus raises their thermodynamic activity and enhances the affinity of their binding to one another . see , e . g ., minton , biopolymers , vol . 20 , pp 2093 - 2120 ( 1981 ). it is advantageous to have the antibody immobilized on beads before it is complexed to the pseudo - antigen - probe . this allows all the antibody sites to be occupied by exposing them to a high concentration of the pseudo - antigen - probe . excess pseudo - antigen - probe is then readily removed by centrifugation and washing of the beads . the immunosensor is most sensitive to antigen concentrations from about 1 nm to about 10 μm ( micromolar ). for an antigen with a relative molar mass of 100 , 000 , this corresponds to about 0 . 1 μg / ml ( micrograms / ml ) to about 1000 μg / ml ( micrograms / ml ). however , the sensor can be modified ( e . g ., by changing the separation between the electrodes , or by applying a different pattern of voltage pulses ) to assay antigen concentrations in the range 0 . 1 nm or less to 0 . 1 mm or more . the maximum detectable limit of the assay is determined by the concentration of pseudo - antigen - probe / antibody in the reaction chamber . this molar concentration is therefore set to correspond to the expected range of molar antigen concentrations that are typically encountered in samples of interest . for example , the concentration of c - reactive protein encountered in a typical pathology laboratory is from about 10 nm to about 10 μm ( micromolar ). examples of antigens that may be assayed include , but are not limited to , alpha - fetoprotein , carcinoembryonic antigen , c - reactive protein , cardiac troponin i , cardiac troponin t , digoxin , ferritin , gamma glutamyl transferase , glycated hemoglobin , glycated protein , hepatitis a , b and c , chorionic gonadotropin , human immunodeficiency virus , insulin , serum amyloid a , thromblastin , prostate specific antigen , prothrombin , thyroxine , tumor antigen ca125 , tumor antigen ca15 - 3 , tumor antigen ca27 / 29 , tumor antigen ca19 - 9 , and tumor antigen nmp22 . the sensors of preferred embodiments are not limited to the assay of human antigens , but are also suitable for use in veterinary and animal husbandry applications . also , if an antigen is too small to be immunogenic , then it can be attached to a carrier as a hapten and antibodies can be raised to it in this way . therefore the invention is not limited to the assay of protein antigens or to large molecules , but is also applicable to small antigens as well . antibodies suitable for use in the sensors of preferred embodiments include , but are not limited to , the natural antibodies , such as igg , igm and iga . suitable antibodies can also be made up of fragments of natural antibodies , such as f ( ab ) 2 or fab . the antibody can be composed of genetically engineered or synthetic fragments of natural antibodies , such as scfv ( single chain fragment variable ) species . the antibodies can be complexed to native antigen probes or to “ pseudoantigen ” probes . examples of pseudo - antigens include antigens from other species . for example , if human c - reactive protein is to be assayed then the pseudo - antigen may include canine , feline , equine , bovine , ovine , porcine or avian c - reactive protein . pseudo - antigens can also be made by modifying the native antigen . for example , if human c - reactive protein is to be assayed , then the pseudo - antigen may include a monomeric form of the native pentamer , or c - reactive protein which has had its amine , carboxyl , hydroxyl , thiol or disulfide groups chemically modified . using the sensor to determine the presence or absence of an antigen the sensor may be used to determine the presence or absence of an antigen in a sample as follows . referring to fig3 and 4 , the strip sensor 100 contains a reaction chamber 124 and a detection chamber 132 . sample is introduced into reaction chamber 124 via port 166 or 168 . the separation between layers 116 and 156 and the surface energy of their internal surfaces is such that the sample will be drawn into reaction chamber 124 by capillary action . reaction chamber 124 contains antibodies 164 immobilized to an internal face 126 of the reaction chamber 124 . pseudo - antigen - probe complexes 162 are bound to antibodies 164 such that substantially all the antibody recognition sites for the antigen are blocked by pseudo - antigen - probe 162 . in this embodiment , the probe is an enzyme . in fig4 the antibody is shown as coated only on one face 126 of the reaction chamber 124 , but it may advantageously be coated on more than one face 126 of the reaction chamber 124 or coated onto a separate support ( not illustrated ) that is contained in the reaction chamber 124 . however , for ease of fabrication it is typically preferred that the antibodies 164 are only coated on one portion of the reaction chamber 124 , or on a single support material . when a separate support is used to immobilize the antibodies 164 , the support is such that it does not enter the detection chamber 132 during the test . this can be achieved by , for example , adhering the support to at least one face 126 of the reaction chamber 124 , or by selecting the size or shape of the support such that it cannot enter through the sample passageway 134 into detection chamber 132 , or by selecting a support of sufficient density such that it remains on the lower face 126 of the reaction chamber 124 when the sample is transferred to the detection chamber 132 . when sample fills the reaction chamber 124 , the pseudo - antigen - enzyme probe 162 bound to antibody 164 contacts the sample and a small fraction of the pseudo - antigen - probe dissociates from the antibody 164 and into the sample . sufficient time is then allowed for the dynamic equilibrium between bound and unbound pseudo - antigen - enzyme probe 162 to be established . if antigen is present in the sample , the antigen , which binds more strongly to the antibody 164 than the pseudo - antigen - enzyme probe 162 , eventually displaces the pseudo - antigen - enzyme probe 162 . thus each antigen that binds to an immobilized antibody 164 will displace one pseudo - antigen - enzyme probe 162 into solution . the end of the reaction step is a predetermined time after the sample is introduced into the reaction chamber 124 . the predetermined time is set such that there is sufficient time for substantially all of the antigen in the sample to displace pseudo - antigen - enzyme probe 162 to bind to the antibody 164 . alternatively , the predetermined time can be set such that a known fraction of the antigen displaces the pseudo - antigen - probe 162 to bind to the antibody 164 . the time that the sample is introduced into the reaction chamber 124 can be indicated by the user , for example , by depressing a button on a meter ( not illustrated ) connected to the sensor 100 . this action is used to trigger a timing device ( not illustrated ). in the case of visual detection , no meter device is necessary . in such an embodiment , the user manually times the reaction period . in the case where electrochemical detection is used to detect the result of the immuno - reactions , the indication that sample has been introduced into the reaction chamber 124 can be automated . as described above , when sample fills the reaction chamber 124 , a small portion of the detection chamber 132 at its opening 140 into the reaction chamber 124 will be wet by sample . if electrochemical detection is employed then at least two electrodes ( not illustrated ) are present in the detection chamber 132 . if these electrodes ( not illustrated ) are placed in the detection chamber 134 , such that at least a portion of each electrode ( not illustrated ) is contacted by the sample during the filling of the reaction chamber 124 , the presence of the sample will bridge the electrodes ( not illustrated ) and create an electrical signal which can be used to trigger the timing device . a predetermined time after the timing device has been triggered , either by the user or automatically , the immuno - reaction phase of the test is deemed to be completed . when the immuno - reaction phase of the test is completed , the vent 158 to the atmosphere is opened . for example , a solenoid activated needle in the meter may be used to pierce layer 156 and / or layer 116 , or additionally layers 114 and 44 , thus opening the distal end 152 of the detection chamber 132 to the atmosphere . the piercing can be automatically performed by the meter , as in the example above , or manually by the user in the case of visual detection wherein no meter may be used , e . g ., the user inserts a needle through the layers 156 , 116 , 114 , and / or 144 into the detection chamber , thereby forming the vent 158 . the opening of the vent 158 to the atmosphere allows the air trapped in the detection chamber 132 to escape , thereby allowing the detection chamber 132 to be filled with reacted sample from the reaction chamber 124 . the reacted sample will be drawn into the detection chamber 132 due to increased capillary force in the detection chamber 132 compared to that present in the reaction chamber 124 . in a preferred embodiment , the increased capillary force is provided by suitably coating the surfaces 138 and 160 of the detection chamber 132 or , more preferably , by choosing the capillary distance for the detection chamber 132 to be smaller than that of the reaction chamber 124 . in this embodiment , the capillary distance is defined to be the smallest dimension of the chamber . when the detection chamber 132 is filled , the reagents 172 dissolve into the sample . the enzyme component of the reagent layer 172 reacts with the enzyme substrate and the mediator to produce reduced mediator . this reduced mediator is electrochemically oxidized at an electrode ( not illustrated ) acting as an anode in the detection chamber 134 to produce an electrical current . in one embodiment , the rate of change of this current with time is used as an indicator of the presence and amount of enzyme that is present in the reacted sample . if the rate of change of current is less than a predetermined threshold value ( taking into account that some pseudo - antigen - enzyme probe 162 is liberated into solution as a result of the dynamic equilibrium that is established between the free and bound pseudo - antigen - enzyme probe 162 ), then it is indicative of no significant amount of pseudo - antigen - enzyme probe 162 present in the reacted sample , indicating the lack of antigen present in the original sample . if the rate of change of current is higher than the threshold rate , it indicates that pseudo - antigen - enzyme probe 162 is present in the reacted sample in an amount greater than the threshold value , and thus antigen is also present in the sample initially . in one embodiment , the rate of change of the current is used to give a measure of the relative amount of antigen initially present in the sample . the above description discloses several methods and materials of the present invention . this invention is susceptible to modifications in the methods and materials , as well as alterations in the fabrication methods and equipment . such modifications will become apparent to those skilled in the art from a consideration of this disclosure or practice of the invention disclosed herein . consequently , it is not intended that this invention be limited to the specific embodiments disclosed herein , but that it cover all modifications and alternatives coming within the true scope and spirit of the invention as embodied in the attached claims . all patents , applications , and other references cited herein are hereby incorporated by reference in their entirety . | 6 |
the drum drilling apparatus of the present invention , comprises a lightweight , portable frame with adjustable telescoping tubular legs supporting a platform adapted to house a pneumatic control panel and a remotely controlled pneumatic drill that has vertical travel capability . the drill is connected to the platform by a vertically angular adjustable mounting plate , such that a drill bit is capable of penetrating any container at right angles to the container &# 39 ; s top surface or bung . with the adjustable features mentioned , this apparatus is capable of infinite adjustment about any container centered within the frame . the source of pressurized air can come from the cylinder of an emergency worker &# 39 ; s self contained breathing apparatus ( scba ) or from a gas powered compressor . from the preferred embodiment there are additional features that may be used , as dictated by the situation . such features are wheels and skid tubes , a suction / purge and sample adapter , and explosive protection . alternate embodiments incorporate adapters for drilling into liquid propane gas ( lpg ) cylinders , and wireless remote control operation . the drill assembly and control panel are commercially available units and their specific configuration or operation is not part of the present invention . the most practical advantage of this apparatus is that it is portable enough for one person to erect about a target container in a remote location with uneven terrain . this erection does not require the target container to physically disturbed . once erected , this apparatus can be powered with only standard emergency crew equipment . the advantages of this invention as applied to use in perforating containers , is best illustrated . referring to fig1 , a perspective view of the preferred embodiment of the drum drill apparatus arranged about a standard 55 gallon drum and with an explosion shield installed , the general arrangement of the various elements of the drum drilling apparatus can be seen . frame 2 holds platform 4 positioned above target container 1 by telescopic engagement between platform supports 6 which are slidingly engaged over leg 8 and front platform tube 10 or rear platform tube 12 . legs 8 have feet 60 for stabilization , and to serve as an anchor point for frame 2 when stakes ( not illustrated ) are driven into the underlying terrain , passing through feet orifices 62 . platform support 6 is made from two pieces of square tubing . leg tube 14 is affixed perpendicularly to platform tube 16 . leg tube 14 is sized so as to allow sliding engagement over the smaller tube of leg 8 . similarly , platform tube 16 is sized so as to allow engagement and telescopic adjustment within larger front platform tube 10 or rear platform tube 12 . bolts 20 are mechanically affixed to leg tube 14 , front platform tube 10 , rear platform tube 12 , and adjusting tube 84 . locking knobs 18 threadingly engage bolts 20 such that clockwise rotation advances pin 22 ( see fig5 ) into leg orifice 24 or substantially identical orifices on platform tube 16 ( not illustrated ). this engagement serves to lock platform 4 at the desired height on legs 8 and to lock legs 8 at the desired width to accommodate target container 1 . side strengthening tubes 80 span between legs 8 . adjusting tubes 84 are affixed to the distal ends of side strengthening tubes 80 and are sized so as to slidingly adjust over legs 8 , locking by engagement between locking knobs 18 and structure tube holes 86 . explosion blanket 82 is mechanically attached to structure tubes 25 of platform 4 by mechanical fasteners 200 . platform 4 is of a generally planar configuration . it has four structure tubes 25 affixed in a square configuration with two parallel mounting tubes 26 , attached perpendicularly between two of the parallel structure tubes 25 . upon the mounting tubes 26 are mechanically attached a first mount plate 28 and second mount plate 30 . between the mounting tubes 26 and the structure tubes 25 are structural strengthening tubes 32 . these serve to add rigidity to the platform . first mount plate 28 and second mount plate 30 are substantially identical , and both define mount plate bolt holes 34 . drill assembly 36 is bolted to pivot plate 56 of drill assembly mounting bracket 38 through pivot plate bolt holes 58 ( see fig8 – 11 ). drill assembly mounting bracket 38 is then secured to first mount plate 28 by threaded engagement between t - bolts 40 ( see fig6 ) and bolt holes 34 with t - bolts 40 passing through mounting bracket holes 42 ( see fig1 ). drill bit 66 is chucked into drill 36 and passes through splash plate 64 via splash plate orifice 70 . rear platform tube 12 has control panel mounting brace 44 mechanically fastened along its longitudinal axis so as to project upward and perpendicular to the plane of platform 4 . pneumatic control panel 46 is bolted to brace 44 with t - bolts 40 . pressurized air is supplied to control panel 46 from scba cylinder 48 through tubing 62 . static grounding clamp 50 , grounding wire 54 , and grounding stake 52 ( see fig2 ) are in electrical continuity by mechanical , non - insulated connection to metal platform 4 . looking at fig2 , a rear side view of the drum drill apparatus , control panel 46 can be clearly seen . scba cylinder 48 provides pressurized air to regulators system 64 through tubing 62 which routes the compressed air to operation switch 68 . operation switch 68 is connected to valve tee 72 by second tubing 74 . plunger 152 of operation switch 68 is attached to push disk 148 . valve tee 72 is hard piped to linear actuator air supply module 76 and drill motor air supply module 78 . suction ring 88 is attached to splash plate 64 such that the longitudinal axis of ring 88 projects normally from splash plate 64 . flexible suction ring seal 90 is attached to suction ring 88 . cam fitting 92 and inert gas / sample line 94 project from suction ring 88 . inside back strengthening tube 156 is slid into outside back strengthening tube 158 and locked into position with locking knob 18 . referring to fig3 and 4 together , the details of suction ring 88 can be seen . suction ring 88 is of a block configuration that defines central passage 96 and attachment holes 98 . bolts pass through attachment holes 98 and splash plate holes 100 . ( fig1 ) suction ring seal 90 is a hollow cylindrical flexible seal mechanically attached to suction ring 88 . cam fitting 92 and inert gas / sample line 94 are friction fit into passages of suction ring 88 that have their longitudinal axis perpendicular to central passage 96 . fig7 shows a perspective view of the drum drill apparatus with a wireless remote control start switch . here , push disk 148 of operational switch 68 has been replaced by wireless actuator 150 . this wireless actuator 150 is adapted to receive signals from a remote electronic transmitter ( not shown ) and respond by depressing plunger 152 so as to start the operation of drill assembly 36 . pressurized air is provided from regulators 65 to switch 68 through second tubing 74 . ( best illustrated in fig2 ) note , at this time pressurized air has also been provided through valve tee 72 to air supply module 76 . when plunger 152 is depressed the pressurized air is allowed to travel through switch 68 and continue through third tubing 75 to limit switch air supply module 78 . limit switch air supply module 78 in turn provides pressurized air to bottom limit switch 170 and top limit switch 174 . operation of the limit switches when conditioned appropriately provides pressurized air to air supply module 76 . air supply module 76 in turn provides pressurized air through pneumatic line 160 to spin air motor 162 and turn drill bit 66 . raising plunger 152 stops the flow of pressurized air through switch 68 . looking at fig2 and fig7 together it can be seen that the pressurized air paths from scba cylinder 48 through tubing 62 to regulators 65 are to both linear actuator air supply module 76 thru fifth tubing 77 , and drill motor air supply module 78 through valve tee 72 . drill motor air supply module 78 provides pressurized air to air motor 162 through fourth tubing 79 dependent upon the position of plunger 152 of switch 68 . linear actuator air supply module 76 provides pressurized air to linear actuator 166 via pneumatic line 160 . looking at fig8 – 13 the drill assembly mounting bracket &# 39 ; s 38 construction and operation can best be seen . side plates 102 are mechanically attached to base plate 104 and front plate 106 so as to maintain all plates in an approximately perpendicular arrangement . base plate 104 has bracket holes 42 for mounting to either first mount plate 28 or second mount plate 30 . spacer 110 and lock pin base 112 project normally from front plate 106 and are sandwiched between front plate 106 and pivot plate 108 . bolt 114 passes through first pivot hole 116 , second pivot hole 118 and third pivot hole 120 and is threaded into nut 122 . arced circumferential slot 124 accommodates locking pin 126 which threadingly engages into threaded lock pin orifice 202 passing through lock pin base 112 . shoulder 128 of locking pin 126 bears against pivot plate 108 generating enough friction to lock the position of pivot plate 108 relative to front plate 106 . when locking pin 126 is loosened , pivot plate 108 may tilt left ( fig1 ) or right ( fig1 ). the amount of tilt travel of pivot plate 108 is limited by the length of slot 124 which bears against locking pin 126 when engaged with pin base 112 . pivot plate bolt holes 58 allow drill assembly 36 to be bolted to pivot plate 108 . fig1 shows a side view of the drum drilling apparatus on uneven terrain . legs 8 remain vertically parallel to each other and substantially perpendicular to the plane of platform 4 , but the engagement of locking knobs 18 through leg tubes 14 and adjusting tubes 84 of side strengthening tube 80 are into different leg orifices 24 . fig1 and 16 illustrate a side view of the drum drilling apparatus with the wheel and skid tube assembly and ccd wireless tv remote controllable camera installed . wheel and skid tube assembly 130 is made from a modified strengthening tube 132 . it has spacer tubes 134 mounted near the distal ends that are adapted to hold a skid tube 136 approximately parallel to the modified strengthening tube 132 . the skid tubes have radiuses 142 at their distal ends . wheel mount plates 138 are mechanically affixed between the modified strengthening tube 132 and the skid tube 136 . wheels 140 are bolted to wheel mount plates 138 . the wheel and skid tube assemblies 130 are removably attached to legs 8 by end tubes 154 . this uses the same mechanical locking arrangement as is provided between the side strengthening tubes 80 and legs 8 . camera 144 resides on camera base 146 which is mechanically attached to platform 4 . now , to describe the overall operation we refer to fig1 , 2 , and 16 to 20 . all components are brought to the location of the container to be vented by drilling . if the terrain will accommodate wheels , or if the terrain is soft or muddy , the wheel and skid assembly 130 may need to be used . the wheels allow for the drum drill apparatus to assembled at a location away from the target container 1 and then wheeled to target container 1 . if the ground is soft , skid tube 136 will provide additional surface area to better bear the weight load of the apparatus . this will prevent feet 60 of legs 8 from sinking into the ground and causing an uneven or partially unsupported platform 4 . the skid tubes , having ends with radiuses 142 , also allow for the sliding of the assembled apparatus into position about target container 1 if the surface is too soft to allow wheels 140 to carry the full weight of the assembled apparatus . two legs 8 are slidingly inserted into end tubes 154 of each of the wheel and skid assemblies 130 and locking knobs 18 are tightened . similarly , side strengthening tubes 80 are connected to legs 8 . note that both the wheel and skid assemblies 130 and the side strengthening tubes 80 are of a fixed length and thus not adjustable . there are now a pair of unconnected leg assemblies . on one of the leg assemblies inside back strengthening tube 156 is slid over one leg 8 , and on the other leg assembly outside back strengthening tube 158 is slid over another leg 8 . outside back strengthening tube 158 is slid over the inside back strengthening tube 156 , and after telescopically adjusting for the width of target container 1 , locking knob 18 is tightened to prevent movement . leg tubes 14 of platform supports 6 are slid over legs 8 . frame 2 is now fully assembled . if needed , suction ring 88 with suction ring seal 90 , is bolted to splash plate 64 . leg tubes 14 are slid into front platform tube 10 and rear platform tube 12 . the two leg assemblies ( which comprise frame 2 ) are now connected . the width between the connected leg assemblies is telescopically adjustable between the leg tubes 14 and the front platform tube 10 and rear platform tube 12 in the same fashion as performed with inside back strengthening tube 156 and outside back strengthening tube 158 . frame 2 and platform 4 are now assembled . the height of platform 4 relative to target container 1 is set by raising platform 4 and tightening locking knobs 18 to engage the appropriate leg orifices 24 . platform height is set so that suction ring seal 90 contacts the top surface of the target container 1 . ( note , that this is also the method by which legs 8 are adjusted to compensate for uneven ground .) drill assembly 36 is generally left bolted to pivot plate 108 such that t - bolts 40 need only be inserted through bracket holes 42 and threadingly engaged with mount plate bolt holes 34 to attach drill assembly 36 to platform 4 . in a similar fashion , control panel 46 is attached to mounting brace 44 with t - bolts 40 . pneumatic line 160 is connected between drill assembly 36 and control panel 46 . in a similar fashion pneumatic line 160 is connected between linear actuator 166 and control panel 46 . scba cylinder 48 is connected to control panel 46 by tubing 62 . grounding stake 52 is pounded into the ground and grounding clamp 50 is clipped onto the target container 1 . camera 144 is mounted on platform 4 such that its viewing angle is correct . drill bit 66 is chucked into drill assembly 36 . the drill bit lengths are provided such as to be of the proper length for operation when platform 4 is set with suction seal ring 90 contacting the top surface of target container 1 . if suction rig 88 was installed , either a standardized , commercially available vacuum system ( not illustrated ) would be connected to cam fitting 92 and used to vent the escaping airborne gaseous or particulate contents of target container 1 or an inert cover gas cylinder would be connected so as to provide a supply of inert gas to blanket central passage 96 . the inert gas would eliminate any potential mechanical or static electrical sparks thus preventing any ignition and subsequent explosion of combustible vapors . the vacuum system may be fitted with the appropriate filtration media to capture the contents of target container 1 , whether particulate or gaseous . now , if needed , explosion blanket 82 is attached to frame 2 by mechanical fasteners 200 that are incorporated onto platform 4 . at this point , the drum drill apparatus in its assembled state is moved around target container 1 and the operator may proceed to drill the container . if not , the drum drill apparatus may be wheeled or slid into position around the container . the operator now either depresses push disk 148 of operation switch 68 or sends a wireless signal to wireless actuator 150 to depress plunger 152 of operation switch 68 , depending upon which configuration of remote operation is being used . both of these actions result in a movement of plunger 152 to send a pneumatic signal to drill motor air supply module 76 ( via the appropriate conditioning of top limit switch 174 and bottom limit switch 170 as discussed earlier ). drill motor air supply module 76 in turn provides the appropriate pressurized air to drill assembly 36 via line 160 . air motor 162 spins drill chuck 164 and causes linear actuator 166 to extend spinning drill chuck 164 downward as illustrated in fig1 . drill bit 66 will contact target container 1 and linear actuator 166 will continue to exert enough downward force to drill through the top surface of target container 1 . once there is a through hole , linear actuator will continue to drive drill chuck downward until bottom limit switch 170 contacts bottom stop 172 . bottom limit switch 170 is in pneumatic communication with drill motor air supply module 76 of control panel 46 such that activation of switch 170 stops the supply of air to drill assembly 36 stopping the spinning of air motor 162 and causes linear actuator 166 to retract spinning drill chuck 164 as shown in fig1 until top limit switch 174 contacts top stop 176 . fig2 shows an alternate embodiment wherein suction ring 88 is not present . when drilling liquid propane gas cylinders ( lpg ) 178 there is an additional obstacle to overcome in the form of the lifting handle 180 . to overcome this physical obstacle , lpg adapter 182 is bolted to splash plate 64 through adapter holes 184 in lpg base 186 . referring to fig1 it can be seen that lpg adapter 182 has down tube 188 affixed normally to base 186 . drill guide 192 has shoulder 198 that matingly conforms to inner recess 196 of down tube 188 . a long drill bit is used ( not shown ) and sized such that when chucked in drill assembly 36 the drill bit will extend through drill guide orifice 194 . this serves to support the drill bit and prevent it from “ wandering ” when drilling at long distances from drilling apparatus 36 . view holes 190 allow the operator to confirm that the bit is chucked tightly and still revolving . in operation , generally there is an absorbent pad placed over the splash plate to ensure there is no contamination from dripping liquids off of the drill bit upon return from drilling . this is not illustrated . while generally the frame 2 and platform 4 is made of aluminum for weight reasons , they may be made of carbon fiber , another metal or metal alloy or a polymer . operation and construction would be substantially the same , except if the frame were of a non electrical conducting material then there would need to be a direct connect between grounding clamp 50 and grounding wire 52 . | 1 |
the hydrocarbon composition of the invention was prepared by blending a ltft process derived hydrocarbon with a htft derived hydrocarbon . dht — refers to the hydroconversion process used primarily to upgrade the distillate contained in the htft slo . dht diesel — it refers to a htft process derived hydrocarbon which has been hydrotreated . gtl — this is a ltft process based on natural gas that optionally can also make use of alternative hydrocarbonaceous feeds to produce synthesis gas . sasol slurry phase distillate ™ ( sasol spd ™) diesel or gtl diesel — it refers to a ltft process derived hydrocarbon that is fully hydroconverted . two base fuels were used to prepare five hydrocarbon compositions including sasol spd ™ diesel and dht diesel for this investigation . the experimental blends contained mixtures of 15 %, 30 %, 50 %, 70 % and 85 % by volume sasol spd ™ diesel with the dht diesel . the properties of the neat sasol spd ™ diesel and dht diesel and blends thereof are summarised in table 1 , 2 , 3 and 4 . an example of the fuel properties of the fischer - tropsch hydrocarbon compositions of the invention and crude oil derived diesel ( us 2 - d diesel ) blends are also tabulated as illustrated in table 5 . another property which was considered was the heating value of the hydrocarbon compositions . there are two values , gross ( or high ) and net ( or low ) commonly quoted which vary according to whether the water content in the products of combustion is considered to be in liquid or gaseous form . the gross heating values ( q gross ) of the sasol spd ™ diesel — dht diesel blends were determined according to the american society for testing and material ( astm ) d240 test method . the net heating value ( q nett ) per mass was calculated using the following equation : where the difference between the two values is a function of the latent heat of condensation of water and hydrogen content of the composition . table 2 shows these results . the issue of lubricity is pertinent in the case of severely hydrotreated low - sulphur diesel . there are two common methods of assessing lubricity ; namely the scuffing load ball - on - cylinder ( sl bocle ) method and the hfrr . lubricity evaluation tests of the various hydrocarbon compositions are shown in table 3 and conducted according to both the astm d6078 and astm d6079 test methods . finally , the long - term storage stability of the neat sasol spd ™ diesel and dht diesel and hydrocarbon compositions comprising blends thereof was investigated according to the standard astm d4625 test method . the acid number and total insolubles formed over a period of 24 weeks at 43 ° c . were measured and reported to be smaller than 0 . 02 mgkoh / g and 1 . 35 mg / 100 ml respectively . the bromine number ( ip 129 procedure ), the acid number ( astm d694 test method ), oxidation stability ( astm d2274 ) and the water content ( astm d1744 test method ) of the fuel and the proposed blends were also measured and the results are shown in table 1 . it is evident that in all blends of dht diesel and sasol spd ™ diesel , the following measured quality characteristics apply : 1 — bromine number below 10 . 0 g br / 100 g . this is an indication of the residual olefin in the product . olefinic compounds are susceptible to gum formation and are less stable . 2 — acid number below 0 . 004 mg koh / g . this is an indication of , mostly , the residual organic acids and alcohols in the product and the tendency of the fuel to corrode . 3 — oxidation stability below 0 . 6 mg / 100 ml . oxygen stability is tested through the calculation of the amount of insolubles formed in the presence of oxygen . this is an indication of the behaviour of the fuel when exposed to atmospheric oxygen under standard storage conditions and measures the fuel &# 39 ; s resistance to degradation . 4 — water content below 0 . 004 % on a volume basis . this is an indication of the quality of the final fractionated product . entrained water can form stable emulsions and suspended matter , which cloud plug filters . characterisation and quantification of the composition of the neat sasol spd ™ diesel and dht diesel was obtained through fluorescent indicator adsorption ( fia ) and high performance liquid chromatography ( hplc ) ( see table 4 ). the diesel properties that are most important to ensure good engine performance and which influence emissions include cetane number , aromatics , density , heat content , distillation profile , sulphur , viscosity , and cold flow characteristics . these properties , among others , will be discussed below for the hydrocarbon compositions . density — diesel density specifications are tending to become tighter . this is due to the conflicting requirements of a lower density fuel to reduce particulate matter emissions , whilst retaining a minimum density to ensure adequate heat content , which relates to fuel economy . increasing ratios of dht to sasol spd ™ diesel would increase the hydrocarbon composition density , even beyond the minimum requirement of 0 . 800 kg / l , but not higher than its upper specified limit of 0 . 845 kg / l @ 15 ° c . ( see fig1 ). fig1 shows a linear relationship of fuel density with various sasol spd ™ diesel — dht diesel blends . heating values — fischer - tropsch synthetic fuels have much higher gravimetrical heating values than severely hydrotreated crude derived diesel and lower net volumetric heating values . aromatic compounds have a much higher density and volumetric heating value than naphthenes or paraffins with the same carbon number . the net volumetric heating value of the hydrocarbon composition increases with increasing dht diesel content . the net volumetric heating value of the composition containing equal amounts of sasol spd ™ and dht is 34 . 5 mj / l ( see fig2 ). fig2 shows gravimetrical and volumetric net heating values of hydrocarbon compositions of the invention viscosity — a fuel viscosity that is excessively low causes the injection spray not to penetrate far enough into the cylinder and could cause idling and hot start problems whereas high viscosity reduces fuel flow rates . all the hydrocarbon compositions described above are within the en 590 : 1999 diesel specification viscosity requirement . distillation profile — dht diesel has a much higher initial boiling point ( ibp ) than sasol spd ™ diesel ( see dht diesel distillation profile in fig3 ) and therefore a higher flash point than that of sasol spd ™ diesel . the hydrocarbon compositions of the invention comply with the en 590 : 1999 t95 diesel specification . fuels with higher end points tend to have worse cold flow properties than fuels with lower final boiling points and therefore the low maximum t95 limit for arctic grade diesel . sasol spd ™ diesel on the other hand has good cold flow properties as well as a high cetane number because of the predominately mono - and to a lesser extent di - methyl branching of the paraffins . sasol spd ™ diesel improves the cold flow properties of dht diesel with its higher t95 to meet the european summer climate grade cfpp values of − 5 ° c . and − 10 ° c . fig3 shows a distillation profile of sasol spd ™ diesel and dht diesel . cetane number — sasol spd ™ diesel , with a cetane number rating of 72 , improves the 57 cetane number of dht diesel linearly ( see fig4 ). fuels with a high cetane number ignite quicker and hence exhibit a milder uncontrolled combustion because the quantity of fuel involved is less . a reduction of the uncontrolled combustion implies an extension of the controlled combustion , which results in better air / fuel mixing and more complete combustion with lower nox emissions and better cold start ability . the shorter ignition delay implies lower rates of pressure rise and lower peak temperatures and less mechanical stress . the cetane numbers of the hydrocarbon compositions of the present invention are far beyond all specification requirements . fig4 shows a linear cetane number relationship of hydrocarbon compositions of the invention . other excellent properties of hydrocarbon compositions of the invention include their ultra - low sulphur content ( less , than 5 ppm ), no unsaturates or polycyclic aromatic hydrocarbons , low bromine number . according to the very low acid number and water content observed , the likelihood of the hydrocarbon compositions of the invention to corrode are very slim . mass and dimension change — ageing of nitrile rubber in the sasol spd ™ diesel caused the swollen pre - conditioned dumbbells to shrink and to loose weight ( see fig5 ). this effect was reduced with the blend of dht and sasol spd ™ causing the nitrile rubber to return to its original thickness and within 1 . 5 % of its original mass . exposure of the pre - conditioned nitrile rubber for another 166 hours to us no . 2 - d diesel causes a total increase of 10 % in the mass of new dumbbells . according to chemical resistance guide for elastomers ii , if loss in dimensions are smaller than 15 % from 30 days to one year , the description of attack can still be seen as excellent and little surface deterioration . fig5 shows percentage change in mass and thickness of new nitrile rubber dumbbells , pre - conditioned in us no . 2 - d and then further aged in a hydrocarbon composition comprising dht / sasol spd ™ diesel and us no . 2 - d diesel . tensile strength — all the diesel samples softens new elastomers . the sasol spd ™ diesel hardens the pre - conditioned nitrile rubber dumbbells and therefore increases its tensile strength ( see fig6 ). the mono - aromatic hydrocarbon content of the dht diesel reduces the tensile strength of the nitrile rubber to a lesser extent than that of us no . 2 - d diesel . elastomer compatibility — the effect of mono - aromatics in sasol spd ™ diesel on the physical properties of seals was studied with a hydrocarbon composition comprising 50 vol % dht with 50 vol % sasol spd ™ ( ft blend ). the physical properties of the untreated elastomers were taken as baseline . the overall change in mass , thickness , tensile strength and hardness of pre - conditioned standard nitrile rubber being exposed to the composition was compared with nitrile rubber being exposed to the base fuels . the nitrile rubber , an acrylonitrile butadiene copolymer , was pre - conditioned in highly aromatic us no . 2 - d diesel for 166 hours according to the astm test method for rubber property — effect of liquids ( astm d471 ), vulcanised rubber and thermoplastic elastomers — tension ( astm d412 ) and durometer hardness ( astm d 2240 ) respectively . average mass change , change in thickness , tensile strength and hardness of five new dumbbells , pre - conditioned and thereafter exposed to us no . 2 - d , fischer - tropsch diesel and a blend thereof are tabulated in table 6 . fig6 shows percentage change in tensile strength of nitrile rubber dumbbells , pre - conditioned in us no . 2 - d and then further aged in a hydrocarbon composition of the invention and us no . 2 - d diesel . hardness — exposure of nitrile rubber to the hydrocarbon composition of the invention makes indentation more difficult and hardens the pre - conditioned dumbbells . continuous exposure of the pre - conditioned dumbbells with us no . 2 - d diesel softens it further . the presence of dht diesel in the sasol spd ™ diesel reduces its hardening effect on the dumbbells . fig7 shows : percentage change in hardness of nitrile rubber dumbbells , pre - conditioned in us no . 2 - d and then further aged in the hydrocarbon composition of the invention and us no . 2 - d diesel . the hydrocarbon compositions of the invention have a very high consistent quality with an ultra - low sulphur content and a high cetane number . these compositions provide future fuel characteristics in a form that is compatible with current infrastructure and technology . synthesis gas can be produced either using reforming 4 of natural gas or gasification 1 of a suitable hydrocarbonaceous feedstock . the first process option results in synthesis gas 10 a and the latter 10 b , two streams possible of being interchangeable and / or manipulated to a required primary composition . this is illustrated by means of the dotted line linking 10 a and 10 b in said fig8 . either synthesis gas or a blend thereof is sent to a htft synthesis process 2 , resulting in a mixture of synthetic hydrocarbons and water . this is separated into at least two streams : stream 11 is an olefinic distillate and stream 17 which for illustration groups all non - distillate range hydrocarbons which might undergo further processing not shown in this description . stream 11 is sent to hydroconversion unit 3 to obtain the dht diesel 12 along with other by - products 16 not specifically defined in this invention but know to a person skilled in the art . in parallel , another portion of either synthesis gas or a blend thereof is sent to a ltft synthesis process 5 , also resulting in a mixture of synthetic hydrocarbons and water . this is separated into at least two streams . stream 13 comprises synthetic hydrocarbon species suitable to be hydroconverted in hydroconversion unit 6 to a distillate range sasol spd ™ diesel 14 and other products that for the purpose of this illustration are lumped as stream 18 . stream 19 from ltft unit 5 comprises all synthesis products not sent to the hydroconversion unit 6 . it will be apparent to a person skilled in the art that this product might be further processed beyond the scope of this invention . streams 12 — dht diesel — and 14 — sasol spd ™ diesel — can then be blended resulting in the ci fuel matter of this invention , stream 15 . the blending ratio for the two synthetic fuels might be between 1 : 100 to 100 : 1 , preferably 1 : 40 to 40 : 1 , and even more preferably 1 : 20 to 20 : 1 on a volume basis . hydroprocessing to obtain the synthetic distillates can be done in parallel units — as described before — or in a single one to optimize the process . in the latter case , illustrated by the dotted line linking streams 11 and 13 in fig8 , the blending ratio for the two synthetic feeds might be between 1 : 100 to 100 : 1 , preferably 1 : 40 to 40 : 1 , and even more preferably 1 : 20 to 20 : 1 on a volume basis . it is noted that while the two ft processes can be operated at separate locations respectively , there might be some significant synergy effects in running them together at the same location . these effects include better utilisation of the synthesis gas and integration of process utilities , as well as those derived from the product blend matter of this invention . | 8 |
in the descriptions that follow , like parts are marked throughout the specification and drawings with the same numerals , respectively . the drawing figures are not necessarily drawn to scale and certain figures may be shown in exaggerated or generalized form in the interest of clarity and conciseness . referring to fig1 and 2 , drawer slide assembly 100 is comprised of fixed member 102 , middle member 104 , drawer member 106 , and drawer retainer mechanism 108 . each member 102 , 104 , and 106 of drawer slide assembly 100 is generally c - shaped and includes a pair of races for housing ball - bearing assemblies . fixed member 102 is mounted to the inside of the cabinet frame of a furniture piece having a drawer using common attachment hardware such as wood screws . although three slides are shown , it is understood that a greater or lesser number of slides may be telescopically engaged with one another . proximate the front end of fixed member 102 is raised indention 114 located in race 115 for engagement with drawer retainer mechanism 108 . proximate the opposite end of fixed member 102 extends tab 112 . bumper 110 is attached to tab 112 . in one embodiment , bumper 110 is formed of rubber or similar deformable yet resilient material and is frictionally held in place on tab 112 via a slot which tab 112 extends through . in other embodiments , bumper 110 is formed of nylon or teflon ®. middle member 104 is slidingly engaged with fixed member 102 via a series of ball bearings 120 held in bearing retainer 124 . drawer member 106 is slidingly engaged with middle member 104 via a second series of ball bearings 122 held in a second bearing retainer 126 . drawer member 106 is mounted to the side of the drawer frame of the cabinet piece using common attachment hardware such as wood screws through a plurality of mounting holes . from rear end 107 of drawer member 106 extend arms 127 and 129 which define cavity 128 . arms 127 and 129 are slightly angled towards one another resulting in the distance between them being smaller than the height of drawer member 106 . the distance between arms 127 and 129 is slightly less the width of bumper 110 so that when engaged , drawer member 106 is frictionally held adjacent bumper 110 . in a preferred embodiment , drawer retainer mechanism 108 is attached to the front facing end of drawer member 106 opposite arms 127 and 129 and cavity 128 . as this front mounted feature is preferred for easier maintenance and replacement , it should be understood that the desired effect of preventing the inadvertent opening of the drawer and the rebound of the closed drawer can be accomplished if drawer retainer mechanism 108 were to be mounted on rear end 107 of drawer member 106 . as seen best in fig2 and 6 , drawer retainer mechanism 108 is comprised of frame 130 mounted to the front facing end of drawer member 106 , housing 140 contained in frame 130 , and detent 142 seated within housing 140 . frame 130 includes flanges 134 , 135 , 136 , 137 , and 138 which form a generally open - sided rectangular box . flange 134 connects frame 130 to drawer member 106 via a weld or other connection means common in the art . flange 135 opposes flange 134 . flange 138 includes threaded hole 132 . flange 138 opposes flanges 136 and 137 . flanges 136 and 137 are separated by gap 141 . as seen best in fig2 , 3 , and 4 , housing 140 is comprised of center support 171 , walls 173 and 175 , base support 177 , and guide wall 179 . the center support , walls , base support and guide wall form cavity 170 . hole 154 passes through center support 171 into cavity 170 . slot 158 is provided in base support 177 and is located opposite from and axially aligned with hole 154 . slot 158 includes open end 160 . open end 160 is less in width than slot 158 thereby creating a stepped recess and retaining detent 142 within cavity 170 . guide wall 179 includes guide ridges 190 and 192 . guide ridges 190 and 192 are integrally formed raised ridges generally parallel to each other and parallel to the longitudinal axis of screw 144 . housing 140 is preferably cast from plastic or similar lightweight yet durable material and is generally rectangular in shape . as shown in fig5 , detent 142 comprises a combined rectangular body 167 and rounded protrusion 166 . detent 142 further includes hole 156 having bottom 157 . channels 162 and 164 flank hole 156 and are spaced to slidingly engage guide ridges 190 and 192 . in one embodiment , channels 162 and 164 contain lubrication to ensure unencumbered linear movement of detent 142 with respect to housing 140 . the axes of channels 162 and 164 are generally parallel with the axis of hole 156 . detent 142 is preferably cast from plastic or similar lightweight yet durable material . in alternate embodiments , detent 142 is constructed of delrin , nylon or teflon ®. screw 144 includes threaded section 152 , spanner head 153 , and shaft 155 . spanner head 153 is shaped to accept a torsional force from a spanner . screw 144 adjustably attaches housing 140 and detent 142 to frame 130 as threaded section 152 engages threaded hole 132 . when assembled , screw 144 , threaded hole 132 , hole 154 , and hole 156 are axially aligned . spring 146 surrounds shaft 155 and is simultaneously constrained by shaft 155 , hole 154 and hole 156 . in an alternate embodiment , shaft 155 is not necessary as spring 146 is constrained by holes 154 and 156 . spring 146 passes through hole 154 and is seated in hole 156 . spring 146 provides a bias between frame 130 and bottom 157 thus forcing detent 142 out of housing 140 and extending protrusion 166 through slot 158 and through gap 141 . as shown in fig7 a , 7 b and 7 c , in use , a pair of drawer slide assemblies 100 are typically mounted one on each side of a drawer and to opposing inside surfaces of a cabinet piece . in an “ opened ” position as shown in fig7 a , the front end of drawer member 106 is extended beyond the front end of fixed member 102 . drawer retainer mechanism 108 is not engaged with raised indention 114 and bumper 110 is not wedged between arms 127 and 129 . as a result the drawer is free to slide in direction 220 to a fully open position . referring to fig7 b , during a closing sequence , a force applied in the closing direction shown by arrow 210 causes drawer member 106 and drawer retainer mechanism 108 to approach fixed member 102 . because spring 146 is compressed between threaded section 152 and detent 142 , the bias of spring 146 tends to force detent 142 out of housing 140 thus extending protrusion 166 through slot 158 and between flanges 136 and 137 through gap 141 . detent 142 is held within housing 140 by the result of the width of body 167 being wider than slot 158 . once protrusion 166 contacts raised indention 114 , raised indention 114 forces protrusion 166 , against the bias of spring 146 , to move in a direction parallel to the longitudinal axis of screw 144 through gap 141 and slot 158 until protrusion 166 has retreated towards housing 140 enough to successfully bypass raised indention 114 . guide ridges 190 and 192 engaged with channels 162 and 164 in cooperation with walls 173 and 175 prevent detent 124 from rotating or jamming within housing 140 during engagement with raised indention 114 . simultaneously , as protrusion 166 clears raised indention 114 , arms 127 and 129 engage bumper 110 . after passing raised indention 114 , spring 146 forces protrusion 166 through slot 158 and gap 141 away from housing 140 until body 167 abuts housing 140 . the force required to open or close the drawer can be adjusted by adjusting the compression of the helical spring . the compression of spring 146 increases as threaded section 152 is advanced . as the compression of spring 146 increases , the force required to move protrusion 166 through slot 158 and gap 141 toward housing 140 also increases . adjusting the position of threaded section 152 relative to detent 142 thus adjusts the force necessary to move protrusion 166 through slot 158 . rotating screw 144 in a clockwise direction shortens the distance between threaded section 152 and detent 142 thus compressing spring 146 and thus requiring a greater force to open or close the drawer . rotating screw 144 in a counter - clockwise direction lengthens the distance between threaded section 152 and detent 142 decompressing spring 146 and thus reducing the force necessary to open or close the drawer . during an opening sequence , a sufficient force is applied in the opening direction shown by arrow 220 . the opening force must overcome the frictional force between bumper 110 and arms 127 and 129 . simultaneously , raised indention 114 forces protrusion 166 , against the bias of spring 146 , through slot 158 . once protrusion 166 clears raised indention 114 , spring 146 forces protrusion 166 through slot 158 and gap 141 until body 167 abuts housing 140 and the drawer is free to slide to its fully opened position unencumbered . in a “ closed ” position as shown in fig7 c , drawer retainer mechanism 108 works cooperatively with bumper 110 and arms 127 and 129 to prevent the drawer from inadvertently opening without a sufficient force applied in the opening direction , as shown by direction arrow 220 . the combination of drawer retainer mechanism 108 and bumper 110 and arms 127 and 129 further prevents the drawer from rebounding from the closed position . in an alternate preferred embodiment shown in fig8 , housing 140 is mounted on tab 194 and constrained on one side by flange 196 . tab 194 extends from drawer slide 106 . tab 194 is integrally formed with drawer slide 106 . flange 196 is integrally formed with tab 194 . in another alternative embodiment , tab 196 is not present . housing 140 is mounted on tab 194 using common attachment hardware such as welding , rivets , or machine screws or with a suitable epoxy adhesive . plug 180 is threaded for engagement with threaded hole 182 and upon rotation advances or retreats through threaded hole 182 . spring 146 is constrained by threaded hole 182 and hole 156 in detent 142 . spring 146 is adjacent plug 180 and bottom 157 . spring 146 biases detent 142 against raised indention 114 . adjusting the position of plug 180 relative to detent 142 adjusts the compression of spring 146 and thus adjusts the bias of detent 142 against raised indention 114 . in an alternate preferred embodiment shown in fig9 , housing 140 is mounted on tab 194 and constrained by flange 196 . flexible member 186 is wedged between center support 171 of housing 140 and detent 142 . flexible member 186 is constructed of rubber or closed shell plastic shock absorbing foam or any resilient substance having compressive shock absorbing and rebounding features . flexible member 186 biases detent 142 against raised indention 114 . it will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof . it is understood , therefore , that this invention is not limited to the particular embodiments disclosed , but it is intended to cover modifications within the spirit and scope of the present invention as defined by the appended claims . | 0 |
throughout this description , the embodiments and examples shown should be considered as exemplars , rather than limitations on the apparatus and methods of the present invention . referring now to fig1 there is shown an air duct or plenum 100 of an hvac system , through which air is discharged in accordance with the operation of a suitable blower or fan 120 . a number of germicidal lamps 110 are mounted in a chamber 105 of the air duct 100 . the germicidal lamps 110 include a germicidal tube 111 coupled to and carried by a base 112 . for the germicidal lamps to operate effectively in the harsh environs of an air duct , it is preferred that germicidal lamps specifically designed for such environments be employed . in particular , the germicidal lamps sold by the assignee of this invention , steril - air u . s . a ., inc , and sold under the trademark , “ uvc emitter ,” are preferred . the base 112 contains electrical circuitry and ballast for energizing the germicidal tube 111 to emit ultraviolet radiation , preferably in the “ c ” band ( uvc ). although not shown in fig1 there may be a number of single - ended germicidal tubes coupled to a single base as shown in fig1 - 18 , with the base mounted on the outside of the duct 100 . such a configuration is disclosed in the co - pending application referred to above , “ single - ended germicidal lamp for hvac systems .” other configurations of germicidal tubes and bases are within the scope of the invention . a horizontal flow , flat heat transfer coil 130 and drain pan 140 of the hvac system are positioned within the chamber 105 , preferably upstream from the germicidal lamp 110 with reference to the air flow . while this is the preferred positioning , it is to be understood that the lamp 110 may also be positioned upstream from the coil 130 and drain pan 140 , whichever provides good uniform radiation coverage of the coil 130 and drain pan 140 and best accommodates the hvac system &# 39 ; s layout . the coil 130 , which is well known in the art , comprises circuited tubes 131 through which refrigerant circulates and a number of substantially flat , planar parallel fins 135 attached at generally regular spaces on the tubes 131 . the relationship between the coil tubes 131 and the fins 135 can be better appreciated from fig3 . the fins 135 increase the effective surface area of the tubes 135 to thereby increase heat transfer from the air to the surface of the coil 130 . because of the excellent heat transfer properties , low expense and ease of manufacture of aluminum , a typical coil is substantially constructed of this material . in general , for heat transfer , cost and manufacturing reasons , the fins 135 are rarely coated . coincidently , aluminum has in excess of 60 % reflectivity for the primary uv emission line , a wavelength of 253 . 7 nm . however , the method of the invention is also applicable to fins of other materials which are relatively good reflectors of uv &# 39 ; s primary emission line . further upstream from the coil 130 may be a number of filters 150 . referring now to fig2 there is shown a diagrammatic perspective view of the fins 135 and the germicidal lamps 110 . for a given fin 135 a , there is defined a plane 136 a of the fin 135 a . for a given germicidal tube 111 a , there is defined a longitudinal axis 113 a . preferably , the longitudinal axis 113 a of the germicidal tube 111 a is at a right angle to the plane 136 a of the fins 135 a . since the fins 135 are parallel and vertical , the germicidal tubes 111 will be at right angles and horizontal to the plane of all of the fins 135 . referring now to fig3 it can be seen that at least one germicidal tube 111 is also positioned so as to irradiate at least part of the drain pan 140 directly . in accordance with the invention , the coil &# 39 ; s tubes 131 and fins 135 reflect uv radiation from the germicidal tube 111 . the fins 135 also reflect uv radiation on into the drain pan 140 . accordingly , the surface of the drain pain 140 will also be irradiated through reflections of the uv radiation from the tubes 131 . in determining the spatial relationship between the germicidal tubes 111 and the coil 130 ( fig1 ), the objective is to obtain a uniform distribution of uv radiation across the coil &# 39 ; s face 130 a . ( the coil &# 39 ; s face 130 a also substantially defines the leading edge of the coil &# 39 ; s fins 135 .) it has been determined that , for a germicidal tube which is positioned in accordance with the invention , the spatial distribution of uv radiation follows precisely that of a diffuse area source and , surprisingly , not an isotropic point source . the pattern of uv radiation from a germicidal lamp is shown in fig4 . it can be seen that although the germicidal tube 111 is a source of radiation , the base 112 is effectively a secondary ( reflected ) source of uv radiation . the diffuse radiation of the germicidal tubes 111 and diffuse reflection is therefore defined as a near field effect , not as an inverse square law . this finding is contrary to normal expectations , and therefore placement of germicidal tubes in accordance with the present invention results in the need for fewer germicidal tubes . put another way , when the germicidal tubes 111 are positioned in sufficient proximity to the coil 130 , the intensity of uv radiation from the germicidal tubes 111 striking the coil 130 is , to a degree , independent of the distance of the germicidal tubes 111 from the coil 130 . in one embodiment of the invention , germicidal tubes , spaced 24 inches apart , were positioned at right angles to the plane of the fins and about twelve inches from the drain pan and twenty inches from the face of the coil . it has been found that positioning the germicidal tubes 111 20 inches from the leading edge 130 a of the fins 135 , in conjunction with appropriate germicidal tube - to - tube spacing , is particularly effective in inhibiting the growth of microorganisms on all surfaces of the coil 130 and in all surface areas of the drain pan 140 . as shown in fig4 the photons emitted from a particular point on the germicidal tube 111 radiate in all directions . because fig4 is an elevational view , the global radiation of these photons is not shown . these photons would , however , also radiate outwardly and inwardly from the plane of the paper upon which the planar representation is illustrated and from all surfaces of the tube 111 . in addition , to increase the photons applied to the coil and drain pan , a germicidal lamp with a reflector ( preferably incorporated in the base 112 ) is utilized . those photons emitted and reflected in a plane parallel to the planes of the fins 135 penetrate into the coil 130 and are reflected by the internal coil structure ( i . e ., the tube 131 and the fins 135 ). as illustrated in fig5 and 6 , because of the global emission of photons from the germicidal tube 111 , photons emitted from all points on the germicidal tube 111 and reflected from the base 112 , other than those emitted in a plane parallel to the planes of the fins 135 strike the fins 135 adjacent to their leading edge 130 a ( the edge closest to the germicidal tube 111 ) are reflected between the spaced parallel fins 135 in accordance to the angle of incidence that the photon takes . the fins 135 and circuited tubes 131 therefore reflect photons amongst one another such that the photons are applied throughout the coil 130 and the drain pan 140 . because the global emission occurs from all points along the longitudinal axis 113 a of the germicidal tube 111 , the flux density and uniformity of incidence to the fins 135 , the circuited tube 131 and the drain pan 140 increases in the manner diagrammatically illustrated by the reflectivity shown occurring between a pair of fins 135 in each of these figures . such increased flux density and dosage occurs between all of the spaced parallel fins 135 and drain pan 140 in this manner . however , for purposes of illustration , such increases are shown in fig5 occurring between only two adjacent fins . as can be seen from these figures , complete and uniform irradiation is achieved . preferably , the number and position of germicidal tubes is selected so that the uv radiation is uniformly distributed across the coil 130 and drain pan 140 . referring now to fig7 there is shown a diagrammatic illustration of the cross section of a vertical flow “ a type ” heat transfer coil 740 to illustrate positioning of germicidal tubes 711 a , 711 b perpendicular to the coil &# 39 ; s fins in accordance with one aspect of the invention . the germicidal tubes 711 a , 711 b , in base 712 , are positioned at right angles to the planes in which the fins 735 lie . the germicidal tubes 711 a , 711 b will also partially directly irradiate the drain pans 740 a , 740 b , while the coil 730 will cause direct and indirect ( reflected ) irradiation of the drain pans 740 a , 740 b in the manner described above . fig1 is a partial top view of the a coil and germicidal tube of fig7 . it has been determined that positioning the germicidal tubes such that their longitudinal axes are perpendicular to the parallel planes in which the fins extend causes the emitted uv radiation to be applied directly and indirectly to the heat transfer coil and surrounding areas in the path of emission and reflection , and on into the drain pan . the actual positioning of the germicidal tubes , and the number of germicidal tubes to be employed in order to attain these objectives , is determined based on the goal that the uv radiation is uniformly distributed across the coil and drain pan . because the uv radiation strikes the fins and circuited tubes at all incident angles , they continuously reflect and effectively direct the uv radiation within and throughout the coil . this continuous reflection and direction of the uv radiation increases the flux density of the photons applied to the coil , the drain pan and continues in the airstream until absorbed . the increased number ( flux density ) of incident photons also assures that organisms in the airstream are struck from all angles . also , the increased distance of photon travel , and thus available time of exposure , provides for a potentially greater dosage ( intensity multiplied by time ) to be received by any surface or airborne microorganism . in this manner the coil , drain pan and surrounding area are completely exposed to the uv radiation sufficiently to eradicate surface and substantially reduce airborne microorganisms . our continued research into the positioning and aiming of germicidal lamps and into various target environments for germicidal lamps has enhanced our understanding of them . for example , we have learned that the greatest “ time weighted ” amount of nutrient and moisture is in the cooling coil and not the drain pan . because of this , the most active region of microbial activity ( number ) in an air conditioning system is in the cooling coil and during and after the cooling cycle . this conflicts with our initial deduction that the drain pan , when the air conditioner is not running , is the most active region . as we focused on the cooling coil , we learned that in order to provide a complete kill throughout the cooling coil , a uniform distribution of germicidal uvc energy must be provided . this conflicts with our initial deduction that there must be a uniform amount of energy throughout the cooling coil . this difference resulted in the inventions claimed in our u . s . pat . no . 5 , 817 , 276 . in order to exploit the need for uniform distribution of energy , we have focused on positioning our uvc emitters to maximize distribution of energy across a heat exchanger and throughout a heat transfer coil by reflection within the heat transfer coil . our research has shown that while a higher output germicidal lamp is important , unexpectedly good results are achieved by aiming and reflecting the uvc radiation to maximize uniform distribution ( irradiation ). our initial focus was on iaq . thus , we expected that the best location for a germicidal lamp is downstream of a cooling coil , working from the highest degree of microbial activity to the lowest . as discussed above , to maximize uniform distribution of the uvc energy , the plane of the tube should be at a right angle to the conforming lines of the cooling coil &# 39 ; s fins . through initial radiation and incident reflection — total irradiation - uvc energy bathes all surfaces of the cooling coil and drain pan as well as the line - of - sight airstream . in order to provide a uniform distribution of photon energy through the deepest part of a heat transfer coil , depending on its height and width , we prefer having several tubes at selected “ tube to tube ” distances and at selected “ tube to coil ” distances . the minimum photon energy striking the leading edge of all heat transfer coil fins is preferably 716 μw / cm 2 at the closest point and through placement , not less than 60 % of that value at the farthest point . this therefore sets the minimum number of tubes , their center lines and their distance from the air - leaving or air - entering surface of the heat transfer coil . if positioned in this manner , nearly equal amounts of energy will also strike the drain pan in most cooling systems , either directly or indirectly . the particular position of a germicidal lamp relative to a heat transfer coil depends on the capabilities and characteristics of the germicidal lamp used . microbial samplings of several experimental sites showed a uniform kill of all microbial activity throughout the tested cooling coils . the killing of mold and bacteria on the cooling coils also reduced or eliminated microorganisms and their products from the airstream with reduction of the following products in the relevant occupied spaces : particle toxins which can cause both sbs and building related illness ( bri ). other bioaerosol related iaq problems such as allergy , asthma , and symptoms such as headache , burning eyes and fatigue . another important discovery from our recent research is that microorganism nutrients are primarily organic in nature . as these minute organic substances impinge on the surfaces of a heat exchanger , both mold and bacteria bind - up this material to the surface of the heat exchanger during their growth and division process to hold moisture and maintain activity . this results in the dingy , dirty appearance which heat exchangers obtain over time . our research has shown that the ionizing radiation from our uvc emitters is a key element in the killing and degradation process of microorganisms in cooling and heating systems . an ion is a particle formed when a neutral atom or group of atoms gains or loses one or more electrons . an atom that loses an electron forms a positively charged ion , called a cation and an atom that gains an electron forms a negatively charged ion , called an anion . our scientific testing has established that the dead microorganisms then further undergo damage through this free radical process . absorption of uvc energy leads to the formation of radical cations , anions and electrons , and electronically excited molecules . one reason is that about 70 % of the energy is absorbed by the available moisture and about 30 % by organic matter and other solutes . water absorption of uvc leads to the formation of oxygen / hydrogen radicals or hydroxyls , solvated electrons and hydrogen atoms which are all very safe to humans and the environment . this process is similar to that produced by outdoor sunshine . in these processes , the atoms are separated , thus disassociating individual whole molecules to produce individual radicals to the original structure . these water - derived radicals are all highly reactive and atomically degrade ( vaporize ) organic material . only after continued study did we learn that the degradation process continues on the dead microorganisms as well as any residual organic nutrients . in time , the heat transfer coil and drain pan become organically clean . we have observed this effect on severely encrusted cooling coils in as little as four weeks of continuous operation . the results from the uvc energy degrading the organic matter are : heat exchangers no longer seed the ductwork or space with bioaerosols . the elimination of organic material from the heat exchanger as shown above has other significant advantages for the user from an energy standpoint . the reduction in pressure drop across the heat exchanger equates to a reduction in air horsepower and is expressed by the following formula : hp = cfm * 5 . 2 * δ pd 33000 η fig1 , 11 , 12 and 13 show graphs of “ before ” and “ after ” conditions at our test site at scacd , discussed above . fig1 shows the air entering dry bulb temperature and air leaving dry bulb temperature over a one month period . we found a 3 . 7 ° greater temperature differential after installation of the uvc emitters . fig1 shows measured cooling coil pressure drop over the same one month period . we found a 28 % lower pressure drop across the cooling coil after installation of the uvc emitters . fig1 shows the air entering wet bulb temperature and air leaving wet bulb temperature over the one month period . we found a 1 . 8 ° greater temperature differential after installation of the uvc emitters . fig1 shows measured system air flow over the one month period . we found an 8 . 6 % increase in system cfm after installation of the uvc emitters . applying the reduction in pressure drop shown results in horsepower savings of 0 . 58 and when taken against the operating hours and the cost per kw , energy savings of approximately $ 163 per year are realized . however , the big savings are in heat transfer as shown in the entering air temperature ( eat ) and leaving air temperature ( lat ) of both the wet bulb ( fig1 ) and dry bulb ( fig1 ). the resulting change in total heat exchanger capacity is expressed as : applying the reduction in wet bulb lat against the above formula , operating hours and cost per kw , energy savings of approximately $ 11 , 724 per year are realized . the impact nationwide of using uvc in this manner would be dramatic to say the least . when germicidal tubes are utilized as described herein , total flux density between each of the fins of a heat transfer coil is at its highest . as such , microorganisms that are not defused to the heat exchanger &# 39 ; s surface and killed are mostly killed in the air due to the increased flux density from the resulting irradiation and lack of shadows . this reduces ( kills ) airborne microorganisms by as much as 90 % on a single pass , reducing the incidence of airborne transmitted infections including such diseases as measles , chicken pox , whooping cough , common colds , influenza and tuberculosis . our research shows that uvc energy at 253 . 7 nm ionizes the organic bonds ( as described above ) of the typical materials deposited on heat exchangers . uvc energy vaporizes these materials at the solid , molecular and atomic level . the process time averages about three weeks of continuous exposure to complete and then maintains the cleanliness of a heat exchanger for the life of the system . this in turn returns airflow to “ as designed ” values . the process has been confirmed repeatedly . the process of cleaning the heat exchanger somewhat differs from the process of controlling the presence of surface and airborne microorganisms . the goal in cleaning the heat exchanger is to eliminate organic matter from all surfaces of the heat exchanger . in contrast , the goal in controlling the presence of surface and airborne microorganisms is to sufficiently kill just those microorganisms which are likely to affect iaq . thus , to maximize energy savings by eliminating organic matter on a heat exchanger , it may be necessary to locate germicidal lamps upstream from the heat exchanger as shown in fig8 . heat transfer coils are typically constructed of aluminum . aluminum can reflect the 253 . 7 nm wavelength of uvc at up to 83 %. under a microscope and to the quarter micron wavelength of uvc energy , a heat exchanger &# 39 ; s aluminum surface shows imperfections that look like peaks , valleys , pits and rocks . installing our uvc emitters at right angles to the plane of a heat transfer coil &# 39 ; s fins results in the entire heat transfer coil surface receiving radiation through direct and / or incident angle reflection . in accordance with the invention , uvc energy at 253 . 7 nm is utilized to vaporize accumulated debris reducing pressure drop and increasing heat exchange efficiency to “ as new .” the uvc light can be utilized upstream or downstream of the heat exchanger , whichever facilitates air handler design . preferably , as described above , a tube &# 39 ; s longitude is at right angles to the plane of a coil &# 39 ; s fins . preferably , tubes are positioned on center lines and distances from the top and bottom of the heat transfer coil to provide a uniform distribution of energy sufficient to clean the entire heat transfer coil surface through direct and reflected uvc energy . the tubes of our uvc emitters are preferably positioned from the heat exchanger surface at a distance which is equal to 80 % of the distance of the light string centerline . for example , if the centerlines were 24 ″, then the distance from the coil should be approximately 20 ″. preferably , the fixtures include a reflector to concentrate the energy produced , and the reflector is aimed toward the heat exchanger . once installed , the germicidal lamps are preferably run 24 hours per day until the heat exchanger is completely cleaned . once the heat exchanger is cleaned , the germicidal lamps may be run intermittently as required to maintain the cleanliness and pressure drop of the heat exchanger . for new heat transfer coils , germicidal lamps may be installed on the same plane as the plane of the fins , as shown in fig9 . the reason is that when the coil is new , the only requirement is to maintain it in the “ as new ” condition . this will save significant energy over the life of the system . while the amount of uvc energy reaching all surfaces of the heat transfer coil is less than in the preferred right angle position , calculations can be made that provide a degradation rate equal to the deposition rate of debris . this will keep the heat transfer coil clean indefinitely , which is the most affordable way to minimize energy use in exchanging heat or flowing air . these savings are shown in the formulas set forth above . fig1 - 18 show various installations of germicidal lamps with respect to a variety of heat exchanger types . the installations of fig1 - 18 were achieved by considering both the desirability of reducing energy consumption , cost of installing a germicidal lamp ( including the cost of the lamp itself ), and structural limitations of the heat exchanger and its environs . fig1 shows an “ m ” coil 1510 , a dual - tube germicidal lamp 1520 including single - ended tubes 1521 , 1522 , insulated duct walls 1530 and drain pans 1540 . fig1 shows a slab coil heat exchanger 1610 , a germicidal lamp 1620 including single - ended tube 1621 , insulated duct walls 1630 and a drain pan 1640 . fig1 shows an “ n ” coil 1710 , a germicidal lamp 1720 including single - ended tube 1721 , insulated duct walls 1730 and a drain pan 1740 . fig1 shows a complex coil 1810 , a germicidal lamp 1820 including single - ended tubes 1821 , 1822 , insulated duct walls 1830 and drain pans 1840 . properly designed hvac - type germicidal devices , such as our uvc emitters , can be installed without interruption of the normal operation of an hvac system . because of the proven energy - saving abilities of germicidal lamps , other more expensive and less beneficial energy - saving devices may not be needed . the germicidal lamps clean the coil to “ as new ” specifications , completely returning heat exchange efficiency ( heat removal ) and pressure drop ( airflow ) to original values . the germicidal lamps keep the heat exchanger in this condition for the life of the system . the process is not destructive to the heat exchanger &# 39 ; s surface or any other inorganic material . the process is environmentally friendly , as it adds nothing to the air or drainage system . the germicidal lamps do the job continuously without shutting down the system or vacating the building . a complete installation of germicidal lamps can cost less than a properly performed heat transfer coil cleaning . although exemplary embodiments of the present invention have been shown and described , it will be apparent to those having ordinary skill in the art that a number of changes , modifications , or alterations to the invention as described herein may be made , none of which depart from the spirit of the present invention . all such changes , modifications and alterations should therefore be seen as within the scope of the present invention . | 5 |
with reference to fig1 , the numeral 1 denotes in its entirety an oven comprising a frame 2 to which a door 3 is connected by two hinges 4 which enable it to rotate in tilting fashion about a first horizontal axis a . as shown in fig5 , each of the two hinges 4 comprises a first body 5 fixed to the frame 2 of the oven 1 , and a second body 6 , fixed to the door 3 . the first and the second body 5 and 6 are kinematically connected by a connecting lever 7 . with reference also to fig2 to 4 , the second body 6 comprises a first internal box - shaped element 61 and a second external box - shaped element 62 located outside the first element and movable relative to the latter , as described in more detail below . as shown in fig4 , the first internal box - shaped element 61 has a substantially c - shaped transversal cross section and extends longitudinally along an axis b . the second external box - shaped element 62 also has a substantially c - shaped transversal cross section and extends longitudinally along the axis b , in practice surrounding the first element 61 . spacing means are interposed between the elements 61 and 62 to allow them to slide correctly relative to each other according to a predetermined direction d 1 parallel to the axis b . with reference to fig3 and 4 , the spacing means preferably comprise a plurality of protruding buttons 63 made by plastic deformation of the metal sheet of one or the other of the box - shaped elements 61 , 62 . in the hinges illustrated in the accompanying drawings , the buttons 63 are made on the first element 61 and protrude towards the second box - shaped element 62 . with reference to the embodiment of fig8 to 11 described below , fig1 clearly illustrates the position of said buttons 63 . again with reference to fig2 to 4 , the connecting lever 7 comprises a first arm 8 , designed to be rigidly connected to the first body 5 , and a second arm 9 connected to the second body 6 . for connecting the second arm 9 to the second body 6 , the hinge 1 comprises a first pin 10 passing through a respective hole made at the end of the second arm 9 and coaxial with the axis a . as illustrated in fig4 to 7 , the hinge 4 also comprises a rod 11 and a stem 12 located one after the other longitudinally along the axis b , inside the first box - shaped element 61 and hooked to each other . advantageously , the rod 11 is also box shaped , with a c - shaped cross section , and has a lower end 11 a pivoted to the lever 7 at a respective pin p , in substantially known manner , and an upper end 11 b for connection to the stem 12 . the second body 6 mounts a first helical spring 13 , fitted round the outside of the stem 12 and stressed by compression . the first box - shaped element 61 comprises an upper wall 14 at right angles to the axis b and having a hole for the passage of the stem 12 . the upper wall 14 forms an abutment surface for a proximal end coil 13 a of the spring 13 . the stem 12 has an upper end longitudinally opposite the one hooked to the rod 11 , the upper end being designed to engage a distal end coil 13 b in such a way as to compress the spring 13 . the spring 13 constitutes for the hinge 4 an elastic element designed to generate a reaction force that opposes the opening of the door 3 . added to the elastic action of the spring 13 , in a substantially known manner not further described , is the action of a second , pre - compressed helical spring 15 , shown in fig4 . pivoting on the opposite side walls of the first box - shaped element 61 , labeled p 1 and p 2 in fig4 , are two rotating rocker elements 16 designed to rotate about a respective axis r transversal of the longitudinal axis b of extension of the box - shaped elements 61 , 62 . as clearly illustrated in fig2 to 4 , each rotating element 16 has , at opposite ends of it , two pins 17 , 18 protruding from opposite faces of the element 16 itself . in other words , a first pin 17 extends towards the inside of the first box - shaped element 61 in order to engage a respective slot 19 made in the rod 11 . a second pin 18 , on the other hand , extends in the opposite direction to the first , that is to say , towards the outside of the first box - shaped element 61 in order to engage a respective slot 20 made in the box - shaped element 62 , as shown in fig2 . as clearly illustrated in fig5 to 7 , respective curved slots 21 , 22 are made on the side walls p 1 , p 2 of the first box - shaped element 61 to allow each rotating rocker element 16 to rotate . more specifically , the slot 21 made on each wall p 1 , p 2 of the first element 61 must allow the pin 17 to go right through the thickness of the wall p 1 , p 2 itself to engage the respective slot 19 made in the underlying rod 11 . in use , as shown by way of example in fig5 to 7 which illustrate a sequence of opening the door 3 , the rotation of the second body 6 in tilting fashion about the axis a relative to the first body 5 causes , in known manner , a movement of the rod 11 and of the first box - shaped element 61 relative to each other . since the first pin 17 is engaged inside the slot 19 , the movement of the rod 11 relative to the box - shaped element 61 causes the rocker elements 16 to rotate about their axis r . during this rotation , however , the second pin 18 , which is engaged in the respective slot 20 made in the second box - shaped element 62 , pushes the latter and causes it to move relative to the first box - shaped element 61 . in other words , the rotation of the rotary rocker element 16 causes relative sliding between the first box - shaped element 61 and the second box - shaped element 62 in the above mentioned direction d 1 . when opened , the door 3 , which is fixed stably to the second box - shaped element 62 , does not interfere with any part that is integral with the frame 2 because the sliding of the elements 61 and 62 relative to each other causes it to move away from the frame 2 , as clearly shown in fig5 to 7 . the rotary rocker elements 16 , the pins 17 , 18 and the respective slots 19 , 20 together form actuator means 23 for imparting the relative sliding movement to the first and second box - shaped elements 61 , 62 . advantageously , by varying the distance of the pins 17 , 18 from the pivot axis r of the rocker elements 16 , it is possible to modify the extent of the relative sliding movement between the two box - shaped elements 61 , 62 and also the effort the user is required to exert to obtain this movement . in alternative embodiments not illustrated , the rotary rocker elements 16 may for this purpose have different alternative positions for the pins 17 , 18 or even pins which are adjustable in position . fig8 to 11 illustrate another embodiment 4 ′ of the hinge 4 described above , where unlike the latter , the body 6 is housed inside the frame 2 and the connecting lever 7 is instead designed to engage a door not illustrated . the operating principle of the hinge 4 ′ does not substantially differ from the one described above with reference to the hinge 4 , since it too involves the sliding of the two box - shaped elements 61 , 62 relative to each other in order to move the door 3 away from the frame 2 of the oven 1 during opening of the door 3 . fig8 to 10 illustrate an example embodiment of the hinge 4 ′ in three different configurations of it : in the first , shown in fig8 , the door is closed ; in the second , shown in fig9 , the door is half open ; and in the third , shown in fig1 , the door is open . it may be immediately inferred from these drawings that the effect obtained with this invention is precisely that of moving the part of the hinge that is integral with the door ( in this case , the lever 7 ) away from the part of the hinge that is integral with the frame ( in this case , the body 6 ). with reference to fig8 , when the door is in the closed configuration , the distance between the distal end of the second box - shaped element 62 — integral with the frame — and the axis a of the pin 10 about which the lever 7 and the door , not illustrated , integral with it rotate , is minimal and represented by the measurement l . when the lever 7 has rotated in the opening direction , for example through 45 °, the box - shaped elements 61 , 62 have already been made to slide relative to each other by the actuating means 23 , thereby increasing the above mentioned distance to a value l ′ greater than l . lastly , when the door has reached its fully open position and the lever 7 has been rotated through 88 ° from its initial configuration shown in fig8 , the distance between the axis a and the end of the second box - shaped element 62 is at its largest and equal to a value l ″, greater than l ′. in an experimental non - limiting example version of the hinge 4 ′, illustrated in fig8 to 11 , the distances l , l ′ e l ″ measure 16 , 19 and 23 millimetres , respectively . fig1 and 13 illustrate an alternative embodiment of the spacing means between the elements 61 , 62 instead of the buttons 63 described above and illustrated in fig3 to 11 . as illustrated in fig1 and 13 , the spacing means comprise a plurality of removable shoes 64 , advantageously made of a material with a low friction coefficient , such as teflon ®, for example . the shoes 64 are hooked to the first box - shaped element 61 at its opposite longitudinal ends , there being two for each side wall p 1 , p 2 . each shoe 64 has two respective convex portions 64 a , protruding towards the second box - shaped element 62 , in such a way as to space the box - shaped elements 61 , 62 from each other and , thanks also to the low - friction material they are made of , to facilitate their relative sliding movement . the invention described has evident industrial applications and can be modified and adapted in several ways without thereby departing from the scope of the inventive concept . moreover , all details of the invention may be substituted by technically equivalent elements . | 8 |
referring to fig1 a thermostat 10 controls a temperature conditioning unit 12 for heating or cooling a room or area within a building 14 . unit 12 is schematically illustrated to represent any temperature conditioning apparatus , examples of which include , but are not limited to , a gas or oil furnace , electric heater , air conditioner , and heat pump . thermostat 10 is schematically illustrated to represent any system monitor or controller adapted to analyze input from a temperature sensor and provide certain feedback in response to the sensed temperature . examples of thermostat 10 include , but are not limited to , an electronic thermostat , a computer , microprocessor , microcomputer , digital circuits , analog circuits , and various combinations thereof . in some embodiments of the invention , thermostat 10 receives an input 16 from an indoor temperature sensor 18 and an input 20 from an outdoor temperature sensor 22 . sensor 18 senses the actual indoor temperature of building 14 , and sensor 22 senses the building &# 39 ; s outdoor temperature . thermostat 10 also includes an input 24 that allows a user to select or establish a desired target indoor temperature . input 24 is schematically illustrated to represent any user interface , such as a dial , push button , keyboard , touch screen , etc . in response to inputs 16 , 20 and 24 , thermostat 10 provides an output signal 26 that varies the capacity of unit 12 to help maintain the actual indoor temperature within a predetermined range ( e . g ., a few degrees or less ) of the desired target indoor temperature . this process is schematically illustrated in fig1 to represent all methods of varying the heating or cooling capacity of a temperature conditioning apparatus . a few examples of such methods include , but are not limited to , varying the speed of a refrigerant compressor , cycling a refrigerant compressor between different stages ( e . g ., a first stage providing a first refrigerant flow rate and a second stage providing a second refrigerant flow rate ), throttling or cycling a valve to vary the flow of refrigerant , throttling or cycling a valve to vary the flow rate of chilled water , etc . in one embodiment of the invention , output signal 26 cycles unit 12 on and off as needed to maintain the indoor temperature at or near the desired target indoor temperature . various on / off control schemes are well known to those skilled in the art . in addition to controlling unit 12 , thermostat 10 can calculate the tolerable outdoor temperature limit ( maximum for cooling systems , minimum for heating ). the tolerable outdoor temperature is the outdoor temperature at which unit 12 would need to operate at its maximum capacity in order to maintain an actual indoor temperature at or near a given desired target indoor temperature . thermostat 10 can also determine whether unit 12 needs servicing by comparing the calculated tolerable outdoor temperature limit to a predetermined specified outdoor temperature limit . in some embodiments , thermostat 10 can also determine the minimum or maximum achievable indoor temperature for a given outdoor temperature . to do all this ( in the example of an on / off control scheme ), thermostat 10 follows the control algorithm outlined in fig2 . in control block 28 , thermostat 10 reads the outdoor temperature through feedback 20 provided by sensor 22 . in block 30 , thermostat 10 reads the actual indoor temperature as sensed by temperature sensor 18 . in block 32 , a user provides thermostat 10 with a desired target indoor temperature . block 34 comprises a conventional on / off control scheme that cycles unit 12 on and off to maintain the indoor temperature at or near the desired target indoor temperature . generally , the greater the difference between the outdoor temperature and the target indoor temperature , the closer unit 12 must operate at its maximum capacity of 100 % ( numeral 35 in fig3 ). for an on / off control scheme , the capacity of unit 12 is in terms of duty cycle ( i . e ., the percentage of time that unit 12 is running : ( on - time )/( on - time + off - time )). in blocks 36 and 38 , thermostat 10 determines and periodically records ( e . g ., temporarily stores , remembers , etc .) the capacity or duty cycle at various operating conditions . the operating conditions may be described in terms of load values ( e . g ., the difference between the outdoor temperature and the target indoor temperature or the difference between the outdoor temperature and the actual indoor temperature ). in blocks 40 and 42 , thermostat 10 compares the various operating capacities or duty cycles to the load values to create performance data . the operations of blocks 40 and 42 are illustrated graphically in fig3 wherein a y - axis 44 represents load values ( e . g ., temperature differential between the outdoor temperature and the target indoor temperature ), an x - axis 46 represents the capacity ( e . g ., duty cycle or percentage of on - time of unit 12 ), and data points 48 represent performance data plotted as load value versus capacity . in blocks 50 and 52 , a line , such as a curved line 54 or a straight line 56 can be fitted through data points 48 . line 54 or 56 can help in extrapolating data points 48 to predict the tolerable outdoor temperature limit at which unit 12 is expected to be able to maintain the actual indoor temperature within a predetermined range of the target indoor temperature ( e . g ., a predetermined range of just a few degrees ). for instance , if unit 12 is used for cooling with a target indoor temperature of 70 degrees fahrenheit , then the maximum tolerable outdoor temperature is 130 degrees ( 70 °+ 60 °, wherein 70 ° is the target temperature and 60 ° is the indoor / outdoor temperature differential when unit 12 is operating at its maximum capacity of a 100 % duty cycle ). or , if unit 12 is used for heating with a target temperature of 70 °, then the minimum tolerable outdoor temperature is 10 ° ( 70 °− 60 °). once determined , the tolerable outdoor temperature 58 can be displayed on thermostat 10 , as shown in fig1 . such a display can provide a user with an indication of how well unit 12 can handle future heating or cooling loads . it should be noted that the graph of fig3 is just for illustration , and that the actual data points may lie in a much different arrangement , depending on the particular temperature conditioning unit and other factors . although data points 48 are used for both cooling and heating examples , in reality , heating and cooling may generate completely different sets of data points . moreover , the steps performed by blocks 36 , 38 , 40 , 42 and 50 do not necessarily involve actually plotting data points 48 and physically drawing a line through the points . rather , data points 48 can be stored as numbers or coordinates , and the step of fitting a line can be performed by deriving from points 48 an equation for a curved or straight line that when extrapolated can identify a tolerable outdoor temperature limit . such a method of fitting a line ( e . g ., an equation ) through a set of data points is common knowledge . in block 60 , thermostat 10 uses data points 48 to predict a best achievable indoor temperature for a given outdoor temperature . the expression , “ best achievable indoor temperature ” refers to the approximate expected indoor temperature that is farthest from the outdoor temperature , in the logical right direction of course . in a cooling mode , for example , if the outdoor temperature is 110 °, and data points 48 indicate that at a maximum capacity or 100 % duty cycle , system 12 can handle a load or indoor / outdoor temperature differential of 60 °, then unit 12 should be able maintain an achievable indoor temperature of 50 ° ( 110 °− 60 °). using the same data points 48 , in a heating mode with an outdoor temperature of 30 °, unit 12 would be expected to be able to maintain an achievable indoor temperature of 90 ° ( 30 °+ 60 °). in fig1 thermostat 10 displays an achievable indoor temperature 62 to provide a user with an indication of how much extra capacity ( or lack thereof ) unit 12 has at a particular load condition . block 64 illustrates the step of establishing a specified outdoor temperature limit , i . e ., the tolerable outdoor temperature limit when unit 12 is new or in perfect condition . such a limit is preferably set at the factory or by a service technician . when compared to the actual tolerable outdoor temperature limit , as performed by block 66 , the specified outdoor temperature limit provides the user with an indication of whether the performance of unit 12 has deteriorated . if so , thermostat 10 may display a signal 68 that indicates that unit 12 may need servicing , as indicated by block 70 . signal 68 can be an on / off light or a written message . the arrows interconnecting the blocks of fig2 are there to indicate that the algorithm process is repeated and ongoing . although the invention is described with reference to a preferred embodiment , it should be appreciated by those skilled in the art that other variations are well within the scope of the invention . for example , rather than sensing temperature , other conditions such as indoor air quality , carbon dioxide level , carbon monoxide level , humidity , pressure or the like may be sensed in accordance with the invention . therefore , the scope of the invention is to be determined by reference to the claims , which follow . | 6 |
in our experiments , the undoped polycrystalline and single crystalline samples of znse were grown by chemical vapor deposition . doping of the 1 - 3 mm thick znse polycrystalline and single crystalline wafers was performed by after growth thermal diffusion of fe from the metal or gas phase in quartz evacuated ampoules . alternatively , fe doped thin films of the zns and znse the crystals were grown by pulsed laser deposition on zns / se substrates . in addition , fe : zns and znse were fabricated by hot pressing of zns and znse powders containing iron . demirbis et al estimated the diffusion coefficient for iron and chromium ions to be 7 . 95 × 10 − 10 cm 2 / s and 5 . 45 × 10 − 10 cm 2 / s , respectively at 1000 ° c . in our preparation , the sealed ampoules were placed in a furnace and annealed at 820 - 1120 ° c . for 5 - 14 days . once removed from the furnace and cooled , doped crystals were extracted from the ampoules and polished . this method of production of transition metal doped crystals is covered in u . s . pat . no . 6 , 960 , 486 commonly owned by the assignee of this application and which is incorporated by reference herein for all purposes . the q - switched regime of operation for a er : cr : ysgg laser system has two distinctive qualities : large amplitude pulses and temporally short pulses with respect to free running oscillation . both of these qualities are needed for medical applications as well as to ensure efficient q - switched operation of fe 2 + : znse lasers at room temperature . the absorption spectra of fe 2 + : znse and fe 2 + : zns 5 e --& gt ; 5 t 2 transitions are depicted in fig2 . these transitions feature a broad absorption centered at ˜ 3 μm with fwhm of approximately 1400 nm . further , the absence of exited state absorption makes polycrystalline fe 2 + : znse a very good candidate for a passive q - switch for an er laser . in our experiments a flashlamp pumped er : cr : ysgg laser was used as a test bed for passive q - switching . many cavity designs were tested , however in all cavity designs the laser head includes a 73 mm long er : cr : ysgg crystal with a 3 mm diameter in a gold elliptical pumping chamber pumped with a xenon flashlamp . fig5 schematically illustrates a linear design with a 100 % reflective mirror , hr , and an oc with reflectivity of 83 % or 40 %. the hr was placed approximately 70 mm from the end of the er : cr : ysgg laser crystal and the oc was placed approximately 50 mm from the laser crystal . the fe 2 + : znse was sample placed between 17 - 65 mm from the high reflector in the cavity . the laser was pulsed at 10 hertz . input power was determined by directly measuring the voltage across the capacitor driving the flashlamp . the output was measured with a molectron epm 1000 power meter or a jr - 09 joule meter . for this cavity , at maximum pump energy of 31 j , an output energy of 0 . 5 j was achieved in a free - running mode . using a 4 × 8 × 1 mm 90 % initial transmission at 2 . 8 μm , fe : znse placed at the brewster angle q - switched operation was achieved . we obtained single giant pulse lasing with a pulse duration of approximately 65 to 100 ns fwhm measured with a pyroelectric detector with a rise time of approximately 15 ns ( see fig3 a ). a maximum output energy of 5 mj for 80 % oc and approximately 7 j pump energy was achieved . the ratio of energy of single giant pulse to the respective free - running energy approached 20 % and could be further increased with improvements of fe : znse quality . a multi - pulse regime was also obtained using either the 83 % or the 40 % oc , yielding multiple pulses depending on pump power although better performance was obtained using the 40 % oc . the threshold for lasing with this oc was approximately 9 j . the five pulse regime shown in fig3 b represents a nearly ideal train of pulses with little energy difference from pulse to pulse . the pump energy for five pulses was 14j . multi - pulse output with a maximum of 19 pulses was obtained with 85 mj total output energy at pump energy of 30 j with a 40 % oc as shown in fig3 c . utilization of a 50 % initial transmission fe : znse sample , yielded 9 mj output energy using a 40 % oc and 42 j pump energy . altering the cavity to a folded cavity scheme using three mirrors and two output beams allows the effective reflectance of the oc to be tuned with angle ( see fig6 ). also this design reduced the photon flux upon the fe 2 + : znse sample allowing a sample with a high initial transmission to be more effectively used as a passive q - switch with little difficulty . the hr was located approximately 115 mm from the laser crystal . the cavity was folded at approximately 45 degrees using a 40 % reflecting oc as the folding mirror at approximately 180 mm from the front of the laser crystal . a 82 % reflecting mirror was used as the second hr . the fe 2 + : znse sample was placed on this side as a passive q - switch . the pulse repetition rate was reduced to 4 hz to deal with thermal lensing problems . using this setup enabled maximum q - switched single pulse energy of 13 mj with 65 ns fwhm using 30 j of pump energy . similar results on cr : er : ysgg cavity q - switching were obtained with the use of single thermally diffused fe : znse crystals as well as with hot - pressed ceramic fe : znse and thin films of fe : znse grown by pulsed laser deposition . thus we propose these fe 2 + : znse materials for use as a passive q - switch , particularly for er lasers . further , fe 2 + : zns , having similar spectroscopic properties to fe 2 + : znse , is known to have the larger bandgap ( 3 . 84 vs . 2 . 83 ev ), better mechanical and optical damage characteristics , better overlap of absorption band with the cr : er : ysgg lasing wavelength , higher cross - section of absorption at 2 . 8 μm , as well as lower thermal lasing dn / dt (+ 46 × 10 − 6 vs .+ 70 × 10 − 6 /° c .). therefore , the intracavity energy and power handling capability of this material should lie higher ; making fe 2 + : zns very attractive for high energy , high power applications . parallel experiments to those with fe : znse have been performed using fe : zns , fabricated similarly to fe : znse by after growth thermo - diffusion . a ˜ 5 × 8 × 1 mm sample of fe 2 + : zns with an absorption coefficient of 6 cm − 1 and an initial transmission of 75 % at 2 . 8 μm was utilized as a passive q - switch . using a linear cavity design placing the fe 2 + : zns sample at the brewster angle between the hr and er : cr : ysgg crystal , with an 80 % reflectance oc , q - switching experiments were performed . approximately 5 mj per pulse was obtained . similar results on cr : er : ysgg cavity q - switching were obtained with the use of single thermally diffused fe : zns crystals as well as with hot - pressed ceramic fe : zns and thin films of fe : zns grown by pulsed laser deposition . thus we propose these fe 2 + : zns materials for use as a passive q - switch , particularly for er lasers . the q - switched output of the er : cr : ysgg laser was used for saturation studies of fe : znse . the saturation curve of fe : znse was measured ( fig4 ). it &# 39 ; s fitting with the frantz - nodvick equation results in , absorption cross section of 0 . 6 × 10 − 18 cm 2 , which is of the same order of magnitude as the absorption cross - section obtained from spectroscopic measurements ( 1 . 0 × 10 − 18 cm 2 . hence , the described fe - doped znse and zns crystals are very promising as passive q - switches for mid - ir er lasers operating over the 2 . 5 - 4 . 0 μm spectral range . although the invention has been described in various embodiments it is not so limited but rather enjoys the full scope of any claims granted hereon . | 7 |
as described above , the crystal according to the present invention is a crystal of the compound of formula ( i ), its salt or their solvate . the crystal according to the present invention is useful as a synthetic intermediate for the production of 2 - substituted - 1β - methyl carbapenem compounds . in the present invention , the crystal refers to a solid having an internal structure comprising three - dimensionally , regularly and repeatedly ordered constituent atoms or molecules and is distinguished from an amorphous solid or a noncrystalline form free from such regularly ordered internal structure . in general , even in the case of an identical compound , crystals ( crystal polymorphs ) having a plurality of different internal structures and physicochemical properties are formed under some crystallization conditions . in the present invention , the crystal may be any of these crystal polymorphs or may be a mixture of two or more crystal polymorphs . a crystal of a compound of formula ( i ), a crystal of a salt of a compound of formula ( i ), and a crystal of a solvate of a compound of formula ( i ) are of course embraced in the crystal according to the present invention . in addition , a crystal of a solvate of a salt of a compound of formula ( i ) is also embraced in the crystal according to the present invention . in the present invention , the salt of the compound of formula ( i ) is not particularly limited so far as it can be derived using conventional organic acids or inorganic acids . since , however , the final product produced using the compound of formula ( i ) as a synthetic intermediate may be used as an antimicrobial agent , this salt is preferably a pharmaceutically acceptable salt . the term “ pharmaceutically acceptable salt ” as used herein refers to a salt that is suitable for use in pharmaceutical preparation applications and is basically nontoxic to organisms . such pharmaceutically acceptable salts include those derived from pharmaceutically acceptable inorganic or organic acids , that is , inorganic acid salts and organic acid salts . examples of preferred acids include hydrochloric acid , sulfuric acid , nitric acid , perchloric acid , hydrobromic acid , fumaric acid , maleic acid , phosphoric acid , glycolic acid , lactic acid , salicylic acid , succinic acid , p - toluenesulfonic acid , di - p - toluoyltartaric acid , sulfanilic acid , tartaric acid , acetic acid , citric acid , methanesulfonic acid , formic acid , benzoic acid , malonic acid , naphthalene - 2 - sulfonic acid , and benzenesulfonic acid . when the compound of formula ( i ) is placed in a solution or suspended state using a certain solvent , in some cases , the compound , together with the molecules of the solvent , forms a crystal . likewise , when the compound of formula ( i ) is placed in a system in which a certain solvent is brought to a vapor form , in some cases , the compound , together with the molecules of the solvent , forms a crystal . in the present invention , this material formed by crystallization of the compound of formula ( i ) and the solvent in a three - dimensional order will be called a solvate . solvents usable for solvate formation include water , alcohols , ethers , and esters . therefore , in the present invention , the expression “ solvate of the compound of formula ( i ) or its salt ” is used in referring to embrace hydrates . specific examples of solvents usable for solvate formation include water , methanol , ethanol , propanol , isopropyl alcohol , n - butanol , diethyl ether , methyl acetate , ethyl acetate , propyl acetate , and butyl acetate . in a preferred embodiment of the present invention , the crystal according to the present invention is a crystal of a compound of formula ( i ) or its solvate . more preferably , the crystal is a crystal of a hydrate , an alcoholate , or a solvate with an ester solvent . more preferably , the crystal is a solvate of the compound of formula ( i ) with an alkyl acetate solvent . the alkyl acetate refers to an ester of a c1 - 6 ( preferably c1 - 4 ) alcohol with acetic acid and may also be expressed as c1 - 6 alkyl acetate or c1 - 6 alkyl ester of acetic acid . in one particularly preferred embodiment of the present invention , the crystal according to the present invention is a crystal of a solvate of a compound of formula ( i ) with ethyl acetate , a crystal of a solvate of a compound of formula ( i ) with a butyl acetate , or a crystal of a solvate of a compound of formula ( i ) with ethyl acetate or butyl acetate and hexane . in the present invention , that the compound of formula ( i ), its salt , or their solvate is in a crystal form can be confirmed by utilizing observation under a polarization microscope , a powder x - ray crystal analysis , or a single crystal x - ray diffraction measurement . the type of the crystal may also be identified by comparison of the characteristics of the crystal with data based on each index which have been previously measured . thus , in a preferred embodiment of the present invention , the crystal according to the present invention can be identified to be a crystal by utilizing the above measuring means . in a first embodiment of the present invention , there is provided a crystal of a compound of formula ( i ) with an ethyl acetate solvate . the crystal of a compound of formula ( i ) with an ethyl acetate solvate ( hereinafter often referred to as “ crystal i ”) can be produced , for example , by a method described in example 2 which will be described later . the crystal of the ethyl acetate solvate exhibits a powder x - ray diffraction pattern described in example 2 which will be described later . this crystal can be characterized by diffraction angles of diffraction peaks observed in the powder x - ray diffraction pattern . accordingly , in one preferred embodiment of the present invention , the crystal according to the present invention exhibits a powder x - ray diffraction pattern having diffraction peaks at at least diffraction angles ( 2θ ) shown in table i - a below : table i - a diffraction angle ( 2θ ) [°] 10 . 2 ± 0 . 1 11 . 7 ± 0 . 1 17 . 0 ± 0 . 1 21 . 5 ± 0 . 1 as described above , this crystal is a crystal of an ethyl acetate solvate . the powder x - ray diffraction pattern referred to herein may be determined by measurement using a measuring apparatus and measuring conditions in example 2 which will be described later . a more preferred embodiment of the present invention , this crystal exhibits a powder x - ray diffraction pattern having diffraction peaks at at least diffraction angles ( 2θ ) shown in table i - b below : table i - b diffraction angle ( 2θ ) [°] 10 . 2 ± 0 . 1 11 . 7 ± 0 . 1 11 . 9 ± 0 . 1 17 . 0 ± 0 . 1 21 . 5 ± 0 . 1 in the present invention , some errors may be observed in diffraction angle ( 2θ ) values due to various error sources . error sources attributable to sample powder include particle size , water content , density , and crystallinity of sample powder , and error sources attributable to measurement environments include temperature , humidity , atmosphere , and measuring persons . further error sources attributable to the measuring apparatus include , for example , the output of x - ray lamps , counters , various slit widths and scanning speeds . in the present specification , when the crystal is defined by diffraction angles 2θ , the diffraction angle 2θ value is not limited to the value indicated on the basis that a peak exists , and a range based on this , and the range in which errors are possibly observed may be included as the diffraction angle 2θ value in the crystal of the present invention . this range in which errors are observed can easily be predicted by a person having ordinary skill in the art from measuring conditions and the like . this is true of crystal ii and crystal iii which will be described later . in the present invention , the expression “ having diffraction peaks ” at specific diffraction angles ( 2θ ) in a powder x - ray diffraction pattern refers to , for example , a case satisfying the following conditions . specifically , at specific diffraction angles , a value obtained by subtracting background ( sum of noncrystalline scattering and noncoherent scattering ) from absolute intensity is designated as “ signal intensity .” ½ of oscillation of noise at a specific diffraction angle is designated as “ noise level .” when the ratio between “ signal intensity ” and “ noise level ” is not less than 2 , this state may be regarded as “ having diffraction peaks .” lattice constant : a : 14 . 582 ( 5 ), b : 15 . 117 ( 7 ), c : 25 . 663 ( 6 ), α : 84 . 39 ( 3 ), β : 88 . 69 ( 2 ), γ : 89 . 23 ( 4 ), v : 5628 ( 3 ). the crystallographic properties may be determined by measurement using a measuring apparatus and measuring conditions in a single crystal x - ray diffraction analysis in example 2 which will be described later . accordingly , in another preferred embodiment of the present invention , the crystal ( particularly crystal i ) according to the present invention is characterized by at least having crystallographic properties as indicated by the above lattice constant in a single crystal x - ray diffraction analysis . in a second embodiment of the present invention , there is provided a crystal of a solvate of a compound of formula ( i ) with butyl acetate . the crystal of a solvate of a compound of formula ( i ) with butyl acetate ( hereinafter often referred to as “ crystal ii ”) may be produced , for example , by a process described in example 3 which will be described later . the crystal of the butyl acetate solvate exhibits a powder x - ray diffraction pattern as described in example 3 which will be described later . this crystal can be characterized by diffraction angles of diffraction peaks observed in the powder x - ray diffraction pattern . accordingly , in one preferred embodiment of the present invention , the crystal according to the present invention exhibits a powder x - ray diffraction pattern having diffraction peaks at at least diffraction angles ( 2θ ) shown in table ii - a below : table ii - a diffraction angle ( 2θ ) [°] 9 . 3 ± 0 . 1 12 . 5 ± 0 . 2 13 . 7 ± 0 . 2 15 . 7 ± 0 . 2 as described above , this crystal is a crystal of a butyl acetate solvate . the powder x - ray diffraction pattern referred to herein may be determined by measurement using a measuring apparatus and measuring conditions in example 3 which will be described later . in one more preferred embodiment of the present invention , the crystal exhibits a powder x - ray diffraction pattern having diffraction peaks at at least diffraction angles ( 2θ ) shown in table ii - b below : table ii - b diffraction angle ( 2θ ) [°] 8 . 0 ± 0 . 1 9 . 3 ± 0 . 1 9 . 8 ± 0 . 2 12 . 5 ± 0 . 2 13 . 7 ± 0 . 2 15 . 7 ± 0 . 2 lattice constant : a = 16 . 223 ( 7 ) angstroms , b = 18 . 01 ( 1 ) angstroms , c = 15 . 045 ( 7 ) angstroms , α = 90 °, β = 90 °, γ = 90 °, v = 4395 ( 3 ). the crystallographic properties may be determined by measurement using a measuring apparatus and measuring conditions in a single crystal x - ray diffraction analysis in example 3 which will be described later . accordingly , in another preferred embodiment of the present invention , the crystal ( particularly crystal ii ) according to the present invention is characterized by at least having crystallographic properties as indicated by the above lattice constant in a single crystal x - ray diffraction analysis . in a third embodiment of the present invention , there is provided a crystal , different from crystal ii , obtained by crystallization of a compound of formula ( i ) using butyl acetate ( hereinafter often referred to as “ crystal iii ”). this crystal may be produced , for example , by a process described in example 4 which will be described later . crystal iii exhibits a powder x - ray diffraction pattern as described in example 4 which will be described later . this crystal can be characterized by diffraction angles of diffraction peaks observed in the powder x - ray diffraction pattern . accordingly , in one preferred embodiment of the present invention , the crystal according to the present invention exhibits a powder x - ray diffraction pattern having diffraction peaks at at least diffraction angles ( 2θ ) shown in table iii - a below : table iii - a diffraction angle ( 2θ ) [°] 5 . 7 ± 0 . 1 11 . 2 ± 0 . 2 13 . 9 ± 0 . 2 14 . 5 ± 0 . 2 the powder x - ray diffraction pattern referred to herein may be determined by measurement using a measuring apparatus and measuring conditions in example 4 which will be described later . in one more preferred embodiment of the present invention , the crystal exhibits a powder x - ray diffraction pattern having diffraction peaks at at least diffraction angles ( 2θ ) shown in table iii - b below : table iii - b diffraction angle ( 2θ ) [°] 5 . 7 ± 0 . 1 8 . 4 ± 0 . 1 10 . 3 ± 0 . 1 11 . 2 ± 0 . 2 13 . 9 ± 0 . 2 14 . 5 ± 0 . 2 the compound of formula ( i ) may be produced , for example , by processes described in known documents such as j . med . chem ., 30 , 871 ( 1987 ), j . antibiotics , 41 , 780 ( 1988 ), wo 96 / 28455 , or wo 01 / 53305 . a specific example of the production process is to produce the compound of formula ( i ) by the process in example 1 which will be described later . a salt of the compound of formula ( i ) may be produced by a person having ordinary skill in the art by applying conventional means to the compound of formula ( i ). according to the present invention , the crystal of the compound of formula ( i ) may be produced by utilizing a crystallization method in which the organic solvent used in combination with the compound of formula ( i ) is properly selected , for example , a vapor diffusion method utilizing vapor equilibrium of the solvent , or a method utilizing concentration of a solution upon evaporation of the solvent , or saturation solubility . crystals of the salt of the compound of formula ( i ), its solvate , and the solvent of the salt can be produced in the same manner as described above . according to the present invention , there is provided a process for producing a crystal of a compound of formula ( i ) or its salt or solvate according to the present invention , said process comprising dissolving the compound of formula ( i ) in a solvent selected from the group consisting of water , methanol , ethanol , propanol , isopropyl alcohol , n - butanol , diethyl ether , methyl acetate , ethyl acetate , propyl acetate , butyl acetate , and a mixture of any one of said solvents with a solvent for crystallization , and precipitating a crystal from the solution . the solvent for crystallization is not particularly limited so far as it can accelerate the precipitation of the crystal according to the present invention , or can lower the solubility of the crystal , and examples thereof include n - pentane , n - hexane , n - heptane , cyclohexane , petroleum ether , diisopropyl ether , and diethyl ether . n - hexane is preferred . in a preferred embodiment of the present invention , a solvent selected from the group consisting of ethyl acetate , butyl acetate , and a mixture composed of any one of these solvents with a solvent for crystallization is used as the solvent for dissolving the compound of formula ( i ). in a preferred embodiment of the present invention , the process for producing a crystal of the compound of formula ( i ) or its salt or solvate comprises subjecting the above solution and a separately provided solvent for crystallization to the procedure of a vapor diffusion method to precipitate crystals . in this case , the procedure of the vapor diffusion method comprises placing the above solution and the separately provided solvent separately from each other within a hermetically sealable vessel in a volume ratio of 1 : 1 to 1 : 20 , preferably 1 : 2 to 1 : 10 and allowing them to stand . further , the crystal obtained after standing may be if necessary subjected to filtration and drying . in a preferred embodiment of the present invention , the crystal according to the present invention may be obtained by precipitating a crystal from a solution of the compound of formula ( i ) dissolved in ethyl acetate . in a more preferred embodiment of the present invention , when ethyl acetate is used as the solvent for dissolving the compound of formula ( i ), the resultant crystal is a crystal of a solvate of the compound of formula ( i ) with ethyl acetate . in another preferred embodiment of the present invention , the crystal according to the present invention may be obtained by precipitating a crystal from a solution of the compound of formula ( i ) dissolved in butyl acetate or a mixture of butyl acetate with a solvent for crystallization . in a more preferred embodiment of the present invention , when butyl acetate or a mixed solvent composed of butyl acetate and n - hexane is used as the solvent for dissolving the compound of formula ( i ), the resultant crystal is a crystal of a solvate of the compound of formula ( i ) with butyl acetate . in a more preferred embodiment of the present invention , in the production process of the crystal , a compound obtained by dissolving a noncrystalline form of the compound of formula ( i ) in ethyl acetate or butyl acetate , further adding n - hexane to the solution , cooling the mixture , and vacuum drying the resultant solid matter may be used as the compound of formula ( i ) to be dissolved in the solvent . the noncrystalline form of the compound of formula ( i ) is , for example , a compound prepared in example 1 which will be described later . the compounds of formula ( i ) according to the present invention are useful as synthetic intermediates of 2 - substituted - 1β - methyl carbapenem compounds , for example , 2 - aryl - 1β - methyl carbapenem , 2 - ureido - 1β - methyl carbapenem , 2 - imidazo [ 5 , 1 - b ] thiazolium methyl - 1β - methyl carbapenem , and 2 -( 7 - methylthioimidazo [ 5 , 1 - b ] thiazolyl - 1β - methyl carbapenem , which are useful as antimicrobial agents . as described above , 2 - aryl - 1β - methyl carbapenem obtained using the compound of formula ( i ) according to the present invention has higher antimicrobial activity against staphylococcus aureus , enterococcus , escherichia coli and the like than imipenem ( ipm ) and has higher stability against renal dhp - 1 than ipm , as disclosed in j . med . chem ., 30 , 871 ( 1987 ). further , 2 - ureido - 1β - methyl carbapenem has higher antimicrobial activity against enterococcus , escherichia coli , klebsiella pneumoniae and the like than ipm and higher stability against renal dhp - 1 than ipm , as disclosed in j . antibiotics , 41 , 780 ( 1988 ). 2 - imidazo [ 5 , 1 - b ] thiazoliummethyl - 1β - methyl carbapenem has higher antimicrobial activity against staphylococcus aureus including mrsa , enterococcus , escherichia coli , pneumococci , pseudomonas aeruginosa and the like than ipm and has higher stability against renal dhp - 1 than ipm , as disclosed in wo 96 / 28455 . further , 2 -( 7 - methylthioimidazo [ 5 , 1 - b ] thiazolyl )- 1β - methyl carbapenem has higher antimicrobial activity against staphylococcus aureus , enterococcus , pneumococci including prsp , haemophilus influenzae including ampicillin - resistant haemophilus influenzae , moraxella catarrhalis and the like than ipm and has higher stability against renal dhp - 1 than ipm , as disclosed in wo 01 / 53305 . the use of these compounds as a therapeutic agent for infectious diseases attributable to various pathogenic bacteria of animals including humans and the production of pharmaceutical compositions using these compounds will be apparent to a person having ordinary skill in the art by reference to the above documents . further , a production process of an antimicrobial carbapenem compound using the crystal according to the present invention as a synthetic intermediate is apparent , for example , from the above documents ( j . med . chem ., 30 , 871 ( 1987 ), j . antibiotics , 41 , 780 ( 1988 ), wo 96 / 28455 , or wo 01 / 53305 ), more specifically apparent from the above - described schemes 1 to 4 . the present invention is further illustrated by the following examples that are not intended as a limitation of the scope of the invention . ( 3s , 4s )- 3 -[( 1r )- 1 -( t - butyldimethylsilyloxy ) ethyl ]- 4 -[( 1r )- 1 - carboxyethyl ]- 2 - azetidinone used was a commercially available one ( for example , available from kanefuchi chemical co , ltd ., nippon soda co ., ltd ., or takasago international corp .). t - butyldimethylsilyl chloride ( 49 . 74 g , 0 . 33 mol ) and imidazole ( 22 . 47 g , 0 . 33 mol ) were continuously added to a solution of ( 3s , 4s )- 3 -[( 1r )- 1 -( t - butyldimethylsilyloxy ) ethyl ]- 4 -[( 1r )- 1 - carboxyethyl ]- 2 - azetidinone ( 90 . 4 g , 0 . 30 mol ) in 450 ml of dry n , n - dimethylformamide ( dmf ). the mixture was then stirred in an argon atmosphere at 50 ° c . for 4 hr . next , the solution thus obtained was removed by evaporation under the reduced pressure at a bath temperature of 30 ° c . the residue was dissolved in 1 . 5 l of petroleum ether and was washed with 0 . 4 l of water , followed by extraction with 0 . 4 l of petroleum ether from the aqueous phase . the organic phases were combined . the organic phase was washed with 0 . 33 l of cold 1 n hydrochloric acid , cold 5 % sodium bicarbonate water ( 0 . 5 l × 2 ), and 0 . 4 l of saturated brine in a successive manner and was dried over anhydrous magnesium sulfate . thereafter , the organic layer was filtered , and the solvent was removed by evaporation under the reduced pressure to give a solid of a t - butyldimethylsilyl ( tbs ) ester compound ( 117 . 6 g , yield 94 . 3 %). allyl glyoxylate monohydrate ( 42 . 9 g , 0 . 325 mol ) was added to a solution of 102 . 9 g ( 0 . 25 mol ) of the tbs ester compound dissolved in 1 . 25 l of dry toluene . while removing water being produced with a dean - stark device , the mixture was heated under reflux for 10 hr . thereafter , the solvent was removed by evaporation under the reduced pressure . the thick material thus obtained was dissolved in 0 . 8 l of dry tetrahydrofuran . the solution was cooled to − 40 ° c . thereafter , 2 , 6 - lutidine ( 48 . 2 g , 0 . 45 mol ) and thionyl chloride ( 53 . 5 g , 0 . 45 mol ) were continuously added dropwise at an internal temperature of − 25 ° c . or below . thereafter , the mixture was stirred at − 20 ° c . for 1 . 5 hr , and the insolubles were then removed by filtration . the solvent was removed from the filtrate by evaporation under the reduced pressure . thereafter , 1 l of dry ethyl acetate was added to the residue , and the insolubles were removed by filtration . the solvent was removed from the filtrate , by evaporation under the reduced pressure . the brown oil thus obtained was dissolved in 0 . 35 l of dmf , triphenylphosphine ( 118 g , 0 . 45 mol ) was added to the solution , and the mixture was stirred at room temperature overnight . the solvent was removed by evaporation under the reduced pressure , 1 . 5 l of ethyl acetate was then dissolved in the residue , and the solution was washed with 0 . 25 m phosphate buffer ( ph 6 . 9 ) ( 1 l × 2 ) and 1 l of saturated brine in that order . next , the solution thus obtained was dried over anhydrous magnesium sulfate and was filtered . the solvent was removed from the filtrate by evaporation under the reduced pressure to give a brown oil . the brown oil was purified by column chromatography on silica gel ( 1 . 5 kg of silica gel 60 ( spherical )), manufactured by kanto chemical co ., inc ., chloroform : ethyl acetate = 5 : 1 ) to give a compound of formula ( i ) ( 99 . 3 g , yield 71 . 7 %) as a light yellow thick material ( noncrystalline material ). a part of the light yellow thick material obtained above was further purified by column chromatography on silica gel ( wako gel c - 300 , manufactured by wako pure chemical industries , ltd ., n - hexane : ethyl acetate = 1 : 1 ), and the solvent was removed by evaporation . the crude product thus obtained was dissolved in a minor amount of ethyl acetate , and n - hexane was added to the solution to give a crude crystal of the compound of formula ( i ). ethyl acetate ( 2 . 9 l ) was added to 1 . 367 kg of the crude crystal of the compound of formula ( i ), and the mixture was heated to 40 ° c . with stirring for dissolution . thereafter , 3 . 9 l of n - hexane was gradually added to the solution . when crystals began to precipitate , the system was dipped in an iced water bath , and ripening was carried out with slow stirring overnight . the crystals were collected through a glass filter and were washed with 1 l of n - hexane , and this washing was repeated three times . next , the crystals were vacuum dried at a shelf temperature of 30 ° c . overnight to give 1 . 232 kg of colorless crystals of the compound of formula ( i ). nmr ( cdcl 3 ) δ : − 0 . 14 ( 3h , s ), − 0 . 07 ( 3h , s ), 0 . 81 ( 9h , s ), 0 . 98 ( 3h , d , j = 6 . 0 hz ), 1 . 14 ( 3h , d , j = 7 . 1 hz ), 2 . 26 - 2 . 36 ( 1h , m ), 2 . 60 - 2 . 69 ( 2h , m ), 3 . 12 - 3 . 20 ( 1h , m ), 4 . 15 - 4 . 29 ( 2h , m ), 4 . 60 - 4 . 76 ( 2h , m ), 5 . 10 - 5 . 24 ( 1h , m ), 7 . 50 - 7 . 57 ( 6h , m ), 7 . 61 - 7 . 68 ( 3h , m ), 7 . 71 - 7 . 79 ( 6h , m ) ms ( sims ): m / z = 660 ( m + + 1 ) the crystal ( 2 . 5 g ) of the compound of formula ( i ) synthesized according to example 2 - a ) was placed in a 20 ml beaker , and 15 ml of ethyl acetate was added thereto to dissolve the crystal . the 20 ml beaker containing the ethyl acetate solution of the crude crystal was placed in an opened state within a 300 ml beaker containing 50 ml of n - hexane . the opening of the 300 ml beaker was covered with an aluminum foil , and the beaker was allowed to stand at room temperature ( about 25 ° c .) for 4 days . the solid matter thus obtained was collected by filtration and was dried to give a colorless platy crystal ( crystal i ). this crystal was considered to be an ethyl acetate solvate of the compound of formula ( i ). for the crystal ( crystal i ) obtained in the above 2 - b ), powder x - ray diffraction measurement was carried out using the following apparatus under the following measuring conditions . measuring conditions : x - ray : cukα 1 , tube voltage : 40 kv , tube current : 40 ma , scan step : 0 . 02 °, scan speed : 4 °/ min , scanning axis : 2θ / θ , and scan range : 2θ = 3 to 40 ° the above crystal had characteristic diffraction peaks at the following diffraction angle ( 2θ ). diffraction angle ( 2θ ) [°] 10 . 2 ± 0 . 1 11 . 7 ± 0 . 1 11 . 9 ± 0 . 1 17 . 0 ± 0 . 1 21 . 5 ± 0 . 1 for the crystal ( crystal i ) obtained in the above 2 - b ), single crystal x - ray diffraction measurement was carried out using the following apparatus under the following measuring conditions . measuring conditions : x - ray : cukα , tube voltage : 50 kv , tube current : 90 ma , and measuring temperature : − 180 ° c . as a result of the measurement , the crystal had the following crystallographic properties . lattice constant : a : 14 . 582 ( 5 ), b : 15 . 117 ( 7 ), c : 25 . 663 ( 6 ), α : 84 . 39 ( 3 ), β : 88 . 69 ( 2 ), γ : 89 . 23 ( 4 ), v : 5628 ( 3 ) the crystal ( 1 . 66 g ) of the compound of formula ( i ) synthesized according to example 2 - a ) was placed in a 50 ml beaker , and 10 ml of butyl acetate was added thereto to dissolve the crystal . further , 0 . 2 ml of n - hexane was added to the solution . a 50 ml beaker containing a mixed solution prepared by dissolving the crude crystal in butyl acetate and n - hexane was placed in an opened state within a 500 ml beaker containing 100 ml of n - hexane . the opening of the 500 ml beaker was covered with an aluminum foil , and the beaker was allowed to stand at room temperature ( about 25 ° c .) for one day . the solid matter thus obtained was collected by filtration and was dried to give a colorless prismatic crystal ( crystal ii ). this crystal was considered to be a butyl acetate solvate of the compound of formula ( i ). for the crystal ( crystal ii ) obtained in the above 3 - a ), powder x - ray diffraction measurement was carried out using the following apparatus under the following measuring conditions . measuring conditions : x - ray : cukα 1 , tube voltage : 40 kv , tube current : 20 ma , scan step : 0 . 02 °, scan speed : 4 °/ min , scanning axis : 2θ / θ , and scan range : 2θ = 3 to 40 ° the above crystal had characteristic diffraction peaks at the following diffraction angle ( 2θ ). diffraction angle ( 2θ ) [°] 8 . 0 ± 0 . 1 9 . 3 ± 0 . 1 9 . 8 ± 0 . 2 12 . 5 ± 0 . 2 13 . 7 ± 0 . 2 15 . 7 ± 0 . 2 for the crystal ( crystal ii ) obtained in the above 3 - a ), single crystal x - ray diffraction measurement was carried out using the following apparatus under the following measuring conditions . measuring conditions : x - ray : cukα , tube voltage : 50 kv , tube current : 85 ma , and measuring temperature : − 160 ° c . as a result of the measurement , the crystal had the following crystallographic properties . lattice constant : a : 16 . 223 ( 7 ), b : 18 . 01 ( 1 ), c : 15 . 045 ( 7 ), α : 90 , β : 90 , γ : 90 , v : 4395 ( 3 ) butyl acetate ( 3 . 8 ml ) was added to 1 . 22 g of the crude crystal of the compound of formula ( i ) synthesized according to example 1 , the mixture was heated to 60 ° c . to dissolve the crystal , and 1 . 6 ml of n - hexane was further added to the solution . the solution was stirred at room temperature for one hr , and the precipitated crystal was then collected by filtration and was washed with a mixed solution composed of butyl acetate and n - hexane ( 2 : 1 ), followed by vacuum drying for 7 hr to give 630 mg of a colorless crystal ( crystal iii ). butyl acetate ( 2 . 4 ml ) was added to 1 . 21 g of the crude crystal of the compound of formula ( i ) synthesized according to example 1 , the mixture was heated to 60 ° c . to dissolve the crystal , and the solution was allowed to stand at room temperature for 1 . 5 hr . the solution was further cooled on a water bath for one hr , and the precipitated crystal was then collected by filtration and was washed with a mixed solution composed of butyl acetate and n - hexane ( 2 : 1 ), followed by vacuum drying for 4 hr to give 739 mg of a colorless crystal ( crystal iii ). for the crystal ( crystal iii ) obtained in the above 4 - a ), powder x - ray diffraction measurement was carried out using the following apparatus under the following measuring conditions . measuring conditions : x - ray : cukα 1 , tube voltage : 40 kv , tube current : 20 ma , scan step : 0 . 02 °, scan speed : 4 °/ min , scanning axis : 2θ / θ , and scan range : 2θ = 3 to 40 ° the above crystal had characteristic diffraction peaks at the following diffraction angle ( 2θ ). diffraction angle ( 2θ ) [°] 5 . 7 ± 0 . 1 8 . 4 ± 0 . 1 10 . 3 ± 0 . 1 11 . 2 ± 0 . 2 13 . 9 ± 0 . 2 14 . 5 ± 0 . 2 the above - described scheme 4 described in wo 01 / 53305 was actually studied as an example of the production of a carbapenem compound as a final product using the compound of formula ( i ) as a synthetic intermediate . in particular , attention was drawn to the first step of scheme 4 , that is , the step of producing a compound in the second - stage compound in scheme 4 ( compound of formula ( ii )) using the compound of formula ( i ) ( the following scheme 5 ), and the following test was carried out . in the test , a crystal form of the compound of formula ( i ) and a noncrystalline form of the compound of formula ( i ) were used as starting compounds to produce the compound of formula ( ii ) according to scheme 5 . the crystal form of the compound of formula ( i ) was the compound ( crystal i ) prepared according to example 2 , and the noncrystalline form of the compound of formula ( i ) was the compound prepared according to example 1 . test 1 : case where noncrystalline form of compound of formula ( i ) was used ( comparative example ) oxalyl chloride ( 375 g ) was added to a suspension prepared by adding 3 . 0 l of dry methylene chloride to 371 . 7 g of n , n - dimethylaminobenzoic acid . a vessel containing the resultant solution was dipped in an oil bath , and the solution was stirred for 3 hr while controlling the internal temperature at about 40 ° c . the solvent was removed by evaporation under the reduced pressure , and the residue was vacuum dried to give a crude product of n , n - dimethylaminobenzoic acid chloride . a solution of the compound of formula ( i ) ( noncrystalline form ) ( 1 . 338 kg ) dissolved in 3 . 1 l of dry methylene chloride was added to a solution of this crude product was dissolved in 3 . 1 l of dry methylene chloride . next , 12 . 5 g of 4 - n , n - dimethylaminopyridine and 526 g of triethylamine were added to this solution , and the mixture was stirred at room temperature for 1 . 5 hr . the solution was diluted with 10 . 8 l of methylene chloride , and the diluted solution was then washed with 5 . 4 l of 25 % brine , a mixed solution composed of 2 . 7 l of 1 n hydrochloric acid and 2 . 7 l of 25 % brine , a mixed solution composed of 0 . 4 l of 1 n hydrochloric acid and 5 . 4 l of 25 % of brine , and a mixed solution composed of 0 . 21 l of a 1 n aqueous sodium hydroxide solution and 5 . 4 l of 25 % brine in a successive manner . thereafter , 510 g of anhydrous magnesium sulfate was added thereto for drying , followed by filtration . the solvent in the filtrate was removed by evaporation under the reduced pressure to give 1 . 729 kg of a contemplated mixed acid anhydride ( compound of formula ( ii )) ( yield 78 . 0 %, purity 74 . 5 %). test 2 : case where crystal form of compound of formula ( i ) was used ( present invention ) oxalyl chloride ( 371 g ) was added to a suspension prepared by adding 3 . 6 l of dry methylene chloride to 358 g of n , n - dimethylaminobenzoic acid . a vessel containing the resultant solution was dipped in an oil bath , and the solution was stirred for 2 . 5 hr while controlling the internal temperature at about 40 ° c . the solvent was removed by evaporation under the reduced pressure , and the residue was vacuum dried to give a crude product of n , n - dimethylaminobenzoic acid chloride . a solution of the compound of formula ( i ) ( crystal form ) ( 1 . 222 kg ) dissolved in 2 . 4 l of dry methylene chloride was added to a solution of this crude product dissolved in 3 . 3 l of dry methylene chloride . next , 12 g of 4 - n , n - dimethylaminopyridine and 461 g of triethylamine were added to this solution , and the mixture was stirred at room temperature for 0 . 5 hr . the solution was diluted with 10 . 4 l of methylene chloride , and the diluted solution was then washed with 5 . 2 l of 25 % brine , a mixed solution composed of 7 . 1 l of 1 n hydrochloric acid and 2 . 6 l of 25 % brine , and a mixed solution composed of 0 . 65 l of a 1n aqueous sodium hydroxide solution and 5 . 2 l of 25 % brine in a successive manner . thereafter , 382 g of anhydrous magnesium sulfate was added thereto for drying , followed by filtration . the solvent in the filtrate was removed by evaporation under the reduced pressure to give 1 . 545 kg of a contemplated mixed acid anhydride ( compound of formula ( ii )) ( yield 93 . 0 %, purity 90 . 0 %). comparison of the results of test 1 with the results of test 2 shows that , as compared with the use of the noncrystalline form of the compound of formula ( i ), the use of the crystal form of the compound of formula ( i ) could apparently improve the yield and purity of the compound of formula ( ii ). | 2 |
while this invention is susceptible of embodiments in many different forms , this specification and the accompanying drawings disclose only some examples of the use of the invention . the invention is not intended to be limited to the embodiments so described , and the scope of the invention will be pointed out in the appended claims . fig1 and 2 show states before and after setting of a focal - plane shutter according to an embodiment of the present invention . a set lever 1 is urged in the right pivoting direction by a spring 1 c . by driving a charge member 2 in cooperation with a mechanism operated by a motor m shown in fig6 the set lever 1 is pivoted in the left pivoting direction with a shaft 1 d acting as a fulcrum to thereby drive an opening drive lever 3 and a closing drive lever 4 to set positions ( initial states ). the mechanism comprises , for example , a lever mechanism which is not shown in the drawings . when the lever mechanism is operated by the motor m , the charge member 2 is pushed up by the lever mechanism . the set lever 1 is formed with projections 1 a and 1 b for pressing rollers 3 a and 4 a on the respective drive levers 3 and 4 . the set lever 1 also has a projecting locking piece 1 e constrained by a set lever claw 7 , as further described below , at the set position . as described herein , “ the set position ” refers to the position of each member in the initial state shown in fig1 . in this case , at the set position , the locking piece 1 e of the set lever 1 is constrained by the set lever claw 7 . the open drive lever 3 is urged in the left pivoting direction by a spring 3 a about a pin 3 e for evacuating an opening sector group a shown in fig4 from a shutter opening 9 . when the opening drive lever 3 is pivoted about a shaft 3 c in the right pivoting direction to a set position by being pushed up by the set lever 1 , an iron piece 3 b is brought into contact with an iron core 5 a while pressing down an electromagnet 5 against a spring 5 b by a slightly excessive setting . further , the closing drive lever 4 is urged in the left pivoting direction by a spring 4 d about a pin 4 e for covering the opening 9 with a closing sector group b shown in fig4 . when the closing drive lever 4 is pivoted in the right pivoting direction to the set position while centering on a shaft 4 c by being pushed down by the set lever 1 , an iron piece 4 b is brought into contact with an iron core 6 a thereof while pushing down an electromagnet 6 against a spring 6 b by a slightly excessive setting . as described herein , “ a slightly excessive setting ” refers to the sufficient amount of pressure which is applied when the iron piece 3 b is brought into contact with the iron core 5 a and when the iron piece 4 b is brought into contact with the iron core 6 b . stated otherwise , the pressure setting applied must be sufficient to insure that the iron pieces 3 b , 4 b are adsorbed by the iron cores 5 a , 6 b , respectively . the reason for the slightly excessive setting is that the iron pieces 3 b and 4 b are set in consideration of an error amount since an integration error is caused between the set lever 1 provided on the shutter side and the charge member 2 provided on the camera side . the set lever claw 7 is provided for locking the locking piece 1 e on the set lever 1 and for constraining the set lever 1 at a position at which by the slightly excessive setting , the respective electromagnets 5 and 6 respectively press the two drive levers 3 and 4 to a degree of producing the small gap β between the set lever shaft 1 d also serving as a stopper in addition to a stopper 8 . in this regard , when the iron core 5 a is urged by the spring 5 b , the iron core 5 a is “ stopped ” by the set lever shaft 1 d . when the electromagnets 5 and 6 are magnetized , the set lever claw 7 is pivoted in the right pivoting direction with a shaft 7 a as a fulcrum in cooperation with the jumping of a mirror and releases constraint of the set lever 1 and returns the set lever 1 . the mirror , not shown , is located in front of the shutter before the exposure . the mirror is jumped up so as to move above the shutter in order to expose . a holding lever 10 is urged in the left pivoting direction by a spring 10 b with a shaft 10 a acting as a fulcrum and is provided with a bent portion 10 c and a pin 10 d projected to a side of a rear cover c of the camera . fig5 shows the state in which the rear cover c is closed . when the rear cover c is opened , the holding lever 10 is pivoted in the left pivoting direction by the spring 10 b and the bent portion 10 c is engaged with a hook portion 4 f of the closing drive lever 4 . in fig4 the opening sector group a has a conventional construction , covers the shutter opening 9 and is operated by the pin 3 e of the opening drive lever 3 . the closing sector group b also has a conventional construction and is operated by the pin 4 e of the closing drive lever 4 . as shown in fig6 the camera main body is provided with a switch sc which is closed when the rear cover c is opened and which is connected to an electric circuit e provided at the camera main body . the electric circuit e can conduct electricity to the electromagnets 5 and 6 , and such conduction of electricity is controlled by a cpu 11 in the electric circuit e . an explanation of a normal shutter operation will be given as follows . in response to a release operation of the camera , a main switch s of the electric circuit e on the camera side shown in fig6 is closed . fig1 shows an initial state of the shutter . when the cpu 11 magnetizes the electromagnets 5 and 6 from the initial state , the iron pieces 3 b and 4 b of the respective drive levers 3 and 4 are adsorbed onto the iron cores 5 a and 6 a . at same time , a member , such as a movable lever not shown in the drawings , in cooperation with the jumping of the mirror , pivots the set lever claw 7 in the right pivoting direction . therefore , the set lever 1 returns to an original position after releasing depression on the respective levers 3 and 4 . further , the opening drive lever 3 and the closing drive lever 4 execute a desired exposure operation by successively h operating the opening sector group a and the closing sector group b by demagnetizing the electromagnets 5 and 6 after intervals of desired timings . next , an explanation will be given of an operation in the case in which the rear cover c of the camera is opened . referring back to fig5 when the rear cover c of the camera is opened , the rear cover c is moved from the camera main body d to the left side . as result , a pin p pushed by the rear cover c is returned to the left side by a spring , not illustrated , to thereby release the pin 10 d which has been pushed down in the lower direction by a taper portion at its front end . since the pin 10 d is provided at the holding lever 10 in fig1 by releasing the pin 10 d the holding lever 10 is pivoted in the left direction by the spring 10 b from the state shown in fig1 . by pivoting the spring 10 in the left pivoting direction , the bent portion 10 c locks the hook portion 4 f of the closing drive lever 4 . as a result , the holding lever 10 holds the closing sector group in a nonoperational state . in parallel with the operation , when the rear cover c is opened , the switch sc provided at the camera main body shown in fig6 is closed and electricity is conducted to the electromagnets 5 and 6 by the cpu 11 . further , the release operation of the camera is carried out similar to the case of closing the switch s . that is , as described above , the set lever claw 7 is operated and the set lever 1 is pivoted in the right pivoting direction from the state shown in fig1 . thereafter , when electricity conduction to the electromagnet 5 is cut , the opening drive lever 3 is pivoted in the left pivoting direction to thereby evacuate the opening sector group a from the shutter opening . the holding lever 10 holds the drive lever 4 until the rear cover c is closed . accordingly , the opening and closing shutter sectors do not emerge in the opening and a camera user does not touch the shutter sectors . that is , as shown in fig3 the holding lever 10 holds the closing drive lever 4 and even when the electromagnet 6 is demagnetized , the closing drive lever 4 cannot be operated . when the rear cover c is closed , by pushing the pin 10 d to the lower side of the drawing by the taper portion of the pin p and pivoting the holding lever 10 in the right pivoting direction , the closing sector group b is operated as a result of releasing the hook portion 4 f by the bent portion 10 c . fig2 shows such a state . next , an explanation will be given of a second embodiment of a focal - plane shutter according to the present invention . although a holding lever 10 is provided in the first embodiment , there is no need for the holding lever 10 in the second embodiment . when rear cover c of the camera is opened , the switch sc provided at the camera main body shown in fig6 is closed and the cpu 11 conducts electricity to the electromagnets 5 and 6 . further , an operation of releasing the shutter is carried out in a similar manner to the case of closing the switch s . in this case , the set lever claw 7 is operated and the set lever 1 is pivoted in the right pivoting direction from the state of fig1 . thereafter , when electricity conduction to the magnet 5 is cut , the opening drive lever 3 is pivoted in the left pivoting direction to thereby evacuate the open sector group a from the shutter opening . however , electricity conduction to the electromagnet 6 is not cut but maintained until the rear cover c is closed . therefore , the opening and closing shutter sectors do not emerge in the opening and the camera user will not touch the shutter sectors , such as during a film replacement operation . accordingly , there is no concern of causing deformation of the shutter sectors and abnormal operation of the shutter is prevented . in comparison with the first embodiment , the second embodiment achieves an advantage in which there is no need of providing the holding lever 10 although electricity needs to be conducted to the electromagnet 6 until the rear cover c is closed . further , in the case in which the rear cover c is opened before setting the shutter , when the switch sc shown in fig6 is closed , the cpu 11 operates the motor m built in the camera after confirming that the shutter has not been wound and carries out the above - described operation after the setting operation of the shutter . such operation is carried out instantaneously and therefore , the camera user cannot directly touch the shutter sectors . further , when the shutter has not been set , as in the above - described embodiment , the above - described operation is carried out after setting the shutter . further , the problem of direct contact with the shutter sectors by the camera user can be avoided by providing a member , such as a locking lever , for preventing the rear cover from being opened instead of finishing to wind up the shutter as mentioned above when the shutter has not been set , and by providing a shutter construction in which the preventive operation is released in cooperation with setting of the shutter to thereby prevent the rear cover from being opened before setting of the shutter . next , an explanation will be given of a third embodiment as follows . although in the first embodiment the holding lever 10 is held at the nonoperational position by the pin p when the rear cover c is closed , the holding lever 10 can be held at the nonoperational position by other methods . for example , a permanent magnet can be provided at a vicinity of the holding lever 10 and an electromagnet apparatus can be provided at a position capable of applying reverse magnetic field on the permanent magnet . by constructing such a constitution , the holding lever 10 can be held at the nonoperational position by being adsorbed and held by the permanent magnet at a position at which the hook portion 4 f of the closing drive lever 4 and the bent portion 10 c are not engaged with each other . further , when the rear cover c is opened by closing the switch sc , holding of the holding lever 10 is released by conducting electricity to the electromagnet apparatus to demagnetize the adsorbing and holding force of the permanent magnet by the reverse magnetic field to thereby enable to operate the holding lever 10 . further , in the above - described embodiments , the opening drive lever 3 and the closing drive lever 4 are controlled by the electromagnets 5 and 6 , however , the present invention is not limited thereto . that is , the invention is applicable to a focal - plane shutter in which the set lever 1 starts operating by operating the set lever claw 7 and mechanical engagement of the open drive lever 3 and the close drive lever 4 is successively operated . although an embodiment has been described in which the shutter is operated in response to a signal of a switch or the like operated when the rear cover of the camera is opened , a similar problem is posed even in the case in which a mirror is pushed up from a front side of a single - lens reflex camera . therefore , even in the case in which a photographing lens is removed and thereafter a mirror is pushed up , a full open state of the shutter is necessary in which both the opening and closing sector groups have been evacuated from the shutter opening . in this case , the full open state may be achieved by inputting into the cpu 11 a signal indicating the removal of a photographing lens of the camera and a signal indicating that the mirror of the camera has been pushed up . according to the present invention , a focal - plane shutter is provided in which shutter sectors evacuate from the shutter opening by opening of a rear cover of the camera . by this construction , a camera user does not contact the shutter sectors , such as during a film replacement operation , thereby preventing damage to the shutter sectors and ensuring a continuous and accurate operation of the focal - plane shutter . from the foregoing description , it can be seen that the present invention comprises an improved focal - plane shutter for a camera . it will be appreciated by those skilled in the art that obvious changes can be made to the embodiments described in the foregoing description without departing from the broad inventive concept thereof . it is understood , therefore , that this invention is not limited to the particular embodiments disclosed , but is intended to cover all obvious modifications thereof which are within the scope and the spirit of the invention as defined by the appended claims . | 6 |
general — phase correlation holography functions as a truly two - dimensional ( 2d ) holographic multiplexing process . preferred embodiments may or may not use a medium which is sufficiently thin to preclude bragg selectivity for differentiation of successive holograms . it has many valuable attributes , and will likely become the long - sought practical digital recording process . selection is now entirely based on the content of the reference beam — on inclusion of rays of differing angle of incidence and non - uniform phase . adequacy is measurable in terms of the auto - correlation function of the phase mask or of the corresponding function for the beam . a first consequence is to make selection independent of direction in the place of the medium — selectivity in y - and x - directions , or in intermediate directions , can be made identical in the absence of limitations imposed by the medium or by processing conditions . selection also can be improved in a thick medium by combining phase correlation selectivity with bragg selectivity inherent in a thicker medium . the system — general discussion is aided by reference to fig1 . elements shown in phantom indicate alternatives and enable discussion of system variations . both versions of fig1 use an illuminating beam 11 , which is converted into a phase beam by a phase mask . in the example , use of the single lens 12 , with the mask positioned on plane 10 , produced a image 27 of the mask on the medium . the phase mask is rotatable to access different holograms that are angularly separated from one another in a given location of a storage medium . the phase mask used was a random binary phase mask and had a pixel pitch of 20 μm , was of approximate overall dimensions , 2 cm × 2 cm ( 1024 × 1024 pixels ). half of the randomly located pixels imposed a phase - shift of 180 °, so that changing phase across the beam front averaged at zero . the signal beam 26 is modulated by “ spatial light modulation ” 15 producing a signal pattern from a computer not shown . the experimental arrangement shown process for signal introduction through lenses 16 , 17 and 18 , and for readout by means of lenses 19 , 20 and 21 . with lenses in standard 4f configuration , a fourier transform hologram 27 is recorded on medium 13 , and is reconstructed to produce an image on detector 22 . 4f configuration requires focal distance spacings so that object - to - lens 16 spacing is equal to the focal distance of lens 16 , f 16 , lens 21 - to - detector spacing is equal to the focal distance f 21 , and lens to lens spacing are the sum of focal distances , i . e ., f 16 + f 17 for the distance between lenses 16 and 17 . the specifics of the arrangement are only illustrative . 4f optics are not required — relay optics are acceptable . spatial filtering may be done between lenses , in the lens series 1921 , to improve snr . the phase mask need not be located at either the focal plane nor the focus of lens 12 , nor is it required that medium 13 be located at the other focal plane . lens 24 , shown in phantom , illustrates an alternative arrangement providing for imaging the mask , now located at place 10 , onto the medium . it is not required that beam 11 be a plane wave — e . g ., a spherical beam can be substituted . selectivity is not very sensitive to the exact position of the phase mask , but it is required that the position be the same during reconstruction . omission of lenses in the reference beam results in some loss in selectivity which may be tolerable . the apparatus shown is otherwise illustrative only . arrangement for fourier transform holography storage is only one option . for example , with successive elements still located on fourier planes , omission of one lens in each of the 16 - 18 and 19 - 21 lens series results in an image hologram and continues to provide for image reconstruction . a phase mask in contact with slm 15 or at plane image plane 23 assures uniform brightness of the signal beam for better recording . in addition , the signal beam may be filtered to eliminate higher - order diffraction modes or miscellaneous noise . for thick media — for media & gt ; 1 mm — best results have been obtained for imaging of the phase mask on the recording medium . for thick media , it has been found useful to filter out zeroth order diffracted waves by use of a blocking filter of fourier plane 25 in the reference beam . such a dc filter , consisting of a central blocking region , may in addition have horizontal and vertical lines crossing at this region , so as to additionally block x - and y - components . for thin media , the fourier plane filter may not be necessary but is still desirable . while a fourier transform of the phase mask could be nearly as effective as a mask image , use of a spatial filter with a transform , rather than an image , may result in some increase in snr . filtering is desirably on the plane of the phase mask . [ 0042 ] fig2 is a simplified conceptual diagram of a portion of a holographic storage system 200 in accordance with an embodiment of the invention . the role of fig2 is to highlight some of the physical movements required in one type of illustrative holographic storage system . the functionality of the embodiment of fig2 will be understood by reference to the drawings and corresponding description of fig1 . moreover , the drawings of fig2 are simplified in order to illustrate some advantages of the invention with respect to its application with a medium 202 that has a disk shaped format . a phase - ordered reference beam 203 is provided to an optical system , represented in simplified form by wedge 204 , which directs the reference beam to a phase mask 206 . in order to simplify the drawing , the signal beam and corresponding signal beam optics are not shown . the phase mask 206 imparts phase content to the reference beam and outputs a phase beam 207 that illuminates a spot on the disk 202 . in order to access a given stack of holograms at a given location of the disk 202 , the position of the disk is changed by rotating it to an angular position corresponding to the given stack location as indicated by arrows 208 . at least a portion of the lens optics 204 , and perhaps the phase mask 206 , are moved so as to steer the reference beam to a radial position corresponding to the given stack location . arrows 210 indicate radial movement of the reference beam . once the disk 204 has been moved to the desired angular position and the reference beam has been steered to the desired radial position , individual holograms in the given stack can be accessed by changing the orientation of the phase mask 206 as indicated by arrow 211 . in accordance with a present embodiment of the invention , individual holograms are accessed by rotation of the phase mask as indicated by arrow 211 . rotation of the phase mask results in a change in the orientation of the phase mask relative to the medium 202 which in turn results in a change in the reference beam structure incident on the medium at the given location selected by the disk rotation movement indicated by arrows 208 and by the beam translation movement indicated by arrow 210 . during recording , simultaneously shining a signal beam and a phase beam upon a given medium location with the phase beam rotated to a given angular rotation , results in recording of a hologram at that given location . during reconstruction , shining a phase beam upon a given medium location with the phase beam rotated to a given angular orientation , results in reconstruction of a hologram associated with such angular rotation and medium location . thus , selective access ( both recording and reconstruction ) of holograms can be achieved at different angular positions in the same given medium location . in the example , a set of 140 fully overlapping holograms was stored at one - degree rotation intervals in a single stack . it will be noted , however , that any rotation of the phase structure longer than the correlation length of the phase mask is sufficient for such phase rotation correlation multiplexing . an advantage of rotation correlation multiplexing is that it greatly simplifies the mechanics needed for a storage system using a phase beam as a reference . from an engineering perspective , the ability to move to a single location and write and / or recover a large number holograms with limited motion of a small optic offers a great advantage . the illustrative drawings of fig3 a - 3 b show prior hologram layouts in a storage medium . in fig3 a , holograms are partially overlapping . in fig3 b , groups of partially overlapping holograms are stored in spatially separated sectors . in the &# 39 ; 145 and &# 39 ; 691 patents it is assumed that the media when recorded would have a 2 - d array of partially overlapped holograms shown in fig3 a . to access an individual page of data stored as shown in fig3 a or 3 b one would need to move a relatively large optical head , ( tracking with very high precision ) successively stopping at each page to be recovered . in contrast , fig4 illustrates storage of a plurality of completely overlapping holograms using rotational selection in accordance with an embodiment of the present invention . one can array stacks of holograms on the disk . each stack has many overlapping holograms at the same medium location . the holograms are completely overlapping , not just partially overlapping . the motions required are first a translation from stack to stack and then accessing the pages within a stack by mask rotation . rather , there is a high precision move from one stack to the next , but once at the new location , one can individually write or recover a large number of individual stacked holograms by rotating one relatively small optic element such as phase mask or a small optical train that is tube mounted . an additional problem with the implementation of the &# 39 ; 145 and &# 39 ; 691 patents involves a sectoring penalty . with prior arrays of partially overlapping stacks as shown in fig3 a - 3 b one typically must write large blocks of data to use the media efficiently . in contrast , the stack - wise approach afforded by rcm allows more flexibility in recording even smaller blocks of data while still using the medium efficiently . that is , with rcm , multiple holograms can be stacked in one location . thus , there is not a great a need to write large hologram blocks of data to use the medium efficiently . another alternative embodiment of the invention involves a combination of correlation multiplexing plus rotation correlation multiplexing . through such process , overlapping stacks of holograms can be created . for example , assume that 1 , 000 holograms are to be stored . in accordance with the embodiment of fig4 all 1 , 000 of the holograms could be multiplexed in a completely overlapping fashion in one location using rotation correlation multiplexing . alternatively , a combination of rotation correlation multiplexing and shift correlation multiplexing , can be used to store overlapping stacks of holograms . more particularly , for example , one can multiplex 100 holograms at one location using rotation correlation multiplex ( rcm ); and then shift the relative position of the reference beam relative to the medium by some fraction of a hologram dimension ( e . g . 100 microns ); and then again use rcm to store another 100 holograms ; and then again shift the relative position by the same fraction ; and store another 100 holograms using rcm , etc . each relative position shift is by an amount that is small enough so that there is partial overlap between adjacent stacks of completely overlapping holograms . the result of this example process would be the storage of ten stacks of 100 holograms apiece in which the holograms in any given stack completely overlap with each other and in which adjacent hologram stacks partially overlap with each other . [ 0048 ] fig5 is a plot showing diffracted energy versus angular rotation of the phase mask for the example . fig6 shows the plot of diffracted energy versus angular rotation of the phase mask of the last seventeen holograms of the example on an expanded scale . the recording and reconstruction geometry may use transmissive media . for instance , holographic data storage , pages 242 - 256 , which is expressly incorporated herein by this reference , discloses systems for use with transmissive media . alternatively , the recording and reconstruction geometry may use reflective media . it will be appreciated that changing the orientation of the phase mask has the effect of changing the orientation of a reference phase beam incident upon the holographic storage medium . during recording , the phase orientation is changed to permit different individual holograms to be stored in overlapping fashion at the same given location of the medium . during reconstruction , the phase orientation is changed to permit reading of the different individual holograms that were stored previously in overlapping fashion at the same given medium location . [ 0051 ] fig7 is an illustrative drawing showing one embodiment of the invention in which a change in the orientation of a phase beam is achieved by rotating a phase mask about an axis parallel to phase - ordered beam . different individual angular orientations of the phase mask relative to the phase ordered beam result in different individual orientations of the phase beam relative to the storage medium . different individual orientations of the phase beam relative to the storage medium can be used to access ( write or read ) different individual holograms at a given single location of the storage medium . [ 0052 ] fig8 is an illustrative drawing showing one embodiment of the invention in which a change in orientation of a phase beam can be achieved by changing the tilt of a phase mask relative to an axis of the phase - ordered beam through a cantilever motion of the phase mask . different individual angular tilts of the phase mask relative to the phase ordered beam result in different individual orientations of the phase beam relative to the storage medium . different individual orientations of the phase beam relative to the storage medium can be used to access ( write or read ) different individual holograms at a given single location of the storage medium . fig9 a - 9 b are illustrative drawings of two embodiments of the invention in which a change in the orientation of a phase beam can be achieved by changing the orientation of an optic relative to the phase mask . in fig9 a , the optic comprises a lens positioned to direct a phase - ordered beam to the phase mask . changing the tilt of the lens relative to the phase mask , through a cantilever motion of the lens , results in a change in the orientation of the phase - ordered beam upon the phase mask this change in phase - ordered beam orientation results in a change in the orientation of the phase beam that emanates from the phase mask relative to the storage medium . different individual orientations of the lens relative to the phase beam can be used to produce different individual phase beam orientations relative to the storage medium that can access ( write or read ) different individual holograms at a given single location of the storage medium . in fig9 b , the optic comprises a lens positioned to direct a phase beam emanating from the phase mask onto the medium . changing the tilt of the lens relative to the phase mask , through a cantilever motion of the lens , results in a change in the orientation of the phase beam upon the medium . different individual orientations of the lens relative to the phase mask can be used to produce different individual phase beam orientations relative to the storage medium that can access ( write or read ) different individual holograms at a given single location of the storage medium . one could also steer a phase ordered beam or phase beam with a mirror to the same effect . while the above embodiments employ a phase mask , a suitably complex phase can be imparted using other optical elements that impart a suitably complex phase to a beam , such as a holographic medium with a complex phase reference beam stored in it as a hologram . alternatively a suitably phase - mismatched diode array could be employed . for instance , phase locked diode arrays have been proposed for use in holographic neural networks . see optoelectronics , vol . 8 , no . 1 , pp . 21 - 34 march 1993 . a series of properly directed lenslets could be employed as explained in optoelectronic , vol . 8 , no . 1 , pages 111 - 123 ( march 1993 ). alternatively , a suitably phase mismatched array of reflecting surfaces , could be employed . for each such alternative , a change in the reference beam structure incident on the medium at the given location can be achieved through rotation of the optical element . in the case of electronically reconfigurable diode arrays and the reconfigurable arrays of reflective surfaces , effective rotation may be achieved by appropriate changes in the operative states of individual lenses or reflective surfaces . moreover , it will be appreciated that the invention can be practiced using a reference beam having correlated phase content as described in u . s . pat . no . 6 , 191 , 875 . phase beam — in the generally discussed embodiments , the phase mask is illuminated by a phase - ordered beam such as a plane wave , and only thereafter is a reference beam with proper phase and angle content produced . more generally , the requirement for the reference beam is that it contain the proper phase information when interfering with the signal beam — produced either at inception , or by modulation of a phase mask , or by a combination of the two . phase mask — the nature of the phase mask is well known to the artisan . the term includes both ground glass with its very large number of small dissimilar pixels , and binary phase masks with a smaller number of nominally identical pixels , as well as intermediate phase mask structures . in all events , traversal time for radiation varies across the exit surface of the mask , to produce the changing phase delay which is the essence of the mask . for a very high level of perfection , a binary phase mask containing 20 pixels , each { fraction ( 1 / 20 )} th of the mask area is sufficient for the invention . expected imperfections are accommodated by a 10 pixel × 10 pixel mask , and such a mask is regarded as a minimum requirement for the invention . for the nominal phase mask in which 50 % of the surface is altered from planarity , etch pits introducing a phase change of , at least 15 ° is operative , although a phase change of at least 45 ° is preferred . for minimizing noise , the average phase variation for the entire mask should be close to zero , in turn requiring a phase change of 180 ° in the instance of the binary phase mask . this is achieved in a conventional binary mask in which etch pits occupy 50 % of the mask surface . the requirement is statistically satisfied in the most complex phase mask — in ground glass — in which widely varying pixels , most varying one from another by many wavelengths , occupy the entire surface . the functioning characteristic of the phase mask is defined in terms of its auto - correlation functional . in inexact terms , this is a measure of the position - to - position self - similarity of the mask . the requirement , that the mask have the desired selectivity , may be measured in terms of the auto - correlation peak width — with the peak width approximately equal to the needed selectivity . this assumed correspondence is descriptive of high - quality , commercially - available phase masks . ( accordingly , one suitable commercial phase mask is a random phase mask specified by : a ) wavelength ; b ) number of pixels ; and c ) pixel pitch .) experimentally , sufficient phase content has been introduced into a plane wave beam with a random mask constituted of pixels of a pitch ( size ) of 10 - 20 μm , with at least 100 pixels in each of the x - and y - directions in the mask . in theory not required , maximal varied pixel delay times approaching 180 ° lessen effects of compositional and physical non - uniformity &# 39 ; s , and relax manufacturing specifications . alternative to the usual commercial random binary phase mask in which identical etch pits are randomly positioned , differing pixel - associated delay times may be associated with an ordered pixel array . various techniques offered randomness both in position and in individual pixel characteristics ( such as in ordinary ground glass ). an averaged mask delay time of zero statistically assures cancellation of overlapping hologram regions and lessens noise . in other mask structures , differing delay times are due to refractive index variations . there may be economic or other circumstances in which it is desirable to use an ordered phase mask to yield a deliberately repeated sequence over a relatively small fraction of the field . this consideration may outweigh the usual objective of absolute independence of multiplexed holograms , so that some additional noise may be tolerated . in the same fashion , a deterministic phase mask — a mask with prescribed pixel - to - pixel order , may be used e . g ., to maximize diffraction efficiency of the hologram or optical throughput of the system the apparatus used to demonstrate rcm was set up as follows . a coherent radiation 532 nm doubled nd : yag laser was used as the system source . its output was beamsplit to generate the sources for the object and reference beams . the object beam input was spatially filtered , ( to produce a plane wave ), and directed into a transmissive liquid crystal spatial light modulator . ( the modulator is encoded with the information to be recorded .) the encoded signal beam is fourier transformed using a 110 mm haselblad lens into the recording media . the reference input is also spatially filtered , ( producing a phase ordered beam ) and directed through a phase mask which is comprised of 1000 × 1000 array of pixel 10 μm square pixels , each randomly etched to produce a 0 or π phase shift of the input producing a phase beam . this phase beam is imaged onto the recording media using a simple 4f system . the phase mask in addition is mounted on a newport research computer controlled motorized actuator allowing rotation of the mask with 0 . 001 deg resolution . ( the two beams cross and are overlapped within the volume of the media .) holograms were recorded at 1 deg phase mask rotation intervals . the reconstructed holograms are inverse fourier transformed using a 100 mm haselblad lens and imaged onto a cd camera . various modifications to the preferred embodiment can be made without departing from the spirit and scope of the invention . for instance , the medium format may be a rectangular card , and rectilinear movement of the optics may be required to steer the phase beam to shine on a given location of the card medium so that phase rotation correlation multiplexing can be used to access individual holograms associated with that given location . thus , the foregoing description is not intended to limit the invention which is described in the appended claims . | 6 |
according to an embodiment of the invention the tool comprises an internal combustion engine as drive motor to which a generator for producing electric power or electric current is coupled in a suitable manner . according to an embodiment of the invention the at least one device comprises a microwave generator that is capable of generating electromagnetic radiation energy in the range of microwave radiation . according to an embodiment of the invention the at least one microwave generator is arranged in the at least one handle in an integrated manner . according to an embodiment of the invention the electromagnetic radiation energy is conducted by one or several waveguides or hollow conductors ( or waveguide ) for electromagnetic radiation . the waveguides or hollow conductors are coupled to this end in a suitable manner to the at least one microwave generator and designed in such a manner that the one or the several electromagnetic waveguides decouple ( s ) the conducted electromagnetic radiation energy in the at least one area of the at least one handle . according to an embodiment of the invention the tool comprises two handles for manual manipulation . at least one microwave generator is arranged in an integrated manner in each of the two handles in order to generate the electromagnetic radiation energy . according to an embodiment of the invention two microwave generators are integrated in one of the two handles whereas one microwave generator is integrated in the other one of the two handles . furthermore , the microwave generators are arranged at positions that are preferably assumed by the hands of the user for manually guiding the tool . according to an embodiment of the invention the tool comprises at least one control device adapted in such a manner as to regulate the electromagnetic radiation energy . according to an embodiment of the invention the tool comprises a sensor for detecting a measured temperature value by means of which measured value the radiated energy can be regulated . according to an embodiment of the invention the tool comprises a manually operable adjusting device that generates a regulating value with which the radiated energy can be regulated . the invention is described in detail below with reference made to the attached drawings . the invention is described using the hand - guidable , activatable tool in the form of a chain saw and shown in fig1 to 4 with an internal combustion engine and components of it presented solely by way of example . the invention can also be used in other tools such as , e . g ., abrasive cutting - off machines , hedge shears , hammer drills , chisel tools , etc . similar or identical components are designated with the same reference numerals . fig1 shows a schematic view of a generic chain saw as example for a hand - guidable , activatable tool . the chain saw comprises a first handle 1 and a second handle 2 with the aid of which the chain saw user handles it . the chain saw shown is driven by internal combustion engine 3 that comprises a generator for generating electric power . as regards the problem of the invention , the chain saw also comprises adjusting device 4 , integrated control device 6 or integrated control electric circuitry , first , second and third microwave generators 21 , 22 , 23 as well as current feed lines 31 , 32 , 33 to the corresponding microwave generators 21 , 22 , 23 . integrated control device 6 is supplied with current ( or power ) by the generator coupled to internal combustion engine 3 . for its part , control device 6 supplies microwave generators 21 , 22 , 23 with current ( or power ) and controls the feeding of current ( or power ) to microwave generators 21 , 22 , 23 . adjusting device 4 can be operated by the chain saw user and is adapted to generate a control signal corresponding to a power regulating value with which the power [ performance ] of microwave generators 21 , 22 , 23 is selected . the control signal of adjusting device 4 is supplied to integrated control device 6 that controls or regulates the individual microwave generators . adjusting device 4 is also suitable for generating a switching signal that serves to turn the microwave generators on or off . integrated control device 6 is preferably designed as an electric circuit or as electronic control circuitry . furthermore , one or several temperature signals can be supplied from temperature sensors ( not shown ) to integrated control device 6 which sensors detect an outside ( or external , ambient ) temperature and / or temperatures in the area of one or more hand positions on one or more handles . these temperature signals act with the previously described regulating value signal on the regulating of integrated control device 6 . a suitable electrically or electronically designed control - or regulating algorithm brings about the power regulation of the microwave generators . a microwave generator is based substantially on a power transformer that generates a high - voltage signal supplied to a magnetron capable of generating electromagnetic radiation in the microwave range by means of the high - voltage signal . the high - voltage signal is preferably a direct voltage signal . when the magnetron is supplied with alternating voltage it is to be provided with a rectifier with possibly suitable capacitive smoothing . a hollow conductor can be coupled to the magnetron in order to conduct the generated electromagnetic radiation to a predetermined location . the frequency of the electromagnetic microwave radiation is selected so that when the radiation enters into water - containing substances , especially into body tissue , a vibrational excitation of the water molecules takes place which results in an elevation of the temperature of the substance and / or of the body tissue . this effect of electromagnetic microwave radiation is also used , e . g ., in medicine for heat treatment . the microwave generators used in the present invention are based on this technology . care is to be taken that the power capacity of microwave generators 21 , 22 , 23 used in the present invention is adapted in such a manner that no damaging effects are produced on the body of the user of the chain saw or tool . since microwave technology is also used in various medical fields , medical limit values are available for such microwave generators that assure , when observed , that no damage occurs in tissues of bodies irradiated with microwaves . microwave generators 21 , 22 , 23 are arranged in the handle in such a manner that , in particular , hands located at typical holding positions of the handles are warmed . to this end at least one microwave generator per handle can be used . the arrangement of the microwave generators used in the handles and the handle design are preferably selected so that a radial , substantially uniform radiation field is formed at least in the area of the hand positions of the used in order that a substantially constant radiation power is volumetrically ( or radially , present over the area ) present . due to the reflective action of metals on microwaves , care is to be taken when designing the handles that either no metal material is used or that at least precautions that make possible a passage of microwave radiation in a suitable manner are taken when using metallic materials . in fig1 the two microwave generators 21 , 22 are arranged in the first handle 1 . microwave generators 21 , 22 are arranged in preferred handle positions ( above and laterally ) that are used by a user of the tool when handling it . microwave generators 21 , 22 radiate the microwave radiation generated by them in a radial direction so that a substantially volumetrically uniform microwave radiation field is present in the associated partial areas of handle 1 that warms a hand located in the radiation field . current feed lines 32 , 31 feed associated microwave generators 21 , 22 with an appropriate power or make an appropriate power control signal available to microwave generators 21 , 22 . in an analogous manner microwave generator 23 is arranged in second handle 2 in a preferred handle position used by a user of the tool when handling it . microwave generator 23 radiates the microwave radiation generated by it in a radial direction so that a substantially volumetrically uniform microwave radiation field is present in the associated partial area of handle 1 that warms a hand located in the radiation field . current feed line 33 feeds associated microwave generators 23 with an appropriate power or make an appropriate power control signal available to microwave generator 23 . fig2 shows a magnet wheel ( or field spider ) generator coupled to the internal combustion engine of the chain saw according to fig1 . magnet wheel generator 40 is coupled to the drive shaft of the internal combustion engine ( not shown ). magnet wheel generator 40 is received by the shown housing part of the internal combustion engine . in particular , fig2 shows a magnet wheel generator 40 composed of a magnet wheel and a generator armature and fastened by a generator carrier . magnet wheel generator 40 is received in crankcase 41 of the internal combustion engine . the generator windings are housed in the generator armature . magnet wheel generator 40 can be designed as a direct - voltage or alternating - voltage generator . as previously described , microwave generators are preferably operated with a direct voltage signal so that in the case of an alternating - voltage generator one or more suitable rectifiers are to be used . fig3 shows an alternative arrangement of a microwave generator in a first handle . microwave generator 24 is arranged in a first position in the area of an end of first handle 1 and is supplied with current or power by means of current sockets ( or jacks ) 39 . the power supply takes place regulated with the aid of integrated control device 6 . hollow conductor 34 is coupled to microwave generator 24 and designed in such a manner that the microwave radiation generated and supplied by the microwave generator is radiated over the entire extent of hollow conductor 34 vertically ( radially ) to its direction of extension so that a microwave radiation field is present around the area of handle 1 which area is associated with hollow conductor 34 . the radiation field is advantageously constant over the entire handle range defined by hollow conductor 34 . alternatively , e . g ., a radiation field can be present in the area of the previously described handle positions ( corresponding to the positions of microwave generators 21 , 22 ). hollow conductor 34 can be provided , e . g ., with suitably arranged recesses that make possible a passage of part of the microwave radiation conducted in hollow conductor 34 so that a radiation of microwaves along hollow conductor 34 results . fig4 shows an alternative arrangement of a microwave generator in a second handle . microwave generator 25 is arranged in a first position in the area of an end of first handle 2 and is supplied with current or power by current feed line 38 . the power supply takes place in a regulated manner by integrated control device 6 . hollow conductor 35 is coupled to microwave generator 25 and designed in such a manner that the microwave radiation generated and supplied by the microwave generator is radiated over the entire extent of hollow conductor 35 vertically ( radially ) to its direction of extension so that a microwave radiation field is present around the area of handle 2 which area is associated with hollow conductor 35 . the radiation field is advantageously constant over the entire handle range defined by hollow conductor 35 . alternatively , e . g ., a radiation field can be present in the area of the previously described handle positions ( corresponding to the position of microwave generator 23 ). hollow conductor 35 can be provided , e . g ., with suitably arranged recesses that make possible a passage of part of the microwave radiation conducted in hollow conductor 35 so that a radiation of microwaves along hollow conductor 35 results . analogously to fig3 in which a microwave generator 24 , 25 is present per handle 1 and 2 , e . g ., a centrally arranged microwave generator can be used as an alternative . this microwave generator would furthermore be provided , e . g ., with two hollow conductors that couple in the microwave radiation generated by the microwave generator and conduct it to handles 1 and 2 , in which instance the two hollow conductors in the area of the handles are designed in such a manner that a decoupling ( or coupling out ) of the microwave radiation takes place so that a suitably formed radiation field is present in the area of the handles or in partial areas of the handles in order to warm the hands of a user in a previously described manner . it should be noted that the handle heating was presented based on microwave generators using the example of a tool that can be driven by an internal combustion engine , in particular based on a chain saw . however , the invention is limited neither to a chain saw nor to a tool that can be driven by an internal combustion engine . the handle heating based on microwave generators can also be used in a current - driven tool such as , e . g ., an electric saw , electric hedge shears , etc . | 8 |
according to the invention , the pacemaker investigates the presence of a pmt by measuring the correlation between an interval t 3 , for signals generated by the heart and an interval d 2 , for signals generated by the pacemaker . reference is now made to fig4 where a non - pmt situation is illustrated to the left and a pmt situation is illustrated to the right . the lower part of the figure illustrates the atrial ( a ) and the ventricular ( v ) conduction levels and the dashed and the continuous lines indicate antegrade and retrograde conduction , respectively . the cycle time of a pmt comprises two delay intervals , one ( d 1 ) related to the retrograde heart tissue conduction , and the other one ( d 2 ) related to the pacemaker introduced interval or time delay between atrial and ventricular activity ( av - interval ). d 1 can be stable , vary regularly or stocastically . however , for short time periods , d 1 is limited and substantially constant . the av - interval , d 2 , is in this invention made to vary stocastically or in accordance with a predetermined pattern . by varying the interval d 2 in a known way , the correlation between d 2 and t 3 is calculated for a short time period . typically 2 to 6 heart cycles are needed to reach a reasonably safe decision that the value of the correlation exceeds a predetermined value and , consequently , that a pmt is present . the high correlation for d 2 and t 3 when a pmt is present is explained by way of example below . let the interval t 3 be the interval ( pp ) between two consecutive p - waves . if no pmt is present , the pp - interval is the interval between two spontaneous atrial beats , and the correlation between d 2 and t 3 is low as the pp - interval variation is independent of d 2 . if , in contrast , a pmt is present , the pp - interval is the sum of the retrograde conduction interval d 1 and the pacemaker generated interval d 2 . consequently , during a pmt , there is a very high correlation between d 2 and t 3 ( the pp - interval ). alternatively , instead of using the pp - interval as t 3 , quantities related thereto , for instance the atrial frequency or the interval between a ventricular stimulus and a p - wave , could be employed . in the last case , it is obvious that the expression &# 34 ; signals generated by the heart &# 34 ;, previously used in connection with t 3 , is intended to comprise signals related to ventricular stimuli , and further , that the correlation between d 2 and t 3 is contrary to where t 3 denotes the pp - interval . in fig1 the heart is designated 11 and the pacemaker is generally designated 10 . the pacemaker 10 is connected to the heart through an electrode lead 112 for the atrium and an electrode lead 113 for the ventricle . the electrode leads 112 and 113 are respectively connected to signal sensors and amplifiers 12 and 13 for the atrium and the ventricle . the electrode lead ( or possibly a further , separate electrode lead ), not shown for the ventricle 113 , is connected to a stimulating unit 14 . the stimulating unit 14 delivers stimuli to the heart . a further stimulating unit ( not shown ), could possibly be provided for stimulating the atrium through electrode lead 112 , or , anther through separate electrode lead ( not shown ). the basic pacemaker timing and logic unit 15 is controlled by the sensed signals applied thereto through leads 121 and 131 . the sensed signals are related to spontaneous heart activities , viz . atrial p - wave or ventricular r - wave . if the heart fails to beat normally , stimulation pulses are emitted by the pacemaker in order to maintain the normal heart function . it is also possible to deliver correctly timed stimulation pulses even if spontaneous heart beats exist . the stimulation unit 14 is connected to the basic unit 15 through lead 156 . the basic logic and timing unit 15 ( to be described later ) is connected to the calculating unit 16 ( to be described later ) through data bus 161 . in response to e . g . a sensed atrial signal on lead 121 , the basic timing and logic unit 15 ( fig2 ) generates basic pacer escape intervals ( pp - intervals ) in the time base generator and time base register 151 . a control signal on lead 152 triggers the av - interval counter 153 simultaneously with the triggering of the time base generator 151 . after the av - interval has been timed out , a control signal on lead 154 triggers the stimulation pulse width generator and time register 155 , generating a control signal on lead 156 , which controls the stimulating unit 14 . a further control circuit , similar to the one just described and also starting from the time base generator 151 but delivering stimuli for the atrium through electrode lead 112 or another separate ( not indicated ) electrode lead for the atrium can also be provided . in order to prevent incorrect control due to false signal sensing after , for instance , a stimulation pulse has been delivered or a heart signal just sensed , the refractory period registers 122 and 132 and their respective leads 123 and 133 are provided in connection with atrial and ventricular signal sensing , respectively . a communication and data register unit 171 is provided for the pacemaker programming and functional control . the communication is preferably carried out by telemetry means 172 . the data bus 161 provides for the internal pacemaker transmission of programmed parameter values , control signals and time register values . the calculating unit 16 ( fig3 ) comprises time registers , logic circuits and arithmetic processing circuits . preferably , a microprocessor is employed , and the microprocessor is operated in accordance with a correlation calculating program . arithmetic processing , time measurement and control are then carried out from a ram and rom program memory 163 connected to a central processing unit ( cpu ) 162 . measured time intervals ( d 2 , t 3 ) and calculation results are stored in read - write memory 164 . detected atrial and ventricular signals are received via interrupt registers 166 and 167 , respectively . data from the microprocessor can be placed in the input - output register 168 via the internal bus 165 for subsequent communication with the basic timing and logic unit 15 . it should be noted that , for explanatory purposes , the timing and logic unit 15 and the calculating unit 16 have been disclosed as separate units . it is , however , possible to arrange unit 16 to carry out the functions of timing and logic unit 15 . the calculation of the correlation is carried out in accordance with well - known mathematical theory in the cpu 162 , with interaction with the program memory 163 and the read / write memory 164 , as needed , and can be made in different ways . as an example , the mean value and the deviation from the mean value is calculated for each interval t 3 and each interval d 2 , respectively . the deviation for each interval t 3 and for each corresponding interval d 2 are multiplied and the products added for all t 3 , d 2 intervals . the resulting sum is then divided by the sum of the absolute values of the deviation for the d 2 intervals . if the result of this division exceeds a predetermined value , a pmt is present . the pmt decision can also be referred to two correlation levels . below the lowest level , there is no pmt and above the highest , a pmt is present . a value between the two levels indicates that a decision cannot be made with the intervals available , and therefore further intervals d 2 , t 3 should be included until a decision can be reached . another way of calculating the correlation would be to subtract d 2 from t 3 for each corresponding d 2 , t 3 interval , calculate the mean value for the resulting differences and the deviation therefrom for each resulting difference . correspondingly , the mean value and the deviations therefrom for the intervals d 2 are calculated . these last deviations are compared to the corresponding difference deviations , and , if substantially equal , the correlation is high . finally , for a reliable detection of a pmt , the variation in d 2 should be of the same magnitude or greater than the variation in d 1 . however , the number of intervals are also of importance for the reliability , and should the variation in d 1 be greater than that in d 2 , the number of intervals should be correspondingly increased . although modifications and changes may be suggested by those skilled in the art , it is the intention of the inventor to embody within the patent warranted hereon all changes and modifications as reasonably and properly come within the scope of his contribution to the art . | 0 |
the starting of an hid lamp consists of several phases : breakdown , glow , glow - to - arc and thermionic arc . fig1 shows voltage and current waveforms during the starting of 100 w metal halide lamp . all four phases of starting are indicated ( breakdown , glow , glow - to - arc , thermonic arc ). fig2 shows expanded glow phase voltage and current waveforms for a 100 w metal halide lamp having electrodes covered with condensate . technically , the initial discharge that occurs during hid lamp starting with electrodes covered with condensate is not glow , however for purposes of this application the glow phase in lamp starting refers to the period between breakdown and glow - to - arc transition whether the electrodes are covered with condensate or not . the extremely low voltage and high current waveforms seen during this time period are thought to be due to a higher number density of ionizable species ( mostly mercury ) removed from the electrodes and driven into the vapor phase . fig3 shows glow phase waveforms from the same lamp after the electrodes have been cleaned of almost all condensate . the voltage across the lamp remains high during the main portion of each half cycle . in contrast , the voltage collapsed to a very low value early in each half cycle when condensate covered the electrodes . the transition to thermionic arc ( glow - to - arc ) starts at the moment the electrodes are totally cleared of all condensate . thus , by exploiting the difference in current and voltage waveforms during the glow phase of lamp starting , one can readily determine the condensate location within the lamp . a typical circuit for the acquisition of these waveforms is shown in fig4 . the 100 w metal halide lamp , in this case , is operated from a conventional ballast and ignitor which is included to provide high voltage starting pulses . the advance m90 ballast and ignitor which produces 277 v ( rms ) open circuit , 1 . 1 a ( rms ) short circuit current and 5 - 8 starting pulses ( per half cycle ) each 3 . 5 kv in magnitude and 4 μsec in duration was used in the present invention . current and voltage waveforms are obtained from a current probe and high voltage probe attached to the operating circuit in a manner shown in fig4 . a tektronik am503 can be used for the current probe and a tektronik p6015 can be used for the voltage probe . the outputs of these probes are directed to two input channels of a storage oscilloscope . it is convenient to use a lecroy 9400 storage oscilloscope due to its rather large memory depth . the oscilloscope is triggered from the voltage waveform in order to synchronize both channels properly . the voltage waveforms observed during the glow phase of starting are either those pictured in fig2 or those pictured in fig3 . in general , glow discharge waveforms characteristic of those where the electrode is covered with condensate ( fig2 ) are followed in time by waveforms characteristic of those from clean electrodes ( fig3 ). this is due to the vaporization of the condensate which occurs as the electrodes heat up . this indicates that the cleaning process is complete and the lamp will shortly go into the thermionic arc phase . if the voltage drop during the glow phase is very low and has a correspondingly high current , then much or all of the volatile component of the fill condensed on the electrode during the previous cool down period . in this case , the glow phase portion of the starting process is lengthened . if a glow discharge with predominately high voltage and low current is observed then most of the condensate has localized itself on the arc tube wall during the last cool down . the glow phase in this case is relatively short . by examining the voltage and current waveforms during lamp starting and particularly the glow phase a lamp designer can verify that the condensate has located itself on the electrodes or on the arc tube wall . the scope of this invention is not limited to the visual diagnosis of the electrical waveforms from an oscilloscope but extends to associated discrimination circuitry which would provide pass / fail outputs utilized in automated manufacturing control systems in computer aided manufacturing . the pass / fail output of the discrimination circuitry would identify lamps within each production batch which possess condensation properties other than expected . a block diagram for a discrimination circuit based upon the starting characteristics of 100 w metal halide lamps , is given in fig5 . here , a signal from the current probe is directed to a zero - crossing detector . outputs from the zero crossing circuit go both to counter 1 which determines the number of elapsed half cycles , n 1 , and to trigger the sampling of the voltage probe signal . this second output is delayed for example , 2 . 5 msec and has an on time window of up to 4 . 0 msec . it has to be delayed at least a few msec to avoid interference from oscillations which often appear at the leading edge of each half cycle . the voltage signal is sent through a full wave rectifier and compared with a preset dc voltage of 30 v chosen to be suitable for metal halide lamps operated by ballasts with short circuit currents higher or about 1 amp . in all other cases this dc voltage should be chosen individually for each lamp - ballast system . if the voltage signal is less than 30 v , counter 2 is triggered and a low voltage event is registered . the whole recording procedure continues until n 1 reaches a preset number of half cycles . then the total number of low voltage events , n 2 , is recorded . since only the glow discharge phase is of concern , the glow - to - thermionic arc transition has to be avoided . for example , n 1 for the case shown in fig1 should be about 20 . although this discrimination circuit uses parameter values derived from 100 w metal halide lamps , with suitable parametric adjustments , this circuit can be used for other lamps as well . the ratio ( n 2 / n 1 ) determines the presence of condensate . in an ideal situation , two electrodes are covered with condensate if ( n 2 / n 1 )= 1 and one electrode is covered with condensate if ( n 2 / n 1 )= 0 . 5 . when no condensate is on either electrode then ( n 2 / n 1 )= 0 . in reality , small traces of condensate may be present on a presumably clean electrode and are removed in one or two discharge cycles . if ( n 2 / n 1 ) is less than 0 . 1 both electrodes can be considered clean . volatile species within the arc tube condense , over a period of many minutes , on the coolest point . subtle changes in arc tube or electrode cooling rates can have a significant effect on the distribution of condensate . this invention relates to a unique method of determining the condensate location within the arc tube of an hid lamp . this method , as described in this application , can be used in its simplest form ( shown in fig4 ) to evaluate developmental hid lamps or in its more complex form ( an example of which is shown in fig5 ) to monitor arc tube condensate location in a production environment . although the present invention is concerned with determining condensate location , different arc tube lamps have different requirements so preferred condensate location is lamp dependent . thus , the present invention allows one to non - destructively evaluate potential lamp designs to determine condensate location . while there has been shown and described what are at present considered the preferred embodiments of the invention , it will be obvious to those skilled in the art that various alterations and modifications may be made therein without departing from the scope of the invention . | 7 |
this disclosure relates to an adapter in which a cable tie may be installed in order to provide added and / or reusable functions . fig1 illustrates the preferred embodiment of the cable tie adapter 10 which essentially provides an added or alternative securing head 12 with which one may tighten and secure materials . the front of the adapter 10 consists of a head 12 with a securing slot 14 . the rear of the adapter 10 consists of a cavity 16 and a securing mechanism 18 . fig2 shows a side view of the preferred embodiment of the adapter 10 with head 12 and pawl release lever 20 which is employed when pushed upward toward the adapter 10 . fig3 depicts cross - section a - a of the length of the adapter embodiment 10 shown in fig1 with a cable tie head 22 in the cavity 16 and the cable tie strap 24 fed under the securing mechanism 18 so that the head 22 remains in position within the cavity 16 . this configuration of the adapter allows an existing cable tie pawl 26 to be augmented with a releasable pawl 28 . cable tie strap 24 may be fed into securing slot 14 and secured via the engagement of the releasable pawl 28 with the cable tie strap 24 . the strap 24 may be disengaged and released by pushing the release lever 20 toward the body of the adapter 10 , therefore separating the releasable pawl 28 from the strap 24 so that it may be withdrawn from the securing slot 14 . therefore a user may choose to permanently employ the adapter 10 in the field with its releasable pawl 28 or the adapter 10 may be used temporarily . for example , upon the proofing of a design , the adapter 10 may removed by pulling the cable tie head 22 from the cavity 16 and the strap 24 from under the securing mechanism 18 . then the cable tie head 22 and strap 24 may be used as originally designed . this temporary use of the adapter 10 provides flexibility for the user when design changes are likely or possible , for example . fig4 shows the top , side perspective of an embodiment of an adapter 10 with the head 12 , the securing slot 14 in which the releasable pawl 28 resides , and an additional cavity bracket 30 , against which the cable tie head 22 may rest in the cavity 16 . fig5 shows the bottom , side perspective of this embodiment with the cavity bracket 30 which supports the cable tie head 22 in the cavity 16 . this view of the embodiment reveals the release lever 20 which , when pushed toward the body of the adapter 10 , moves the releasable pawl 28 such that the securing slot 14 enlarges , therefore releasing a cable tie strap 29 from the securing slot in the head 12 of the adapter 10 . the releasable pawl 28 within the adapter head 12 essentially functions as a replacement for the cable tie head 22 which is secured within the cavity 16 of the adapter 10 . fig6 depicts an alternate embodiment of an adapter 34 with a head 36 and a mounting hole 38 through which some sort of fastening device may be inserted if desired . this allows the user to utilize a cable tie in its typical fashion by securely wrapping its strap around material of interest . however the adapter 34 provides the addition of a mounting hole 38 so any gathered material may be secured to a location preferred by the user . fig7 depicts the adapter 34 with a cable tie head 46 and strap 48 installed within the cavity 40 and securing mechanism 44 , respectively . fig8 shows cross section b - b from fig7 , revealing the mounting hole 38 which provides an attachment point through which a user may fasten the adapter 34 to a desired location . this embodiment of the adapter 34 has the same manner of securing the cable tie head 46 and strap 48 , however the adapter 34 provides a means of attaching the cable tie head 36 and strap 48 to a certain location , as selected by the user . fig9 depicts another embodiment of the adapter 50 with a head 51 , two cavities 52 , 54 and a mounting hole 56 . fig1 shows the adapter 50 with a head 51 and two cable tie heads 58 , 60 installed within the two cavities 52 , 54 and two straps 62 , 64 installed within the securing mechanisms 66 , 68 . this embodiment is similar to that which is shown in fig6 - 8 , however it allows the user to essentially connect two groups of gathered materials , and attach them both through the mounting hole 56 to a location chosen by the user . the mounting hole 56 may be utilized with the use of a fastener of some sort , to attach the adapter 50 to a location , therefore keeping the materials gathered by the installed cable tie heads 58 , 60 and straps 62 , 64 together and secured to a specific selected location . fig1 shows cross section c - c of the adapter 50 from fig1 , revealing the mounting hole 56 through the head 51 which provides the attachment point through which a user may fasten the adapter 50 to a desired location . this embodiment may be constructed and arranged to allow the installation of any number of cable ties , each requiring a means of securing a cable tie head 51 and strap 62 in each additional cavity 52 and securing mechanism 66 , 68 . fig1 depicts another embodiment of an adapter 70 with a cavity 72 and an identification plate 74 on which a user may include relevant information . this embodiment allows the user to utilize a cable tie in its typical fashion , however it provides a surface on which one may enter information such as identifying data regarding the gathered contents , while not affecting the function of the cable tie . fig1 depicts the adapter 70 with a cable tie head 76 and strap 78 installed within the cavity 72 and securing mechanism 80 , respectively . fig1 shows cross section d - d of adapter 70 from fig1 , revealing the nature of the connection between the identification plate 74 when a cable tie head 76 and strap 78 are installed . a number of implementations have been described . nevertheless , it will be understood that additional modifications may be made without departing from the scope of the inventive concepts described herein , and , accordingly , other embodiments are within the scope of the following claims . | 8 |
this invention will be further described with reference being made to the accompanying drawings in which : fig1 is a depiction of the chemical structures of ten nrts preferred for use in the practice of the invention ; fig2 is a series of bar graphs illustrating the effect of nrts in preventing lipid peroxidation in bovine retinal homogenates ; fig3 is a series of bar graphs illustrating the effect of nrts in preventing lipid peroxidation in isolated bovine retinal pigment epithelium cells ; fig4 is a graph illustrating the degree of corneal neovascularization observed in a lipid hydroperoxide - induced vascular growth experiment in the presence of compounds of the invention and in the absence of such compounds ; fig5 is a graph of the concentration of vegf in the cornea in the presence of lipid hydroperoxide with and without added nrt ; and fig6 is a graph of the concentration of vegf in the retina in the presence of lipid hydroperoxide with and without added nrt . fig7 is a graph of the concentration of tumor necrosis factor alpha in the cornea in the presence of lipid hydroperoxide with and without added nrt ; and fig8 is a graph of the concentration of tumor necrosis factor alpha in the retina in the presence of lipid hydroperoxide with and without added nrt . this description of preferred embodiments is broken into the following segments : the nrts which are employed in the practice of this invention are generally classed as spin - trapping agents . they include aromatic nitrones , including the best known nitrone , alpha - phenyl - n - t butyl nitrone (“ pbn ”) and derivatives thereof ; pyrolline n - oxides such as 5 , 5 - dimethyl pyrroline n - oxide (“ dmpo ”) and derivatives thereof ; pyridyl n - oxide nitrones such as alpha -( 4 - pyridyl - 1 - oxide )- n - butyl nitrone (“ pobn ”) and derivatives thereof . examples of useful materials are described in u . s . pat . no . 5 , 622 , 994 and published pct application number wo 92 / 22290 , both of which are incorporated herein by reference . among the nrt materials , aromatic nitrones are preferred . aromatic nitrones are generally depicted by the formula wherein x is an aromatic group , particularly a phenyl group or a phenyl group with at least one and particularly up to about three substituents selected from the following : lower alkyls of from one to about four carbon atoms , which may be linear or branched , and particularly methyls ; lower alkenyls ; halogens ; haloalkyls ; hydroxys ; primary , secondary and tertiary amines ; nos ; amides ; lower alkoxyls , of from one to about four carbon atoms and particularly methoxyls ; carboxylic acid functionalities , present as free acid — cooh groups or as suitable salts or esters such as lower alkyl esters of from one to about four carbon atoms and particularly methyl esters ; sulfur - containing acid functionalities such as sulfates , sulfites and sulfonates , with the sulfates and sulfites being present as free acids or as salts . in this formula r is most typically hydrogen but can also be a lower alkyl , lower alkoxyl or the like , wherein “ lower ” has the one to four carbon atom meaning set forth above . in this formula y is most commonly a one to twelve carbon alkyl group which may be straight chain or branched chain and which may be unsubstituted hydrocarbyl or may contain one or more heteroatoms substituents such as oxygen , sulfur , nitrogen or the like . these heteroatoms can be present as substituents in the y group &# 39 ; s main structural chain , for example as ether oxygens . alternatively , the heteroatoms can be in the form of groups depending from the y group main chain . most commonly y is from about two to about eight carbon atoms in size with no or one hydroxy or alkoxy substituents . representative y groups include methyl ; ethyl ; the propyls including n - and i - propyl ; the butyls , especially t - butyl , heteroatom - substituted ( such as hydroxy - substituted -) t - butyl and n - butyl ; pentyls such as 1 , 1 - dimethyl propyl and n - pentyl ; the hexyls , heptyls and octyls . some of these compounds include sulfate , sulfone , sulfoxide , sulfonamide or carboxylate groups . the sulfate groups can be present in an at least partially protonated acid form as a solid and in solution at low ph conditions . the weaker acid groups , such as carboxylates , are present as acids at somewhat higher ph &# 39 ; s . these ionizable acid groups can also exist at higher phs in an ionized salt form in combination with pharmaceutically acceptable cations . most commonly , these cations are a monovalent material such as sodium , potassium or ammonium , but can also be a multivalent cation in combination with a pharmaceutically acceptable monovalent anion , for example calcium with a chloride , bromide , iodide , hydroxyl , nitrate , sulfonate , acetate , tartrate , oxalate , succinate , palmoate or the like anion ; magnesium with such anions ; zinc with such anions or the like . when reference is made herein to these sulfate or carboxylate groups or the like it will be understood to include the acid form as well as these salt forms , unless otherwise expressly stated . often the salt forms are more stable than the corresponding free acids . among these acid groups , the simple sodium , potassium and ammonium salts are most preferred with the calcium and magnesium salts also being preferred but somewhat less so . in the case of the other general types of nrts , such as those based upon pobn or dmpo , the same types of substitutions can be employed as described with reference to the pbn type nitrones . thus , in summary , the nrts preferably used in this invention can be selected form the groups of aromatic nitrones of the formula x — c ( r )═ n ( o )— y , wherein x , r and y are defined above ; pbn derivatives of the formula x — c ( r )═ n ( o )— y , wherein x is a phenyl or a phenyl with substituents , and r and y are defined above ; wherein a and b are each methyls or are each of the substituents listed with reference to the general aromatic nitrone formula ; and pobn and derivatives thereof of the general formula wherein y is as defined above , n is 0 to 4 and r 2 is any of the substituents listed with reference to the aromatic nitrones . a group of most preferred nrts is depicted in fig1 . these materials include the following compounds which are at times described using the noted compound references : of these , 3 , 5 - dimethyl , 4 - hydroxyphenyl - n - n hexyl nitrone is the most preferred at this time . pharmaceutical preparations based upon the nrts include one or more nrt in combination with a pharmaceutically acceptable carrier . the particular carrier employed will depend upon the mode of administration . our studies provide evidence that the nrts are effective in the treatment of angiogenesis when administered systemically , such as parenterally or orally . we also have evidence that the nrts are active against angiogenesis when administered locally such as by intravitreal injection to the eye or topically to the eye via ointments , via eye drops of solutions or suspensions of particles or of liposomes or from a drug - releasing ocular insert . the compositions for oral administration can take the form of bulk liquid solutions or suspensions or bulk powders . more commonly , however , the compositions are presented in a unit dosage form to facilitate accurate dosing . typical unit dosage forms include prefilled , premeasured ampules or syringes of the liquid compositions or pills , tablets , capsules or the like in the case of solid compositions . in such compositions , the nrt is usually a minor component ( 0 . 1 to say 50 % by weight or preferably from about 1 to about 40 % by weight ) with the remainder being various vehicles or carriers and processing aids helpful for forming the desired dosing form . a liquid form may include a suitable aqueous or nonaqueous vehicle with buffers , suspending and dispensing agents , colorants , flavors and the like . a solid form may include , for example , any of the following ingredients , or compounds of a similar nature : a binder such as microcrystalline cellulose , gum tragacanth or gelatin ; an excipient such as starch or lactose , a disintegrating agent such as alginic acid , primogel , or corn starch ; a lubricant such as magnesium stearate ; a glidant such as colloidal silicon dioxide ; a sweetening agent such as sucrose or saccharin ; or a flavoring agent such as peppermint , methyl salicylate , or orange flavoring . in the case of injectable compositions , they are commonly based upon injectable sterile saline or phosphate - buffered saline or other injectable carriers ( both aqueous and nonaqueous ) known in the art . again the active nrt is typically a minor component , often being from about 0 . 05 to 10 % by weight with the remainder being the injectable carrier and the like . these components for orally administrable or injectable compositions are merely representative . other materials as well as processing techniques and the like are set forth in part 8 of remington &# 39 ; s pharmaceutical sciences , 17th edition , 1985 , mack publishing company , easton , pa ., which is incorporated by reference . when treating ocular neovascularization conditions , one can also administer the compounds of the invention topically to the eye in the form of an ocularly acceptable eye drop or suspension of particles or liposomes , from ointments or from a suitable sustained release form . eye drops include a liquid carrier which is typically isotonic and sterile and also includes a suitable preservative and thixotropic material . representative topical ocular preparations are described in chapter 2 “ pharmacokinetics : routes of administration ”, pages 18 - 43 , of ocular pharmacology , fifth edition , william havener , the c . v . mosby company , st . louis , 1983 , which is also incorporated herein by reference . as pointed out there , eye drop formulations may be based on simple aqueous vehicles or may employ more viscous vehicles such as thickened aqueous vehicles or nonaqueous materials such as vegetable oils or the like all with various buffers and salts to adjust the ph and tonicity to non - irritating levels . in these eye drop formulations the nrt can be present as a solute or as a suspension or in the form of liposomes based on phospholipids and the like . ocular ointments include a gel or ointment base as described in havener &# 39 ; s ocular pharmacology . in these topical compositions the amount of nrt will range from about 0 . 05 to 10 % by weight with the remainder being the carrier and the like . typical concentrations for eye drops are 0 . 25 - 2 % by weight . when direct delivery of nrt to the eye is desired , it may also be accomplished using sustained release forms or sustained release drug delivery systems . a description of representative sustained release materials such as soft contact lenses , soluble drug inserts and membrane - controlled diffusional systems , can be found in the incorporated materials in havener &# 39 ; s ocular pharmacology . the conditions treated with the nrt - containing pharmaceutical compositions may be classed generally as malignant neovascularization ( angiogenesis ) conditions . these occur with particular severity as ocular neovascularization associated with macular degeneration , diabetic retinopathy and retinopathy of prematurity . angiogenesis is also observed in psoriasis , rheumatoid arthritis , and solid tumors . each of these conditions is characterized by a progressive loss of function , such as vision , range of motion or skin integrity . the nrt compounds , when administered orally or by injection such as intravenously , can slow and delay and possibly even to some extent reverse the loss of function . injection dose levels such as by intravenous administration for treating these conditions range from about 0 . 01 mg / kg / hr to about 10 mg / kg / hour . such intravenous therapy might last for from less than a hour to as long as eight hours or more . a preloading bolus of from about 0 . 1 mg / kg to about 10 mg / kg or more may also be administered to achieve adequate steady state levels . the maximum total dose is not expected to exceed about 2 g / day for a 40 to 80 kg adult patient . many of the conditions treated are chronic in nature . with these chronic conditions , the regimen for treatment usually stretches over many months or years so oral dosing is preferred for patient convenience and tolerance . with oral dosing , one to five and especially two to four and typically three oral doses per day are representative regimens . using these dosing patterns , each dose commonly provides from about 1 to about 20 mg / kg of nrt , with preferred doses each providing from about 1 to about 10 mg / kg and especially about 1 to about 5 mg / kg . in the case of treating angiogenesis associated with solid tumors , one can of course use systemic administration as just described . one can also use more localized delivery to the tumor site . this can be accomplished by close intra - arterial delivery where the artery chosen is one delivering blood to the tumor site where the angiogenesis is occurring . in the case of close intra - arterial administration one typically administers doses of up to about 10 mls , e . g . from about 0 . 25 to about 10 mls , containing from about 0 . 1 to about 10 and preferably from about 0 . 5 to about 5 mg / ml of active nrt . in the case of treating angiogenesis associated with solid tumors , the doses of nrt can be delivered daily or more often during the therapy period . one could also administer the active nrt by a continuous pumping into the arterial delivery route or continuously from a depot or other site within or near the tumor . of course , one can administer an nrt as the sole active agent or one can administer it in combination with other agents , including other active nrts . many of the nrts employed herein are known compounds which may be purchased or which may be prepared by methods described in the literature . in addition , in the case of the nrts which are simple nitrones , such as the pbn analogues described above as most preferred materials , these materials can be produced using a two step synthesis . in the first step , a commercially available nitroalkane ( wherein the alkane corresponds to the r group present on the nitrogen in the final nitrone functionality ) ( for example 2 - nitropropane or 2 - nitrobutane ) is converted to the corresponding hydroxylamine using a suitable reagent such as activated zinc / acetic acid , activated zinc / ammonium chloride or an aluminum / mercury amalgam . this reaction can be carried out in 0 . 5 to 12 hours and especially about 2 to 6 hours or so at a temperature of about 0 to 100 ° c . in a liquid reaction medium such as alcohol / water mixture in the case of the zinc reagents or an ether / water mixture in the case of the aluminum amalgam reactant . in the second step , the freshly formed hydroxylamine is reacted in slight molar excess with a formyl - substituted aromatic compound which corresponds to the aromatic portion of the desired nrt . if the aromatic portion carries an acid substituent such as sulfonic acid or carboxylic acid functionality , this group will be present in the salt form . the position of the formyl group corresponds to the position of the nitrone in the final product , for example 2 , 4 - dihydroxy benzaldehyde . the number ( 0 , 1 , 2 or 3 ) and position ( 2 , 3 , 4 , 5 , or 6 ) of the substituents on the aromatic ring corresponds to the number and position in the final product . this reaction can be carried out at similar temperature conditions described with reference to the first step . this reaction is generally complete in 1 to 48 hours and especially 10 to 24 hours . if the product so formed contains a sulfate , carboxylate or the like , such group is typically present as the salt . these salts can be converted to the free acid form by suitable acidification . other salts can be easily formed by admixing the free acid in aqueous medium with the appropriate base , for example , koh for the potassium salt , and the like . this invention will be further described with reference being made to the following experiments . these are intended to exemplify preferred aspects of this invention and are not to be construed as limiting its scope . two in vitro experiments were conducted as example 1 and 2 to determine whether or not nrts showed promise as active agents against neovascularization . in the first test , selected nrts were tested for their ability to prevent lipid peroxidation of bovine retinal homogenates . lipid peroxidation was induced by the addition of 2 . 5 mm fe + 2 . nrts were added to give concentrations of 10 and 100 μg / ml which is approximately 40 - 400 μm depending on the molecular weight of the nrt tested . lipid peroxidation was measured by a tbars assay . this assay is based on a modification of a fluorescent method reported by yagi ( biochem . med . 25 : 373 - 378 ( 1981 )). of the eight nrts tested , all were active as shown in fig2 and in table 1 . in the second test , selected nrts were tested to determine their effect on preventing lipid peroxidation of isolated bovine retinal pigment epithelium cells . lipid peroxidation was induced by the addition of 2 . 5 mm fe + 2 . nrts were added to give concentrations of 10 and 100 μg / ml which is approximately 40 - 400 μm depending on the molecular weight of the nrt tested . lipid peroxidation was measured by a tbars assay . this assay is based on a modification of a fluorescent method reported by yagi ( biochem . med . 25 : 373 - 378 ( 1981 )). of the eight nrts tested , five were active as shown in fig3 and in table 1 . in one animal model for neovascularization , new zealand white rabbits were treated with lipid hydroperoxide (“ lhp ”). in comparison to animals not so treated or treated with non - hydroperoxidized lipid ( 18 : 1 linoleic acid ), these animals develop high degrees of neovascularization in their corneas and retina . a test material &# 39 ; s effectiveness is measured by its ability to intervene in the neovascularization event . in one study , neovascularization of the cornea was examined . vessels in the superior quadrant which were stimulated by lhp served as the positive control . they grew progressively to a mean length of 2 . 4 mm . there were approximately 20 separate vessels arising from the parent limbal vessels . multiple branches were observed in this quadrant especially at the distal ends . vessels in the center were always longer than at the edges . this was because neovascularization is a function of distance between the stimulus and the limbus . thus , vessels were never observed in the inferior or intermediate quadrants . the controls using nonperoxidized linoleic acid ( 18 : 1 ) were essentially negative for vessel growth . to quantitate the neovascular response , kodachrome slides taken from each group of animals were projected onto a screen and the entire vascular bed traced with an opsiometer . this provided a cumulative index of total vessel proliferation at the various time intervals . these results are shown in fig4 . this study showed that compound 1 was the most effective inhibitor of corneal neovascularization ( 38 % at 3 days , 61 % at 7 days , 67 % at 10 days and 75 - 85 % at 14 days post - exposure . compound 6 was also effective ; 42 % at 4 days , 37 % at 7 days 46 % at 11 days and 58 % at 14 days post - exposure . compound 2 showed anti - neovascular properties , but was the least effective of the drugs tested ( 17 % at 4 days , 27 % at 7 days , 33 % at 11 days and 37 % at 14 days post - exposure ). from analysis of the slope and development of growth curves , it was determined that from 3 days until the end of the experiment , vessel proliferation was stopped completely by compound 1 . at 14 days , there was evidence for vessel retraction ( from 7 . 5 mm to 6 mm ). in contrast , vessels from compound 6 - and compound 2 - treated animals continued to grow in length and numbers until 10 - 11 days post - exposure . compound 1 and compound 6 showed the greatest amount of vessel retraction ( 20 and 23 %, respectively ). similar findings were obtained when the retina was examined . new vessels grew extensively in the lhp - treated animals without drug intervention . numerous small branches were observed proximally and some were markedly dilated . at the distal end of vessels , there was extensive dilation and hemorrhage . in contrast , vessels in control animals injected with 18 : 1 showed no edema , neovascularization , or hemorrhage . an animal treated with compound 1 showed a reduction in neovascularization , but only slight effects on dilation and hemorrhage . vasodilation edema and hemorrhage are prominent in an animal treated with compound 2 , however , no neovascularization was evident . only dilation is observed in the retina treated with compound 6 . as shown in table 2 , compounds 1 , 2 and 6 all greatly retarded the neovascularization process . the degree of retardation ranged from 87 . 5 % for compound 2 , to 75 % for compound 6 , to 62 . 5 % for compound 1 . compounds 1 , 2 and 6 showed differing effects on neovascular - associated phenomena in the retina . vasodilation , hemorrhage , retinal detachment and edema were observed in 75 % of the eyes injected with lhp . in contrast , the control vehicle ( 18 : 1 linoleic acid ) evoked none of these responses in either right ( od ) or left eyes ( os ). compounds 1 , 2 and 6 were ineffective in controlling dilation or hemorrhage , although compound 2 reduced the incidence to 37 . 5 %. retinal detachment was also reduced to a level of 25 % by compounds 2 and 6 and to a level of 37 . 5 % by compound 1 ). retinal edema was reduced to 12 . 5 % by compound 6 , to 37 . 5 % by compound 1 and to 50 % by compound 2 . an additional study was conducted . this study was based on the suggestion that certain cytokines play a role in the neovascularization process with the concentration of these cytokines being abnormal when the undesirable neovascularization takes place . an effective agent would correct these abnormalities . in one study , the concentration of the cytokine , vascular endothelial growth factor (“ vegf ”) was studied . vegf concentration was measured by immunoassay ( r & amp ; d systems quantkine kit ). measurements were made in control animals , control animals receiving an injection of lhp and test animals receiving lhp plus test compound . measurements were carried out at the injection site and in the superior quadrant . lhp stimulated the maximum synthesis of vegf between 6 to 24 hours . since both areas ( injection site and superior quadrant ) were decreased in treated animals , the values were added together and averaged . the degree of reduction produced by nrt compounds at 12 hours post - injection of lhp ranged from 55 % for compound 6 , to 48 % for compound 1 to 40 % for compound 2 . the concentration of vegf declined further to 50 % to 75 % levels at 7 days and 14 days . these results are presented graphically in fig5 . vegf was reduced by nrt compounds to a greater extent than observed in cornea . at 12 hours , 7 or 14 days , the difference was 30 % greater in the retina ( fig6 ). by 14 days post - injection , compound 1 inhibited vegf production 92 %, compound 2 inhibited 86 % and compound 6 inhibited 76 %. this placed all 3 drugs within the range of control samples . these results are presented graphically in fig6 . measurements of tumor necrosis factor alpha ( tnfα ) were added to the protocol to obtain a more comprehensive understanding of alterations occurring in the initiation of the angiogenic cytokine cascade . tissue levels were quantified using a weh1 cell bioassay which is specific for tnfα . previous studies in our laboratory have demonstrated that during the first day after lhp exposure , there is a dramatic increase in tnfα and if inhibitors ( anti - tnfα or pentoxifylline ) are added in vivo , neovascularization is markedly retarded . in the cornea , compound 2 depressed tnfα levels at 12 hours by 36 % and at 7 days was still 25 % below lhp control levels . ( these results are shown in fig7 ) corneal samples at 12 hours from compound 1 and compound 6 were contaminated . compound 1 - and compound 6 - treated rabbits had tnfα levels that were increased above the baseline at 7 and 14 days post - injection . in the retina , compounds 1 , 2 and 6 all inhibited tnfα synthesis , with compound 6 showing the greatest effect at 12 hours post - injection . compound 2 and compound 1 appeared to stimulate new synthesis , at 7 days after exposure , and then dropped to low levels , whereas compound 6 remained near baseline over the 14 days experimental period . ( these results are presented in fig8 ) while early response of tnfα provides localized signals for synthesis of other cytokines to sustain growth and can be considered a pathological event , the increases at 7 days in retina and 14 days in cornea may represent secondary repair process . for example , tnfα may be cytotoxic in one situation and restorative in another . therefore , repair stimuli may be regulated differently than the initial oxidative stress which initiated neovascularization from the parent vessel . in summary , in this study all three nrt compounds tested showed an inhibitory effect on lhp induced neovascularization in both cornea and retina . as a model for studying diabetic retinopathy , the effect of nrts in protecting against induction and associated pathophysiologic changes by lhp was important . nrt compounds were observed to affect the synthesis of both tnfα and vegf which are essential growth factors for the initiation and propagation of new vessels . the collective reduction of these cytokines would be expected to abate the neovascular responses . retinal neovascular proliferation was reduced best ( 88 %) by compound 2 with the other two drugs ranging from 63 % to 75 %. compound 6 appeared to be more effective against controlling edema , hemorrhage and retinal detachment . these results suggest the efficacy of using nrt compounds in the management of proliferative diabetic retinopathy . using a more easily visualized corneal model , a marked inhibitory effect was also observed . this , too , was correlated with statistically significant reductions in the cytokine growth factors tnfα and vegf . | 0 |
in fig1 the piston shoe 11 , which is one of the embodiments of the invention is shown . the right fig1 - a is a cross - section through the left fig1 - b along the line a -- a and the right fig1 - a is a cross - section along line b -- b through the right fig1 - b of fig1 . the piston shoe 11 has a medial portion 12 . this is a part of a cylinder and can therefore be machined on a lathe machine or on a round grinding machine , which was not possible for the medial portions of my former patents . thus , the medial portion of the piston shoe is simplified by this embodiment of the invention and it can now be easily machined . the medial portion 12 is integral with the end - portions 13 , which extend into the guide portions 14 , whereby the entering or deep - diving piston shoe has the said &# 34 ; h &# 34 ; - form in the view upon it in fig2 . the term &# 34 ; h - formed piston shoe &# 34 ; has become standard procedure at the west german patent office for the entering and deep diving piston shoes of the inventor . the axial end - portions 13 and the guide portions 14 do not principially differ from my beforementioned earlier patents of the entering or deep - diving piston shoes . however , for the radial stabilization of the piston shoe it is preferred to provide support portions 113 endwards of the medial portion 12 at least in a suitable axial extent . the piston shoe further has the outer face 16 and the inner guide faces or the end - guide faces 17 and 18 may be provided , if so desired . the faces 16 to 18 are also known from my mentioned earlier patents and do not differ principially from the piston shoes therein . portions 13 may have radial support portions 113 . thereby portions 113 extend axially from medial portion 12 to act as radial supports . the piston shoe , shown in the sectional fig3 is equal to that of fig1 with the only one difference , that outcuts or depressions 19 are provided radially of the pivot - centre 22 . the reason for the provision of depressions 19 will become understood from the following description of fig4 . fig4 shows the piston 3 with its novel radial extension 1 and 2 . it has the bearing bed 4 for the pivotable reception and bearing of the medial portion 12 of the piston shoe , for example of fig1 . shoe 11 swings or pivotes in bed 4 around pivot - centre 22 . extensions 1 and 2 form outer face portions 1111 , 2222 respectively in the direction of the respective portions of the outer faces and outer diameters of the respective pistons 3 and they are guided at least partially by and sliding at least partially after their assembly into the respective rotor 24 along the respective wall portions 1026 of the respective radial extension segments 124 of the respective rotor 24 of my mentioned u . s . pat . nos . 3 , 223 , 046 or 3 , 277 , 834 . the wall portions 1026 are also shown for example in fig8 to 10 and they are extending in the faces of the respective portions of the walls of the respective cylinders 26 radially outwards from the respective cylinder 26 . the extensions 1 , 2 which are also visible in fig5 are novel portions of the invention . a further novel matter of the invention is , that the retainer members 96 may be applied in the extensions 1 and 2 , after the assembly of piston shoe 11 into piston 3 . these retainers 96 will then enter into the depressions 19 of piston shoe 11 , whereby they retain the piston shoe within the piston , allow the piston shoe to pivot in the piston , but retain the piston shoe from escaping out of the piston . the piston shoes medial portion 12 of the piston shoe of fig3 has therefore a bottom portion 20 of wider extension and an upper portion 21 of smaller lateral extension . the depressions 19 are formed on the upper portion and may end about in a radial height equal or close to the medial pivot - centre 22 . the piston shoes of fig1 to 3 can now be forged or cast or pressed , because any embracement over more than 180 degrees as in my former patents , is spared and faces with equal radii of less than 180 degrees around a centre can be cast , pressed , forged or machined even with surface grinding machines and formed grinding wheels . the piston shoes of the new system are therefore very inexpensive and can be easily and quickly produced . the described retaining assembly does not necessarily force the inner face 23 of the respective piston shoe for close engagement on the surface of the bearing bed 4 . but it can be forced to such engagement by addition of other retaining means of others of the figures . however , such forced engagement of faces 23 on the bed 4 is not always required , because at the pressure strokes in the device the pistons force themselves against the faces 23 of medial portions 12 , whereby the faces 23 are closely sealing and bearing in beds 4 of pistons 3 . this said &# 34 ; forcing themselves &# 34 ; is obtained by the pressure below the bottom of the respective piston in the respective cylinder at the high - pressure stroke of the respective piston 3 . the referentials 1 to 23 are basic referential numbers , which cite parts or portions , which will repeat in many of the later figures . they will get a pre - digit in other figures or may appear in other figures without a further pre - digit . but in the description of the other figures , the pre - digit will be left out . that means , that regarding referential numbers 1 to 23 only the one or two end - digits will be mentioned in the description of the other figures . because thereby it will be easier visbile and understandable , that the respective parts , portions , or faces , centres and like of the other figures have basically equal functions as in fig1 to 5 . fig2 demonstrates the assembly of the piston shoe of fig3 into the piston of fig4 whereby the entering of retaining members 96 into the depressions 19 becomes visible . in fig6 another retaining means for the holding of the piston shoe in the bed in the piston is demonstrated . in this figure a pin means 7 is inserted into piston 33 at a radial height slightly above the outer face 16 of the respective piston shoe 11 . pin means 7 extends from piston extension portion 1 through the opening gap 5 of the pivot bed 4 into or through piston extension portion 2 . thereby the retaining of the piston shoe in the pivot - bed 4 of the piston with end digit 3 is assured . as seen from fig4 the piston &# 39 ; s pivot - bed 4 has a bearing bed surface 6 of a configuration of a face with equal radius around a common centre 22 . such centre may be a centre line or a centre point 22 . the bearing face 6 of equal radius around centre 22 may be a part - cylindrical face with equal radius around a centre line 22 or it is a part - ball - formed face with an equal radius around a centre point 22 . in fig8 rotor 24 contains cylinders 25 and 26 in that portion of the rotor , which is shown in the figure . piston 43 reciprocates in cylinder 26 and piston 53 reciprocates in cylinder 25 . in piston 43 the piston shoe 11 of fig1 is pivotably borne in bed 4 without mechanically provided retaining means . it is kept in bed 4 simply by the pressure of fluid in cylinder 26 . such pressure forces the piston 43 outwards , whereby the face 6 of bed 4 automatically engages the pivot face 23 of medial portion 20 of the piston shoe 11 . referential 27 shows the piston stroke actuator guide face . 29 is the outer diameter of the rotor segments 124 of rotor 24 . the annular ring groove 34 of the piston stroke actuator ring extends from inner faces 27 to the outer face 28 of the groove in piston stroke actuator 35 . it is seen in this portion of the figure , that the extensions 1 and 2 of piston 43 extend in operation of the device radially beyond the outer face 16 of piston shoe 11 into the said annular ring groove 34 of the actuator 35 . piston 53 shows another embodiment of a retaining means for holding piston shoe 11 in the bed 4 of the piston 53 . in this embodiment a pin 30 is inserted through the inner portion 20 of the medial portion 12 or through the medial portion 12 of the piston shoe 11 . the said retaining pin 30 extends beyond the said medial portion 12 into recesses 31 and 32 in the extension portions 1 and 2 of piston 53 . the recesses 31 and 32 are slightly wider in cross - sectional area , than the respective cross - sectional area of the pin means 30 is , in order to permit the pivot - movement of the piston shoe within the piston bed 4 . the cross - sectional area of recesses or slots 31 , 32 is however so located and dimensioned and resticted , that the pin ends of pin 30 can not move too much radially outward . thereby the piston shoe 11 is also by this retaining means of the invention effectively contained within gap 5 and bed 4 in piston 53 . the embodiment of fig8 is especially convenient for application as a motor . because the lateral or tangential component of forces than acts at a great radial distance from the centre of the rotor against the cylinder walls . that gives relatively slight forces onto the cylinder walls , but provides a great torque . the embodiment of fig9 may also be used as a motor , but it is also suitable to be used as a pump . the difference compared to fig8 is , that the pivot - centre 22 in fig9 is located deeper in the pistons than in fig8 . the pivot centres 22 of pistons 63 of fig9 are thereby closer to the centre axis of rotor 24 than in fig8 and consequently the arms of the torque - action are shorter . the tangential forces onto the cylinder walls are therefore higher than in the embodiment of fig8 . an analysis of pumps and motors will show , that both are equal devices , acting just in the reversed way . it would therefore appear on first glimpse , that the same devices of equal parts and dimensions can be used as pumps as well as also as motors . and , this assumption is in fact true . when however , the highest quality of a device is desired , such assumption on first glimpse is not absolutely true any more . because in a pump the piston moves radially inwardly at its pressure stroke or power stroke . but in a motor the piston moves radially outwardly at the pressure and power stroke . in those devices , where the swing or pivot - centre 22 is in the middle of the acting guide face length of the piston on the cylinder wall , the actual actions between the piston wall and the cylinder wall are equal in pumps and motors . but , when the pivot - centre 22 is not in the middle of the guide face length of the piston , the matter becomes different . when in a pump , the pivot - centre is too much inwards of the piston , the lateral forces will too strongly press the inner corners of the pistons against the cylinder walls and wear and weld there . when in a motor the pivot - centre is too much radially outward in the piston , the outer corners of the pistons will be pressed under the lateral forces too strongly against the cylinder wall portion and they will wear there and finally weld there . it is this basic consideration , which discovers , that in the devices of the former deep diving piston shoes , the guide faces of the pistons were too short radially outward of the pivot - centres 22 of the pistons , whereby the described wearing and welding of the outer corners of the pistons could occur in motors . consequently , the gist of the invention is , to elongate the guide face of the piston on the cylinder wall portion drastically radially outward of the pivot - centre 22 . the invention does so by providing the piston extensions 1 and 2 and by extending them radially outwardly beyond the pivot - centre 22 and in the embodiments of the fig8 also into the annular ring groove 34 radially beyond the outer face 16 of the piston shoe 11 . in fig9 the extensions 1 and 2 may also be an integral extension 1 , surrounding a ball - part formed portion 20 of the piston shoe . portion 1 or portions 1 and 2 extend in such a case , ( not illustrated in figure ) only radially outwards beyond the pivot -- centre 22 but not into the annular groove 34 and not beyond the outer face 16 of the piston shoe . the consequence thereof is , that the device of fig9 is applicable to highest pressures and speeds only in a pump . in motors its application is restricted to slightly higher than medial pressure in fluid , for example about 4000 psi . the simplicity of manufacturing and the possibility to operate without a retaining means however leads to use of this device also as motor as far as the said medial pressure in the motor is satisfactory . fig1 demonstrates in three sectional views 10 - a to 10 - c with views 10 - b and 10 - c taken along the arrows in fig1 - a respectively an embodiment of the invention for application in the highest advanced technology motor . it may also be used in a pump . cylinder 26 contains the therein reciprocating piston 73 . the piston extension portions 1 and 2 extend beyond the pivot - centre 22 and beyond the piston shoe &# 39 ; s outer face 16 into the annular ring groove 34 of piston stroke actuator 35 . this embodiment has a novel retaining means 9 in the form of a spring - plate inserted into groove portions 77 provided in extensions 1 and 2 . spring plate 9 may have a medially inwardly directed portion 78 to press flexibly against the outer face 16 of the piston shoe to maintain close contact between faces 6 , 23 . spring plate 9 may also have extensions 79 , visible in the left portion of the figure , in order to embrace narrower outer extensions 101 and 102 of extensions 1 and 2 in order to prevent rotation of the spring plate 9 relatively to the piston and the piston shoe . another feature of the invention of this embodiment is , that , when the extensions 1 and 2 extend into the ring groove 34 , they are prevented from rotation . that means , that the piston can not rotate around its axis . the same effect is also already obtained , when the extensions 1 and 2 extend beyond the pivot - centre 22 . because then , since the piston shoe can not rotate , the entrance of the extensions 1 and 2 into the recesses of the &# 34 ; h &# 34 ; of the &# 34 ; h - formed &# 34 ; piston shoe prevents rotation of the piston relatively to the piston shoe and thereby also prevents rotation of the piston around its axis . the described prevention of rotation of the piston 3 around its axis makes it possible to accurately provide fluid pressure balancing pockets between the piston wall and the respective portion of the cylinder wall . these fluid pressure pockets take over the major portion of the lateral , tangential load which is exerted by the pivot - motion of the piston shoe over the piston onto the cylinder wall . the figure shows , that these fluid pressure pockets , which are recesses which are filled with pressure fluid , are located in the figure exactly in the middle of the radial guide of the piston . pressure in fluid enters through piston passage 51 into recesses 59 or 60 respectively , depending on the pivot - direction of the piston shoe . recesses 59 and 60 are also radial fluid pressure balancing recesses which take over a large portion of the radial forces between piston 73 and shoe portion 20 . they are communicated by the outer recesses 57 , visible in the upper portion of the figure . when recess 59 or 60 communicates with passage 56 or 66 , the fluid and its pressure is led either into tangential balancing fluid pressure pocket 54 or 55 . these pressures either in fluid in recess 54 or 55 provide forces which are about equal , but oppositionally directed , relatively to the force exerted by the lateral component of fluid pressure forces under the pivot - angle of the piston shoe onto the piston . the communication between passages 56 or 66 and pockets 54 or 55 starts , according to design , about at 40 to 50 degrees rotary angle alpha of the rotor . one of the pockets 54 or 55 becomes loaded with high pressure and the other is excluded from high pressure supply . that is required to direct the force of fluid into that portion of the piston which is pressed toward the respective cylinder wall by the respective angle of inclination of the piston shoe at its pivoting motion . the piston 73 may also be provided with secondary balancing recesses or fluid pressure pockets 71 and - or 72 . when they are provided , then communication passages 74 and 75 are precisely set into the respective walls of the cylinders . the function of such provison is , that , when the rotary angle alpha of the rotor increases to about 75 to 105 degrees , the lateral thrust component of the forces on the piston increases further , because the inclination angle gamma of the pivoting shoe increases steeper . the schematic fig7 shows the results of calculation of the strokes , inclinations , etc . of a sample of a radial piston device . therefrom it is seen , that the lateral forces of the piston increase towards about 45 degrees to become extensive there and that they increase further towards about alpha ninety degrees to become a maximum there . the communication passages 74 and 75 are now provided at a radial distance from the centre axis of the rotor , that they start to communicate recess 54 with secondary recess 71 or recess 55 with secondary recess 72 at rotary angles alpha from about 75 or 85 to about 95 or 105 degrees . thereby the first recesses 54 , or 55 , in combination with the secondary recesses 71 or 72 take over the peak of the lateral forces of the piston at the peak occurance around the 90 degrees rotary angle alpha . at other rotary angles alpha the communication to the secondary recesses 71 or 72 does not exist , so , that at other rotary angle alpha the recesses 71 and 72 are not loaded with high pressure fluid and therefore are not or not fully acting . instead of providing first and secondary fluid pressure balancing recess pairs 54 , 55 and 72 , 71 it is also possible to set pluralities of higher number of such tangential balancing recesses and a respective plurality of communication passage pairs 74 , 75 . as more such steps are set as closer the take over of lateral forces nears the stepless and perfect take over of the lateral , tangential forces of the pistons . costs of producing the recesses and communication passages however leads in practical application to only one or two recess pairs , when no complete stepless or almost stepless take over of lateral forces by fluid pressure pockets is required . the top portion 10 - c of the figure is a cross - sectional view through the bottom right fig1 - a along line e . it shows the respective configuration of the piston shoe in the presently most advanced form , containing also the passages 58 which lead the pressure fluid into the balancing pockets 61 an 62 in the outer face 16 of the piston shoe to prevent wearing between the actuator ring inner face ( s ) 27 and outer face 16 of the piston shoe . the bottom left portion 10 - b of fig1 is a cross - sectional view through the bottom right portion 10 - a along line f in order to see clearly the configuration of spring retainer 9 , the narrowed portions 101 and 102 of extensions 1 and 2 , to see the extensions 79 which embrace portions 101 and 102 in order to prevent rotation of retainer 9 and in order to see , that the top - piston assembly remains axially seen within the axial extension of the rotor extension segments 124 , whereby they remain narrow enough to remain within annular groove 34 . fig1 shows in three views 11 - a to 11 - c the piston 73 of fig1 in a separate demonstration to show the members described at hand of fig1 more clearly . the figure is shown in a 1 : 1 scale for a 42 cc motor . medial portion 11 - a is a section along line g -- g of the left portion 11 - b . the left portion 11 - b is a sectional view along line h -- h of the medial portion 11 - a and the right fig1 - c is a view onto the left portion 11 - b along view j -- j . fig1 shows an example of the spring plate or retainer means 9 in a separated view . the fig1 is a section through it and the bottom figure , namely fig1 , shows a view from top onto it . fig1 is a longitudinal sectional view through a piston 3 of my former art technology . it is again drawn in a 1 : 1 scale for a 42 cc motor for comparison with the novel piston of the invention . the guide length of the piston of fig1 of my former technology is 22 mm compared to a guide length of 36 mm for my novel piston of fig1 . that gives an elongation of the piston guide of 36 : 22 = 1 , 65 times elongation of the guide length of the novel piston of the invention compared to the piston of the former art . in fig1 the piston and shoe of fig1 and 11 is assembled into a radial piston device for 42 cc / revolution in a one to one scale . the right portion 14 - a of the figure is a section along line l -- l of the left portion 14 - b and the left portion 14 - b is a sectional view through the right portion 14 - a of the figure along the line k -- k . the respective referentials which are known from the description of the earlier figures are shown in the figure to demonstrate their locations in a radial piston fluid handling device . the functions and configurations of the portions , parts and like are already known from the description in the earlier figures . the piston of fig1 is similar to that of fig1 and shown in the same scale and sections or views for a 42 cc motor with the one difference , that the piston of fig1 has a part - cylindrical pivot - bed 4 , while the piston of fig1 has a part - part - ball - formed pivot - bed 104 . accordingly the piston shoe of fig1 , which can be assembled into or laid into piston of fig1 , has a part - ball - formed inner pivot - portion 120 instead of the part - cylindrically formed portion of fig1 . important is , that the piston of fig1 requires outcuts 91 and 92 in order to be able to extend through the slot of the &# 34 ; h - form &# 34 ; of the piston shoe and into the annular ring groove 34 of the actuator ring 35 . the piston shoe of fig1 , shown in sectional view fig1 - a and 16 - b with fig1 - a being taken along the arrowed line of fig1 - b , which can be laid or be assembled into the piston of fig1 , shows the outcuts or recesses or slots 93 and 94 which form the &# 34 ; h &# 34 ; of the entering or of the deep diving piston shoe of my earlier patents . what matters in this present invention , is , that the radial extensions or portions 1 , 2 of the piston can extend through slots 93 and 94 of the piston shoe of fig1 and pass with their outer ends 1 , 2 and 101 , 102 beyond the outer face 16 of the piston shoe of fig1 . the bottom fig1 - d of fig1 is a view from top upon the left portion of fig1 in order to clearly make visible the narrower portions 101 and 102 in relation to the extensions 1 , 2 and in relation to the pivot bed 104 with face 6 . in fig1 a respective retaining spring plate is shown . as already explained at the description of fig1 . in fig1 the piston and piston shoe of fig1 and 16 are assembled into a respective portion of a radial piston device . again , this figure is shown in a 1 : 1 scale for a 42 cc / revolution device with 7 pistons of 20 mm diameter each . the scale can be obtained from the reduced scale patent drawing by comparing the 22 mm and the 36 mm of fig1 . figure portions 18 - a and 18 - b are sectional views along the medial lines of the other figure portion respectively . in fig1 three sections , namely figure portions 19 - a to 19 - c through the radial outer portion of another embodiment of the invention demonstrate a plurality of retaining pins assembled into the outer portion of the respective piston . pins 96 extend into the extensions 1 , 2 and through the gap 5 , whereby they retain the respective piston shoe in the gap 5 or in the pivot - bed 4 . it can also be recognized from fig1 , that the outermost portion of the piston does not need a guide face on the cylinder wall and can be reduced in diameter , if so desired , in order to prevent friction or scratching of the ends of pins 96 on the cylinder &# 39 ; s walls . that gives space for rivetting of the pins 96 on the extensions 1 , 2 of the respective pistons . however , such rivetting is not shown in the figure , because it is not in all cases of practical application required . as will be seen from the references of the former art , the piston shoes of axial and radial piston devices are sometimes called &# 34 ; piston shoes &# 34 ; and in other literatures are also called slippers . the rotors of radial or axial piston devices are sometimes called &# 34 ; rotors &# 34 ; and in other literatures called &# 34 ; barrels &# 34 ;. the terms &# 34 ; piston shoe &# 34 ; and &# 34 ; slipper &# 34 ; shall therefore define equal elements in the specification or claims and the term &# 34 ; rotor &# 34 ; in the specification and claims shall be the equivalent of the term &# 34 ; barrel &# 34 ; of the respective literatures as far as the structures are not in detail defined differently in the specification and figures . the term &# 34 ; pivoting &# 34 ; also means &# 34 ; tilting &# 34 ;; &# 34 ; tiltable &# 34 ; means &# 34 ; pivotable &# 34 ;. fig7 gives the actual data of tangential force , friction losses , pivot - angle gamma , movements of pistons and of pivoting in a schematic , but accurate diagram for the values written in the figure . it may be appreciated , that these values show with overwhelming impression , how important the losses due to friction in the pivot - faces and at the movement of the piston wall along the cylinder wall are . that these losses , except in some of my earlier patents are heretofore neglected , is perhaps the consequence of the fact , that axial piston devices with inclined plates obtain only small piston strokes and that those radial piston devices which were studied by big enterprises at the inventor &# 39 ; s research institute in the early sixties by big corporations , neglected his patents and built around them , which restricted those leading enterprises to short piston strokes in radial piston devices which they are building and selling since the early seventies . the refusal to buy licences of patents of advanced technology by the industries led to inferior devices which neglected the requirements of the lateral fluid pressure balancing recesses of my inventions and therefore to the supply of inferior products in this respect to the industries , to the customers and to the public . since according to this invention , the lateral friction losses between the piston and the cylinder wall can be reduced to a very small or neglectible remainder , it is sure , that the devices of this invention are technologically superior in efficiency , life time or power to devices of axial piston types with inclined plates as piston stroke guides and naturally also superior in power and efficiency to those newer designs , which tried to copy or to improve my inventions of the early sixties and thereby brought products in the early seventies , which neglected the fluid pressure pockets between the piston wall and the cylinder wall and which neglected the need for a long stroke at a given size of the piston stroke actuator by the application of the entering or of the deep diving piston - shoe . and , which also neglected the requirement of a long piston guide as in my earlier patents and as specifically provided for by this present invention . it should also be recognized , that the angle of inclination of pivoting and thereby the resulting lateral forces of the pistons are greater the deeper the pivot - centre is located inside the piston . this is seen for example from fig3 and 9 . the extensions of the invention make it possible to transfer the said pivot - centre more radially outward , whereby the resulting lateral forces are decreasing in principle . | 5 |
to be of practical use , any signal processing scheme that exploits dynamic ( time - varying ) properties of signals must adapt to those properties . such a scheme is termed adaptive . using x ( t ) to represent the input signal as a function of time and y ( t ) to represent the output signal , a nonlinearity obeys the following relationship for some time period : for arbitrary constants b and c and distinct input signals x 1 ( t ) and x 2 ( t ). a nonlinear signal transformation is referred to as being &# 34 ; memoryless &# 34 ; ( or as having zero memory ) when the output at an arbitrary instant in time depends on the input at the same instant and not on previous values of the input . the band - limited input to a voltage nonlinearity , x ( t ), is modeled in complex envelope notation as having a center frequency f o , a time - varying amplitude a ( t ), and a time - varying phase shift φ ( t ). to make notation simpler , the time variable may be suppressed . a general voltage nonlinearity results in harmonic components at dc and an integer multiples of f o . there are amplitude and phase transfer functions associated with each harmonic component . these transfer functions may be denoted by g m ( a ) and f m ( a ), respectively , and each set is referred to as the &# 34 ; mth - harmonic envelope nonlinearity &# 34 ;. the subscript &# 34 ; 1 &# 34 ; is suppressed in references to the first harmonic ; if a harmonic is not specified , the first harmonic is assumed . the unfiltered output of a voltage nonlinearity is called v ( x ), which is v ( x ( t )) or v ( t ) for short . using &# 34 ; re {}&# 34 ; to denote the real portion of a number , the signals associated with a voltage nonlinearity are expressed in terms of their complex envelope representations as : ## equ1 ## this representation is based on well known theory of random signals and noise , or as otherwise explained herein . the dc component and the mth harmonic components of v ( t ) for 2 ≦ m ≦∞ ( the mth zones ) are normally not desired ; they are removed by a first zone bandpass filter ( bpf ). the output of this bpf is expressed as : when the output amplitude is a negative number , this disclosure uses the convention of inverting its polarity and setting f ( a ) to 180 ° otherwise , g ( a ) is left alone and f ( a ) is zero . any physical device may have additional phase shift characteristic contained in the f ( a ) function , e . g . &# 34 ; am / pm conversion &# 34 ; of a traveling wave tube amplifier . the combination of the phase shift f ( a ) with the cascade of a voltage nonlinearity and a first zone bpf is called a &# 34 ; bandpass nonlinear device &# 34 ;. fig1 e shows an equivalent bandpass nonlinear device model . in the figure , the bandpass nonlinear device 15 receives an input signal x ( t ), which is passed to an rf nonlinearity 16 . the nonlinearity output v ( x ) is applied to a bandpass filter 17 ( first zone ) and is output from the bandpass nonlinear device 15 . the input signal x ( t ) also is sent to a phase shifter 18 which converts the envelope a into a phase variable function f ( a ). at the output of device 15 , the signal comprises the bandpass filtered first harmonic output phase shifted by f ( a ). a block diagram of the smart agc ™ which embodies a &# 34 ; biased inverting limiter &# 34 ; is illustrated in fig2 . as seen from a comparison with fig1 a , the arrangement and composition of system elements are basically the same , but for a substitution of one component . specifically , the new nonlinear signal processor 10a contains an adaptive nonlinear amplifier 12a that has a biased inverting limiter and has an operational characteristic that does not contain a null zone . the envelope nonlinearity of the biased inverting limiter is pictured in fig3 a and 3b . the am / am transfer function , g ( a ), of the biased inverting limiter is illustrated in fig3 a and has a zero at a = v t . the nonlinearity effectively traps and eliminates the interference from the first zone while preserving the wanted signal . the am / pm transfer function , f ( a ), is illustrated in fig3 b and causes the rf phase to reverse by 180 ° when the input envelope crosses the threshold value of 2 /√ 3 v t , rf . the biased inverting limiter differs from the biased hard limiter only in that it contains an inverted hard limiter in the location of the null zone , between input voltages of - v t , rf and v t , rf ( the &# 34 ; rf threshold &# 34 ;), as seen in fig3 c . the biased inverting limiter can readily be implemented in real - time hardware , since its output consists of only two discrete voltages which can be obtained from high - speed digital logic outputs . also , the biased inverting limiter has odd symmetry , meaning that v ( x )=- v (- x ) and that dc and even harmonic outputs are zero under ideal conditions . on the assumption that input additive gaussian noise is negligible , the unfiltered output of the biased inverting limiter , v ( t ), when a single cw signal , x ( t )= a cos ( 2πf o t + φ ) is input , is given in fig4 a when the input amplitude is less than v t , rf . as shown in fig4 a , the biased inverting limiter reduces to an inverted hard limiter -- the output is - 1 when the input is positive and + 1 when the input is negative . when the input signal amplitude is larger than v t , rf , as seen in fig4 b and 4c , the biased inverting limiter goes through six transitions in the output during each period of the input signal . hence , during one period of the input , the output is positive in three distinct time intervals and negative in three distinct time intervals . because there are three on / off output cycles ( not necessarily equal in length ) for every input cycle , the third harmonic component of the output is significant . the ratio of a to v t , rf dictates the length of each output cycle . when a is much larger than v t , rf , the voltage of the input signal is above v t , rf or below - v t , rf for an amount of time much greater than the amount of time that it is between - v t , rf and v t , rf . hence , the device reverts to a hard limiter ( output a positive constant when input is positive , output a negative constant when input is negative ) when the rf threshold approaches zero . quantitative analysis of bandpass nonlinear devices reduces to finding the first - harmonic envelope functions g ( a ) and f ( a ) and their analogs in the higher harmonics . these functions are determined by expanding the response of the voltage nonlinearity to a cw signal of peak amplitude a and frequency f o as a fourier series . the coefficients of the fourier series represent the envelope nonlinearities corresponding to the given frequencies . this technique may be applied to a general voltage nonlinearity v ( x ). the result is the well - known chebyshev transform : ## equ2 ## where v m ( a ) corresponds to the envelope transfer characteristic at the mth harmonic component of the output . here , the amplitude transfer functions g m ( a ) are equal to the absolute values of v m ( a ). if v m ( a ) ( for a fixed value of m ) is positive , then the mth - harmonic phase shift function f m ( a ) is zero ; if v m ( a ) is negative , then f m ( a ) is 180 °. typically , the subscripts in g 1 ( a ) and f 1 ( a ) are . dropped . sometimes , g ( a ) is called the &# 34 ; am / am transfer function &# 34 ; and f ( a ) is called the &# 34 ; am / pm transfer function .&# 34 ; solving equation ( 5 ), we find that the first - harmonic envelope nonlinearity for the biased inverting limiter is : sketches of g ( a ) and f ( a ) for the biased inverting limiter are given in fig5 a - 5c . the quantity v t , is called the &# 34 ; envelope threshold &# 34 ;. this point on the g ( a ) curve is also referred to as an &# 34 ; amplitude trap &# 34 ;, since the nonlinearity traps and eliminates signals with envelopes at that point . for the biased inverting limiter , v t is calculated by letting g ( a )= 0 in equation ( 6b ), then solving for a . this process yields v t =( 2 /√ 3 ) v t , rf ; therefore , an adaptively obtained value of v t , must be attenuated by approximately 1 . 25 db in order to obtain a suitable rf threshold . the behavior of g ( a ) and f ( a ) in the vicinity of v t , provides the rfi suppression properties of the biased inverting limiter . the wanted signal causes the composite input envelope to fluctuate above and below the interference envelope ; these fluctuations are retained by the nonlinearity , since the amplitude trap acts only on the larger , interfering waveform . due to the 180 ° phase difference between the two sides of the trap , the envelope fluctuations due to the wanted signal on both sides of the interferer are preserved - thus overcoming one of the limitations of the biased hard limiter ( and all other null zone devices ), which removes portions of the wanted signal . the physical manifestation of the amplitude trap at a = v t can be understood by examining the unfiltered time - domain response v ( t ) of the rf nonlinearity to the cw input x ( t )= v t cos ( 2πf o t + θ ). this is illustrated in fig6 . note that v ( t ) is a bipolar ( i . e . no dc component ) square wave that repeats every t / 3 seconds , where t = 1 / f o is the period of the input signal . the fundamental frequency of v ( t ) is 1 /( t / 3 ) or 3 f o . because the output is bipolar , there will be no even harmonic components ; the harmonics occur at 3 f o , 9f o , 15f o , 21f o , and so forth . hence , g m ( a ) evaluated at a = v t is nonzero for m = 6k - 3 ( with k representing all positive integers ) and zero for all other values of m , including for m = 1 ( the fundamental frequency of the input ). this qualitative approach is validated by evaluation of the biased inverting limiter third - harmonic envelope nonlinearity , which has been by solving equation 5 . f . sub . 3 ( a )= 0 ° for 0 & lt ; a & lt ;( 1 - cos . sup . 2 ( π / 9 )). sup .- 1 / 2 v . sub . t , rf (≈. 2 . 92v . sub . t , rf ), 180 ° otherwise ( 7c ) sketches of the first - and third - harmonic envelope nonlinearities are shown in fig7 a - 7d . the peak of the g 3 ( a ) curve in fig7 c is located at the same value of a as the first - harmonic amplitude trap . the maximum value of g 3 ( a ) is equal to the maximum value of g ( a ). therefore , the effect of the biased inverting limiter when the rf threshold is properly set is to transfer the interference energy out of the first zone so that a first zone filter can attenuate it . the biased inverting limiter performance is shown in fig3 d . the best possible interference ( i )- plus - intermodulation ( im )- to - carrier ( c ) ratio ( i + im )/ c performance of the biased hard limiter is approximately 5 db ; the best ( i + im )/ c provided by the biased inverting limiter is 0 db . 0 db is the best attainable effective ( i + im )/ c with an optimum amplitude nonlinearity when the input interference is stronger than the input wanted signal and the noise is negligible ; therefore , the ideal biased inverting limiter performs at the theoretical limit for an amplitude - based nonlinear device . note , however , that 0 db is still not the optimum level attainable by any means , since an ideal subtraction circuit ( one which subtracts the cw signal ) will reduce interference to zero . when the envelope threshold is equal to the input amplitude of the interference ( v t / i in = 0 db ), the biased hard limiter leaves interference approximately 3 db stronger than the remaining wanted signal and intermodulation 0 . 5 db stronger than the remaining wanted signal . on the other hand , the biased inverting limiter all but eliminates the interference ( output i / c =- 29 db when v t / i in = 0 db ), leaving intermodulation equal in power to the wanted signal . if the biased hard limiter is used , a tracking error that results in placement of the envelope threshold at a higher value than the peak of the composite input envelope ( v t / i in ≧ 0 . 27 db for an input i / c of 30 db ) will destroy both interfering and wanted signals . the biased inverting limiter does not share the problem ; even when the error in estimating the envelope threshold is as much as 0 . 5 db in either direction , the biased inverting limiter improves ( i + im )/ c by 18 db ( as opposed to 13 db of improvement when the null zone threshold is set 0 . 5 db too low ). the ability of the biased inverting limiter to suppress strong interference has motivated its use in a way which improves upon the previous smart agc ™ approach . in fig8 an input is provided to two parallel paths leading to a single output . the first path comprises a delay 21 and a linear booster amplifier 22 . the second path comprises an envelope detector 23 , whose output is provided in parallel to a tracker 24 and a delay 25 . the tracker 24 outputs to an envelope to rf conversion circuit 26 which itself outputs to an rf threshold control circuit 28 . the delay 25 outputs to a comparator 27 , which compares the envelope to a voltage called &# 34 ; max wanted signal &# 34 ;. the purpose of the comparator is to bypass the use of a voltage window ( v t , rf ) whenever the absolute input envelope is so small that the presence of rfi becomes ambiguous . thus , the rf threshold control circuit 28 output will be either the filtered envelope or zero . a zero output means the estimated rf is too small to provide a correction . the circuit 28 will input in common to a biased inverting limiter 29 together with the output of the linear booster amplifier 22 . a first zone filter 29 is provided before the output of the stage to limit the band of operation to the vicinity of the input band . the mechanism that sets v t , rf from estimation of the interference amplitude 23 , 24 , 26 , 27 , 28 requires time to operate and as such must be equalized with delays in parallel paths 21 , 25 . present - day high - frequency delay devices are lossy ; hence , a linear booster amplifier 22 is required in the rf path . to ensure that the net insertion losses encountered by the tracking path and the rf path are as equal as possible , power compensation , in the form of either an amplifier or an attenuator , must be included in the envelope tracker 24 . after the tracker has been power - compensated , the voltage along the tracking path is v t ; an additional 1 . 25 db of attenuation is required to convert this to the rf threshold , since v t , rf =(√ 3 / 2 ) v t . this factor of 1 . 25 db can easily be accounted for in the power compensation at the output of the tracking filter ; it has only been separately noted as &# 34 ; envelope to rf conversion &# 34 ; 26 for the purpose of illustration . the detected amplitude of the input signal - plus - interference - and - noise ( the output of envelope detector 23 ) is compared with a fixed maximum amplitude - determined from a priori knowledge of the wanted signal -- to ascertain whether the interference is sufficiently high for the biased inverting limiter to have a beneficial effect . if the comparator 27 indicates that the interference does not exist or is not powerful enough to significantly affect the composite envelope , the rf threshold control circuit 28 sets v t , rf to zero ; otherwise , the control circuit 8 passes the value of v t , rf estimated by the tracking path to the biased inverting limiter circuit 29 . the biased inverting limiter circuit processes the rf signal and threshold estimation , then passes the output to the first zone bandpass filter 30 . a functional block diagram of the biased inverting limiter circuit is given in fig9 . there the rf input is provided to the emitter - coupled logic ( ecl ) window comparator 31 and the ecl hard limiter 32 in parallel . the outputs from the two ecl devices are applied to an exclusive nor 33 and then to an ecl - to - bipolar conversion unit 34 before being output as an rf signal . there are three ecl voltage comparators used in the circuit . ideally , the comparators turn on ( output a &# 34 ; logic 1 &# 34 ; which is typically - 0 . 9 volt in ecl ) when the voltage at the noninverting ( positive ) input terminal is greater than the voltage at the inverting ( negative ) input terminal , and turn off (&# 34 ; logic 0 &# 34 ; or typically - 1 . 7 volts ) when the reverse is true . in this mode , the comparators function as one - bit analog - to - digital converters . a combination of wanted and interfering rf signals that are terminated with purely resistive 50 - ohm loads to ground ( the &# 34 ; rf input &# 34 ;) is applied to the noninverting terminals of three voltage comparators ( two of these comprise the &# 34 ; ecl window comparator &# 34 ; unit 31 having an output i / o characteristic shown in fig1 a ; the third is the &# 34 ; ecl hard limiter &# 34 ; unit 32 ). the inverting terminals are biased as follows . the inverting terminal of the ecl hard limiter 32 is grounded ; hence , it has the voltage transfer characteristic ( vtc ) as shown in fig1 c , behaving as a hard limiter that has been attenuated by approximately 8 db and has a negative dc offset of approximately 1 . 3 volts . one of the comparators in the &# 34 ; ecl window &# 34 ; is biased with a dc voltage , v t , rf , that is proportional to the interference amplitude . the other comparator in the ecl window is biased with - v t , rf . the logical complement of the negatively biased comparator output is tied to the output of the positively biased comparator . a third wire that extends from the connection of the two comparator outputs carries the logical &# 34 ; or &# 34 ; of these outputs ( known as a &# 34 ; wired or &# 34 ; because of the absence of a gate ) which is shown above the &# 34 ; ecl window comparator &# 34 ; unit 31 as a function of instantaneous rf input voltage . the outputs of the window comparator 31 and ecl hard limiter 32 are then passed through an &# 34 ; exclusive nor &# 34 ; ( xnor ) gate 33 , which returns a logic 1 when both inputs are the same and a logic 0 when the inputs differ from each other . the resulting vtc is shown in fig1 b . the xnor output waveform is converted to a bipolar signal by a capacitor that blocks its dc component 34 . the design result , shown in fig1 d , matches the ideal vtc except that the design result has approximately 8 db ( 20 log 10 { 1 / 0 . 4 }) less gain . this reduction in gain was expected to influence the wanted signal and interfere equally and , thus , have no effect on interference suppression performance . when the biased inverting limiter is integrated into an rfi suppression system , the rf threshold is set by dynamic tracking of the interference envelope . for this circuit , a tracker may be used or the mechanism that sets v t , rf for the biased inverting limiter prototype may be manually controlled . in the latter case , it is a resistive voltage divider that consists of a &# 34 ; pull - down &# 34 ; resistor connected to the positive dc voltage that powers the integrated circuits (+ 5 . 0 v ) and , through a potentiometer (&# 34 ; pot &# 34 ;), to ground . v t , rf , the voltage across the pot , can be varied between zero and 1 . 7 volts . the additive inverse of v t , rf is obtained from an operational amplifier connected in an inverting loop with two equal feedback resistances . | 7 |
in the process of the invention , metallic zinc or tin is plated on the surface of a steel filament and the zinc or tin - plated filament is contacted with a solution of cupric sulfate , cupric nitrate , cupric chloride , or cupric acetate to plate a copper film on the surface of the zinc or tin - plated steel filament to form a copper - film plated steel filament having an outer layer of copper film . the concentration of cupric salt in the plating solution ranges from 10 to 50 gram per liter . the plating process is preferably carried out with vigorous circulation of the plating solution in the plating bath . the thickness of the zinc or tin plated on the steel filament ranges from 0 . 05 to 2 . 5 μm . the thickness of the copper film plated on the zinc or tin - plated steel filament ranges from 20 to 90 nm . the thickness of the copper film plated on the zinc or tin - plated steel filament preferably ranges from 30 to 70 nm . the copper - film - plated steel filament may also be prepared by plating zinc or tin on the surface of a steel filament , drawing the zinc or tin - plated steel filament , twisting the zinc or tin plated filament , and contacting the drawn filament with a solution of cupric sulfate , cupric nitrate , cupric chloride , or cupric acetate to plate a copper film on the surface of the zinc or tin - plated steel filament . the process of the present invention produces copper - film - plated steel filaments that are adherable to rubber . steel cords suitable for use as tire reinforcing elements are produced from a plurality of copper - film - plated steel filaments . the thus produced steel cords are used in rubber articles such as tires . the rubber articles may additionally contain cobalt salt . the process and products according to the present invention are further described in the following non - limiting examples . zinc of high ionization was plated on a large steel rod which was then drawn to minimize the roughness of the steel rod . copper film was plated on the zinc - plated steel filament by a displacement plating method . the amounts of copper film were controlled by the changes of substitution plating times . substitution plating method enabled copper to be plated from outer surface of steel cord . the thus prepared copper - plated cords were adhered to two different rubber compounds and their adhesion properties were investigated . adhesion improvement of copper - plated cords was acheived with the addition of resin type adhesion promoters into a rubber compound . copper - film - plated plates were also prepared and their adhesion properties were studied . the copper - film - plated plates had superior adhesion properties of copper film when compared to the adhesion properties brass film . metal zinc was plated on the surface of the drawn steel filament ( high tensile , c content : 0 . 82 %) of 0 . 25 mm diameter using electroplating method . after removing fatty acid from the zinc - plated ilaments by the treatment of 5 % naoh solution , copper was plated on the surface of the washed filaments by substitution plating method at 20 ° c . copper content was ranged 17 - 20 g / lsolution as cupric sulfate . after washing the copper - film - plated filaments at 85 ° c . and drying them in 90 ° c . hot air , they were twisted together to be the copper - plated cords of 2 + 2 × 0 . 25 ht construction . the thickness of copper film was conirolied by changing the piafing time . at constant concentration of sulfuric copper acid . the average thickness of three different copper films measured by xrf were 32 , 45 , and 90 nm , respectively . copper - film - plated cords were named as cu ( ) cord , with the thickness in nm being the number in the parentheses . brass - plated steel cord of 2 + 2 × 0 . 25 ht was also used for comparison , of which plating weight and composition were 4 . 2 g / kg and cu / zn = 64 / 36 , respectively . the simplified rubber compound ( here after abbreviated as “ rub - 00 ”) was prepared to clarify the differences in adhesion properties , therefore , bonding agents and silica were not added , and carbon black and anti - degradant were kept at minimum level . the master batch components were as follows ; natural rubber ( lee rubber co ., malaysia , smr - 20 ), 100 phr ; carbon black n351 ( lucky co ., korea ), 30 phr ; aromatic processing oil ( michang co ., korea , a # 2 ), 5 phr ; zinc oxide ( hanil co ., korea ), 10 phr ; antioxidant ( monsanto co ., usa kumanox - rd , 2 , 2 , 4 - trimethyl - 1 , 2 - dihydroquinone ), i phr ; cobalt salt ( rhone pouluenc co ., france , manobond 680c ), 2 . 0 phr . final rubber compound components were as follows : masticated rubber masterbatch , 100 phr ; stearic acid ( pyungwha co ., korea ), 1 . 5 phr ; accelerator ( monsanto co ., usa , santocure mor , 2 -( morpholinothio )- thio - benzothizole ), 0 . 7 phr ; insoluble sulfur ( akzo co ., the netherlands , crystex hs ot 20 ), 5 . 0 phr . the rubber compounds were mixed following the procedures described in astm d - 3184 - 91 , using an internal mixer ( farrel co ., usa , banbury mixer model 82 ). the masterbatch components were mixed for 5 min . at a rotor speed . of 40 rpm and dumped at 150 ° c . after the masterbatch compound was cooled down to room temperature , the final mixing components were mixed for 5 min . at a rotor speed of 30 rpm and dumped at 90 ° c . after dumping , the batches were sheeted out using a two - roll mill ( farrel co ., model mkiii , usa ). the commercial rubber compound ( here after abbreviated as “ rub - bp ”) was prepared with the addition of bonding promoters into the simplified rubber compound and the adhesion properties were investigated with copper - plated cords . 2 . 0 phr of rfr ( resorcinol formaldehyde resin , indespec ., u . s . a ) and 3 . 7 phr of hmmm ( hexamethoxymethylmelamine , sytec co ., u . s . a ) were added into the master batch and final mixing of the simplified rubber compound , respectively . the mixing procedure of the commercial rubber compound was the same as that of simplified rubber compound . by the procedure described in astm - d2229 - 91 , specimens for t - test were cured at 160 ° c . on a cure press . curing was maintained 7 min . longer than t90 time . for humidity aging , rubber samples and adhesion samples were placed in a humidity chamber ( weiss technik ., model 305b ) for 5 , 10 , and 15 days under conditions of 85 ° c . and 85 % relative humidity . thermal aging was performed at 95 ° c . for 5 , 10 , and 15 days and salt solution aging at 25 ° c . naci solution for 5days . pullout force was determined as the maximum force exerted by the tensile tester ( model 6021 , instron , usa ) on a t - test adhesion sample during pullout test , with 100 mm / min . of crosshead speed . rubber coverage was also noted . the rubber coverage which denoted the relative extent of rubber covered on the pulled out cord was determined by the naked eye with a 5 % interval ; bare steel cord as 0 % to fully covered rubber as 100 %. each value reported was the average derived from six specimens . ( 5 ) the adhesion properties of copper - plated cord with simplified rubber compound table i shows the adhesion properties between copper - plated cords and the simplified rubber compound before and after thermal aging . the unaged and thermally - aged adhesion properties of copper - plated cords were inferior to those of the brass - plated cord . however , the adhesion properties of copper - plated cords were high when the copper film was thin . the unaged pull - out force of the cu ( 32 ) cord , which had the thinnest copper film , was almost half of that of brass - plated cord ; as was the rubber coverage of cu ( 32 ) cord . rubber coverage also became higher with the decrease in the thickness of copper film . rubber coverage was found to be zero on the cu ( 90 ) cord , but on the cu ( 32 ) cord it was 45 %, almost half of that of the brass - plated cord . pull - out force and rubber coverage were better as the thickness of copper film decreased . with an aging period , the adhesion properties of copper - plated and brass - is plated cord were all decreased , but the thermal adhesion stability was better with the decrease in the thickness of copper film ; i . e ., the pullout force of the thinnest copper film cord cu ( 32 ) at 15 days after thermal aging was recorded 273 n , 82 % of unaged force , and the rubber coverage was noted 55 % which was rather higher than the unaged coverage 45 %. on the other hand , the unaged pullout force of the brass - plated cord was as high as 589 n , but at 15 days after thermal aging it was reduced to 335 n , which was only 57 % of unaged force . it is worth noting that in the unaged state the pullout force of cu ( 32 ) cord was just a half of the brass - plated cord , but that of cu ( 32 ) cord 15 days after thermal aging was the almost same as that of brass - plated cord , and the rubber coverage of brass - plated cord was slightly lowed during thermal aging , but that of cu ( 32 ) was more improved . the adhesion stability of copper - plated cords was also superior in humidity aging as shown in table ii . although the unaged adhesion properties of copper - plated cord were inferior to those of brass - plated cord , both pullout force and rubber coverage of cu ( 32 ) cord after humidity aging for 15 days were all superior to those of brass - plated cord . the pull - out force of brass - plated cord was 193 n , whereas that of cu ( 32 ) cord 273 n , and the rubber coverage of brass - plated cord was 25 %, whereas that of cu ( 32 ) cord 55 %. with the humidity aging the pullout forces of both cords were decreased , but the degree of the decrease was lowered on the cu ( 32 ) cord . even though the rubber coverage of brass - plated cord was so much decreased with humidity aging , that of cu ( 32 ) cord was rather improved . the adhesion properties between the simplified rubber compound and the copper - plated cords were also stable during salt solution aging . the adhesion properties after salt solution aging for 5 days were tabulated in table iii . the adhesion properties after salt solution aging were greatly dependent on the copper film thickness , as were those after humidity and thermal aging . the pull - out force of the cu ( 32 ) cord with the thinnest copper film after salt solution aging of 5 days was as low as 246 n compared with 332 n of the unaged force of ; however , the rubber coverage of 45 % was retained even after salt solution aging . on the other hand , the pull - out force of the brass - plated cord dropped from 589 to 163 n with salt solution aging , and the rubber coverage was reduced from 100 % to 20 %. although the unaged adhesion properties of the brass - plated cord were better than any of the copper - plated cords , those 5 days after salt solution aging were considerably superior on the cu ( 32 ) cord w ith a thin copper film . ( 6 ) the adhesion properties of copper - plated cords with a commercial rubber compound . the adhesion properties between copper - plated cords and a commercial rubber compound ( rub - bp ) containing cobalt salt and bonding promoter were investigated by t - test method . their adhesion properties after thermal aging treatment at 95 ° c . were tabulated table iv . even though the commercial rubber compound was designed for brass - plated cord , the unaged adhesion properties of copper - plated cords with a commercial rubber compound could be comparable with those of brass - plated cord . pull - out force and rubber coverage of cu ( 32 ) cord with the thinnest copper film were 542 n and 90 %, respectively , sowing almost the same level as those of brass - plated cord . the degradation of adhesion properties was relatively low on copper - plated cords after thermal aging ; therefore pull - out force of cu ( 32 ) cord , the thinnest copper film , 15 days after thermal aging was 430 n , indicating higher than 396 n of brass - plated cord . unaged pull - out force and rubber coverage of cu ( 45 ) and cu ( 90 ) with relatively thick copper film were inferior to those of brass - plated cord , however the additional degradation with thermal treatment was relatively low on copper - plated cords . on the other hand , the pull - out force of cu ( 32 ) cord 15 days after humidity aging was 325 n , retaining 60 % of that of unaged force , that of brass - plated cord was 226 n , 42 % of unaged , being reduced more severely . at unaged state , rubber coverage of cu ( 32 ) cord after humidity aging was 90 % which is lower than 100 % of brass - plated cord , but 15 days after humidity aging , 60 % of cu ( 32 ) cord was higher than 50 % of brass - plated cord as shown table v . although the pull - out force and rubber coverage of all the cords become lowered , the degree of degradation was relatively low on copper - plated cords ; therefore , adhesion stability of copper - plated cords against humidity aging was better than that of brass - plated cord . after salt solution aging treatment , the pull - out force of cu ( 32 ) cord was similar to that of brass - plated cord , and rubber coverage was slightly low ; therefore adhesion stability of a commercial rubber with copper - plated cords against salt solution aging was comparable to that of brass - plated cord . ( see table vi ) the surface of iron plate of 100 mm long , 32 mm wide , 0 . 4 mm thick was ground with sandpaper of 4000 mesh and cleaned by dipping it into acetone for 2 ˜ 5min . to remove grease and other contaminants . after getting rid of oxide layer formed on surface by treating with 5 % sulphuric acid for 60 sec ., zinc was plated onto it in zinc sulfate solution of 20 g / l for 40 sec . using electoplating . subsequently , copper was coated on the surface of zinc - plated plate by contacting a copper sulfate solution of 2 . 5 g / l and dipped into anhydrous methanol for 30 sec . to suppress the formation of oxide film by removing water . the thickness of the copper film was controlled by changing the contact time of the zinc - plated plate at constant copper sulfate solution . the thickness of copper for the copper - plated plates measured by the xrf ( x - ray fluorescence ) were 30 , 65 , 90 nm . copper - plated were named as cu ( ) plate , with the thickness in ni being the number in the parentheses . adhesion properties of copper - plated plates with the rubber compounds were evaluated by pad - test method . the copper - plated plates of 0 . 4 mm thick were inserted between rubber pads of 2 mm thick , and they were cured at 150 ° c . and 13 mpa on a cure press . curing was maintained for 3 min longer than t 90 time to compensate for heat transfer ; therefore , rub - 00 rubber was cured for 11 min and rub - bp rubber , to which resin type bonding promoters added , was cured for 17 min . in order to investigate the influence of cure condition , adhesion specimens of rub - bp rubber were also prepared at undercure and overcure condition , curing for 8 min about 60 % of t 90 time , and 45 min about 350 % of t 90 time , respectively . peeling force was determined as the maximum force exerted by the tensile tester ( inston model 6021 , usa ) on a peel - test adhesion sample while peeling - out test at 300 mm min − 1 of crosshead speed . each value reported was the average derived from five specimens . the adhesion properties were investigated adhering rub - 00 and rub - bp rubber to copper - plated plates of different amounts of copper film . as shown in table vii , peeling forces of copper - plated plates and brass - plate adhered to rub - 00 rubber with no bonding promoters were not high and almost same between them . rub - bp rubber containing bonding promoters showed greatly strong adhesions to copper - plated plates and brass - plate compared to rub - 00 rubber though they were dependent on the cure conditions . although adhesion properties are mainly determined by the property of metal plate , they are also dependent on physical properties of a rubber compound . it is considered that strong adhesion of rub - bp rubber is attributed to the high degree of crosslinking density by the addition of cobalt salt and the increased modulus by resin type bonding promoter . adhesion strengths are different from cure conditions . at under - cure condition , peeling force of brass - plate is better than those of copper - plated plates , however , at normal and over - cure condition , peeling forces of copper - plated plates are superior . cu ( 65 ) and cu ( 90 ) plate , the plating thickness of which are in the range of 65 ˜ 90 nrm , exhibited superior peeling forces to cu ( 30 ) of thin copper film . whereas the copper - plated cords showed the better adhesion as their thickness of copper film was lowered , among the copper - plated plates , cu ( 90 ) plate of thick copper film showed the best adhesion . differently from the copper - plated cord , copper - plated plate is unable to be drawn after plating zinc ; thus remaining deep troughs generated from grinding the surfaces of the plate . so troughs are observed even at the copper - plated plates of relatively thick copper film . especially superior adhesion of cu ( 90 ) plate could be attributed to the relatively uniform plating of copper on the plate . copper is more stable to moisture than brass . differently from brass - plate , since copper - plated plates has no zinc to readily erupt by moisture , it is expected that the degree of degradation in their adhesions is relatively low due to no change of adhesion interphase by exposure to moisture . in order to evaluate the stability of copper - plated plates on moisture , they were placed in a humidity chamber ( weiss technik , model 305b ) for 6 days under conditions of 60 ° c . and 65 % relative humidity . the green humidity aged copper - plated plates were attached to rub - bp rubber and cured for 17 min on a cure press as well as brass - plate . ( see table viii ) the peeling forces of copper - plated plates were lowered with green humidity aging compared with those of no green humidity aging treatment . however , peeling force of cu ( 65 ) and cu ( 90 ) plate is superior to that of brass - plate , meaning that the adhesion properties is decreased with the change of adhesion interphase by mosture , but durability against green humidity aging is superior because of a high stability of copper - plated plate against moisture . the method of process of preparing copper - film - plated steel cord by plating copper upon the surface of zinc plated steel cord was illustrated in the above detailed description . the example of using tin instead of zinc is omitted because it could be readily implemented by those having an art in this field . using the solution of sulfuric copper acid was also exemplified for substitution plating method , however nitric copper acid , hydrochloric copper acid , or acetic copper acid instead of sulfuric copper acid can be used for substitution plating . as the invention described above in detail , within the limit of uniform plating , 1 ) the adhesion properties were better as the thickness of copper film was decreased , 2 ) copper - plated cord was very stable against humidity and salt solution aging compared with brass - plated cord , 3 ) the adhesion properties of copper - plated cord were much dependent on the composition of rubber compound , 4 ) the unaged adhesion properties of copper - plated cord with the rubber compound containing cobalt salt and resin type bonding promoter was similar to those of brass - plated cord , 5 ) the adhesion properties of copper - plated cord could exceed those of brass - plated cord by optimizing the cure condition and the composition of a rubber compound . manufacturing a tire using copper - plated cord described in the invention instead of brass - plated cord enables to reduce cure time by rapid forming of adhesion interphase , to extend storage period by improving stability against moisture , and to retard adhesion degradation . | 3 |
the present disclosure provides a method of driving a multipath - accessible shared bank memory device for low - level burst communications . exemplary embodiments will be described . a multipath - accessible shared bank memory device is disclosed in co - pending u . s . patent application ser . no . 11 / 829 , 859 , entitled “ multipath accessible semiconductor memory device with host interface between processors ”, filed jul . 27 , 2007 , which is incorporated herein by reference in its entirety . a multipath - accessible shared bank memory device may comprise a onedram ™, for example , which is a fusion dram manufactured by samsung electronics co ., ltd . an exemplary multipath - accessible shared bank memory device includes at least one mailbox . the multipath - accessible shared bank memory device with mailbox may be disposed between a modem and a processor executing an application process ( ap ) to facilitate low - level burst communications . a device driver for the multipath - accessible shared bank memory device supports communications between the processor and the modem , which may be further connected to another modem or external communications device . the device driver supports a bi - directional burst mode with burst control between the processor and the modem . alternatively , the multipath - accessible shared bank memory device may be disposed between two or more processors in a multiprocessor system to facilitate smooth access to at least one shared bank of the memory device by the multiple processors . a device driver for the multipath - accessible memory device supports inter - processor communications . the device driver supports a multi - directional burst mode with burst control between the multiple processors . as shown in fig1 , a multiprocessor system is generally indicated by the reference numeral 100 . the system 100 includes a first processor 120 in signal communication with an inter - processor communications ( ipc ) device 140 . the ipc device 140 comprises a multipath - accessible shared bank memory device . the system 100 further includes a second processor 130 in signal communication with the ipc device 140 . the ipc device 140 has a first outgoing interrupt port 142 and a first bi - directional data port 144 , each in signal communication with the first processor 120 . in addition , the ipc device 140 has a second outgoing interrupt port 146 and a bi - directional data port 148 , each in signal communication with the second processor 130 . turning to fig2 , a computer - readable memory device is indicated generally by the reference numeral 200 . the device 200 includes an application module 230 in signal communication with a kernel 240 . the kernel 240 includes an inter - processor communications ( ipc ) driver 220 in signal communication with the application module 230 and a device driver 210 . the drivers 210 and 220 and the application 230 are executable by the processor 120 of fig1 . turning now to fig3 , another computer - readable memory device is indicated generally by the reference numeral 300 . the device 300 includes a first multi - threaded application module 330 and a second multi - threaded application module 350 , each in signal communication with a kernel 340 . the kernel 340 includes an inter - processor communications ( ipc ) driver 320 in signal communication with the application modules 330 and 350 , and further in signal communication with a device driver 310 . the drivers 310 and 320 and the applications 330 and 350 are executable by the processor 130 of fig1 . as shown in fig4 , an application programming interface ( api ) is indicated generally by the reference numeral 400 . the api 400 comprises the device drivers 210 and 310 of fig2 and 3 , respectively , and a device api 411 . turning to fig5 , application programming interface ( api ) functions are generally indicated by the reference numeral 500 . the api functions include command functions , data functions and miscellaneous functions . the command functions include a writecommand function to write a command or message to a mailbox , and a readcommand function to read a command or message from a mailbox . the data functions include a writedata function to write data to a shared bank , and a readdata function to read data from a shared bank . the miscellaneous functions include an init function to initialize a device driver , a checkownership function to check the current ownership of a shared bank , a getlasterror function to retrieve the last error code , and a getchaaddr to retrieve an address of a channel . these functions are each supported by the device drivers 210 and 310 of fig2 and 3 , respectively . turning now to fig6 , a driver with application programming interface ( api ) is generally indicated by the reference numeral 600 . the driver 600 comprises the ipc driver 220 of fig2 and 3 . here , the ipc driver includes an ipc api 621 , a plurality n of ipc channels 623 in signal communication with the ipc api , and an ipc thread 622 in signal communication with the ipc channels . thus , the ipc api 621 is supported by the ipc drivers 220 and 320 of fig2 and 3 , respectively . while one ipc channel 623 may be sufficient for exemplary applications , multiple channels may be provided for the convenience of user applications , since they may help to keep data in context thus , the data packets include a channel number in embodiments having more than one channel . as shown in fig7 , application programming interface ( api ) functions are generally indicated by the reference numeral 700 . these api functions are supported by the inter - processor communications ( i pc ) drivers 220 and 320 of fig2 and 3 , respectively . the ipc api commands include data functions and miscellaneous functions . the data functions include an ipcsend function to send a data packet , and an ipcreceive function to receive a data packet . the miscellaneous functions include an ipcopen function to open an ipc channel handle , an ipcclose function to close an ipc channel handle , and an ipciocntl function to control settings of the ipc driver . for example , when an ipc channel status is closed , no more reads or writes are permitted . turning to fig8 , an exemplary inter - processor communications ( ipc ) channel is indicated generally by the reference numeral 800 . the ipc channel 800 is supported by the ipc driver 220 of fig2 , 3 and 6 , and comprises one of the plurality of channels 623 of fig6 . the ipc channel 800 includes a transmit side 824 and a receive side 825 . the transmit side 824 includes a plurality m of transmit packets 841 , 842 . . . 843 . each transmit packet includes a transmit packet pointer tx_ptr and a transmit packet length tx_len . the receive side 825 includes a plurality n of receive packets 851 , 852 . . . 853 . each receive packet includes a receive packet pointer rx_ptr and a receive packet length rx_len . turning now to fig9 , an inter - processor communications ( ipc ) device 140 of fig1 is indicated generally in greater detail by the reference numeral 900 . the ipc device 900 includes a plurality of ports 931 - 932 in signal communication with at least one bank 911 - 914 , and a semaphore / mailbox area 920 . here , a first bi - directional data port 931 and a second bi - directional data port 932 are both in bi - directional signal communication with at least one dual - port bank 912 . optional banks 911 , 913 and 914 are in bi - directional signal communication with one or more of the ports . in this example , the bank 911 is connected to the first port 931 , while the banks 913 and 914 are connected to the second port 932 . the banks 911 , 912 , 913 and 914 may be implemented in dynamic random access memory ( dram ) cells , for example . the semaphore / mailbox area 920 is in bi - directional signal communication with each of the ports , and includes a semaphore area 921 , a mailboxatob area for messages from a processor connected to the first port to a processor connected to the second port , and a mailboxbtoa area for messages from the processor connected to the second port to the processor connected to the first port . the mailboxatob area includes a first interrupt int 1 from the processor connected to the first port to the processor connected to the second port , and the mailboxbtoa area includes a second interrupt int 2 from the processor connected to the second port to the processor connected to the first port . the semaphore area 921 defines the current ownership of the shared bank . for embodiments with two ports , the semaphore may be just one bit , for example . only the processor that is the current owner can write or change the semaphore . for ease of explanation , the ipc device 900 includes just one dual - port bank 912 , one semaphore bit 921 , two ram ports 931 and 932 , and two mailboxes 922 and 923 , but alternate embodiments having a greater number of ram ports , dual - port banks , semaphore bits , and / or mailboxes are contemplated . for example , an alternate embodiment with n ports may have up to n ( n − 1 )/ 2 dual - port banks , up to n ( n − 1 )/ 2 semaphore bits and up to n ( n − 1 ) mailboxes . thus , a fully versatile three - port embodiment might have three dual - port port banks , three semaphore bits and six mailboxes ; while a fully versatile four - port embodiment might have six dual - port banks , six semaphore bits and twelve mailboxes . on the other hand , reduced versatility embodiments , where all processors need not communicate in burst mode with every other processor , are also contemplated . for example , an eight - port embodiment for which four pairs of processors need to communicate within the pair , but not with processors of the other three pairs , might include four dual - port banks , four semaphore bits , the four ram ports , and eight mailboxes . as shown in fig1 , a shared storage region or bank is indicated generally by the reference numeral 1000 . the bank or shared storage region 1000 may be any dual - port bank , such as the dual - port bank 912 of fig9 . the bank 1000 includes a plurality n of channels ch 1 - chn , each channel including a plurality l of transmit buffers tx_buf and a plurality m of receive buffers rx_buf . turning to fig1 , another shared memory or bank is indicated generally by the reference numeral 1100 . the bank 1100 supports a modem embodiment of the present disclosure by providing one ipc channel for a voice mail service ( vms ), one ipc channel for a modem database in non - volatile random access memory ( nvram ), four ipc channels for network data service packets ( ndis ), and three ipc channels for modem commands ( at ). here , each channel has ten transmit buffers and ten receive buffers , and uses a memory area of ( 2 kb + 4 b )*( 10 + 10 ) bytes in alternate embodiments , the number of transmit and receive buffers is user selectable . turning now to fig1 , a shared bank channel , which may hold the actual data corresponding to the pointers of the ipc channel 800 of fig8 , is indicated generally by the reference numeral 1200 . user or application data is stored in buffers 1210 of the channel 1200 of a shared bank , such as the bank 912 of fig9 . the buffers 1210 may include a plurality l of transmit buffers tx_buf , and a plurality m of receive buffers rx_buf . it shall be understood that the designation of transmit and receive buffers for the shared buffers are different with respect to each of the processors . that is , a shared buffer known as a transmit buffer to one processor may be known as a receive buffer to the other processor . each buffer 1210 includes a pck_sz packet size field 1212 , which may be four bytes , for example , and a pck_data packet data field 1214 , which may have a maximum size of 2 kbytes , for example . a table 1250 further describes the user data buffers 1210 for this exemplary embodiment . according to the table , the pck_sz field is four bytes long and contains the size of the data packet , and the pck_data field is up to 2 kbytes long and contains the data to be transferred . as shown in fig1 , message data for a mailbox of fig9 is indicated generally by the reference numeral 1300 . here , the message data may be formatted into four fields 1310 . the fields may include an eight - bit command field , an eight - bit channel number field , an eight - bit packet count field , and an eight - bit reserved field . for example , the message data may be formatted into at least three fields 1340 , including a command ( cmd ) region 1341 , a channel index ( ch_idx ) region 1342 , and a packet number storage region ( pck_cnt ) 1343 . command values 1350 are further described . the eight - bit cmd field 1341 may hold any value between 0x01 and 0xff . here , the command value 0x01 is an ownership request command , the command value 0x02 is an ownership release command , the command value 0x03 is a transmit suspension command , the command value 0x04 is a transmit resumption command , the command value 0x05 is a transmit completion command , the command value 0x06 is an ipc channel status command , the command value 0x07 is a transmit completion and ownership request command , the command value 0xf0 is a reset request command , and the command value 0xff is an error command . turning to fig1 , a method of communication between two processors through a mailbox is indicated generally by the reference numeral 1400 . the method 1400 includes a start block s 100 that passes control to function block s 110 , where a first processor writes a command to a first mailbox . the first processor passes control to a function block s 130 , where an ipc device generates a first interrupt signal . the ipc device passes control to a function block s 150 , where a second processor receives a first interrupt signal . the second processor , in turn , passes control to a function block s 170 , where it reads a command from its mailbox , and then passes control to an end block s 180 . turning now to fig1 , a method to change ownership of the shared region from a second processor to a first processor is indicated generally by the reference numeral 1500 . the method 1500 includes a start block s 200 that passes control to function block s 211 , where a first processor checks ownership by accessing a semaphore . the block s 211 passes control to a decision block s 213 , which determines from the semaphore whether the first processor has ownership of the shared bank . if so , control is passed to an end block s 230 . if not , control is passed to a function block s 215 , where the first processor writes an ownership request to the first mailbox , and passes control to a function block s 217 . at function block s 217 , an ipc device generates a first interrupt signal , and passes control to a function block s 219 . at s 219 , a second processor receives the first interrupt signal , and passes control to a function block s 221 . at block s 221 , the second processor reads the ownership request command from the first mailbox , and passes control to a function block s 223 . at block s 223 , the second processor writes an ownership release command to a second mailbox , and passes control to a function block s 225 . at block s 225 , the ipc device generates a second interrupt signal , and passes control to a function block s 227 . at block s 227 , in turn , the first processor receives the ownership release command , and passes control to a function block s 229 . at the block s 229 , the first processor reads the ownership release command from the second mailbox , and passes control to an end block s 230 . as shown in fig1 , a method to exchange data through a shared region is indicated generally by the reference numeral 1600 . the method 1600 includes a start block s 300 that passes control to function block s 310 , where a first processor acquires ownership of a shared bank , and passes control to a function block s 320 . at block s 320 , the first processor writes a data packet to the shared bank , and passes control to a function block s 330 . at block s 330 , the first processor writes a transmit completion command and information about the stored data packet to a first mailbox , and passes control to a function block s 340 . at block s 340 , in turn , an ipc device generates a first interrupt signal , and passes control to a function block s 350 . at block s 350 , a second processor receives the first interrupt signal , and passes control to a function block s 360 . at block s 360 , the second processor reads the transmit completion and information about the stored data packet from the first mailbox , and passes control to a function block s 370 . at block s 370 , the second processor reads a data packet from the shared bank based on the information about the stored data packet , and passes control to an end block s 380 . turning to fig1 , a processor and ipc device interconnected to minimize memory copy operations in the processor are generally indicated by the reference numeral 1700 . the processor may be the first or second processor 120 or 130 of fig1 , for example , and the ipc device may be the ipc device 140 of fig1 . the processor 120 includes the application module 230 , the ipc driver 220 and the device driver 210 , all of fig2 . here , the application module 230 includes a transmit buffer 1711 and a receive buffer pointer 1727 . the ipc driver includes a transmit buffer pointer 1713 and a receive buffer 1725 . the ipc device 140 includes a transmit buffer 1717 and a receive buffer 1721 . the application module 230 is disposed to send a call by pointer for its transmit buffer 1711 to the transmit buffer pointer 1713 of the ipc driver 220 . the device driver 210 is disposed to perform a copy of the application module transmit buffer 1711 indicated by the ipc driver transmit buffer pointer 1713 to the ipc device transmit buffer 1717 . the device driver 210 is disposed to perform a copy from the receive buffer 1721 of the ipc device 140 to the receive buffer 1725 of the ipc driver 220 . the ipc driver is disposed to return a pointer for its receive buffer 1725 to the receive buffer pointer 1727 of the application module 230 . turning now to fig1 , a method for ownership acquisition , data transfer and data suspension is indicated generally by the reference numeral 1800 . at a step s 400 , a first processor 120 of fig1 has an active device driver 210 and an active ipc driver 220 , both of fig2 . the ipc driver 220 has an ipc transmit channel 824 of fig8 presently containing packets pck 3 , pck 4 and pck 5 . an ipc device 140 of fig1 is disposed between the first processor 120 and a second processor 130 of fig1 , which has an active device driver 310 and an active ipc driver 320 , both of fig3 . the ipc driver 320 has an ipc receive channel 825 of fig8 presently containing packets pck 1 and pck 2 . at a subsequent step s 410 , ownership acquisition is performed . here , the first processor uses the ipc driver 220 to send an ownership request command through the device driver 210 , which writes to the ipc device 140 of fig1 the ownership request command value 0x01 , as set forth in table 1350 of fig1 , to the highest order byte of the mailbox 922 of fig9 according to the format 1340 of fig1 , where the two lower order bytes are not needed for this particular command . in the second processor , the ipc driver 320 reads the ownership request command through the device driver 310 , which copies the value 0x01 from the mailbox 922 . the ipc driver 320 then writes to the ipc device an ownership release command through the device driver 310 , which writes the ownership release value of 0x02 to the second mailbox 923 of fig9 . back in the first processor , the ipc driver 220 reads the ownership release command through the device driver 210 , which copies the value 0x02 from the mailbox 923 . at a subsequent step s 420 , data transfer is performed . here , the first processor uses its ipc driver 220 to write data packets pck 3 , pck 4 and pck 5 through its device driver 210 to the data packet buffers 1210 of a first processor transmit side channel 1200 of a shared bank 912 of the ipc device 140 . the first processor then writes a transmit completion command with arguments to the mailbox 922 , where the value of the transmit completion command is 0x05 , the value of the channel index is 0x01 , and the value of the packet count is 0x03 . in the second processor , the ipc driver 320 reads the transmit completion command through the device driver 310 , which copies the transmit completion command value 0x05 , the channel index value 0x01 , and the packet count value 0x03 from the mailbox 922 . next , the ipc driver 320 reads the data packets pck 3 , pck 4 and pck 5 through the device driver 310 from the buffers 1210 of the shared bank 912 , and appends them to the receive side ipc channel 825 . here , the receive side ipc channel 825 has a total of five packets , which exceeds its suspend threshold of four packets in this particular example . thus , at a step s 430 , transmission suspension is performed . here , the second processor writes a transmission suspension command having a value of 0x03 through the device driver 310 to the second mailbox 933 of the ipc device 140 . the first processor uses its ipc driver 220 to read the transmission suspension command through its device driver 210 from the mailbox 923 . therefore , the first processor does not yet try to send two more packets pck 6 and pck 7 that are present in its ipc channel 824 . as shown in fig1 , an ipc channel is indicated generally by the reference numeral 1900 the ipc channel 1900 may be any pointer - type ipc channel 623 of fig6 , for example , as used by the ipc drivers 220 or 320 of fig2 or 3 , respectively . the channel 1900 includes a transmit side channel and a receive side channel , both with respect to one of the processors . the transmit side channel includes n transmit side buffers 1941 , 1942 . . . 1943 . here , unlike the ipc channel 800 of fig8 , the receive side channel has a different number m of receive side buffers 1951 , 1952 . . . 1953 , but alternate embodiments may have any number of buffers , where the number of receive side buffers need not be the same as the number of transmit side buffers . each packet includes a packet pointer ptr and a packet length len . turning to fig2 , a method for transmission resumption and data transfer is indicated generally by the reference numeral 2000 . at a step s 440 , the first processor 120 of fig1 has an active device driver 210 and an active ipc driver 220 , both of fig2 . the first processors ipc driver 220 has an ipc channel 824 that presently contains packets pck 6 and pck 7 . an ipc device 140 of fig1 is disposed between the first processor 120 and the second processor 130 of fig1 , which has an active device driver 310 and an active ipc driver 320 , both of fig3 the ipc driver 320 has an ipc channel 825 of fig8 presently containing two packets pck 4 and pck 5 , where two packets is the resumption threshold . here , the second processor uses its ipc driver 320 to write a transmit resumption command through its device driver 310 to the ipc device mailbox 923 of fig9 , where the transmit resumption command has a value of 0x04 in accordance with table 1350 of fig1 . the first processor , in turn , uses its ipc driver 220 to read the transmit resumption command through its device driver 210 from the mailbox 923 on the ipc device . at a subsequent step s 450 , the first processor &# 39 ; s ipc driver 220 empties its ipc channel 824 by writing data packets pck 6 and pck 7 through its device driver to the first processor &# 39 ; s transmit side channel 1200 of a shared bank 912 of the ipc device 140 . the first processor then writes a transmit completion command with arguments to the mailbox 922 , where the value of the transmit completion command is 0x05 , the value of the channel index is 0x01 , and the value of the packet count is 0x02 . in the second processor , the ipc driver 320 reads the transmit completion command through the device driver 310 , which copies the transmit completion command value 0x05 , the channel index value 0x01 , and the packet count value 0x02 from the mailbox 922 . next , the ipc driver 320 reads the data packets pck 6 and pck 7 through the device driver 310 from the second processor &# 39 ; s receive side channel 1200 of the shared bank 912 , and appends them to the receive side ipc channel 825 . here , the receive side ipc channel 825 has a total of four packets , which does not yet exceed its suspend threshold of four packets in this particular example . turning now to fig2 , a method for data transfer in single packet mode is indicated generally by the reference numeral 2100 . at a step s 500 , the first processor 120 has a transmit side ipc channel 824 containing packets pck 1 , pck 2 and pck 3 . the second processor 130 has a receive side ipc channel 825 that is empty . at a step s 510 , the first processor writes an ownership request command of 0x01 to the first mailbox 922 on the ipc device . the second processor 130 , in turn , reads the ownership request command from the first mailbox 922 and writes an ownership release command of 0x02 to the second mailbox 923 . the first processor reads the ownership release command from the mailbox 923 . at a step s 520 , the first processor writes one data packet pck 1 to the first processor &# 39 ; s transmit side channel 1200 of a shared bank 912 of the ipc device 140 , and then writes a transmit complete command of 0x05 with arguments for channel index of 0x01 and packet count of 0x01 to the mailbox 922 . the second processor reads the transmit completion command with arguments from the mailbox 922 , and then reads the data packet pck 1 from the second processor &# 39 ; s receive side channel 1200 to the second processor &# 39 ; s receive side ipc channel 825 . thus , the first processor 120 has a transmit side ipc channel 824 containing packets pck 2 and pck 3 , while the second processor 130 has a receive side ipc channel 825 containing packet pck 1 . at a step s 530 , the first processor writes an ownership request command of 0x01 to the first mailbox 922 on the ipc device . the second processor 130 , in turn , reads the ownership request command from the first mailbox 922 and writes an ownership release command of 0x02 to the second mailbox 923 . the first processor reads the ownership release command from the mailbox 923 . at a step s 540 , the first processor writes one data packet pck 2 to the first processors transmit side channel 1200 of a shared bank 912 of the ipc device 140 , and then writes a transmit complete command of 0x05 with arguments for channel index of 0x01 and packet count of 0x01 to the mailbox 922 . the second processor reads the transmit completion command with arguments from the mailbox 922 , and then reads the data packet pck 2 from the second processor &# 39 ; s receive side channel 1200 to the second processors receive side ipc channel 825 . thus , the first processor 120 has a transmit side ipc channel 824 containing packet pck 3 , while the second processor 130 has a receive side ipc channel 825 containing packets pck 1 and pck 2 . at a step s 550 , the first processor writes an ownership request command of 0x01 to the first mailbox 922 on the ipc device . the second processor 130 , in turn , reads the ownership request command from the first mailbox 922 and writes an ownership release command of 0x02 to the second mailbox 923 . the first processor reads the ownership release command from the mailbox 923 . at a step s 560 , the first processor writes one data packet pck 3 to the first processor &# 39 ; s transmit side channel 1200 of a shared bank 912 of the ipc device 140 , and then writes a transmit complete command of 0x05 with arguments for channel index of 0x01 and packet count of 0x01 to the mailbox 922 . the second processor reads the transmit completion command with arguments from the mailbox 922 , and then reads the data packet pck 3 from the second processors receive side channel 1200 to the second processors receive side ipc channel 825 . thus , the first processor 120 has a transmit side ipc channel 824 that is empty , while the second processor 130 has a receive side ipc channel 825 containing packets pck 1 , pck 2 and pck 3 . turning now to fig2 , a method of transferring data in a burst mode is indicated generally by the reference numeral 2200 . at a step s 600 , the first processor 120 has a transmit side ipc channel 824 containing packets pck 1 , pck 2 and pck 3 . the second processor 130 has a receive side ipc channel 825 that is empty . at a step s 610 , the first processor writes an ownership request command of 0x01 to the first mailbox 922 on the ipc device . the second processor 130 , in turn , reads the ownership request command from the first mailbox 922 and writes an ownership release command of 0x02 to the second mailbox 923 . the first processor reads the ownership release command from the mailbox 923 . at a step s 620 , the first processor writes data packet pck 1 , pck 2 and pck 3 to the first processor &# 39 ; s transmit side channel 1200 of a shared bank 912 of the ipc device 140 , and then writes a transmit complete command of 0x05 with arguments for channel index of 0x01 and packet count of 0x01 to the mailbox 922 . the second processor reads the transmit completion command with arguments from the mailbox 922 , and then reads the data packets pck 1 , pck 2 and pck 3 from the second processor &# 39 ; s receive side channel 1200 to the second processor &# 39 ; s receive side ipc channel 825 . thus , the first processor 120 has a transmit side ipc channel 824 that is empty , while the second processor 130 has a receive side ipc channel 825 containing packets pck 1 , pck 2 and pck 3 . as shown in fig2 , a comparative plot of single packet mode versus burst modes with different burst lengths is indicated generally by the reference numeral 2300 . here , burst lengths of 10 packets and of 20 packets are compared to single packet mode . the burst length may be implemented by setting the suspend threshold of the receiving processor &# 39 ; s ipc driver to the desired length . alternatively , the burst length may be implemented by setting the number of buffers in the transmit side ipc channel 824 to the desired length . the plot 2300 puts transfer speed in mbps on the vertical axis against packet size in bytes on the horizontal axis . the plot 2300 includes a first curve 2310 for single packet mode , a second curve 2320 for a burst mode of length 10 , and a third curve 2330 for a burst mode of length 20 . as indicated , the burst mode of length 20 is about 10 times faster than single packet mode . turning now to fig2 , another embodiment multiprocessor system is generally indicated by the reference numeral 2400 . the system 100 includes a an external communications link 2410 in signal communication with a first processor or modem 2420 , the modem 2420 in signal communication with an inter - processor communications ( ipc ) device 2440 . the ipc device 140 comprises a multipath - accessible shared bank memory device . the system 2400 further includes a second processor 2430 comprising an application and / or media in signal communication with the ipc device 2440 . the system 2400 includes a flash memory 2450 in signal communication with the application processor 2430 , and a system bus 2490 in signal communication with the application processor 2430 . the system 2400 further includes an lcd display 2960 , an audio speaker 2970 , and an input device 2480 , each in signal communication with the system bus 2490 . in an alternate embodiment , the lcd display 2960 and the input device 2480 may be combined in a touch screen device . as shown in fig2 , device specifications for an exemplary ipc device 140 of fig1 are indicated generally by the reference numeral 2500 . the device 2500 includes 64 mb of dram cells organized into four banks , including one bank dedicated to a first port , two banks dedicated to a second port , and one shared bank . the access control is per bank , the i / o width is not necessarily the same for each port , and the ports operate independently of each other . such a device may comprise a onedram ™, for example . turning to fig2 , a driver comparison is indicated generally by the reference numeral 2600 . a universal asynchronous receiver - transmitter ( uart ) driver with multiplexer ( mux ) 2610 includes a serial channel application 2612 in signal communication with a serial mux driver 2614 the mux driver 2614 is in signal communication with a uart driver 2616 , which , in turn , is in signal communication with a uart 2618 . the speed of the uart driver with mux 2610 is on the order of about 1 mbps . a multipath - accessible shared bank memory device may be embodied in a onedram ™ device . a onedram ™ with mux 2620 includes a serial channel application 2622 in signal communication with a serial mux driver 2624 . the mux driver 2624 is in signal communication with a onedram ™ driver 2626 , which , in turn , is in signal communication with a onedram ™ 2628 . the speed of the onedram ™ with mux 2620 is on the order of about 10 mbps . ipc and device drivers may be adapted to a onedram ™ multipath - accessible shared bank memory device . a onedram ™ with ipc driver 2630 includes a serial channel application 2632 in signal communication with a onedram ™ ipc driver 2634 , such as the ipc driver 220 of fig2 . the onedram ™ ipc driver 2634 is in signal communication with a onedram ™ device driver 2636 , such as device driver 210 of fig2 , which , in turn , is in signal communication with a onedram ™ 2638 . the speed of the onedram ™ with ipc driver 2630 is on the order of about 100 mbps . thus , the onedram ™ with ipc driver 2630 may more fully utilize a high - speed ipc between a modem , such as the modem 2420 of fig2 , and an ap processor , such as the processor 2430 of fig2 . serial devices include uart , spi , usb and the like . shared memory devices include dpram , onedram ™, and the like . while a mux driver may be adequate for a serial device , it is not fast enough for a multipath - accessible shared bank memory device , such as a onedram ™, for example . here , a onedram ™ ipc driver with multiple channels and high - speed capabilities is significantly more efficient . turning now to fig2 , a memory copy method comparison for a mux driver versus a onedram ™ ipc driver is indicated generally by the reference numeral 2700 . a memory copy method 2702 uses a onedram ™ ipc driver to communicate between a an ipc application on a processor and an ipc device , here a onedram ™. the processor may be the first or second processor 120 or 130 of fig1 , for example , and the ipc device may be the ipc device 140 of fig1 . here an ipc application module 230 communicates with a onedram ™ ipc driver 220 , both of fig2 . the application module 230 includes a transmit buffer 2711 and a receive buffer pointer 2727 . the ipc driver 220 includes a transmit buffer pointer 2713 and a receive buffer 2725 . the ipc device 140 includes a transmit buffer 2717 and a receive buffer 2721 . the application module 230 is disposed to send a call by pointer for its transmit buffer 2711 to the transmit buffer pointer 2713 of the ipc driver 220 . a copy of the application module transmit buffer 2711 indicated by the ipc driver transmit buffer pointer 2713 is performed to the ipc device transmit buffer 2717 . on the receive side , copy is performed from the receive buffer 2721 of the ipc device 140 to the receive buffer 2725 of the ipc driver 220 . the ipc driver is disposed to return a pointer for its receive buffer 2725 to the receive buffer pointer 2727 of the application module 230 . in contrast , a memory copy method 2701 uses a mux driver to communicate between a an ipc application on a processor and a physical device . here an ipc application module 2730 communicates with a mux driver 2722 . the application module 2730 includes a transmit buffer 2712 and a receive buffer pointer 2728 . the mux driver 2722 includes a transmit buffer 2714 and a receive buffer 2726 . a physical device 2742 includes a transmit buffer 2718 and a receive buffer 2724 . the application module 2730 is disposed to perform an actual copy from its transmit buffer 2712 to the transmit buffer pointer 2714 of the mux driver 2722 . another copy of the mux driver transmit buffer 2714 is performed to the physical device transmit buffer 2718 . on the receive side , copy is performed from the receive buffer 2724 of the physical device 2742 to the receive buffer 2726 of the mux driver 2722 . the mux driver then performs another actual copy from its receive buffer 2726 to the receive buffer pointer 2728 of the application module 2730 . thus , while the data is actually copied only two times in the method 2702 using the ipc driver 220 , the data is actually copied four times in the method 2701 using the mux driver 2722 . therefore , the method 2702 using the ipc driver is more efficient , and should be applied to minimize the number of memory copy operations . as shown in fig2 , a comparative plot of performance test results for single mode versus burst mode is indicated generally by the reference numeral 2800 . a table 2840 sets forth the test environment , in which a modem has an arm clock of 282 mhz and a memory clock of 69 mhz , and an application processor ( ap ) has an arm clock of 533 mhz and a memory clock of 133 mhz . the plot 2800 puts transfer speed in mbps on the vertical axis against decreasing packet size in bytes on the horizontal axis . the plot 2800 includes a first curve 2810 for single packet mode , a second curve 2820 for a burst mode having a length of 10 packets , and a third curve 2330 for a burst mode having a length of 20 packets . a table 2850 sets forth the test results . as indicated in the table , a packet size of 2048 bytes produced speeds of 3 . 0 mbps , 36 . 70 mbps and 26 . 67 mbps for single , burst of length 20 and burst of length 10 modes , respectively . a packet size of 1500 bytes produced speeds of 2 . 3 mbps , 28 . 67 mbps and 21 . 74 mbps for the single , burst of length 20 and burst of length 10 modes , respectively . a packet size of 1024 bytes produced speeds of 1 . 4 mbps , 19 . 95 mbps and 13 . 72 mbps for the single , burst of length 20 and burst of length 10 modes , respectively . thus , the burst mode of length 20 is greater than 10 times faster than single packet mode for all of the tested packet sizes . turning to fig2 , comparative methods for single mode versus burst mode are indicated generally by the reference numeral 2900 . here , a single packet mode method 2910 is compared to a burst mode method 2920 . in the single packet mode method 2910 , a modem has a transmit side ipc channel or queue 824 containing three packets . an application processor has a receive side ipc channel or queue 825 that is empty . the modem writes an ownership request command to the first mailbox on the ipc device , and the ipc device sends a mailbox interrupt to the application processor . the application processor , in turn , reads the ownership request command from the first mailbox and writes an ownership release command to the second mailbox . the ipc device sends a mailbox interrupt to the modem . the modem reads the ownership release command from the second mailbox . next , the modem writes one data packet to a channel of a shared bank on the ipc device , and then writes a transmit complete command to the first mailbox . the ipc device sends a mailbox interrupt to the application processor . the application processor reads the transmit complete command from the first mailbox , and then reads the data packet from the channel on the ipc device to the second processor &# 39 ; s receive side ipc channel or queue 825 . thus , the modem now has a transmit side ipc channel 824 containing two packets , while the application processor has a receive side ipc channel or queue 825 containing the transferred packet . to transfer the second packet , the modem writes an ownership request command to the first mailbox on the ipc device , and the ipc device sends a mailbox interrupt to the application processor . the application processor , in turn , reads the ownership request command from the first mailbox and writes an ownership release command to the second mailbox . the ipc device sends a mailbox interrupt to the modem . the modem reads the ownership release command from the second mailbox . next , the modem writes one more data packet to the channel of the shared bank on the ipc device , and then writes a transmit complete command to the first mailbox . the ipc device sends a mailbox interrupt to the application processor . the application processor reads the transmit complete command from the first mailbox , and then reads the data packet from the channel on the ipc device to the second processor &# 39 ; s receive side ipc channel or queue 825 . thus , the modem now has a transmit side ipc channel 824 with one packet remaining , while the application processor has a receive side ipc channel or queue 825 containing a total of two transferred packets . to transfer the third packet , the modem writes another ownership request command to the first mailbox on the ipc device , and the ipc device sends a mailbox interrupt to the application processor . the application processor , in turn , reads the ownership request command from the first mailbox and writes an ownership release command to the second mailbox . the ipc device sends a mailbox interrupt to the modem . the modem reads the ownership release command from the second mailbox . next , the modem writes the third and final data packet to a channel of a shared bank on the ipc device , and then writes a transmit complete command to the first mailbox . the ipc device sends a mailbox interrupt to the application processor . the application processor reads the transmit complete command from the first mailbox , and then reads the data packet from the channel on the ipc device to the second processor &# 39 ; s receive side ipc channel or queue 825 thus , the modem has now emptied its transmit side ipc channel 824 , while the application processor has a receive side ipc channel or queue 825 containing all three transferred packets . in the burst mode method 2920 , the modem begins with a transmit side ipc channel or queue 824 containing three packets , and the application processor begins with a receive side ipc channel or queue 825 that is empty . these are the same starting conditions as for the single mode 2910 . the modem writes an ownership request command to the first mailbox on the ipc device , and the ipc device sends a mailbox interrupt to the application processor . the application processor , in turn , reads the ownership request command from the first mailbox and writes an ownership release command to the second mailbox . the ipc device sends a mailbox interrupt to the modem . the modem reads the ownership release command from the second mailbox . next , the modem performs a burst write of all three packets to a channel of a shared bank on the ipc device , and then writes a transmit complete command to the first mailbox . the ipc device sends a mailbox interrupt to the application processor . the application processor reads the transmit complete command from the first mailbox , and then reads all three data packets from the channel on the ipc device to the second processors receive side ipc channel or queue 825 . thus , the modem has now emptied its transmit side ipc channel 824 , while the application processor has a receive side ipc channel or queue 825 containing all three packets transferred in the burst mode . thus , only one data packet can be transferred at a time in the single mode 2910 , while multiple data packets can be transferred at once in the burst mode 2920 . further , the single mode generates more interrupts than the burst mode , which creates additional overhead for the processor . in addition , the use of the burst mode can save the time spent on additional ownership requests in single mode . turning now to fig3 , a system comparison of a mux driver versus an ipc driver is indicated generally by the reference numeral 3000 . a mux driver system 3001 includes a serial channel application 2730 for receiving data from a mux driver 2722 . the mux driver 2722 is in signal communication with a uart driver 3010 , which , in turn , is in signal communication with a uart 2742 . the mux driver 2722 includes a plurality of mux units 3021 , each in signal communication with a plurality of mux channels 3023 . the mux channels , in turn , are all in signal communication with a mux process 3022 , which is in signal communication with mux driver ( muxd ) control unit 3029 . an ipc driver system 3002 includes a serial channel application 230 for receiving data from an ipc driver 220 , both introduced in fig2 . the ipc driver 220 is in signal communication with a device driver 210 , which , in turn , is in signal communication with an ipc device 140 . here , the ipc device 140 may be an exemplary onedram ™, for example . the ipc driver 220 includes an ipc interface api 621 in signal communication with a plurality of ipc channels 623 , all as introduced in fig6 . the plurality of channels , in turn , are all in signal communication with an ipc thread 622 . the ipc driver 220 supports multiple channels , and its ipc interface api 621 is used in the upper layer to control the ipc channels . as introduced in the table 700 of fig7 , functions supported by the ipc interface api include ipcopen , ipcclose , ipcsend , ipcrecv , ipcloctl , and the like . thus , each ipc channel is configurable , and has a tx / rx message queue for buffering data . the ipc channel handles the data as packets . just one ipc thread manages all of the ipc channels . the ipc thread operations include sending messages , receiving messages , and interpreting ipc control commands . the onedram ™ device driver 210 provides interface functions to manage and control a onedram ™ ipc device 140 . as shown in fig3 , a method of flow control using receive buffer thresholds is indicated generally by the reference numeral 3100 . in flow control for a send suspend operation 31101 a receive ( rx ) queue 3112 contains a number of data packets that exceeds its suspend threshold 3114 . thus , in a function block 3118 , the ipc driver performs an enqueues the data , and transfers control to another function block 3116 . in the function block 3116 , the ipc driver sends a transmission suspend command to the transmit ( tx ) side . in flow control for a send resume operation 3120 , the receive queue 3122 contains a number of data packets that is less than a resume threshold 3124 . thus , in a function block 3128 , the ipc driver dequeues the data , and passes control to another function block 3126 . in the function block 3126 , the ipc driver sends a transmission resume command to the transmit side . the tx side may now transmit a new data packet 3130 to be received by the rx side . thus , the receive buffer queue threshold is used for flow control in the receive side &# 39 ; s ipc driver , which suspends the sending operation if the number of received packet buffers is greater than the rx queue suspend threshold , and sends the ‘ tx suspend ’ command to ipc driver on transmit side to make sure that the tx side does not send any more packets . the rx side &# 39 ; s ipc driver orders resumption of the sending operation if the number of received buffers is less than the rx queue resume threshold by sending the ‘ tx resume ’ command to tx side to permit the tx side to send more packets . turning to fig3 , a method for flow control example with send suspend is indicated generally by the reference numeral 3200 . in the method 3200 , the receive ( rx ) queue size is 6 , the transmit ( tx ) queue size is 3 , the rx suspend threshold is 3 , and the rx resume threshold is 2 . a semaphore value of 0x01 means that the application processor ( ap ) has ownership of the shared bank , while a semaphore value of 0x00 means that the modem has ownership of the shared bank . the mailbox format 1310 and commands 1350 are those of fig1 . here , the modem begins with a transmit side ipc channel or queue 824 containing three packets , and the application processor begins with a receive side ipc channel or queue 825 containing two packets . the initial semaphore bit value of 0x01 means that the ap currently has ownership . the modem writes an ownership request command to the first mailbox 922 on the ipc device . the ipc device sends a mailbox interrupt to the application processor . the ap , in turn , reads the ownership request command from the first mailbox . next , the ap writes an ownership release command to the second mailbox 923 , and writes a value of 0x00 to the semaphore bit 3226 , giving ownership to the modem . the modem reads the ownership release command from the second mailbox . next , the modem performs a burst write of all three packets to a channel 1200 of a shared bank on the ipc device , writes a transmit complete command to the first mailbox 922 , and writes a value of 0x01 to the semaphore bit 3226 , giving ownership to the ap . the ipc device sends a mailbox interrupt to the application processor the application processor reads the transmit complete command from the first mailbox 922 , and then reads all three data packets from the channel on the ipc device to the second processors receive side ipc channel or queue 825 . thus , the modem has transferred the three packets from its tx side ipc channel or queue 824 , while the ap has received the additional three packets into its rx side ipc channel or queue 825 , and has a total of five packets in the rx queue . in the meantime , the modem has generated two new packets in its tx queue 824 . however , the five packets in the ap &# 39 ; s rx queue exceeds its suspend threshold of three packets . thus , the ap issues a transmit suspend command to the second mailbox 923 , maintains ownership of the shared block and does not change the semaphore bit 3226 . the ipc device sends a mailbox interrupt to the modem , and the modem reads the tx suspend command from the ipc device . turning now to fig3 , a method of flow control with send resume is indicated generally by the reference numeral 3300 . the method 3300 picks up where the method 3200 of fig3 ends . here , the modem has two new data packets in its tx queue 824 . the application processor has reduced the number of packets in its rx queue 825 to one packet , which is less than its resume threshold of two packets . thus , the ap writes a tx resume command to the second mailbox 923 of the ipc device , and a value of 0x00 to the semaphore bit of the ipc device , transferring ownership to the modem . the ipc device , in turn , issues a mailboxinterrupt to the modem . the modem reads the tx resume command from the second mailbox 923 , sends its two data packets to the shared bank channel 1200 , writes a tx complete command to the first mailbox 922 , and writes a value of 0x01 to the semaphore bit , transferring ownership back to the ap . the ipc device issues a mailbox interrupt to the ap . the ap , in turn , receives the tx complete command from the first mailbox 922 , and receives the two new message packets from the shared bank channel 1200 , increasing the number of packets in its rx queue to three . thus , embodiments of the present disclosure feature multiple channels , efficient flow control , a minimized number of memory copy operations , and burst send and receive operations . a plurality of channels may be provided for two or more processors , and support multiple processes per processor . ipc drivers of the present disclosure use pointer operations rather than copy operations , and fully support burst transfer modes . for example , hsdpa requirements may be easily satisfied by embodiments using burst modes with a length of 20 packets . alternate embodiments are contemplated . for example , mailboxes and / or semaphores may be implemented in software rather than hardware . ownership of individual channels may be accomplished with additional semaphores and / or an increased number of bits per semaphore . in addition , parallel channel communications for transmit and receive channels with different ownerships can be implemented . although illustrative embodiments have been described herein with reference to the accompanying drawings , it is to be understood that the present disclosure is not limited to those precise embodiments , and that various other changes and modifications may be effected therein by those of ordinary skill in the pertinent art without departing from the scope or spirit of the present disclosure . all such changes and modifications are intended to be included within the scope of the present disclosure as set forth in the appended claims . | 6 |
fig1 a - 1 h represent the recombinant proteins of the invention , with the various letters indicating known protein sequences , as follows . the figs . are schematic diagrams of the recombinant t . cruzi proteins , comprised of segments a through l . solid segments ( a , c , d , f , h , i , and k ) represent nonrepetitive proteins having amino acid sequences that are unrelated to each other . saw - tooth segments ( b , e , g , j , and l ) represent repetitive proteins having amino acid sequences that are unrelated to each other and unrelated to those of the nonrepetitive proteins . the relative sizes and numbers of repeats in the repetitive proteins are roughly represented in the figs . the sizes and shapes of the nonrepetitive segments bear no relation to the actual proteins . the following information refers to fig1 and 1 a - 1 h in which the recombinant proteins ag15 , fp3 , fp4 , fp5 , fp6 , fp7 , fp8 , fp9 and fp10 are depicted schematically . these proteins are derived from t . cruzi , the protozoan parasite that causes chagas disease , and are formed from of proteins a through l as indicated , and defined herein . there are no substantive amino acid similarities among proteins a through l . similarly there are no substantive dna sequence similarities among the segments that encode proteins a through l . the t . cruzi dna sequences that encode proteins a through l were cloned in combination into pgex and pet plasmid vectors , such as pet - 32a . strains of escherichia coli were transfected with the recombinant vectors bearing the t . cruzi dna sequences , and the bacteria were incubated in liquid culture under conditions favoring synthesis of the recombinant proteins . the latter proteins were subsequently affinity - purified and then used as target antigens in elisas . elisas in which proteins ag15 , fp3 , fp4 , fp5 , fp6 , fp7 , fp8 , fp9 , and fp10 , alone or in combination are employed as target antigens are useful as sensitive and specific detectors of anti - t . cruzi antibodies in blood specimens obtained from persons who are chronically infected with this parasite . the detection of such antibodies is the primary means of identifying persons who are chronically infected with t . cruzi . the following paragraphs contain information relating to the naming , localization , and function of proteins a through l , as well as the corresponding genbank accession numbers of the sequences to which they are related and relevant publications . it should be noted that the t . cruzi gene segments that encode protein segments a through l generally are shortened versions of the native coding regions . in this context , the constructs that encode single segments ( i . e ., fp5 and fp9 ), as well as all the others that encode more than one segment , are all unique , because , even if the individual components from which the various recombinant proteins of this invention are known , the segments of the invention have not been combined previously as described herein . protein ab . this hybrid recombinant protein , also designated ag15 [ seq id no . 2 ] in fig1 , is derived from the tcr27 gene of t . cruzi [ seq id no . 1 ]. protein a is the amino terminal nonrepetitive portion of the tcr27 protein , and protein b is comprised of approximately 18 of the 14 amino acid repeats that make up the central portion of the tcr27 protein . the two native tcr27 genes sequenced contained approximately 69 and 105 of the 14 - amino acid repeats . nucleotide sequence data that include the ag15 dna sequence were deposited with genbank and embl databases by keiko otsu , john e . donelson , and louis v . kirchhoff with the accession number l04603 and are described in u . s . pat . no . 5 , 876 , 734 and no . 6 , 228 , 601 , issued to louis v . kirchhoff and keiko otsu ( each of which is herein incorporated by reference in its entirety ). these references also present dna and inferred protein sequences that include the ag15 dna and inferred protein sequences . the ag15 dna and inferred protein sequences are additionally presented in otsu k , donelson j e , kirchhoff l v . “ interruption of a trypanosoma cruzi gene encoding a protein containing 14 - amino acid repeats by targeted insertion of the neomycin phosphotransferase gene .” mol biochem parasitol 1993 ; 57 : 317 - 330 , herein incorporated by reference in its entirety . protein c . this is a calcium binding protein of t . cruzi , initially called 1f8 and later designated the flagellar calcium binding protein ( fcabp ) [ seq id no 4 ]. the accession number of the original 1f8 dna sequence [ seq id no 3 ] deposited in genbank is k03278 . the protein c dna and inferred protein sequences are presented in gonzalez a , lerner t j , huecas m , sosa - pineda b , nogueira n , lizardi p m . “ apparent generation of a segmented mrna from two separate tandem gene families in trypanosoma cruzi . ” nucleic acids res 1985 ; 13 ( 16 ): 5789 - 804 , herein incorporated by reference in its entirety . fig1 a shows a first protein ( fp3 ) [ seq id no . 22 ] in accordance with the invention . specifically , fp3 corresponds essentially to the combination of ag15 ( fig1 ), and by protein c . the dna sequence encoding fp3 [ seq id no 21 ], also essentially corresponds to the sequences coding for ag15 and protein c . protein d . this is the protein core of a surface glycoprotein of t . cruzi that is referred to as gp72 [ seq id no 6 ]. the accession number of the original gp72 dna sequence [ seq id no 5 ] deposited in genbank is m65021 . the protein d dna and inferred protein sequences are presented in cooper r , inverso j a , espinosa m , nogueira n , cross g a . “ characterization of a candidate gene for gp72 , an insect stage - specific antigen of trypanosoma cruzi . ” mol biochem parasitol 1991 ; 49 ( 1 ): 45 - 59 , herein incorporated by reference in its entirety . fig1 b shows a second protein ( fp4 ) [ seq id no 8 ] in accordance with the invention . the dna sequence [ seq id no 7 ] that encodes protein dabc which is a single continuous coding region , essentially corresponds to the dna sequences from which it was constructed . protein e . this is a segment of the flagellar repetitive protein ( fra ) [ seq id no 10 ] of t . cruzi comprised of approximately nine repeats consisting of 68 amino acids each , shown as fig1 c ( fp5 ). the accession number of the original protein e dna sequence [ seq id no 9 ] deposited in genbank is j04015 . the protein e dna and inferred protein sequences are presented in lafaille j j , linss j , krieger m a , souto - padron t , de souza w , goldenberg s . “ structure and expression of two trypanosoma cruzi genes encoding antigenic proteins bearing repetitive epitopes .” mol biochem parasitol 1989 ; 35 ( 2 ): 127 - 136 , herein incorporated by reference in its entirety . protein fgh . this is a protein [ seq id no 12 ] encoded by a modified version of the t . cruzi tcr39 gene that was artificially constructed [ seq id no 11 ], shown as fig1 e ( fp7 ). the modification entailed reducing the length of the central portion of the tcr39 gene that encodes the 12 - amino acid repeats . protein f is the amino terminal nonrepetitive segment of the tcr39 protein . protein g is comprised of approximately 13 of the 12 - amino acid repeats that make up the central portion of the tcr39 protein . protein h is the carboxy terminal nonrepetitive segment of the tcr39 protein . the accession number of the original , i . e ., the unmodified , protein fgh dna sequence deposited in genbank is u15616 . the tcr39 dna and inferred protein sequences , which include the entire protein fgh sequences , are presented in gruber a , zingales b . “ trypanosoma cruzi : characterization of two recombinant antigens with potential application in the diagnosis of chagas &# 39 ; disease .” exp parasitol 1993 ; 76 ( 1 ): 1 - 12 , herein incorporated by reference in its entirety . fig1 d shows another hybrid recombinant protein ( fp6 , protein fghe ) [ seq id no 14 ] in accordance with the invention . the dna sequence that encodes protein fghe [ seq id no 13 ], which is a single continuous coding region , essentially corresponds to the dna sequences from which it was constructed . protein ijk . this is a protein [ seq id no 16 ] encoded by a modified version of the t . cruzi shed acute phase antigen ( sapa ) gene that was artificially constructed [ seq id no 15 ], as shown in fig1 f ( fp8 ). the modification entailed reducing the length of the central portion of the sapa gene that consists of 12 - amino acid repeats . protein i is the amino terminal nonrepetitive segment of the sapa protein . protein j is comprised of approximately nine of the 12 - amino acid repeats that make up the central portion of the sapa protein . protein k is the carboxy terminal nonrepetitive segment of the sapa protein . the accession number of the original , i . e ., the unmodified , protein ijk dna sequence deposited in gen bank is j03985 . the sapa dna and protein sequences , which include the entire protein ijk sequences , are presented in affranchino j l , pollevick g d , frasch a c c . “ the expression of the major shed trypanosoma cruzi antigen results from the developmentally - regulated transcription of a small gene family .” febs lett 1991 ; 280 : 316 - 320 , herein incorporated by reference in its entirety . protein l . this is a microtubule - associated repetitive protein ( map ) [ seq id no 18 ] of t . cruzi that is comprised of approximately five repeats consisting of 38 amino acids each , as depicted in fig1 g ( fp9 ). the accession number of the original protein l dna sequence [ seq id no 17 ] deposited in genbank is s68286 . the protein l dna and inferred protein sequences are presented in kerner n , liegeard p , levin m j , hontebeyrie - joskowicz m . “ trypanosoma cruzi : antibodies to a map - like protein in chronic chagas &# 39 ; disease cross - react with mammalian cytoskeleton .” experimental parasitology 1991 ; 73 ( 4 ): 451 - 459 , herein incorporated by reference in its entirety . fig1 h shows another hybrid recombinant protein ( fp10 , protein ijkl ) [ seq id no 20 ] in accordance with the invention . the dna sequence that encodes protein ijkl [ seq id no 19 ], which is a single continuous coding region , essentially corresponds to the dna sequences from which it was constructed . additionally , combinations of the various recombinant proteins depicted in the figs . may be used . while it is possible to combine one or more of the recombinant proteins to form longer recombinant proteins , typically more than one recombinant protein is used simultaneously . for example , simultaneous uses of fp4 and fp5 , fp5 and fp6 , as well as fp4 and fp6 , and combinations using more than two recombinant proteins ( e . g ., fp4 , fp6 and fp10 ) are considered within the scope of the present invention . it is believed that the sensitivity and specificity of the assays according to the invention are sufficient to meet fda standards for screening the blood supply of the united states . additionally , as described in u . s . pat . no . 6 , 228 , 601 ( herein incorporated by reference in its entirety ), polypeptides need not correspond exactly over their entire lengths to be considered within the scope of the invention . for example , a wide variety of polypeptides which contain at least one epitope embodied in the polypeptides of the invention can be used in accordance with the present invention . based on the nucleotide sequences , polypeptide molecules also can be produced ( 1 ) that include sequence variations , relative to the naturally - occurring sequences , ( 2 ) that have one or more amino acids truncated from the naturally - occurring sequences and variations thereof , or ( 3 ) that contain the naturally - occurring sequences and variations thereof as part of a longer sequence . in this description , polypeptide molecules in categories ( 1 ), ( 2 ) and ( 3 ) are said to “ correspond ” to the amino acid sequences of the recombinant proteins of the invention . such polypeptides also are referred to as “ variants .” the category of variants within the present invention includes , for example , fragments and muteins of proteins a though l , as well as larger molecules that consist essentially at least one protein sequence a through l , alone or in combination with other proteins a to l . in this regard , a molecule that “ consists essentially of ” protein a to l , alone or in combination with any other proteins a to l , is one that is immunoreactive with samples from persons infected with t . cruzi , but that does not react with samples from patients with leishmaniasis , schistosomiasis , and other parasitic and infectious diseases , with samples from patients with autoimmune disorders and other illnesses , and with specimens from normal persons . a “ mutein ” is a polypeptide that is homologous to the protein to which it corresponds , and that retains the basic functional attribute — the ability to react selectively with samples from persons infected with t . cruzi — of the corresponding region . for purposes of this description , “ homology ” between two sequences connotes a likeness short of identity indicative of a derivation of the first sequence from the second . in particular , a polypeptide is “ homologous ” to the corresponding protein if a comparison of amino acid sequences between the polypeptide and the corresponding region reveals an identity of greater than 40 %, preferably greater than 50 % and more preferably 70 %. such sequence comparisons can be performed via known algorithms , such as those described in pearson w r , lipman d j . “ improved tools for biological sequence comparison .” proc natl acad sci usa 1988 ; 85 ( 8 ): 2444 - 2448 , herein incorporated by reference in its entirety , which are readily implemented by computer . a fragment of a protein of the invention is a molecule in which one or more amino acids are truncated from that protein . muteins and fragments can be produced , in accordance with the present invention , by known de novo synthesis techniques . also exemplary of variants within the present invention are molecules that are longer than a protein of the invention , but that contain the region or a mutein thereof within the longer sequence . for example , a variant may include a father fusion partner in addition to the protein of the invention . such a fusion partner may allow easier purification of recombinantly - produced polypeptides . for example , use of a glutathione - s - transferase ( 26 kilodaltons , gst ) fusion partner allows purification of recombinant polypeptides on glutathione agarose beads . the portion of the sequence of a such molecule other than that portion of the sequence corresponding to the region may or may not be homologous to the sequence of a protein of the invention . it will be appreciated that polypeptides shorter than the corresponding protein of the invention but that retain the ability to react selectively with samples from persons infected with t . cruzi are suitable for use in the present invention . thus , variants may be of the same length , longer than or shorter than the protein of the invention , and also include sequences in which there are amino acid substitutions of the parent sequence . these variants must retain the ability to react selectively with samples from persons infected with t . cruzi . in one embodiment , the assay of the invention uses fp4 as target antigen . table ii compares the results obtained by testing 45 pre - screened argentinean specimens in an table ii ripa + − fp4 elisa + 9 0 − 0 36 the data in table ii show that in this group of specimens , the sensitivity and specificity of the fp4 elisa were both 100 % similarly , the performance of an fp4 + fp6 elisa in comparison to rda was table iii ripa + − fp4 + fp6 elisa + 10 1 − 0 78 the data shown in table iii indicate that in this group of samples , the sensitivity of the fp4 + fp6 elisa was 100 % and the specificity was 98 . 7 %. as shown in fig2 , in a fp4 + fp6 elisa , performed using standard procedures , a group of previously characterized ripa - positive samples from several chagas - endemic countries gave a mean reactivity ( absorbance ) of 2 . 99 . thus fp4 + fp6 is the preferred embodiment among the recombinant proteins tested alone and in combination in that experiment . it should be apparent that embodiments other than those specifically described above may come within the spirit and scope of the present invention , such as recombinant proteins comprised of different combinations and / or spatial arrangements of proteins a to l . hence , the present invention is not limited by the above description . | 8 |
fig1 illustrates the principles in an embodiment of the present invention as seen from above . it comprises a workstation 1 preferably comprising a workstation table 2 and a platform 3 suitable for an operator to stand on when working at the workstation table 2 . the configuration of the workstation table and platform may be designed according to the work to be carried out at the workstation . the workstation of fig1 forms part of a food processing system comprising several such workstations , e . g . a so - called trim table , flowline or cut - up table , and possibly also other processing , pre - processing and post - processing stations , e . g . registration stations , initial cut - up stations , sorting stations , quality control stations , packing stations , etc . the kind of specific items being processed in a system according to the present invention is not essential and can comprise any kind of items which have to be individually processed during production , e . g . slaughtered animals , e . g . pigs , beeves , calves , fish , poultry , etc ., in any stage of processing , i . e . entire carcasses , half , quarter or smaller parts of carcasses , small parts ready for trimming , filleting or portion cutting , etc . the several workstations comprised by a food processing system need not be assigned for the same processing work , but are in fact according to the present invention preferably assigned so that one type of processing is performed at some workstations , and other types of processing is performed at other workstations . fig1 further illustrates a conveyor means 4 arranged to carry items 10 and processed items 11 , to , past and / or from the workstation . the conveyor means is illustrated as a conventional conveyor belt , on which items are lying while being transported in one , typical linear direction , but any suitable conveying means is within the scope of the present invention a computer system 8 keeps track of the items 10 and processed items 11 which are being transported by the conveyor means 4 . in particular , the computer system 8 should keep track of the sequential positioning of each item and processed item , but further information may be processed by the computer system , e . g . the exact physical positions of the items and processed items , characteristics of the items and processed items , e . g . weight , bone , fat and meat distribution , shape , quality , colour , etc ., predetermined or dynamically determined sorting , processing and packaging parameters associated with each item and processed item , traceability information , i . e . information about origin of each item and processed item to a certain , predetermined extent , e . g . the country of origin , the farm , the batch , the specific animal , etc . in order to improve the tracking of items on the conveyor means , suitable sensors may be provided along the conveyor means to monitor the precise positions of items , and / or a tachometer or other suitable device may be provided to monitor the real speed of the conveyor means . also cameras , scanners , tag readers , etc ., may be employed for tracking the items . in fig1 is as mentioned above illustrated using a conventional conveyor belt for conveying means 4 , and in that case a suitable device for unloading items comprises a sweeper arm 5 , preferably controlled by the computer system 8 . when the items should go past the workstation 1 , the sweeper arm 5 is lying stationary along the conveyor belt not interfering with the transportation of items . on the other hand , when an item should be unloaded to the workstation 1 , the sweeper arm 5 is rotated so as to extend over the full width of the conveyor means 4 as illustrated in fig1 and thereby bar the transportation of an item 10 , which is instead directed onto the workstation table 2 . as mentioned above , the items 10 may comprise any kind of food in any stage of processing . in a preferred embodiment , the items 10 comprise pieces of meat which have to be trimmed for excessive fat , and in order to comply with a predetermined weight range . the processing , e . g . cutting , trimming , filleting , shaping , etc ., performed at the workstation 1 typically results a processed item 11 and one or more pieces of waste or secondary processed items 14 , e . g . fat , meat with too much fat in it , or meat of lower quality . in some processes , e . g . simple cutting up of big meat chunks , the processing results in two or more processed items 11 , possibly with no waste or secondary processed items 14 . when the relevant processing has been carried out , the processed items 11 are returned to the conveyor means 4 . in the principle embodiment of fig1 no specific means for this return are shown , as any suitable means , including manual loading , is within the scope of the present invention . according to the present invention , when the system is started , the conveyor means 4 will typically only comprise items 10 that are not processed . after some time , when some items have been processed at the workstation 1 , the conveyor means 4 may comprise both non - processed items 10 and processed items 11 , and if some items are passing the workstation 1 on the conveyor means without being processed by that workstation , the conveyor means will comprise a mix of non - processed and processed items , or more accurately items which has been processed to different extents . for each item or processed item being returned to the conveyor means 4 from the workstation 1 a registration should be made in the computer system 8 to keep the register of items on the conveyor accurate at all times . apart from carrying on the further information that may be comprised in the computer system about that item before the processing , the registration can be made with any suitable detail , ranging from simply inserting an item reference number of the returned item between the two relevant items already on the conveyor , over updating existing information , e . g . about initial weight , shape , fat distribution , etc ., to adding new information about weight , shape , any trimming or cutting performed , further traceability information such as operator name , etc ., further processing parameters , etc . the registration in the computer system should also be able to handle when an item is cut into two or more processed items which all are returned to the conveyor , as opposed to the secondary processed items 14 or waste which is typically handled by other means , e . g . baskets or a separate , secondary conveyor . the registration in the computer system 8 about the return of a processed item to the conveyor can be made automatically , e . g . by a sensor monitoring any items being loaded onto the conveyor from the workstation 1 , or manually , e . g . by the operator pushing a button each time he returns an item to the conveyor . the return itself , i . e . the loading onto the conveyor , can also be performed either automatically or semi - automatically by means of a transverse transportation means , another sweeping arm , a robot gripper , a tray with computer controlled release mechanism , etc ., or it can be done manually or semi - automatically by having the operator simply laying the processed items on the conveyor or in a chute leading to the conveyor . fig2 illustrates a food processing system , e . g . a flowline or trim table , comprising several workstations 1 as the one described with reference to fig1 . as described above , each workstation 1 preferably comprises a workstation table 2 , a platform 3 for an operator 13 to stand on and a sweeper arm 5 . the workstations 1 are arranged on both sides along a conveyor means 4 . in the configuration of fig2 all workstations are illustrated as being substantially equally configured , and symmetrically located along the conveyor . it is noted , however , that any configurations , e . g . including different types of workstations for different processing tasks , or parts of the conveyor means 4 not being associated with any workstations , etc ., are within the scope of the present invention . moreover , the conveyor means 4 needs not be linearly arranged as in fig2 within the scope of the present invention . the sweeper arms 5 are each connected to a computer system 8 , which keep track of the items as described above , and is thereby able to control which items should be unloaded to which workstations at which times . in fig2 is illustrated each workstation being equipped with a computer registration device 9 e . g . for obtaining information about a return of a processed item to the conveyor means 4 as described above , and sending this information to the computer system 8 . the food processing system in fig2 further comprises an initial characteristics determining device 6 , e . g . comprising a short conveyor band arranged together with a scale to establish the weight of an item 10 being transported by the initial characteristics determining device . any suitable initial characteristics determining devices are within the scope of the present invention , e . g . scales , scanners , sensors , manual inspection , etc ., are within the scope of the invention , as well as any combinations thereof . the initial characteristics determining device 6 is connected to the computer system 8 , e . g . in order to establish the initial register of the sequence of items , preferably together with additional information , e . g . initial item weights , initial shapes , initial bone , fat and meat distributions , initial sizes , etc . instead of an initial characteristics determining device , the same information may be obtained from a pre - processing system , e . g . a sorting system , coarse cutting system , etc ., whereby the initial characteristics determining device can be dispensed with . the information available in the computer system when items 10 are provided to the conveyor means 4 should be sufficient to keep track of the sequence of items , but should in a preferred embodiment also keep track of associated weights , traceability information , planned processing steps , etc . in a food processing system where the workstations are configured for different processing , e . g . by different arrangements or different operators with different skills , the computer systems should preferably also have access to such information in order to control the allocation of items to the relevant workstations by means of the sweeper arms 5 or other distribution means . when the computer system knows both the sequence of items as well as the available processing means , i . e . differently configured workstations , it can plan the process most efficiently with respect to speed , quality , other aims , or compromises thereof . fig2 further illustrates a final characteristics determining device 7 arranged at the termination area a of the conveyor means 4 . the final characteristics determining device 7 may comprise any of the devices mentioned as suitable for the initial characteristics determining device 6 , but need not be the same in a specific configuration . the final characteristics determining device 7 is connected to the computer system 8 in order to obtain information about the items when they leave the processing system , e . g . information about final weights , final shapes , final distributions of bone , fat and meat , final colour , etc . this information may be used by the computer system 8 for comparing with the initial information obtained from the initial characteristics determining device 6 and from the computer registration device 9 . as the computer system 8 has been keeping track of the items during the processing , the computer system knows which item measured by the final characteristics determining device 7 compares to which item measure by the initial characteristics determining device 6 , and / or the computer registration devices 9 . this information is preferably used for yield control , i . e . determining how much each item has been decreased due to e . g . trimming , how accurate the processing has been performed , etc . this can be used for overall quality and efficiency measurements and improvements , as well as for specific operator quality and efficiency measurements . the information obtained by the final characteristics determining device 7 may further be used in post - processing tasks , e . g . packing , sorting , further processing , etc . for an embodiment of the present invention to work , basically only the keeping track of items &# 39 ; position in the sequence , taking into account items being “ out ” for processing at the different workstations is necessary . the initial characteristics determining device 6 or other means for obtaining information at earlier stages facilitates planning the allocation of items to relevant workstations , and / or instructions towards the specific processing needed for each item . the final characteristics determining device 7 or other means for obtaining information at subsequent stages facilitates yield control for efficiency and quality measurements , as well as planning subsequent stages . the computer registration devices 9 may be used instead of either the initial or the final characteristics determining devices 6 or 7 , or may be applied in addition thereto , to obtain even more detailed information , or to minimise the risk of item sequence errors . a particularly advantageous possibility facilitated by the present invention whereby processed items are returned to the same conveyor means 4 , is the possibility of allocating an already processed item 11 to a downstream workstation for even further processing . this concept is illustrated in fig2 where a processed item 11 is allocated to a workstation 1 and processed , resulting in a further processed item 12 , which is again returned to the conveyor means 4 . the conveyor means 4 may thus after a while be transporting items of different degrees of processing , but as every necessary information , e . g . the unloading and loading of items on the conveyor means is registered in the computer system , it is possible to keep track and always know which items are finished being processed , and which items need more processing . in principle , by arranging the conveyor means long enough or travelling slowly enough , it is possible to have as many separate processing steps as necessary . fig3 illustrates a workstation 1 according to an embodiment of the invention in more detail . it comprises a workstation table 2 and preferably a platform 3 . a conveyor means 4 transports items 10 and processed items 11 to , past and / or from the workstation 1 . the allocation of an item to the workstation is performed by means of a sweeper arm 5 controlled by a computer system . an item 10 may be allocated to the workstation , processed , e . g . by an operator , resulting in one or more processed items 11 and possibly waste and / or secondary processed items 14 . in a preferred embodiment one or more bins , chutes , trays , openings 18 or other means are provided for the operator to get rid of waste and / or secondary processed items 14 . in a preferred embodiment one or more secondary conveyors 19 are provided , preferably underneath the workstations , preferably parallel to the conveyor means 4 , for transporting waste and / or secondary processed items 14 away . in a preferred embodiment of the invention , a weight determining device 16 , e . g . corresponding to a computer registration device 9 described above with reference to fig2 , e . g . comprising a scale , is provided with a short conveyor band with a direction transverse to the direction of the conveyor means 4 . when a processed item 11 is placed on the weight determining device 16 , information about the processed item 11 can be obtained and transmitted to the computer system . as the computer system itself allocated the item for the workstation by means of the sweeper arm 5 , the computer system knows which processed item is on the scale . when the processed item 11 should be loaded onto the conveyor means 4 the short conveyor band transports it forward until it falls down on the transverse conveyor means 4 . the short conveyor of the scale 16 may be manually or automatically operated . if manually operated , a sensor or button should be used to inform the computer system about the exact time the processed item is returned to the conveyor means 4 . if automatically operated , the computer system because of its keeping track of the items knows when a suitable empty space is available on the conveyor means 4 , and drops the processed item 11 accordingly , and can in that case make the registration of the return automatically , or , in other words , the planning of when to drop the processed item on the conveyor means 4 can be seen as the registration of a return itself . in a preferred embodiment of the invention , a display , preferably with touch screen or buttons 17 is provided at each or some workstations . this display may be used for the computer system to show the operator instructions related to the processing , e . g . a text explaining how to cut or a graphical view of a certain cut , information about the current or next items to be processed , information about the calculated yield in terms of efficiency or quality , etc . the display may further comprise buttons either integrated in the display as a touch screen or provided somewhere else within reach of the operator , or other kind of input device , e . g . a keyboard , proximity sensors , infrared sensors , a bar code reader , rfid tag reader or chip reader , etc . thereby is facilitated that the operator can provide further information to the computer system . when no automatic loading of processed items is provided , the operator may use the buttons to signal to the computer system when a processed item is put on the conveyor means 4 . other use of the buttons may include signalling to the computer system that the item is discarded , i . e . that no processed item is available for return to the conveyor means 4 . in that case , the computer system should remove that item from the track keeping register . the operator may be enabled to signal to the computer system which kind cut - off he is making , i . e . waste , bones , fat , meat with excessive fat , etc . the operator may also be able to signal to the computer that he has parted a single item into two or more processed items , in which case the track keeping register should split the relevant one item into two or more . the operator may also be able to signal to the computer that further processing of a particular item is needed , or that he is not skilled to do the requested processing , or that he needs a break and the computer therefore should stop allocating items to his workstation . likewise is any further suitable use of communication between the workstations and the computer system within the scope of the present invention . in a preferred embodiment of the present invention , the workstation comprises a queuing means 15 for facilitating a queue of items to build up at the workstation without becoming a mess , and without the computer system loosing track of the item sequence . the queuing means preferably comprises a free rolling conveyor band or rollers without motor drive or braking means , whereby each new item delivered to the queuing means 15 by the sweeper arm 5 causes any existing items to be moved forward with very limited friction . thereby the items are not piling up or getting mixed and any fragile surfaces are not damaged . the length of the queuing means should correspond to the number of items which would possibly be queued at a workstation when taking into consideration the typical size of the items . it is noted that several of the above - mentioned features are not necessary for a simple form of the present invention to work and so is any combination of or leaving out in particular queuing means 15 , display 17 , openings 18 , secondary conveyor 19 , scale with conveyor 16 , etc ., within the scope of the present invention . fig4 illustrates an embodiment of the present invention as described above with reference to fig3 as seen from the side transverse to the direction of the conveyor means 4 , i . e . as seen from an operator &# 39 ; s point of view . due to clarity not all features of fig3 are shown . it shows a workstation table 2 , a sweeper arm 5 , a weight determining device 16 , preferably a scale with a conveyor band , and a display 17 . fig4 illustrates the relative vertical displacement and the vertical extents of the features of a preferred embodiment , though noting that any displacements and extents are within the scope of the present invention . the height of the above surface of the scale 16 is selected so that items will drop down onto the transverse conveyor means 4 . the vertical displacement of the display 17 should be selected for easiest use by the operator , and should preferably be adjustable or at least tiltable and pivotable . fig5 illustrates an embodiment of the present invention as described above with reference to fig3 and 4 as seen from the side parallel to the direction of the conveyor means 4 . due to clarity not all features of fig3 are shown . it shows workstation tables 2 on both sides of the conveyor means 4 , and sweeper arms 5 , weight determining devices 16 , and displays 17 associated with each workstation . fig5 further illustrates a possible location of the openings 18 for waste and / or secondary processed items and underlying secondary conveyors 19 . fig5 illustrates the relative vertical displacement and the vertical extents of the features of a preferred embodiment , though noting that any displacements and extents are within the scope of the present invention . the horizontal extent and displacement of the scale conveyor band 16 is selected so that the scale conveyor termination area b protrudes out over and above the conveyor means 4 so that items will drop down onto the conveyor means a suitable distance from the edge thereof . fig6 illustrates an example of a food processing system using the workstations 1 described above with reference to fig3 - 5 . as described above , each workstation 1 preferably comprises a workstation table 2 , a platform 3 for an operator 13 to stand on and a sweeper arm 5 . the workstations 1 are arranged on both sides along a conveyor means 4 . in the configuration of fig6 all workstations are illustrated as being substantially equally configured , and symmetrically located along the conveyor . it is noted , however , that any configurations , e . g . including different types of workstations for different processing tasks , or parts of the conveyor means 4 not being associated with any workstations , etc ., are within the scope of the present invention . moreover , the conveyor means 4 needs not be linearly arranged as in fig2 within the scope of the present invention . the sweeper arms 5 are each connected to a computer system 8 , which keep track of the items as described above , and is thereby able to control which items should be unloaded to which workstations at which times . the workstations in fig6 further comprise a queuing means 15 for receiving a number of items for processing , and one or more openings 18 preferably in connection with one or more secondary conveyors 19 for transporting waste and / or secondary processed items , e . g . fat , away from the workstations . further , the workstations comprise a scale 16 arranged with a conveyor as described above , and a display 17 , which preferably comprises means for input , e . g . a touch screen or buttons as described above . in fig6 is illustrated different locations of the displays 17 relative to the workstations 1 , and it is recognised that any suitable locations are within the scope of the present invention . the same applies to the general layout and configuration of the workstations , in that , even for workstations configured to perform the same processing tasks , the different elements may be placed different for various purposes . in fig6 the workstation layouts are mirrored by the conveyor means 4 in the centre so that operators on the left side of the conveyor means 4 have the queuing means at their right and work from right to left , whereas operators on the right side of the conveyor means have their queuing means to their left , thus working from left to right . other possibilities comprise having equal layout on both sides so that all operators work from left to right or vice versa , or laying the individual workstations out according to the wishes of the operators working there , or the obvious configuring workstations aimed at different processing tasks differently . in the embodiment of fig6 the scales 16 performs the act of obtaining information about a return of a processed item to the conveyor means 4 , and sending this information to the computer system 8 , preferably together with information about the new weight of the item enabling yield control . the food processing system in fig6 further comprises at the entrance of the conveyor means 4 an initial characteristics determining device 6 , e . g . comprising a short conveyor band arranged together with a scale to establish the weight of an item 10 being transported by the initial characteristics determining device . any suitable initial characteristics determining devices are within the scope of the present invention , e . g . scales , scanners , sensors , manual inspection , etc ., are within the scope of the invention , as well as any combinations thereof . the initial characteristics determining device 6 is connected to the computer system 8 , e . g . in order to establish the initial register of the sequence of items , preferably together with additional information , e . g . initial item weights , initial shapes , initial bone , fat and meat distributions , initial sizes , etc . instead of an initial characteristics determining device , the same information may be obtained from a pre - processing system , e . g . a sorting system , coarse cutting system , etc ., whereby the initial characteristics determining device can be dispensed with . the information available in the computer system when items 10 are provided to the conveyor means 4 should be sufficient to keep track of the sequence of items , but should in a preferred embodiment also keep track of associated weights , traceability information , planned processing steps , etc . in a food processing system where the workstations are configured for different processing , e . g . by different arrangements or different operators with different skills , the computer systems should preferably also have access to such information in order to control the allocation of items to the relevant workstations by means of the sweeper arms 5 or other distribution means . when the computer system knows both the sequence of items as well as the available processing means , i . e . differently configured workstations , it can plan the process most efficiently with respect to speed , quality , other aims , or compromises thereof . it is recognised that even though a final characteristics determining device arranged at the termination area of the conveyor means 4 is not shown in fig6 , the embodiment of fig6 could comprise such a final characteristics determining device as described above with reference to fig2 . in a preferred embodiment , however , the scale 16 or other weight determining device at each workstation 1 is sufficient for keeping track of the items and producing sufficient data for yield control and traceability , whereby a common scale at the end of the conveyor is not necessary . in fact the configuration of the embodiment of fig6 having a scale at each workstations offers better yield control , as data can be obtained for each individual operator and / or processing task , even when exploiting the possibility of performing multiple processing tasks on the same item at the same conveyor , which is only enabled by the present invention . fig7 depicts some details of an embodiment of the present invention in general according to the embodiment illustrated in fig3 - 6 . it shows approximately the half width of a workstation table 2 comprising a sweeper arm 5 and a queuing means 15 configured with a free rolling conveyor band as described above . at each side , parts of scales with conveyors 16 are visible , and to the left a part of a display 17 is visible . behind the sweeper arm 5 can be seen the conveyor means 4 , and opposite sweeper arm and scales . in the embodiment of fig7 the conveyor means 4 , the queuing means 15 and the workstation tables 2 are all at substantially the same vertical level , which is preferred , but differentiations are also within the scope of the invention . fig8 depicts further details of an embodiment of the present invention in general according to the embodiment illustrated in fig3 - 6 . it shows approximately the half width of a workstation table 2 comprising a scale with conveyor 16 , a display 17 and an opening 18 for dismissing waste and / or secondary processed items such as fat . at the sides can be seen parts of sweeper arms 5 and queuing means 15 , as well as the conveyor means 4 . in the embodiment of fig8 the display 17 comprises a touch screen display which enables programmatically providing relevant input functions , e . g . buttons , keyboard , etc ., but it additionally comprises real buttons , too , e . g . for input functions which should definitely always work . as seen , the vertical level of the scale conveyor 16 is above the conveyor means 4 , thereby enabling items to be dropped down on the conveyor means 4 for improved handing over . the conveyor 16 is horizontal so that it is also raised above the level of the workstation table 2 in the embodiment of fig8 . it is noted , however , that any other suitable configurations of scale and conveyor 16 are within the scope of the present invention , e . g . having the conveyor 16 slope from table level to the advanced level above the conveyor means 4 . fig9 is an overview of an entire workstation as described in detail above with reference to fig7 and 8 , comprising the same features . in fig9 can also bee seen part of a secondary conveyor means 19 running beneath the workstation table 2 for transporting away secondary processed items which the operator dumps through the opening 18 . fig9 also implies that the displays can be tilted and turned to best suit the individual operating the workstation . fig1 is an overview of a food processing system comprising several of the workstations described in detail above with reference to fig7 - 9 . the food processing system is depicted from the entrance end of the conveyor means 4 , where also an initial characteristics determining device 6 is illustrated . along the conveyor means 4 , several workstations as described above are located on both sides . in fig1 is clearly seen the end of a secondary conveyor means 19 for transporting away secondary processed items or waste . a computer system 20 is also shown in connection with the initial characteristics determining device 6 . this computer system may be the central computer system referred to by numeral 8 in the above description , which controls the food processing system , but it can also merely comprise a display connected to the main computer system for displaying important information to a supervisor or control person , or simply the current status of the processing system or any other relevant information obtainable , e . g . yield figures , etc . the display , whether acting as main computer system 8 or simply as an input / output device , may also be used for planning the current and future batches or processing tasks , input information about the current operators and workstation configurations , etc ., thereby facilitating better allocation of items for processing at the most relevant workstations . the initial characteristics determining device 6 is in the embodiment of the fig1 of a type corresponding to the weight determining devices 16 at each workstation , however with a conveyor configuration specifically suited for the position at the entrance , handling every single item of the batch . as described above , any suitable initial characteristics determining device is within the scope of the present invention , e . g . scanners , sensors , etc . fig1 is a look along the conveyor means 4 from the initial characteristics determining device 6 showing workstations on both sides . this view clearly illustrates the protrusion of the scale conveyors 16 out over the conveyor means 4 enabling processed items to be dropped on the conveyor means 4 a certain distance d from the edge of the conveyor means . it is recognised that in addition to the embodiments shown in the drawings , several other configurations are within the scope of the present invention , including any combinations of the above described features and embodiments . | 1 |
the process for the production of a synthesis gas and / or hydrogen by the partial oxidation in a membrane wall gasification reactor of a feedstream comprising the heavy residue bottoms consisting of a solid heterogeneous catalyst recovered from a slurry hydrocracking process will be described with reference to the drawing . in general , the integrated process and apparatus for gasification of a feedstream comprising the heavy residue bottoms and solid catalyst from a slurry hydrocracking process includes a slurry hydrocracking zone in which a heavy hydrocarbon feedstock is converted to light fractions , a separation zone in which slurry hydrocracking zone effluent is separated into converted products and heavy residue bottoms , a membrane wall gasification reactor in which the heavy residue bottoms are partially oxidized to produce hydrogen and carbon monoxide as a hot raw synthesis gas and a slag material , a steam - generating heat exchanger to cool the hot raw synthesis gas , and a turbine to produce electricity from the steam generated . in accordance with one or more additional embodiments , a process and apparatus for gasification of the slurry hydrocracking process heavy residue bottoms and solid catalyst further includes a water - gas shift reaction vessel to convert carbon monoxide to hydrogen through the water - gas shift reaction represented by co + h 2 o → co 2 + h 2 , to thereby increase the volume of hydrogen in the shifted synthesis gas . a heavy residue bottoms gasification apparatus 10 includes a slurry hydrocracking zone 20 , a separation zone 30 , a membrane wall gasification reactor 40 , a heat exchanger 50 , a turbine 60 and a water - gas shift reaction vessel 70 . note that while the embodiment of apparatus 10 described herein includes a water - gas shift reaction vessel to enhance the output of hydrogen by conversion of some or all of the carbon monoxide in the synthesis gas , alternative embodiments similar to apparatus 10 can be practiced without the water - gas shift reaction vessel . slurry hydrocracking zone 20 includes an inlet 18 in fluid communication with a conduit 14 for receiving heavy hydrocarbon feedstock , a conduit 12 for introducing a stream of pressurized hydrogen or a hydrogen - containing gas , and a conduit 16 for introducing a solid heterogeneous catalyst into zone 20 . slurry hydrocracking zone 20 also includes an outlet 22 for discharging slurry hydrocracking zone effluent . separation zone 30 includes an inlet 24 in fluid communication with outlet 22 of the slurry hydrocracking zone 20 , an outlet 26 for discharging converted products and an outlet 28 for discharging the remaining slurry of solid catalyst and heavy residue bottoms . membrane wall gasification reactor 40 includes an inlet 32 in fluid communication with outlet 28 of the separation zone 30 , a conduit 36 for introducing a controlled amount of a pressurized stream of oxygen or an oxygen - containing gas , and a conduit 38 for introducing a controlled amount of steam . membrane wall gasification reactor 40 also includes an outlet 42 for discharging hot raw synthesis gas and an outlet 34 for discharging slag material . heat exchanger 50 includes an inlet 44 in fluid communication with outlet 42 of the membrane wall gasification reactor 40 , an outlet 46 for discharging steam , and an outlet 48 for discharging cooled synthesis gas . outlet 46 is in fluid communication with a three - way control valve 52 to withdraw steam via a conduit 54 and / or to convey steam to the turbine 60 . outlet 48 is in fluid communication with another three - way control valve 62 to withdraw cooled synthesis gas via a conduit 64 and / or , optionally , to convey cooled synthesis gas to the water - gas shift reaction vessel 70 . turbine 60 includes an inlet 56 in fluid communication with the three - way control valve 52 and an electrical conductor 58 for transmitting the electricity generated . the optional water - gas shift reaction vessel 70 includes an inlet 68 in fluid communication with the three - way control valve 62 for receiving cooled synthesis gas and a conduit 66 for introducing a controlled amount of steam , and an outlet 72 for discharging the hydrogen rich shifted synthesis gas product . in certain embodiments , outlet 72 is in fluid communication with conduit 12 via a conduit 74 to return a portion of the hydrogen to the slurry hydrocracking zone 20 . in the practice of the method of the invention , a heavy hydrocarbon feed is introduced as a pressurized feedstream via conduit 14 with a predetermined amount of hydrogen or a hydrogen - containing gas via conduit 12 and solid heterogeneous catalyst via conduit 16 into inlet 18 of the slurry hydrocracking zone 20 . the heavy hydrocarbon feed is thermally cracked in the slurry hydrocracking zone 20 to produce light hydrocarbons , such as naphtha and diesel . the slurry hydrocracking zone effluent is discharged via outlet 22 and passed to inlet 24 of the separation zone 30 in which the effluent is separated into converted product discharged via outlet 26 and the heavy residue bottoms containing the solid catalyst is discharged via outlet 28 . the slurry hydrocracking heavy residue is optionally introduced into storage vessel 35 where it can be accumulated over time , if necessary , to assure a continuous feedstream for the gasification reactor , or for mixing as recycle with fresh feed to form the slurry . in certain embodiments , at least a portion of the solid heterogeneous catalyst contained in the slurry hydrocracking heavy residue is optionally recycled back to the slurry hydrocracking zone 20 after the catalyst separation step ( not shown in the figure ). a flowable slurry of the heavy residue bottoms and solid catalyst is introduced as a pressurized feedstock via inlet 32 into the membrane wall gasification reactor 40 along with a predetermined amount of oxygen or an oxygen - containing gas via conduit 36 and a predetermined amount of steam via conduit 38 . the heavy residue bottoms containing the solid catalyst are partially oxidized in the membrane wall gasification reactor 40 to produce hydrogen , carbon monoxide and a slag material . as will be understood by those of ordinary skill in the art , the viscosity and therefore the pumpability of the mixture of the heavy bottoms and solid catalyst mixture from the separator can be affected by various factors , including the nature of the original feedstream , the extent of recycled materials present and the physical characteristics of the catalyst ( s ) used in the slurry hydrocracking process . if the physical state of the heavy bottoms and catalyst mixture is solid to viscous , or a semi - solid liquid , it can be heated to a temperature and / or the pressure raised to render it sufficiently fluid to be pumped . the temperature can range from 25 ° c . to 200 ° c . and the pressure from one bar to 100 bars . the slurry can be introduced into the gasifier reactor alone , or as a suspension using a carrier fluid , such as air , nitrogen , carbon dioxide , carbon monoxide , syngas , hydrogen , steam , nitrogen - free gas , low - oxygen gas , oxygen - free gas , and / or a combination of these carrier fluids . in addition , intermediate refinery streams such as cycle oils from an fcc process can be used as a carrier fluid for the mixture of heavy bottoms and catalyst material . in another embodiment where the mixture is a solid at ambient temperature , it can be dried and pulverized by an appropriate milling or crushing apparatus , such as one or a series of ball mills , to produce a flowable solid . it can then be introduced into the gasifier using a conventional solid feed apparatus or with a carrier fluid . in a further embodiment where the slurry hydrocracking zone 20 is remote from the gasification reactor 40 , e . g ., in another facility , heavy residue bottoms collected in the storage vessel 35 can be dried to pellets by standard methods for easy handling . hydrogen and carbon monoxide are discharged from outlet 42 of the membrane wall gasification reactor 40 as hot raw synthesis gas and passed to inlet 44 of the heat exchanger 50 to cool the hot raw synthesis gas . the slag material , which is the final waste product resulting from the formation of ash from the solid catalyst and its condensation on the membrane walls of gasification reactor 40 , are discharged via outlet 34 . the slag material is optionally recycled via line 34 to the slurry hydrocracking zone 20 to minimize the usage of fresh catalyst after specific material quality treatments such as removal of dust , grinding and sulfiding . the slag material is also optionally recycled back to the gasification reactor 40 ( not shown ) to increase the content of solid ash - forming materials . this is especially beneficial when the minimum requirement for solid materials in the gasification reactor 40 is not provided by the heavy residue bottoms recovered from the separation zone 30 . cooled synthesis gas is discharged via outlet 48 and can be withdrawn via the three - way control valve 62 and conduit 64 for use in other downstream processes . steam discharged from outlet 46 of the heat exchanger 50 can be withdrawn via the three - way control valve 52 and conduit 54 and / or passed to inlet 56 of turbine 60 to produce electricity that is transmitted via conductor outlet 58 . in certain embodiments , at least a portion of the cooled synthesis gas is conveyed to inlet 68 of the water - gas shift reaction vessel 70 with steam introduced via conduit 66 . steam for the water - gas shift reaction can be provided by conduit 54 from the steam - generating heat exchanger 50 . carbon monoxide is converted to hydrogen in the presence of steam through the water - gas shift reaction represented by co + h 2 o → co 2 + h 2 . the content of carbon monoxide is reduced to less than 1 mole % after the water - gas shift reaction . a mixture of hydrogen , carbon dioxide , unreacted carbon monoxide and other impurities is discharged via outlet 72 as shifted synthesis gas . high purity hydrogen gas is optionally recovered by a process such as pressure swing adsorption ( psa ), or by use of membranes , absorption , adsorption , or a combination thereof . the feedstocks for the slurry hydrocracking process described herein are heavy hydrocarbon feedstocks derived from natural sources including crude oil , bitumen , tar sands and shale oils , or from refinery processes including atmospheric or vacuum residue , or products from coking , visbreaker and fluid catalytic cracking operations . the heavy hydrocarbon feedstock has boiling point in the range of about 400 ° c . to about 2000 ° c . the slurry hydrocracking zone consists of one or more plug - flow type tubular reactors operating in the up or down flow modes . in general , the operating conditions for the slurry hydrocracking zone include : a temperature in the range of from 350 ° c . to 650 ° c ., in certain embodiments 425 ° c . to 540 ° c ., in other embodiments 450 ° c . to 510 ° c ., and in further embodiments 470 ° c . to 500 ° c . ; a hydrogen partial pressure in the range of from 20 bars to 200 bars , in certain embodiments 40 bars to 180 bars , and in further embodiments 60 bars to 150 bars ; a liquid hourly space velocity of about 0 . 1 h − 1 to about 10 h − 1 , in certain embodiments 0 . 1 h − 1 to about 4 h − 1 , and in further embodiments 0 . 1 h − 1 to about 2 h 1 ; a hydrogen feed rate of up to about 3000 liters of hydrogen ( normalized ) per liter of oil ( l / l ), in certain embodiments 500 l / l to 2000 l / l , and in further embodiments 500 l / l to 1000 l / l . the solid heterogeneous catalyst used in the slurry hydrocracking zone can include one or more catalytically active metal components selected from groups vib , vb , viib , viib , or viii of the periodic table , such as iron , nickel , molybdenum , vanadium , tungsten , cobalt , ruthenium , and mixture thereof . the catalytically active metal may be present as a solid particle in elemental form or as a metal compound . solid particle can be produced from nanoaggregates of the metal or metal compounds , or from a catalyst precursor such as a metal sulfate . catalyst precursor decomposes or reacts in the slurry hydrocracking zone or in a pretreatment step ( not shown ) to form the desired , well - dispersed and catalytically active solid particle . precursors can also include oil - soluble organometallic compounds containing the catalytically active metal that thermally decomposes to form a solid particle having catalytic activity . other suitable precursors include metal oxides that can be converted to catalytically active metal sulfides . in a particular embodiment , a metal oxide containing a mineral can be used as a precursor on an inorganic refractory metal oxide support . for example , bauxite is a particular precursor in which conversion of iron oxide crystals contained in this mineral provides an iron sulfide catalyst as a solid particle , where the iron sulfide after conversion is supported on the alumina that is predominantly present in the bauxite precursor . in general , the operating conditions for the membrane wall gasification reactor include a temperature in the range of from 1200 ° c . to 1800 ° c . ; a pressure in the range of from 30 bars to 100 bars ; a mole ratio of oxygen - to - carbon content of the feedstock in the range of from 1 : 1 to 5 : 1 ; a mole ratio of steam - to - carbon content of the feedstock in the range of from 0 . 1 : 1 to 10 : 1 . the properties of the synthesis gas subjected to the water - gas shift reaction are a temperature in the range of from 150 ° c . to 400 ° c . ; a pressure in the range of from 1 bar to 60 bars ; and a mole ratio of water - to - carbon monoxide in the range of from 5 : 1 to 3 : 1 . distinct advantages are offered by the apparatus and processes described herein when compared to other disposal methods for heavy residue bottoms and spent catalysts containing sulfur , nitrogen and / or organo - metal compounds that are recovered from a slurry hydrocracking process . valuable synthesis gas and / or hydrogen gas , process steam and electricity can be efficiently produced for on - site refinery use . the integrated process of the invention can be practiced to particular advantage when hydrogen is needed for hydroprocessing and natural gas is not available . this is usually the case in refineries when full conversion is required to meet the demand for cleaner and lighter products , such as gasoline , jet fuel , and diesel transportation fuels . a 100 kg sample of vacuum residue boiling above 520 ° c . derived from arab heavy crude oil was introduced as a pressurized feedstock into a slurry hydrocracking zone . the vacuum residue had an api gravity of 5 . 7 degrees and contained 5 . 3 w % of sulfur , 0 . 45 w % of nitrogen , 19 . 5 w % of c 7 - asphaltenes , 22 . 9 w % of ccr and 222 ppmw combined of nickel and vanadium . the slurry hydrocracking zone was operated at 420 ° c ., 160 bars and liquid hourly space velocity of 0 . 5 h 1 . the catalyst was molybdenum sulfide on a solid support . the slurry hydrocracking conversion of vacuum residue was 85 w % and the resultant process yields are summarized in table 1 below . the total hydrogen consumption was 1 . 6 w % of the feedstock processes . after the separation of converted products , the heavy residue and spent catalyst were conveyed to a membrane wall gasification reactor . the gasification reactor was operated at 1045 ° c . and 28 bars . the ratio of steam - to - carbon was 0 . 6 : 1 by weight . the ratio of oxygen - to - carbon was 1 : 1 by weight . heavy residue bottoms were partially oxidized to produce hydrogen , carbon monoxide and a slag material . hydrogen and carbon monoxide were recovered as a hot raw synthesis gas and passed to a heat exchanger . the cooled raw synthesis gas was sent to a water - gas shift reaction vessel to increase the hydrogen yield . the water - gas shift reaction was conducted at 318 ° c . and 1 bar . the mole ratio of steam - to - carbon monoxide is 3 : 1 . the product yields are summarized in table 2 . as can be seen from a comparison of the data from tables 1 and 2 , 100 kg of vacuum residue produced 8 . 7 kg of light gases , 57 . 6 kg of distillates ( naphtha , gas oil and vacuum gas oil ) and 35 . 3 kg of pitch , from which 9 . 6 kg of hydrogen gas was produced from gasification . the method and system of the present invention have been described above and in the attached drawing ; however , modifications derived from this description will be apparent to those of ordinary skill in the art and the scope of protection for the invention is to be determined by the claims that follow . | 8 |
all of the preferred embodiments explained below can be used for animals , humans , plants or for any living organism referring now to fig1 there is shown one embodiment of the present invention which is of general use for living organisms . the led unit 1 has a generally box shaped housing 2 with a plurality of led &# 39 ; s 3 arranged in an array of rows and columns . there is an electrical connection 4 near the bottom of the housing 2 leading to a control box 5 which will be explained later . the approximate dimensions of led unit 1 are 7 . 4 × 4 . 7 × 1 . 3 inches ( these dimensions are not critical and may vary ). the physical spatial arrangement of the led &# 39 ; s are shown in fig1 a where the red emitting led &# 39 ; s are designated by r in the circles , the ir emitting led &# 39 ; s are designated by i in the circles and the blue emitting led &# 39 ; s are designated by b in the circles . there are 48 led &# 39 ; s in all , 24 led &# 39 ; s emitting red light at 630 nm , 12 led &# 39 ; s emitting infrared ( ir ) light at 880 nm , and 12 led &# 39 ; s emitting blue light at 470 nm . the led array has 6 columns of led &# 39 ; s and 8 rows of led &# 39 ; s . in the first column of the led array , starting with a red emitting led , the red emitting led appears at every other one with a blue emitting led inbetween ; thus , there are four red emitting led &# 39 ; s and four blue emitting led &# 39 ; s . in the second column of the led array , starting with an ir led , there appears an ir led at every other one with a red emitting led inbetween ; thus , there are four ir led &# 39 ; s and four red emitting led &# 39 ; s . in the third column of the led array , starting with a red emitting led , there appears a red emitting led at every other one with an ir led inbetween ; thus , there are four red emitting led &# 39 ; s and four ir led &# 39 ; s . in the fourth column of the led array , starting with a blue emitting led , there appears a blue emitting led at every other one with a red emitting led inbetween ; thus , there are four blue emitting led &# 39 ; s and four red emitting led &# 39 ; s . the fifth column arrangement of led &# 39 ; s is similar to the first column arrangement of led &# 39 ; s and the sixth or last column arrangement of led &# 39 ; s is similar to the second column arrangement of led &# 39 ; s . the number of led &# 39 ; s in the array and , consequently , the size of the housing 2 may vary depending on the particular application . the red , blue and ir light emitting led &# 39 ; s , as well as their availability , are well known in the art and , therefore , are not explained further . referring now to fig2 there is shown a control box 5 which is electrically connected to led unit 1 ( shown in fig1 ) via an electrical connection 6 . the control box 4 contains circuitry therein and has several control knobs for controlling various aspects of the led array . the circuitry and functions of the control knobs will be explained later . [ 0058 ] fig3 shows a portable , hand held model 7 of the present invention . the hand held model 7 has a frusto - conical shaped housing 8 with a disk shaped support 9 for a plurality of led &# 39 ; s 10 arranged in a patterned array . attached to the housing 8 is a handle 11 and a control knob 12 . the handle 11 has an on / off switch 13 and an electrical connection 14 which is connected to a control box 15 . this hand held model 7 is also provided with an electrical ac plug - in connector 16 for the control box 15 . the led support 9 contains 184 led &# 39 ; s arranged in a particular pattern . the patterned array contains 119 red emitting led &# 39 ; s , 40 ir emitting led &# 39 ; s and 25 blue emitting led &# 39 ; s . the particular physical spatial arrangement of led &# 39 ; s is shown in fig3 a where the red emitting led &# 39 ; s are designated by r in the circles , the blue emitting led &# 39 ; s are designated by b in the circles and the ir emitting led &# 39 ; s are designated by 1 in the circles . the support disk 9 has a diameter of approximately 8 inches and the length of the handle 11 is approximately 5 and ⅞ inches ( these dimensions are not critical and may vary ). [ 0059 ] fig4 shows yet a further embodiment of the present invention . a photo - therapy device 17 takes the form of a wall panel 18 . the wall panel 18 has dimensions of 3 feet by 6 feet by 3 inches ; however , the size of the wall panel 18 may vary depending on the size of the subject or object being treated . the wall panel 18 has 24 led &# 39 ; s 19 in each column along its smaller dimension of 3 feet and 48 led &# 39 ; s in each row along its larger dimension of 6 feet . there are a total of 1 , 152 led &# 39 ; s in the wall panel 18 ; 230 led &# 39 ; s emitting red light at 630 nm , 230 led &# 39 ; s emitting ir light at 880 nm , 231 led &# 39 ; s emitting blue light at 470 nm , 231 led &# 39 ; s emitting green light at 565 nm and 230 led &# 39 ; s emitting amber light at 590 nm . each led emitting in a particular color ( wavelength ) would alternate in a repeated pattern , for example , blue , green , amber , red , ir ( repeat , etc .). the led &# 39 ; s 19 in the wall panel 18 are connected to the control box 20 with its control knobs . the wall panel 18 if attached to a wall at an appropriate height and a person , animal or plant would be positioned in front of it for treatment . the subject of the photo - therapy treatment is positioned in front of the wall panel 18 for an appropriate amount of time at a distance from close proximity to several feet . for example , a wall panel 18 is hung on each side of a horse trailer ( inside ) and a horse placed between the wall panels 18 for treatment . another example , a bull rider or horseback rider who is in need of treatment stands between the wall panels 18 in the horse trailer or in a similar enclosure at a competitive event and is treated for relaxation , pain relief or healing . plants could also be placed in a room with a wall panel 18 on each side of the room and be treated by the light generating from the led &# 39 ; s of the wall panels in order to obtain faster and stronger plant growth . referring now to fig5 there is shown another embodiment of a photo - therapy device of the present invention which is used primarily for humans . the photo - therapy device takes the form of a full body bed 22 with a hollow enclosure 23 and a lid 24 and led &# 39 ; s embedded within the hollow enclosure 23 and lid 24 . the full body bed 22 has the following dimensions : 3 feet wide , 6 ½ feet long and a 20 inch depth ; obviously , these dimensions could vary . a control box ( not shown ) is built into the front side of the hollow enclosure 23 and control knobs 26 are connected to the control box . an electrical cord 27 will connect the control box to an electrical outlet or generator . there are a total of 2 , 304 led &# 39 ; s inside the full body bed 22 with 1 , 152 led &# 39 ; s on the inside of the lid 24 and 1 , 152 led &# 39 ; s on the inside floor of the hollow enclosure 23 . on the inside of the lid 24 , there are 230 led &# 39 ; s emitting red light at 630 nm , 230 led &# 39 ; s emitting ir light at 880 nm , 231 led &# 39 ; s emitting blue light at 479 nm , 565 led &# 39 ; s emitting green light at 565 nm and 230 led &# 39 ; s emitting amber light at 590 nm . the numbers of specific led &# 39 ; s emitting in a particular wavelength on the inside of the hollow enclosure 23 are the same as those on the inside of the lid 24 . each led for a given wavelength alternates in a repeated pattern , for example , blue , green , amber , red and ir . a person for treatment would lie down in the full body bed 22 , face up , with the lid 24 partially closed ; the photo - therapy treatment would provide a relaxation effect , pain reduction or healing of the person . this embodiment of the invention could also be used in a hospital or nursing home for the treatment of bedsores or it can be combined with piped - in music and thus produce a “ wave effect ” for deep relaxation or pain relief after an operation . it could also be used to stimulate the immune system of a human with a disease such as cancer , etc . fig5 shows the full body bed 22 with the lid 24 in the fully open position whereas fig5 a shows a patient 28 lying within the full body bed 22 for treatment with the lid 24 being partially closed . [ 0061 ] fig6 shows an application of the hand held model 7 of the present photo - therapy device being applied in close proximity to a small body area of a patient p being treated whereas fig6 b shows the photo - therapy device being applied to a larger body area of a patient p being treated , the latter application demonstrating a diffusion effect of the device . [ 0062 ] fig7 and 7 a are circuit diagrams showing how the led &# 39 ; s of the various embodiments of this invention are connected to a control box with control knobs for controlling or regulating the operation of the led arrays in the various embodiments . the circuit diagrams show the general scheme of a photo - therapy device of this invention that is designed to provide a luminous pattern for a specific therapeutic application . the geometric pattern and color ( s ) of the led array , the frequency and duty cycle of the led array and the total time of operation of the photo - therapy device can be varied to satisfy the requirements of an intended therapeutic application . for example , fig7 shows a circuit diagram for a photo - therapy device of the present invention which operates three different light source types ( led 1 , led 2 and led 3 ) each of which is energized independently by a processor 29 ( or microprocessor ) via a switch network 30 . the series strings of a particular light source type ( led 1 , led 2 and led 3 ) are divided into two groups , a and b , as shown in the circuit diagram . each group a and b of series light strings will normally be switched on and off in an alternate fashion to minimize the maximum power requirements of the system . each series of light strings a and b is energized by a constant current source 31 that insures proper operation of the photo - therapy device under varying conditions of temperature and supply voltage . in some therapeutic applications , the value of the constant current can be modified under the control of the processor 29 to conform to a custom pattern . the processor operation is controlled by the operator of the photo - therapy device by the setting of the control switch positions for time , frequency , pattern and custom . the time control switch will set the desired period of operation , the frequency control switch will set the alternating on / off rate between the a and b groups of light strings , the pattern control switch will directly select which light source type ( s ) ( led 1 , led 2 or led 3 ) to be energized or will select the custom mode of operation , and the custom control switch will select which pattern from the pattern memory module 32 that the processor 29 is to perform in this mode , the processor 29 can vary the time , frequency , power level and light source strings in any prearranged ( programmed ) sequence . for example , the processor 29 can be preprogrammed to provide the following patterns of illumination : a ) each color set on individually , b ) all color sets on simultaneously , c ) at least two color sets on simultaneously and d ) at least two color sets on for preset periods of time . the processor 29 may also be programmed to sequentially pulse the led sets of the photo - therapy device to emit light of different colors . the control circuit may also be adjusted for pulsed operation of at least two sets of led &# 39 ; s with pulse durations of in the range of from about 0 . 001 sec . to about 0 . 2 sec . and pulse repetition rates in the range of from about 4 hz to about 10 , 000 hz . the pulse duration may be approximately half the period of each cycle . the processor 29 can also provide indications of low battery level and an elapsed time of operation in the form of a lamp and , if enabled , an audible beep . for an indication of the elapsed time of operation , the treatment timer may be connected to a visual or audio means for indicating the remaining treatment time . although the means for indicating low battery level and elapsed time of operation are not shown , the addition of such means to the circuitry and equipment of the present invention would be obvious to one skilled in the art and is , therefore , not detailed here . the operation of each of the photo - therapy devices disclosed herein is started by depressing the start / stop push button 33 shown schematically in fig7 and a second depression of the pushbutton 33 will stop the operation independently of the time setting . typical applications of the photo - therapy devices described above do not preclude the use of keyboards for operator input , alternate displays for status information or the use of an external computer for control of the operation of the devices . the block diagram of fig7 shows the use of light emitting diodes ( led &# 39 ; s ) which operate over the application - specific spectrum . however , the general scheme is not limited to led &# 39 ; s but other light sources may be used such as incandescent lamps . the light sources are shown in a series connection to improve electrical efficiency . light sources of the same or different colors may be grouped as required for a particular application ,. light sources for the photo - therapy devices of this invention may include both the visible and invisible portions of the frequency spectrum . although fig7 shows that all the light sources in a given group are enabled at the same time , individual control of series strings is not precluded . the block diagram shown in fig7 a shows the light sources being driven by constant current sources on the low voltage side of the power supply . however , control from the high voltage side of the power supply is not precluded . a typical constant current source operating on the low voltage side of the power supply is shown in the block diagram of fig7 a and consists of an operational amplifier u 1 , an fet transistor q 1 and a resistor r 1 . u 1 will cause q 1 to conduct enough current ir to satisfy the relationship vs = vr = ir × r 1 or iled = ir = vs / r 1 . thus , the current through the led &# 39 ; s , i . e ., iled , is a function of vs and r 1 and independent of the varying characteristics of the led &# 39 ; s as a function of temperature , power levels and individual parts . the value of vs is determined by the switch position ( sw 1 a , sw 1 b , etc .) and is either the output of the digital - to - analog converter d / a or 0 volts . since both the switch and the converter d / a are under control of the processor 29 , the individual light source strings can be turned on and off at various power levels as required by the program . the power supply for the block diagram circuit of fig7 is normally a direct current ( dc ) voltage source converted from the normal house supply or a battery . alternative well known power sources can also be used . the power to drive the photo - therapy devices of this invention ranges from 10 w / cm2 to 30 w / cm2 . modifications of this invention will be readily apparent to those skilled in the art and it is intended that the invention be not limited by the embodiments disclosed herein but that the scope of the invention be defined by the appended claims . | 0 |
the conversion of a sector address into a track address and sector offset within the track . at each track hit or rehit , cached data sufficient to satisfy a number of i / o &# 39 ; s may remain in front of , and / or behind , the current location of the data involved in the current i / o . when either of these two remaining areas contain valid data for less than a set number of i / o &# 39 ; s , the cache - ahead is activated . that minimum number of potential i / o &# 39 ; s is the cache - ahead factor , or the proximity factor . the table which maintains the relationship between disk track identifiers and solid state memory addresses ; also may hold frequency of access and / or other information as required . the solid state memory area which holds user data within the cache system of this invention . the address of a physical sector on the magnetic disk device . the logical section of the caching device which handles the writes to , and reads from , the rotating magnetic disk . the address of the first sector of data in a given track on disk . these addresses correspond to physical locations on the rotating magnetic disk . each sector address as specified in an i / o operation can be converted into a track address and a sector offset within that track . direct memory access ; that is , memory - to - memory transfer without the involvement of the processor . dynamic random access memory . the chip or chips that are used for solid state memory devices . the portion of the caching device which interfaces with the host computer . least recently used , describes the data currently occupying a cache data storage track and which has not been accessed for the longest period of time of all currently cached data . this is a well known concept for determining which cached data to release from a cache track in order to be able to reuse the cache space currently occupied by that data for caching some currently required , uncached data . the table containing the information which allows the caching device &# 39 ; s controller to determine which solid state memory data areas may be reused with the least impact on the cache efficiency . a rotating magnetic disk , optical disk , or other mass media which provides high storage capacity at a relatively low cost per megabyte , but with a low - speed response . that data stored in the cache which has been written from a host to this described device and which has not yet been written by this described device to the mass storage device . one or more contiguous sectors within a logical block which contain data written from the host to the cache and which data has not been subsequently written to the mass storage device . most - recently - used , as pertains to that data storage track which has been accessed in the nearest time past . the condition of the device in which it can use its normal priorities in order to reach its optimal performance level . a value in a table field which indicates the field should be considered to be empty ; depending on usage , will be zero , or will be the highest value the bit structure of the field can accommodate . a complete data track on a disk ; one complete band on one platter of the disk device . the size of a host read transaction as a number of sectors which , when exceeded , causes the transaction to be handled in pseudo disk mode . the term used to describe the retention of data in a track in cache beyond that tracks arrival at the lru position ; such retention may be based on a number of factors , including whether or not the track was used at some time since the data in the track was most recently read from disk into cache , or since the cached data track was last retained in cache by the recycling mechanism . the term used to describe an entire set of procedures whose function it is to retain in cache data beyond the time that data would have been retained had the retention been based solely on the standard lru concept . the recycling mechanism maintains and uses in decisions a recycle flag or recycle register . the term used to describe a register or data field , one of which is associated with each cache track , and whose value is adjusted based on the activity of the data cached in that track . the value in the recycle register is used to help make the decisions as to which cache tracks to be reused when a cache track is required for caching a currently uncached track . in its simplest form , this can be a single bit , and can be considered simply as a recycle flag which is set to one when the data in a cache track qualifies for recycling , and is set to zero when the data in the cache track no longer qualifies for recycling . small computer system interface ; the name applied to the protocol for interfacing devices , such as a disk device to a host computer . a physical connection between devices which uses the scsi protocol , and is made up of logical controllers connected by a cable . the logical sub - unit of a disk track ; the smallest addressable unit of data on a disk . storage media made up of solid state devices such as drams . the address in the solid state memory at which the first byte of the first sector of a given disk track resides . a logical data track on disk , or its equivalent in ssd ; may or may not be identical to a physical track on disk ( one complete magnetic band on one platter of the disk ). it is noted that an i / o operation may involve more than one logical block . the number of sectors considered to be in a disk track ; this may or may not be equal to the actual number of sectors in a physical disk track . the condition of the device in which it must shift priorities in order to maintain at least magnetic disk level performance . the size of a host write transaction as a number of sectors which , when exceeded , causes the transaction to be handled in pseudo disk mode . in accordance with the teachings of this invention , a computer peripheral data storage device is provided comprising a combination solid state memory and rotating magnetic disk ; such device having the large capacity of magnetic disk media with near solid state speed at a cost per megabyte approaching that of magnetic disk media . for the purposes of this discussion , embodiments will be described with regard to magnetic disk media . however , it is to be understood that the teachings of this invention are equally applicable to other types of mass storage devices , including optical disk devices , and the like . the caching device described herein derives its large storage capacity from the rotating magnetic disk media . its high speed performance stems from the combination of a private channel between the two storage media , multiple microprocessors utilizing a set of unique data management algorithms , a unique prefetch procedure , combined in a methodology which incorporates simultaneity of memory management and data storage operations and an ample solid state memory . this hybrid storage media gives overall performance near that of solid state memory for most types of computer workloads while practically never performing at less than normal magnetic disk speeds for any workload . to the host computer , the device of this invention appears to be a single , directly addressable entity . by the combination , within the device , of a solid state memory and one or more magnetic disk devices , private data communication lines are established within the device which avoids contention between normal data transfers between the host and the device , and transfers between the solid state memory and the disk media . this private data channel permits unrestricted data transfers between the two storage media with practically no contention with the communication between the host computer and the described device . utilization of ample solid state memory permits efficient retention of data for multiple , simultaneously active data streams . management of the storage is via microprocessors which anticipate data accesses based on historical activity . data is moved into the solid state memory from the disk media based on management algorithms which insure that no table searches need be employed in the time - critical path . host computer accesses to data stored in the solid state memory are at near solid state speeds ; accesses to data stored on the magnetic disk are at near disk device speeds . all data sent from the host to the device is transferred at solid state speeds limited only by the channel capability . a device constructed in accordance with the teachings of this invention is depicted in fig2 . memory device 200 is a self - contained module which includes interfaces with certain external devices . its primary contact is with host computer 201 via host interface 204 . host interface 204 comprises , for example , a dedicated scsi control processor which handles communications between host computer 201 and memory manager 205 . an operator interface is provided via the console 207 , which allows the user to interrogate as well as exercise overall control of the memory device 200 . another method of interfacing with the caching device 200 is by means of dial - in line 202 operating through the console . memory manager 205 handles all functions necessary to manage the storage of data in , and retrieval of data from disk drive 210 ( or high capacity memory devices ) and solid state memory 208 , the two storage media . the memory manager 205 consists of one or more microprocessors associated firmware 205 - 2 , and management tables , such as address translation ( adt ) table 205 - 3 and least recently used ( lru ) table 205 - 4 . solid state memory 208 is utilized for that data which memory manager 205 , based on its experience , deems most useful to host computer 201 , or most likely to become useful in the near future . magnetic disk 201 is the ultimate storage for all data , and provides the needed large storage capacity . disk interface 209 serves as a separate dedicated control processor ( such as an scsi processor ) for handling communications between memory manager 205 and disk drive 210 . information about functional errors and operational statistics are maintained by diagnostic module - error logger 206 . access to module 206 is obtained through console 207 . console 207 serves as the operator &# 39 ; s access to the memory device 200 for such actions as reading or resetting the error logger , or inquiring of the caching device &# 39 ; s status or operating statistics . the memory device 200 includes power backup system 203 which includes a rechargeable battery . backup system 203 is prepared to maintain power to memory device . 200 should normal power be interrupted . if such a power interruption occurs , the memory manager 205 takes whatever action is necessary to place all updated data stored in solid state memory 208 onto magnetic disk 210 before shutting down memory device 200 . fig3 depicts a hardware controller block diagram of one embodiment of this invention . as shown in fig3 hardware controller 300 provides three i / o ports , 301 , 302 , and 303 . i / o ports 301 and 302 are differential scsi ports used to connect hardware controller 300 to one or more host computers 201 ( fig2 ). i / o port 303 is a single - ended scsi port used to connect controller 300 to disk drive 210 ( which in this embodiment is a 5 . 25 &# 34 ; magnetic hard disk drive ). disk drive 210 provides long - term non - volatile storage for data that flows into controller 300 from host computers 201 . &# 34 ; differential &# 34 ; and &# 34 ; single - ended &# 34 ; refer to specific electrical characteristics of scsi ports ; the most significant distinction between the two lies in the area of acceptable i / o cable length . the scsi aspects of i / o ports 301 , 302 , and 303 are otherwise identical . cache memory 308 ( corresponding to memory 208 ) is a large , high - speed memory used to store , on a dynamic basis , the currently active and potentially active data . the storage capacity of cache memory 308 can be selected at any convenient size and , in the embodiment depicted in fig3 comprises 64 megabytes of storage . cache memory 308 is organized as 16 megawords ; each word consists of four data bytes ( 32 bits ) and seven bits of error - correcting code . typically , the storage capacity of cache memory 308 is selected to be within the range of approximately one - half of one percent ( 0 . 5 ) to 100 percent of the storage capacity of the one or more magnetic disks 210 ( fig2 ) with which it operates . a small portion of cache memory 308 is used to store the tables required to manage the caching operations ; alternatively , a different memory ( not shown , but accessible by microcontroller 305 ) is used for this purpose . edac circuitry 306 performs error detecting and correcting functions for cache memory 308 . in this embodiment , edac circuitry 306 generates a seven - bit error - correcting code for each 32 - bit data word written to cache memory 308 ; this information is written to cache memory 308 along with the data word from which it was generated . the error - correcting code is examined by edac circuitry 306 when data is retrieved from cache memory 308 to verify that the data has not been corrupted since last written to cache memory 308 . the modified hamming code chosen for this embodiment allows edac circuitry 306 to correct all single - bit errors that occur and detect all double - bit and many multiple - bit errors that occur . error logger 307 is used to provide a record of errors that are detected by edac circuitry 306 . the information recorded by error logger 307 is retrieved by microcontroller 305 for analysis and / or display . this information is sufficiently detailed to permit identification by microcontroller 305 of the specific bit in error ( for single - bit errors ) or the specific word in error ( for double - bit errors ). in the event that edac circuitry 306 detects a single - bit error , the bit in error is corrected as the data is transferred to whichever interface requested the data ( processor / cache interface logic 316 , host / cache interface logic 311 or 312 , and disk / cache interface logic 313 ). a signal is also sent to microcontroller 305 to permit handling of this error condition ( which involves analyzing the error based on the contents of error logger 307 , attempting to scrub ( correct ) the error , and analyzing the results of the scrub to determine if the error was soft or hard ). in the event that edac circuitry 306 detects a double - bit error , a signal is sent to microcontroller 305 . microcontroller 305 will recognize that some data has been corrupted . if the corruption has occurred in the adt or lru tables , an attempt is made to reconstruct the now defective table from the other , then relocate both tables to a different portion of cache memory 308 . if the corruption has occurred in an area of cache memory 308 that holds user data , microcontroller 305 attempts to salvage as much data as possible ( transferring appropriate portions of cache memory 308 to disk drive 210 , for example ) before refusing to accept new data transfer commands . any response to a request for status from the host computer 201 will contain information that the host computer 201 may use to recognize that memory device 200 is no longer operating properly . microcontroller 305 includes programmable control processor 314 ( for example , an 80c196 microcontroller available from intel corporation of santa clara , calif . ), 64 kilobytes of eprom memory 315 , and hardware to allow programmable control processor 314 to control the following : i / o ports 301 , 302 , and 303 , cache memory 308 , edac 306 , error logger 307 , host / cache interface logic 311 and 312 , disk cache interface logic 313 , processor / cache interface logic 316 , and serial port 309 . programmable control processor 314 performs the functions dictated by software programs that have been converted into a form that it can execute directly . these software programs are stored in eprom memory 315 . in one embodiment , the host / cache interface logic sections 311 and 312 are essentially identical . each host / cache interface logic section contains the dma , byte / word , word / byte , and address register hardware that is required for the corresponding i / o port ( 301 for 311 , 302 for 312 ) to gain access to cache memory 308 . each host / cache interface logic section also contains hardware to permit control via microcontroller 305 . in this embodiment i / o ports 301 and 302 have data path widths of eight bits ( byte ). cache memory 308 has a data path width of 32 bits ( word ). disk / cache interface logic 313 is similar to host / cache interface logic sections 311 and 312 . it contains the dma , byte / word , word / byte , and address register hardware that is required for disk i / o port 303 to gain access to cache memory 308 . disk / cache interface logic 313 also contains hardware to permit control via microcontroller 305 . in this embodiment , i / o port 303 has a data path width of eight bits ( byte ). processor / cache interface logic 316 is similar to host / cache interface logic - sections 311 and 312 and disk / cache interface logic 313 . it contains the dma , half - word / word , word / half - word , and address register hardware that is required for programmable control processor 314 to gain access to cache memory 308 . processor / cache interface logic 316 also contains hardware to permit control via microcontroller 305 . in this embodiment , programmable control processor 314 has a data path width of 16 bits ( half - word ). serial port 309 allows the connection of an external device ( for example , a small computer ) to provide a human interface to the system 200 . serial port 309 permits initiation of diagnostics , reporting of diagnostic results , setup of system 200 operating parameters , monitoring of system 200 performance , and reviewing errors recorded inside system 200 . in other embodiments , serial port 309 allows the transfer of different and / or improved software programs from the external device to the control program storage ( when memory 315 is implemented with eeprom rather than eprom , for example ). the address translation table , along with the lru table , maintains the information required to manage the caching operations . there are two sections in the adt table , the indexed , or tabular portion , and the set of unindexed , or single - valued items . the unindexed portion of the adt table contains two types of data fields ; the first are those items which are essential to the cache management , the second category contains those data items which maintain records of the unit &# 39 ; s performance . the first group of unindexed items , or those requisite to the cache management , includes the following single - valued items . 1 ) adt - cnl . the number of tracks on the cached disk spindle ; also equals the number of lines in the adt table . this is set at the time the caching device is configured and is not changed while the unit is in operation . 2 ) adt - head - pos . the current position of the read / write head of the cache disk . this is updated every time the head is positioned . 3 ) adt - sweep - dir . the direction in which the current sweep of the background writes is progressing . this is updated each time the sweep reverses its direction across the disk . 4 ) adt - mod - count . the total number of tracks in the cache which have been modified by writes from the host and are currently awaiting a write to disk by the disk server . this is increased by one whenever an unmodified cache track is updated by the host , and it is decreased by one whenever a modified cache track is copied to the cache disk . adt - mod - urgent . the number of cache slots which , when in the modified condition , causes the caching device to shift priorities to maintain optimal performance . the second group of unindexed items are those which record the unit &# 39 ; s performance , and are all used to compute the current operating characteristics of the unit . they include the following single - valued items . 1 ) adt - read - hits . the number of cache read - hits encountered since the last reset . this value is set to zero by a reset operation from the console . it is incremented by one for each read i / o which is entirely satisfied from data which is resident in the cache memory . 2 ) adt - read - misses . the number of cache read - misses encountered since the last reset . this value is set to zero by a reset operation from the console . it is incremented by one for each read i / o which cannot be entirely satisfied from data which is resident in the cache memory . 3 ) adt - write - hits . the number of cache write - hits encountered since the last reset . this value is set to zero by a reset operation from the console . it is incremented by one for each write i / o for which the corresponding track or tracks are found to be in cache memory . 4 ) adt - write - misses . the number of cache write - misses encountered since the last reset . this value is set to zero by a reset operation from the console . it is incremented by one for which at least one of the corresponding track is not found to be in cache memory . there is one line in the tabular portion for each data track on the spindle . a line is referred to by its line number , or index . that line number directly corresponds to a track number on the disk . when the host wants to access or modify data on the disk , it does so by referencing a starting sector address and indicating the number of sectors to be accessed or modified . for caching purposes , the starting sector address is converted into a track identifier and offset within that track . a disk sector address is converted into a track number and a sector offset by dividing it by the number of sectors per track . the remainder is the offset into the track . the quotient is the track identifier and is the index into the adt table . using this index , the condition of the specified disk track can be determined directly from data in the adt table ; no search is required to determine cache - hits or misses . 1 ) adt - slot . the number of the cache slot which contains the data for the disk track corresponding to this adt table line number . by design , the value in adt - slot also points to the line in the lru table related to the cached disk track . if the disk track is not in cache memory , the value in this field is meaningless and is set to its null value . it is by means of this field that cache - hits can be serviced completely without any table search . a null value in this field indicates the corresponding disk track is not stored in the cache . this field is updated each time a track is entered into or removed from the ssd area . 2 ) adt - modified . a flag indicating whether or not the corresponding cached track has been modified by a write operation from the host , and thus , needs to be copied from the cache to the disk . the lru table maintains the information relative to the times when cached tracks of data were last accessed . this information is necessary for the unit to always be aware of which cache slots are available for overwriting whenever uncached data tracks must be placed in cache . its contents also provide redundancy for the data kept in the adt table , thus contributing to system reliability . there are two sections in the lru table , the indexed , or tabular portion , and the set of unindexed , or single - valued items . the unindexed portion of the lru table contains data required to manage the caching process . the tabular portion is composed of pointers for lru chaining purposes , pointers into the adt table , and the recycle control registers or flags . it is by means of this lru information and the adt table information that the system determines which cached track to overwrite when a cache area is needed for an uncached disk track . the unindexed items are requisite to the cache management , and includes the following single - valued items . the number of track - equivalent slots in the cache area ; this is equal to the number of lines in the lru table . the lru - lru table element points to the cache area track - slot containing the cached data which has been left untouched for the longest time . it is updated when new activity for the referenced slot makes it no longer the least - recently - used . the referenced slot is the top candidate for overwriting when new data must be written into the cache . the lru - mru table element points to the cache area track - slot containing the cached data which has been most - recently referenced by the host . lru - mru is updated every time a track is touched by either a read or a write from the host . at that time , the address of the accessed track is placed in lru - mru and the lru chains are updated in the indexed portion of the lru table . there is one line in the tabular portion for each cache area slot in the cache data area . a line is referred to by its line number , or index . that line number directly corresponds to a slot in the cache data area . each lru table line contains pointer fields plus other control fields . the pointer to the adt line which references the disk track currently resident in the corresponding cache slot . by design , this value is also the identifier of the disk track whose data currently resides in the corresponding cache slot , if any . this is part of the bidirectional chaining of the cache data slots . lru - last is the pointer to the next - older ( in usage ) cache slot . if this slot is the oldest , lru - last will contain a zero . this is the other half of the bidirectional chaining of the cache data slots . lru - next is the pointer to the next newer ( in usage ) cache slot . if this slot is the newest , lru - next will contain a zero . a field containing the track - relative number of the lowest sector of this cached track which contains valid cached data . a field containing the track - relative number of the highest sector of this cached track which contains valid cached data . a field containing the track - relative number of the lowest sector of this cached track which contains modified cached data . a field containing the track - relative number of the highest sector of this cached track which contains modified cached data . a flag indicating whether or not the corresponding cached track is currently the target of some operation , such as being acquired from the disk , being modified by the host , or being written to the disk by the cache controller ; such operation making the track unavailable for certain other operations . this field is used to control the recycling mechanism . it is increased or reduced based on the usage of the data cached in the corresponding track and based on other system factors such as the amount of modified data in the entire cache at various relevant times . this register &# 39 ; s adjusted value is used to determine whether to decache or recycle the data in this cache track when this track arrives at a decision point such as when it reaches the lru position in the lru table . in its simplest form , this register becomes a single - bit recycle - flag . in this simplified case , a single bit marker is maintained to indicate whether or not the corresponding track should be recycled . this flag is set to 1 ( on ) whenever the data in the track is referenced by the host ; the flag is set to 0 ( off ) when the corresponding track is recycled ( moved to the mru position ). the flag is initially set to 0 when a track is brought into cache as a result of a cache - ahead decision . for a track brought in to satisfy a cache miss , it is set to 1 . in the more complete form , the recycle register can assume values from zero to n and the value is controlled by a set of recycling rules . see recycling mechanism examples elsewhere in this document . when a unit is first powered on , the adt table is in an indeterminate state . in order to become operational , initial values must be entered into their appropriate table elements . initial values for unindexed fields of the adt table are as follows : the adt - cnl field must be set to the size of the cache disk as a number of tracks . the adt - head - pos field is set to zero to indicate the head is currently at the edge of the disk . this may , or may not , be true , but it does not matter ; it will become correct on the first access to the disk . the adt - sweep - dir field is arbitrarily set to one ( 1 ) to indicate the head is moving in an upward ( based on track addresses ) direction . this will be corrected at the initiation of the first background sweep . the adt - mod - count field is set to zero to reflect the fact that no modified tracks are waiting in cache to be copied to disk . the adt - read - hits field is set to zero to reflect the fact that no cache hits have occurred during read operations . the adt - read - misses field is set to zero to reflect the fact that no cache misses have occurred during read operations . the adt - write - hits field is set to zero to reflect the fact that no cache hits have occurred during write operations . the adt - write - misses field is set to zero to reflect the fact that no cache misses have occurred during write operations . all indexed fields of all lines of the adt table are initially set to zero to indicate that no tracks are resident in cache . when the described caching device is first powered on , the lru table is in an indeterminate state . in order to become operational , initial values must be entered into their appropriate table elements . while there are many acceptable ways to initialize the chaining fields , a simple one has been selected , and is described here . initial values for unindexed fields of the lru table are as follows : the lru - cnl field must be set to the size of the cache , as a number of track - equivalent slots . the lru - lru field is set to one to represent the lowest numbered cache slot as being the oldest . this is an arbitrary choice in keeping with the chaining values selected , below . the lru - mru field is set equal to lru - cnl to represent the highest cache slot as being the most recently used . this is an arbitrary choice in keeping with the initial chaining values selected , below . initial values for indexed fields of the lru table are as follows : the lru - track field of every line of the lru table is set to zero to indicate that no disk data tracks are currently held in cache . the lru - last field of every line of the lru table is set to that line &# 39 ; s index minus one . this action , along with the settings for the lru - next values , produce a chained list suitable for the cache start - up operation . the lru - next field of every line , except the highest , of the lru table is set to that line &# 39 ; s index plus one . the lru - next field of the highest line is set to zero . these settings , along with the settings for the lru - last values , produces a chained list suitable for the cache start - up operation . the lru - cached - low field of every line is set to its null value to indicate that no portion of the disk track is currently held in cache . the lru - cached - high field of every line is set to its null value to indicate that no portion of the disk track is currently held in cache . the lru - mod - low field of every line is set to its null value to indicate that no portion of the disk track currently held in cache is in a modified condition . the lru - mod - high field of every line is set to its null value to indicate that no portion of the disk track currently held in cache is in a modified condition . the lru - locked field of every line of the lru table is set to zero to indicate no cache slot is currently locked . the lru - recycle - register field of every line of the lru table is set to zero to indicate that no slot is currently a candidate for recycling . while any set of recycling algorithms could have been used , the following rules have been chosen for this example : 2 ) cache tracks whose data is originally cached due to a cache read miss will have their recycling register set to one at the time of their original caching . this will give that data a longer life in cache than data cached for some of the other reasons ; 3 ) cache tracks whose data is originally cached by prefetch ( based on proximity ) will have their recycling register set to zero . this will give that data the minimum time in cache unless the data is referenced by the host before it is decached when it reaches the lru position . 4 ) cache tracks whose data is originally cached by a cache write miss will have their recycling register set to zero . again , data cached in this manner will be given a minimum time in cache unless the data is referenced by the host before it is decached when it reaches the lru position . 5 ) cache tracks whose data is subsequently referenced by a host operation will have their recycle register set to one . the operational state adt table examples illustrate the conditions after the very first ( sample ) i / o has occurred and after the system has reached a fully active condition . these fully active examples show the effects of several i / o &# 39 ; s on the state of the adt table contents . also included in these examples is the effect of a background sweep which wrote modified tracks from cache to disk . a detailed description of these specific sample operations appears under the lru table discussion , below . the operational state lru table examples illustrate the conditions after the very first i / o has occurred and after the system has reached a fully active condition . these fully active examples show the effects of several i / o &# 39 ; s on the state of the lru table contents . for purposes of illustration , a sample of i / o &# 39 ; s were chosen to be discussed in detail . those chosen for discussion are i / o numbers 1 , 1000 , 1001 , and 1002 taken from a trace of actions at an operational site ; they are detailed in table t - 0 as projected into the described system . the following discussions of the sample i / o &# 39 ; s include the effects on both the adt and the lru tables . actions related to i / o operation number 1 : 1 . this i / o is a read involving disk track numbers 46 and 47 ; since nothing is in cache , it must be a cache - miss . a portion of track 46 , and all of track 47 is brought into cache . the adt table is modified to show the locations of the tracks in cache ; the amount of each track now cached is recorded ; the chains are relinked to show the tracks to be the mru and the next - to - mru tracks ; and they are both marked for recycling . they are marked for recycling since the data in these cache tracks were cached due to a read miss . according to the recycling rules set out for this example , cache tracks containing data brought from the disk as a result of a cache read miss are to be given a recycle register value of one . 2 . based on the i / o size and the distance from the end of the data requested in the i / o operation number 1 to the end of track 47 , a prefetch of track 48 is initiated . that activity is not reflected in the adt and lru tables since it is initiated as a background operation after the completion of the current i / o . after 999 i / o &# 39 ; s have occurred , the adt and lru tables have reached a certain status . i / o number 1000 is a read of 68 sectors starting at sector address 14 , 190 . this occupies sectors 11 through 78 of disk track 56 . based on these conditions , the following actions relate to i / o operation number 1000 : 1 . this i / o is a read involving track 56 which is not in cache ; the required portion of it must be brought into cache . while fetching this required data , the portion of track 56 from the end of the requested data to the end of the track is also fetched . this is done here since this is the most expeditious time to do so , and satisfies the prefetch rules . the lru table is updated to reflect the caching of track 56 and slot into which this data is fetched is placed at the mru position in the lru chain . 2 . to make room for caching track 56 , the old lru track was decached . 3 . a read i / o operation does not affect the need for a background sweep . there are three tracks in cache that need to be copied to disk ; this condition remains unchanged by the current i / o . 4 . several cache tracks have non - zero recycling registers , including the track at the lru end of the chain and the track it points to . before any prefetch is initiated , these tracks will be moved to the mru and next - to - mru positions and their recycle registers will have been set to zero . this is in accordance with the recycle rules chosen for the current example wherein the recycle register is a single bit which is either 1 ) a one to indicate the data in the cache track is to be retained beyond its arrival at the lru position ; or 2 ) a zero which indicates the data in the cache track should be detached when it arrives at the lru position and a cache track is needed for data from some other disk track . 5 . since track 57 is already in cache , no prefetch is needed for it . 5 . the size of the i / o ( 68 sectors ) and the current i / o &# 39 ; s proximity to the first sector in track 56 indicate that track 55 should be prefetched by a cache - ahead action . that prefetch will be initiated as a background operation . based on the lru chain and the recycling situation , track 55 will be cached into slot 10 . for the moment it will occupy the mru position in the chain . 1 . prefetching of track 55 , which was initiated by i / o 1000 has now been completed . 2 . i / o number 1001 is a write involving sectors 191 - 256 of track 61 , and sectors 1 - 2 of track 62 . the lru and adt table references to them are updated . 3 . this i / o action modified two cached tracks , bringing the total number of tracks which need written to disk up to the trigger point for the background sweep . 4 . the background sweep is initiated and starts writing the modified tracks from cache to disk . 5 . since the background sweep is using the disk spindle , no cache - ahead is initiated , even though the unit would consider the prefetch of track 60 into cache . 1 . the background sweep completed writing all modified tracks from cache to disk ; it then went into the dormant state . 2 . i / o 1002 was a write involving track 214 which is already resident in cache . the track is marked in the adt table as having been modified . in the lru table , track 214 in slot number 13 is removed from the mru - lru chain , and the amount modified is recorded in the lru - mod - low and lru - mod - high fields . 3 . a prefetch of track 215 is initiated since the position of the current i / o in track 214 is near enough to the end of the track to warrant a cache - ahead operation . this activity does not appear in the adt and lru tables for i / o 1002 since it will occur in the background after the completion of the current i / o . 4 . since a prefetch of track 215 has been initiated , track 213 is not considered for prefetching . the memory controller of this invention goes into a semi - dormant state when there is no activity that it needs to handle . as depicted in the flow chart of fig4 there are three types of occurrences that may cause the controller to become active : insofar as possible , the host computer commands are given priority over other memory device activities . thus , when a command is received from the host , it is immediately turned over to the host command handler ( described elsewhere ). at the completion of the activity called for by that command , the memory controller determines if the background sweep is active . if it is not active , the background status is inspected and action is taken as appropriate , as described later with regard to the background check . following the background status check , the cache - ahead status is checked , as described later with regard to the cache - ahead management . the controller then waits for the next host command . the controller may not be completely inactive at this time , inasmuch as either the background sweep or the cache - ahead may have initiated or continued some disk activity . if the background was found to be active , its activity is continued until such time as it has no more immediate work to do , as described later with regard to background continuation . when the background sweep completes a command , the controller is given an interrupt with a signal that indicates the sweep needs its attention . at that time , the controller initiates the next sweep event , if any is waiting , and schedules the next write from cache to disk also based on need , as described later with regard to the background continuation . at the completion of each sweep event , the controller determines if there is a need to continue the sweep . if no such need exists , the background sweep is placed in the dormant state . in either case , when the controller has completed its housekeeping , it becomes inactive awaiting its next task . the background sweep can be activated in either of two ways ; it will be activated when a set number of cached tracks have been modified and are in need of being written from cache to disk . the sweep may also be activated by a timeout . a timeout occurs whenever the sweep is inactive , and there exists any modified track waiting to be written from cache to disk which has been waiting more than a preset amount of time . when a timeout occurs , the controller is signaled that the sweep requires its attention . the controller initiates the background sweep ( see description of background initiation ) and , after completing the appropriate housekeeping , awaits the next command or event requiring its attention . the background sweep itself continues in operation until there is no more immediate need for its services . at that time it is returned to the dormant state . whenever a command is received from the host computer , it is given the highest possible priority and handled as depicted in fig5 . to determine what actions are required , the command must be analyzed . a portion of the firmware is dedicated to that purpose ( see description of host command analysis ). the analysis of the command determines the type of command ( read , write , seek , or other ) and , where meaningful , will make a cache hit / miss determination . the analysis also sets up a table of one or more lines which will be used later in servicing the command . if the command is a read and it can be serviced entirely from cache ( i . e . a cache hit ), the command is serviced by the read - hit portion of the controller ( see description of read - hit handling ). if any portion of the read cannot be serviced from cached tracks ( i . e . a cache miss ), the command is turned over to the read - miss portion of the controller ( see description of the read - miss handling ). if the command is a write and all tracks involved in the operation are already in cache , the command is serviced by the write - hit portion of the controller ( see description of write - hit handling ). if any portion of the write involves an uncached track or tracks , the command is turned over to the write - miss portion of the controller ( see description of the write - miss handling ). if the command is a seek , and the target track is already cached , no action is required . if the target track is not cached , the command is turned over to the seek - miss portion of the controller ( see description of seek - miss handling ). as depicted in fig6 the analysis of a host command includes creation of a track address list which contains the locations of each track involved in the operation ( see description of track address list setup ). for each such track , the list contains the track &# 39 ; s current location in cache , if it already resides there ; or where it will reside in cache after this command and related caching activity have been completed . in the case that a track is not already cached , the space for it to be put into in cache is located , and the current track resident in that space is decached . the analysis includes setting the cache hit / miss flag so that the controller logic can be expedited . as shown in fig7 the controller segment which sets up the track address list uses the i / o sector address and size to determine the disk track identifying numbers for each track involved in the i / o operation ( see description of address translation ). the number of tracks involved is also determined , and for each track , the portion of the track which is involved in the operation is calculated . fig8 describes the operation for this translation . a sector address can be converted into a track address by dividing it by the track size . the quotient will be the track number , and the remainder will be the offset into the track where the sector resides . refer to fig9 . a read hit is satisfied entirely from the cached data . in order to reach this module of the controller , the command will have been analyzed and the track address table will have been set up . with this preliminary work completed , the host read command can be satisfied by using each line of the track address table as a subcommand control . since all required portions of all affected tracks are already in cache , all required data can be sent directly from the cache to the host . in addition to transferring the data to the host , this module will rechain the affected tracks to become the most - recently - used tracks in the lru table . finally , the recycle register value is adjusted according to the recycling rules in effect . as a minimum , in the simplest case the recycle register is set to one to indicate that this cache track is to be considered for recycling . if more complex recycling rules have been specified , the recycle register is incremented according to those rules . a cache read - miss ( fig1 ) is satisfied in part or wholly from the disk . in order to reach this module of the controller , the command will have been analyzed and the track address table will have been set up . with this preliminary work completed , the host read command can be satisfied by using each line of the track address table as a subcommand control . for an i / o whose size exceeds the read - miss - maxsize , uncached portions are sent directly from the disk to the host without affecting the cache in any way . for an i / o whose size does not exceed the read - miss - maxsize , the operation is handled based on the caching device &# 39 ; s current mode . if the unit is not in urgent mode : for track segments which are already in cache , the data can be sent directly from the cache to the host . for a track segment not resident in the cache , the data is sent from the disk to the host , and simultaneously , the portion of the track from the first sector of the requested data to the end of that track is sent to the cache . the lru - cached - low and lru - cached - high fields of the corresponding lru table line ( s ) are set to reflect the portions of those tracks which have been brought into cache . if the unit is in urgent mode : for a track not resident in the cache , the data is sent directly from the disk to the host without being entered into the cache . in either mode , in addition to transferring the data to the host , this module will rechain affected , cached tracks to become the most - recently - used slots in the lru table . a cache write - hit ( fig1 ) is handled entirely within the cache . in order to reach this module of the controller , the command will have been analyzed and the track address table will have been set up . with this preliminary work completed , the host write command can be satisfied by using each line of the track address table as a subcommand control . since all affected tracks are already represented in cache , all data can be sent directly from the host to the cache without any concern for post - transfer staging of partial tracks . in addition to transferring the data to the cache , this module will , if the slot was linked into the lru chain , remove the affected cache slot from the lru chain . in every case , the corresponding lru - mod - low , lru - mod - high , lru - cached - low , and lru - cache - high fields are updated to reflect the existence of this new data . finally , the recycle register value is adjusted according to the recycling rules in effect . if the i / o size exceeds the write - miss - maxsize , uncached tracks or track segments are written directly to disk with no effect on the cache . for an i / o whose size does not exceed write - miss - maxsize , the operation is handled based on the caching device &# 39 ; s current mode . if the caching device is operating in normal mode , a write miss is handled entirely within the cache but requires the placing of information into the lru - cached - low , lru - cached - high , lru - mod - low , and lru - mod - high fields to insure that any data required to fill gaps between the modified portions of any partial tracks can be read from the disk into the cache memory , as depicted in fig1 . in order to reach this module of the controller , the command will have been analyzed and the track address table will have been set up . with this preliminary work completed , the host write command can be satisfied by using each line of the track address table as a subcommand control . since this is a cache - miss , some or all of the affected tracks are not in cache ; however , all data can be sent directly from the host to the cache . the cache controller has the responsibility for reading from disk into cache that data required to fill any gaps in the modified portion of tracks . in actuality , only the first and / or last tracks involved in the transfer can be partial tracks ; all interior tracks must be full tracks , and thus require no data to be read from the disk to fill gaps in the modified portion of the cached data in any case . for those tracks requiring post - transfer staging , the controller sets up a list of caching events to bring any required track segments into cache to maintain the integrity of the cached tracks . in addition to transferring the data to the cache , this module removes the affected tracks from the lru chain . if the caching device is operating in urgent mode , the handling of a write miss bypasses the cache for any tracks which are not currently cached , sending the data directly from the host to the disk . the lru and adt tables are updated for any cached tracks which may have been affected . finally , the recycle register value is adjusted according to the recycling rules in effect . as shown in fig1 , the controller has the option of ignoring a seek command since the controller will ultimately be responsible for fulfilling any subsequent , related i / o command . for a seek command for which the target track is already in cache , no controller action is needed or appropriate . for a seek command for which the target track is not in cache , the controller , if the disk to which the seek is directed is not busy , will cache that target track . this action is based on the assumption that the host would not send a seek command unless it was to be followed by a read or a write command . if the disk to which the seek is directed is busy when a seek command is received from the host , the seek command is ignored . it is a well known concept that the basic lru methodology is a way to keep data in cache based on its very recent history . the recycle feature extends the amount of history considered for data retention with the older portion of history having a lesser effect on the decision to retain the data in cache . the recycling of currently cached tracks is a method of maintaining in cache the tracks of data which have the highest likelihood of being reused . in its simplest form , any cached track which has been read from or written into since it was most recently cached or similarly reused since it was last moved to the mru position is a candidate for recycling . when a cached track is reused , the recycle register is set and the cached track is moved to the mru position in the lru table . when a cached track reaches the lru position in the lrutable , its recycle register is checked . if the recycle register is zero , indicating the cached track was not reused in its most recent trip from the mru position to the lru position , the cached track is a candidate for reuse . if , however , the recycle register is nonzero , indicating the cached track had recently been reused , the cached track is moved to the mru position of the lru table , and the recycle register is cleared . in this manner , a track of data whose recent history indicates reusage is allowed to remain in cache for a longer time than a track of data without such recent use . the effect of this procedure is to allow tracks containing data which has had a low frequency of usage to be reused for caching new material in preference to reusing those tracks whose data have exhibited a higher rate of usage , and to allow the more frequently used data to remain in cache for a longer time . in its more complex form , the recycle register for each cache track is more than a single bit , allowing for a maximum value of n based on the number of bits allocated to the register . the recycle register value is set or adjusted based on certain events in a cached track &# 39 ; s life . for example , 1 . when a cache track is initially assigned to a specific disk track , the cache track recycle register is given some initial value . 2 . when a cached track is rehit , such as by a read or write hit , its recycle register value is adjusted by some amount to increase the tracks chances of being retained in cache at some future time when it would otherwise be a candidate for decaching . 3 . when a cached track reaches the lru position in the lru table , and if , based on the recycle register value , the cached track is not decached , then , as a penalty for not being rehit during its last trip from the mru position to the lru position , its recycle register value is adjusted by some amount to reduce the track &# 39 ; s chances of being retained in cache upon some future examination . the important of the recycle register is in making the correct determination of whether or not to decache a cached track when it has reached the lru position in the lru table . when a cached track reaches the lru position in the lru table , its recycle register is examined . if the recycle register value does not meet some set criteria , such failure indicating the history of the cached track does not justify retention in cache , the cached track is a candidate for decaching and its space can be made available for reuse . if , however , the register value meets the preset condition , indicating the cached track has had a level of activity that indicates the cached track should be retained in cache for some more time , the cached track is moved to the mru position of the lru table , and the recycle register value is adjusted by some amount to indicate the track was moved to the mru position based on its history , rather than due to a reusage such as an instant read hit . some of the factors to be considered in determining the initial setting of the recycle register when the track is first cached are : 1 . the reason for caching the track such as read miss , write miss , or read - ahead ; 2 . the current system status , such as the proportion of cache which is now in a modified condition and needs written to the disk . some of the factors to be considered in determining the amount of adjustment of the recycle register value when the cached track is reused are : 2 . the original reason for caching the track such as read miss , write miss , or read - ahead ; 3 . the nature of the most recent activity of the cache track , such as a read hit , it has just been written to disk following one or more writes from the host into it , or that it has just been cached by a read - ahead operation . 4 . the current system status , such as the proportion of cache which is now in a modified condition and needs written to the disk . some of the factors to be considered in determining the action to be taken , and the amount of adjustment to the recycle register value if any , when the cached track reaches the lru position are : 2 . the original reason for caching the track such as read miss , write miss , or read - ahead ; 3 . the nature of the most recent activity of the cache track , such as a read hit , it has just been written to disk following one or more writes from the host into it , or that it has just been cached by a read - ahead operation . 4 . the current system status , such as the proportion of cache which is now in a modified condition and needs written to the disk . the following is one possible example of a set of the controlling factors and corresponding register adjustments for one incarnation of the recycle register concept . this is a simple example which favors quick release of data cached by read - ahead , and also reduces retention of cached material when the caching device is encountering heavy data modification ( host writes ). for the sake of illustration in this example , one can assume p % to be 50 %. 1 . when a cache track is initially assigned to a specific disk track , the recycle register is set according to the following table : ______________________________________reason for caching : read misscache modified : none & lt ; p % & gt ; p % set register to : 2 1 0reason for caching : read - aheadcache modified : ignore this factorset register to : 0reason for caching : write misscache modified : none & lt ; p % & gt ; p % set register to : 2 1 0______________________________________ 2 . adjustment to recycle register when rehit ( in all cases of a rehit , the track is moved to the mru position ): ______________________________________reason for caching : read missmost recent activity : read hit read hit read hitcache modified : none & lt ; p % & gt ; p % current value : 2 2 2adjust register : + 2 + 1 + 1reason for caching : read aheadmost recent activity : read hit read hit read hitcache modified : none & lt ; p % & gt ; p % current value : 2 2 2adjust register : + 2 + 1 + 1reason for caching : write missmost recent activity : read hit read hit read hitcache modified : none & lt ; p % & gt ; p % current value : 2 2 2adjust register : + 2 + 1 + 1______________________________________ ______________________________________reason for caching : anymost recent activity : read hit read hit read hitcache modified : none & lt ; p % & gt ; p % current value : n n nadjust register : value / 2 value / 2 value / 2actions 1 ) if newvalue & gt ; or = 1 : move to move to move to2 ) else : mru mru mru decache decache decachereason for caching : ( read ahead ) most recent activity : read aheadcache modified : anycurrent value : anyadjust register : set to 0action : decache decache decachereason for caching : anymost recent activity : write hit write hit write hitcache modified : none & lt ; p % & gt ; p % current value : n n nadjust register : value / 2 value / 2 value / 2actions 1 ) if newvalue & gt ; or = 1 : move to move to move to2 ) else : mru mru mru decache decache decache______________________________________ for every cache - miss i / o that occurs , and for every cache - ahead operation , some previously cached track or tracks of data must be decached . the primary function of the lru table is to allow the controller to expeditiously determine which cached track of data is the best candidate for decaching . the decaching module depicted in fig1 chooses the track to be decached . normally , the track with the longest elapsed time since its last usage will be the track to be decached . this is the track which is pointed to by the lru - lru element of the lru table . the lru - lru pointer is maintained in such a way as to always point to the least - recently - used track . in the described device , the decision of which track to decache is based not only on the lru concept , but also takes into account the recycling factors as described in the sections of this document regarding recycling . the first condition that must be met in order to decache a track is that the track must be inactive and the cached data must be unmodified ; that is , it is not at this instant the subject of any activity such as being written from the cache to the disk . it is highly unlikely that the lru - lru track would be the current subject of any activity since most activities on a track reposition it out of the lru - lru slot . also , for modified data , it is most likely it would have been written to disk before the cached track has moved down through the lru table to the lru position . however , the possibility is covered by the decaching algorithm . the second condition that must be satisfied before a track can be decached is that the track to be decached must not be a candidate for recycling . the recycling mechanism provides for moving cached tracks from the lru position to the mru position in the lru table . normally , recycling will be done as a background task . in the event a track which should be recycled is found in the lru position when a track is needed for caching new data , that recycle candidate can be recycled at that time . the recycling mechanism described above will determine the desirability of recycling of each track as it reaches the lru position . when a track reaches the lru position , the recycle mechanism also makes the appropriate adjustment to the recycle register . as stated in the recycling description , the effect of this procedure is to allow the tracks containing the more frequently used data to remain in cache for a longer time . if , for any of the above reasons , the lru - lru track is unable to be decached , the lru chain will point to the next - to - lru track . while it is possible for the lru track to be a candidate for recycling , it will be an unusual situation in which the decaching module will need to inspect more than one lru slot to find the track to be decached . when the actual candidate for decaching has been identified , both the lru and adt tables are updated to reflect that the chosen candidate is no longer cached . this is a minor amount of work ; no disk activity is involved . the cache hit and management operation is depicted in fig1 . the controller attempts to cache - ahead after every host i / o which is a read operation regardless of whether the i / o was a cache hit or a cache miss . operations which write data from the host to the device need no cache - ahead operations since data can always be accepted from the host into the cache &# 39 ; s ssd . however , a read cache - ahead action is a background type of activity , and only uses the private channel between disk and cache , it will have a very minimal negative impact on the caching device &# 39 ; s response time to host i / o activity . to further limit the impact , the cache - ahead is given a lower priority than any incoming host i / o request . a major factor in limiting the cache - ahead activity is the lack of need for its operation following most host i / o &# 39 ; s . as depicted in fig1 , the caching device determines the number of data segments of the same size as the current host i / o which remain between the location of the end of the current host i / o data and the end of the cached track containing that data . if this computed number of data segments is more than a predetermined number , the cache unit can handle that number of host i / o &# 39 ; s before there is a need to fetch data for the succeeding track from the disk into the cache memory . if , on the other hand , the computed number of data segments is not more than the predetermined number , it is possible for the host to access all those segments between the end of the current host i / o data location and the end of the cached track in the same or less time than it would take for the caching device to fetch the succeeding track of data from the disk into the cache memory . in this case , the caching device should immediately initiate action to fetch the succeeding data track from the disk so that the service to the host can proceed with the least disk - imposed delays . conversely , if the caching device were to ignore the above - described locality factor and always fetch the next data track after every cache read - miss , many unneeded tracks of data would be fetched from disk into cache memory . such excessive fetches would use up more of the caching device &# 39 ; s resources with a negative impact on the caching device &# 39 ; s host service time . there are only two candidates for cache - ahead : they are the single track immediately following that involved in the host i / o and the track immediately preceding that of the host i / o . since these tracks will often have already been cached by previous cache - ahead activity , the cache - ahead activity is largely a self - limiting process . only one track is cached - ahead for any given host i / o : the track succeeding the host i / o is the primary candidate . if it is not already cached , and the proximity factor indicates the cache - ahead should occur , the forward track is cached at this time . if the succeeding track is already cached , the track preceding the host i / o is considered ; if it is not already cached , and the proximity factor favors caching , this preceding track is cached at this time . of course , if both of these candidate tracks had been cached previously , the cache - ahead module has no need to do any caching . a very important benefit accrues from this cache - ahead , cache - back feature . if related tracks are going to be accessed by the host in a sequential mode , that sequence will be either in a forward or backward direction from the first one accessed in a given disk area . by the nature of the cache - ahead algorithm , an unproductive cache - ahead will only involve one track which lies in the wrong direction from the initial track in any given track cluster . this , coupled with the proximity algorithm , makes the cache - ahead behavior self - adapting to the direction of the accesses . when a write i / o from the host is serviced by the controller , the data from the host is placed in the cache . it is written from the cache to the disk in the background , minimizing the impact of the disk operations on the time required to service the i / o . the module that handles this background activity is the background sweep module . to limit the sweep activity , and thus limit contention for the spindle , only those portions of tracks which have been modified are written from ssd to disk during a sweep . in the interest of further efficiency , the background sweep module does not always copy data from cache to disk as soon as it is available . rather , it remains dormant until some minimum number of modified tracks are waiting to be copied before going into action . in order to avoid having a single modified track wait an inordinately long time before being copied from cache to disk , the background sweep will also be activated by a timeout . thus , if any modified track has been waiting a certain minimum time , and the sweep is not active , the sweep will be activated . after the sweep has copied all modified portions of tracks from cache to disk , it returns to a dormant state . a timeout occurs when some cached data track has been modified and the corresponding track on disk has not been updated after a certain minimum time has elapsed . when a timeout occurs , by definition there will be at least one cached track which needs to be copied to disk . at this time , the background will be changed into the active state . the timeout module ( fig1 ) also causes the first background event to be set up ( see description of background event generation ), and if no conflict exists with the host for access to the disk , the execution of the event will be initiated . after this event is initiated , the next event , if one is known to be needed , is also set up and held for later execution . when these things have been done , the background sweep waits for circumstances to cause it to continue its operation or to return to a dormant state . at the completion of each host i / o operation , the sweep initiation module ( fig1 ) is entered . one of three cases may exist . the first case is that the sweep is dormant , and there are not a sufficient number of modified tracks waiting to be copied to disk to cause the sweep to be enabled at this time . in this case , which is the most common one , there is no action to be taken at this time . in the second case , the sweep is active , and a background event is operating . in this situation , no new action is needed at this time . in the final case , the sweep is active , but no background event is currently in operation . under these conditions , a background event is generated ( see description of generate sweep event ) and , if appropriate , its execution is initiated . the need for the generation of a background sweep event is predicated on there being no other ongoing activity involving the disk . if the event generation module of fig1 is entered when any such activity is in progress , no event is generated . at times , the event generation module will find that there are no more modified tracks waiting to be copied to the disk . in this case , the background sweep is returned to the dormant condition . at other times , the background sweep is in the active mode , but has been temporarily interrupted to handle the higher priority activity of servicing a host i / o . such interruption requires the background sweep to be restarted . it does this by finding the modified track which is nearest , but not directly at , the disk head ; initiating a seek to that track ; and then setting up a write event for the track . this write event will not be initiated until later , but its existence signals the sweep continuation module ( see description of continuation module ) that , if possible , this write is the next thing to be done . the effect of this method of handling background writes is to minimize the impact on the host operations . the controller has an opportunity to service host i / o misses between the background seek and the corresponding write operation . none of this has any significant effect on servicing host i / o cache hits since hits are always handled immediately . the disk is not involved in a hit . the sweep handles the writing of modified tracks differently depending on whether all the sectors in the track have been modified , or only some of the sectors have been modified . further , the number of wholly modified tracks and the number of partially modified tracks are both taken into consideration in the setting of priorities for writing individual tracks to disk . when a larger number of wholly modified tracks exist , as opposed to the number partially modified , the wholly modified tracks are given preference by the sweep operation . writing a modified track from cache to disk is limited to handling only the modified portion of the track as defined by the corresponding lru - mod - low and lru - mod - high values . once the modified track or track segment has been written to disk , the track &# 39 ; s cache slot , which has been in an unchained status , is placed in the lru chain at the mru position if the track had been only partially modified , and is placed at the lru position if the track had been wholly modified . at the same time , the corresponding lru - mod - low and lru - mod - high fields are set to their null value to indicate that no part of the cached data differs from that in the corresponding disk track . as depicted in the flow chart of fig2 , each background sweep event , whether a seek or a write , prepares a waiting event for the sweep &# 39 ; s subsequent action . thus , the initiation of a seek always prepares the subsequent , related write event ; the initiation of a write prepares the subsequent , unrelated seek event , if another track is waiting to be copied to disk . the continuation module is entered upon the completion of each sweep event . if the host has issued an i / o command which requires the disk ( in other words , a cache - miss ), the background sweep sequence is interrupted , and the waiting event is erased . this action is taken in order to expedite the servicing of the host &# 39 ; s commands , and is taken regardless of the type of sweep event which is waiting . it can result in wasting background seek actions . this is acceptable ; the aborted write will be handled later when time permits . 0f course , once a sweep command , whether a seek or a write , has actually been initiated , it cannot be aborted . if the sweep continuation module is entered after the sweep operations have been interrupted , it will use the event generation module ( see description of event generation ) to restart the sweep sequence . finally , if the continuation module finds that the just completed sweep operation was a write , and no more modified tracks are waiting to be copied to the disk , the sweep is put into the dormant state . as depicted in the flow chart of fig2 , this portion of the firmware is invoked when the unit senses that the line power to it has dropped . since some of the data in the unit may be in the cache portion in a modified state and awaiting transfer to the disk , power must be maintained to the cache memory until the modified portions have been written to the disk . thus , a failure of the line power causes the unit to switch to the battery backup unit . the battery backup unit provides power while the memory device goes through an intelligent shutdown process . if the host is in the process of a data transfer with the memory device when power drops , the shutdown controller allows the transfer in progress to be completed . it then blocks any further transactions with the host from being initiated . the shutdown controller then must initiate a background sweep to copy any modified portions of data tracks from the solid state memory to the disk so that it will not be lost when power is completely shut off to the control and memory circuits . after the sweep is completed ( which will take only a few seconds ), all data in the solid state memory will also reside on the disk . at this point the disk spindle can be powered down , reducing the load on the battery . most power outages are of a short duration . therefore , the controller continues to supply battery power to the control circuits and the solid state memory for some number of seconds . if the outside power is restored in this time period , the controller will power the spindle back up and switch back to outside power . in this case , the operation can proceed without having to reestablish the historical data in the solid state memory . in any case , no data is at risk since it is all stored on the rotating magnetic disk before final shutdown . the final background sweep ( fig2 ) copies modified portions of tracks from the solid state memory to the magnetic disk . there will usually be only a few such tracks , or portions of tracks to copy since the number that can reach this state is intentionally limited by the operations of the system . the final sweep makes use of logic developed for the normal operation of the background sweep . the sweep is initiated in much the same manner as for a timeout during normal operation . if no tracks need to be copied , the sweep is left in the dormant state , and no further sweep action is required . if any tracks need copied , the sweep initiator sets up and initiates the first background seek , as well as sets up the related write event . at the completion of this first seek , control goes to the background continuation module which alternately executes the previously created , waiting event and generates the next event and puts it into a wait status . when no modified tracks remain to be copied , the sweep is finished . this specification refers to items which are not given specific quantities or identities . these have been purposely left unquantified so as not to imply any absolute limits or restrictions . for purposes of illustration , and to provide known workable dimensions and identities , the following ranges of values and identifiers are provided , along with a set which is satisfactory for a sample configuration . sample configuration : 80c196 , 24 mhz ( intel corporation of santa clara , calif .). size range : any appropriate for the host system and the selected disk drive . size range : one megabyte to 100 percent of the capacity of the attached disk capacity . size range : one sector to any size appropriate for the selected disk drive . table f - 1______________________________________table formatsaddress translation ( adt ) table format - unindexed elementstableitem description______________________________________adt - cnl number of tracks on the cached disk spindle ; equals the number of lines in the adt table . adt - head - pos position of read / write head of cache disk . adt - sweep - dir direction of current disk server sweep ; 1 = sweep is progressing from low - to - high . 0 = sweep is progressing from high - to - low . adt - mod - count total number of tracks in the cache which have been modified by writes from the host and are currently awaiting a write to disk by the disk server . adt - mod - urgent the number of cache slots which , when in a modified condition , causes the device to shift priorities to maintain optimal performance . adt - read - hits number of cache read - hits encountered since last reset . adt - read - misses number of cache read - misses encountered since last reset . adt - write - hits number of cache write - hits encountered since last reset . adt - write - misses number of cache write - misses encountered since last reset . ______________________________________ table f - 2______________________________________address translation table format - indexed elementstable maximum itemitem value description______________________________________ ( index ) ( adt - cnl ) adt table index ; equivalent to the corresponding disk track number . there is one adt table line for each disk track . adt - slot ( lru - cnl ) number of the cache slot which contains the disk track of data corresponding to this adt index ; also points to line in lru table related to the disk track . if the disk track is not in cache , this field is set to its null value to indicate that fact . adt - modified 1 flag indicating whether or not this ( cached ) track has been modified by a write operation from the host , and thus , needs to be written from the cache to the disk . 0 = this track ( if cached ) is unmodified and does not need to be written to disk . 1 = this track needs written to disk . ______________________________________ table f - 3______________________________________least - recently - used ( lru ) table format - unindexed elementstableitem description______________________________________lru - cnl number of lines in the lru table ; equal to the number of slots in the cache area . lru - lru pointer to least - recently - used end of the lru chain . lru - mru pointer to most - recently - used end of the lru chain . ______________________________________ table f - 4__________________________________________________________________________least - recently - used table format - indexed elementstable maximum itemitem value description__________________________________________________________________________lru - track ( adt - cnl ) disk track number for data stored in this cache slot ; also points to line in adt table related to the disk track . lru - next ( lru - cnl ) pointer to following link in lru chain ; 0 = this is last ( lru ) link in chain . lru - last ( lru - cnl ) pointer to previous link in lru chain ; 0 = this is first ( mru ) link in chain . lru - cached - low ( track size ) lowest track - relative sector number within the cached track which contains valid data . lru - cached - high ( track size ) highest track - relative sector number within the cached track which contains valid data . lru - mod - low ( track size ) lowest track - relative sector number within the cached track which contains modified data . lru - mod - high ( track size ) highest track - relative sector number within the cached track which contains modified data . lru - locked 1 flag indicating whether or not this ( cached ) track is currently the target of some operation , such as being acquired from the disk , being written to the disk by the cache controller . 0 = the ( cached ) track is not locked ; it is available for any operations . 1 = the ( cached ) track is locked ; it cannot , at this moment , become the target of another , conflicting operation . lru - recycle - register n recycle register ; used for maintaining the recycling value . used as a means for retaining data in cache beyond its arrival at the lru position in the lru table . __________________________________________________________________________ table t - 0______________________________________sample i / o &# 39 ; s for illustrationthe lru and adt table examples are based on i / o samplestaken from an actual operating computer system and projectedinto the system &# 39 ; s environment . for each i / o , the following information is available :( i / o size ( computedref sector in tracknbr ) address sectors number ) comment______________________________________ 1 11 , 742 68 46 , 47 read starts in 46 , ends in 47 . . . .. . . .. . . . 1000 14 , 190 68 56 read com - pletely in 561001 15 , 550 68 61 , 62 write starts in 61 , ends in 621002 54 , 582 68 214 write entirely in 214 . . . .. . . .. . . . ______________________________________ table t - 1______________________________________initial adt tablethe adt table is set to initial conditions to indicate that nodisk tracks are cached . note : a &# 34 ;*&# 34 ; indicates a null value . ______________________________________adt - cnl = 14628adt - head - pos = 0adt - sweep - dir = 1adt - mod - count = 0adt - mod - urgent = 11adt - read - hits = 0adt - read - misses = 0adt - write - hits = 0adt - write - misses = 0______________________________________disk ssdtrack slot modified______________________________________1 * 02 * 03 * 04 * 05 * 06 * 0 . . .. . .. . . ( adt - cnl ) ______________________________________ table t - 2__________________________________________________________________________initial lru tablethe lru table is arbitrarily chained to allow initialoperations to proceed with a minimum of special handling duringstartup of the caching operations . table is listed in mru - to - lru order . note : a &# 34 ;*&# 34 ; indicates a null value . cnl = 22 lru = 1 mru = 22ssd lru lru disk cached modified lru re - slot last next track low high low high lock cycle__________________________________________________________________________22 21 0 0 * * * * 0 0 ( slot 22 is arbitrarily designated the mru ) 21 20 22 0 * * * * 0 020 19 21 0 * * * * 0 019 19 20 0 * * * * 0 018 17 19 0 * * * * 0 017 16 18 0 * * * * 0 016 15 17 0 * * * * 0 015 14 16 0 * * * * 0 014 13 15 0 * * * * 0 013 12 14 0 * * * * 0 012 11 13 0 * * * * 0 011 10 12 0 * * * * 0 010 9 11 0 * * * * 0 09 8 10 0 * * * * 0 08 7 9 0 * * * * 0 07 6 8 0 * * * * 0 06 5 7 0 * * * * 0 05 4 6 0 * * * * 0 04 3 5 0 * * * * 0 03 2 4 0 * * * * 0 02 1 3 0 * * * * 0 01 0 2 0 * * * * 0 0 ( slot 1 is arbitrarily designated the lru ) __________________________________________________________________________ table t - 3a______________________________________adt table after one i / o operation ( a read involving tracks 46 and 47 ) note : a &# 34 ;*&# 34 ; indicates a null value . ______________________________________adt - cnl = 14628adt - head - pos = 47adt - sweep - dir = 1adt - mod - count = 0adt - mod - urgent = 11adt - read - hits = 0adt - read - misses = 1adt - write - hits = 0adt - write - misses = 0______________________________________disk ssdtrack slot modified comments______________________________________1 * 02 * 03 * 04 * 05 * 06 * 0 . . .. . .. . . 46 1 0 from read - miss ( 2 - track ) 47 2 0 from read - miss ( 2 - track ) 48 * 049 . . ( adt - cnl ) . . ______________________________________ table t - 3b__________________________________________________________________________lru table after one read i / o operation ( a read involving track 46 ) lru - cnl = 22lru - lru = 3lru - mru = 2ssd lru lru diskcached - modified lru re - slot last next track low high low high lock cycle 2 1 0 47 1 256 * * 0 0 ( slot 2 becomes the new mru ) 1 22 2 46 222 256 * * 0 0 ( slots 1 and 2 have been used to cache the 2 - trackread - miss .) 22 21 1 * * * * * 0 0 ( slot 22 was old mru ) 21 20 22 * * * * * 0 0 20 19 21 * * * * * 0 0 19 18 20 * * * * * 0 0 18 17 19 * * * * * 0 0 17 16 18 * * * * * 0 0 16 15 17 * * * * * 0 0 15 14 16 * * * * * 0 0 14 13 15 * * * * * 0 0 13 12 14 * * * * * 0 0 12 11 13 * * * * * 0 0 11 10 12 * * * * * 0 0 10 9 11 * * * * * 0 0 9 8 10 * * * * * 0 0 8 7 9 * * * * * 0 0 7 6 8 * * * * * 0 0 6 5 7 * * * * * 0 0 5 4 6 * * * * * 0 0 4 3 5 * * * * * 0 0 3 0 4 * * * * * 0 0 ( slot 3 becomes the new lru ) __________________________________________________________________________ table t - 3c__________________________________________________________________________lru table after 1000 i / o operationsi / o 1000 was a read involving track 56 . table is listed in mru - to - lru order . note : a &# 34 ;*&# 34 ; indicates a null value . lru - cnl = 22lru - lru = 3lru - mru = 21ssd lru lru diskcached - modified lru re - slot last next track low high low high lock cycle 21 18 0 56 110 256 * * 0 1 ( read - miss on a cache - ahead slot ) 18 19 21 213 1 256 * * 0 0 ( cleaned by writing modified portion to disk ) 19 5 18 212 227 256 * * 0 0 5 17 19 8071 255 256 * * 0 0 17 1 5 63 1 256 * * 0 0 ( cached - ahead for read of track 62 ) 1 8 17 62 1 256 * * 0 0 ( cached by read miss spanning tracks 61 - 62 ) 8 9 1 61 191 256 * * 0 0 9 14 8 48 117 256 * * 0 0 14 20 9 65 1 256 * * 0 0 ( cached - backward for read of track 66 ) 20 16 14 66 135 256 * * 0 0 ( cached due to read - miss of track 66 ) 16 2 20 57 127 256 * * 0 0 2 12 16 46 153 256 * * 0 0 12 22 2 52 181 256 * * 0 0 22 4 12 67 1 256 * * 0 0 4 15 22 41 1 256 * * 0 0 15 10 4 42 21 256 * * 0 0 10 6 15 43 1 256 * * 0 0 6 3 10 58 1 256 * * 0 0 3 0 6 215 1 256 * * 0 0 ( slot 3 is now the lru slot ) __________________________________________________________________________ following slots have been modified but not yet cleaned by writing modified portion to disk ; thus , they are not chained . ______________________________________7 * * 45 1 256 1 2 0 011 * * 44 191 256 191 256 0 013 * * 214 55 256 55 122 0 0______________________________________ table t - 3ca__________________________________________________________________________lru table after recycling following 1000th i / o operationi / o 1000 was a read involving track 56 . table is listed in mru - to - lru order . note : a &# 34 ;*&# 34 ; indicates a null value . lru - cnl = 22lru - lru = 3lru - mru = 6ssd lru lru diskcached - modified lru re - slot last next track low high low high lock cyclea 6 3 0 58 1 256 * * 0 0b 3 21 6 215 1 256 * * 0 0 21 18 3 56 110 256 * * 0 1 ( cached due to a read - miss of disk track 56 ) 18 19 21 213 1 256 * * 0 0 ( cleaned by writing modified portion to disk ) 19 5 18 212 227 256 * * 0 0 5 17 19 8071 255 256 * * 0 0 17 1 5 63 1 256 * * 0 0 ( cached - ahead for read of track 62 ) 1 8 17 62 1 256 * * 0 1 ( cached by read miss spanning tracks 61 - 62 ) 8 9 1 61 191 256 * * 0 1 9 14 8 48 117 256 * * 0 0 14 20 9 65 1 256 * * 0 0 ( cached - backward for read of track 66 ) 20 16 14 66 135 256 * * 0 1 ( cached due to read - miss of track 66 ) 16 2 20 57 127 256 * * 0 0 2 12 16 46 153 256 * * 0 0 12 22 2 52 181 256 * * 0 0 22 4 12 67 1 256 * * 0 0 4 15 22 41 1 256 * * 0 0 15 10 4 42 21 256 * * 0 0 10 0 15 43 1 256 * * 0 0 ( slot 10 is now the lru slot ) __________________________________________________________________________ following slots have been modified but not yet cleaned by writing modified portion to disk ; thus , they are not chained . ______________________________________7 * * 45 1 256 1 2 0 011 * * 44 191 256 191 256 0 013 * * 214 55 256 55 122 0 0______________________________________ table t - 3cb__________________________________________________________________________lru table after prefetch following 1000th i / o operationi / o 1000 was a read involving track 56 . table is listed in mru - to - lru order . note : a &# 34 ;*&# 34 ; indicates a null value . lru - cnl = 22lru - lru = 15lru - mru = 10ssd lru lru diskcached - modified lru re - slot last next track low high low high lock cyclea 10 6 0 55 1 256 * * 0 0b 6 3 10 58 1 256 * * 0 0c 3 21 6 215 1 256 * * 0 0 21 18 3 56 110 256 * * 0 1 ( cached due to a read - miss of disk track 56 ) 18 19 21 213 1 256 * * 0 0 ( cleaned by writing modified portion to disk ) 19 5 18 212 227 256 * * 0 0 5 17 19 8071 255 256 * * 0 0 17 1 5 63 1 256 * * 0 0 ( cached - ahead for read of track 62 ) 1 8 17 62 1 256 * * 0 1 ( cached by read miss spanning tracks 61 - 62 ) 8 9 1 61 191 256 * * 0 1 9 14 8 48 117 256 * * 0 0 14 20 9 65 1 256 * * 0 0 ( cached - backward for read of track 66 ) 20 16 14 66 135 256 * * 0 1 ( cached due to read - miss of track 66 ) 16 2 20 57 127 256 * * 0 0 2 12 16 46 153 256 * * 0 0 12 22 2 52 181 256 * * 0 0 22 4 12 67 1 256 * * 0 0 4 15 22 41 1 256 * * 0 0 15 10 4 42 21 256 * * 0 0 ( slot 15 is now the lru slot ) __________________________________________________________________________ following slots have been modified but not yet cleaned by writing modified portion to disk ; thus , they are not chained . ______________________________________7 * * 45 1 256 1 2 0 011 * * 44 191 256 191 256 0 013 * * 214 55 256 55 122 0 0______________________________________ table t - 3d__________________________________________________________________________i / o table after 1001 i / o operationsi / o 1001 was a write involving tracks 61 and 62 . table is listed in mru - to - lru order . note : a &# 34 ;*&# 34 ; indicates a null value . lru - cnl = 22lru - lru = 15lru - mru = 21ssd lru lru diskcached - modified lru re - slot last next track low high low high lock cycle 10 6 0 53 1 256 * * 0 1 ( slot 10 is still the mru ) 6 3 10 58 1 256 * * 0 0 19 5 18 212 227 256 * * 0 0 5 17 19 8071 255 256 * * 0 0 17 9 5 63 1 256 * * 0 0 9 14 17 48 117 256 * * 0 0 14 20 9 65 1 256 * * 0 0 20 16 14 66 135 256 * * 0 0 16 2 20 57 127 256 * * 0 0 2 12 16 46 153 256 * * 0 0 12 22 2 52 181 256 * * 0 0 22 4 12 67 1 256 * * 0 0 4 15 22 41 1 256 * * 0 0 15 10 4 42 21 256 * * 0 0 10 6 15 43 1 256 * * 0 0 6 3 10 58 1 256 * * 0 0 3 0 6 215 1 256 * * 0 0 ( slot 15 is still the lru slot ) __________________________________________________________________________ following slots have been modified but not yet cleaned by writing modified portion to disk ; thus , they are not chained . since five tracks have been modified , the background sweep will be turned on . ______________________________________ 1 * * 62 1 256 1 2 0 7 * * 45 1 256 1 2 0 8 * * 61 191 256 191 256 0 11 * * 44 191 256 191 256 0 13 * * 214 55 256 55 122 0______________________________________ table t - 3e__________________________________________________________________________lru table after 1002 i / o operationsi / o 1002 was a write involving track 214 . table is listed in mru - to - lru order . note : a &# 34 ;*&# 34 ; indicates a null value . lru - cnl = 22lru - lru = 15lru - mru = 11ssd lru lru diskcached - modified lru re - slot last next track low high low high lock cycle 11 7 0 44 191 256 * * 0 0 ( slot 11 is new mru , based on cleaning operations ) 7 8 11 45 1 256 * * 0 0 8 1 7 61 191 256 * * 0 0 1 10 8 62 1 256 * * 0 0 10 6 1 55 1 256 * * 0 0 6 3 10 58 1 256 * * 0 0 3 21 6 215 1 256 * * 0 0 21 18 3 56 110 256 * * 0 1 ( cached due to a read - miss of disk track 56 ) 18 19 21 213 1 256 * * 0 0 ( cleaned by writing modified portion to disk ) 19 5 18 212 227 256 * * 0 0 5 17 19 8071 255 256 * * 0 0 17 9 5 63 1 256 * * 0 0 ( cached - ahead for read of track 62 ) 9 14 17 48 117 256 * * 0 0 14 20 9 65 1 256 * * 0 0 ( cached - backward for read of track 66 ) 20 16 14 66 135 256 * * 0 1 ( cached due to read - miss of track 66 ) 16 2 20 57 127 256 * * 0 0 2 12 16 46 153 256 * * 0 0 12 22 2 52 181 256 * * 0 0 22 4 12 67 1 256 * * 0 0 4 15 22 41 1 256 * * 0 0 15 0 4 42 21 256 * * 0 0 ( slot 15 is now the lru slot ) __________________________________________________________________________ following slots have been modified but not yet cleaned by writing modified portion to disk ; thus , they are not chained . since only 1 track is modified , the background sweep will remain inactive . ( this was a hit on cached data ; recycle register is set to one ) the invention now being fully described , it will be apparent to one of ordinary skill in the art that many changes and modifications can be made thereto without departing from the spirit or scope of the appended claims . | 6 |
what we claim as new and desire to secure by letters patent is set forth in the following claims . let jane be a user with a mobile electronic device that has a camera that can record video . without loss of generality , we take it to be a cellphone . this includes the case of a smartphone . but other possibilities for the device are an electronic book reader , tablet , netbook or laptop , if these devices also contain a camera that can record video . two other cases are where the device is a digital camera that can record video , or a digital video recorder . fig1 shows jane 101 using her cellphone 102 . she is near screen 103 . this is an electronic screen that shows dynamic images . this includes 2 cases . the first is where video is shown . the second is where a series of still images is shown . in the context of this invention , both cases are equivalent . to simplify the following description , we shall consider screen 103 to be showing video , on the understanding that this includes the other case . screen 103 can be an active or passive display . active means that it illuminates its image , so that the latter can be seen without an external light source . light comes from the image . passive means that the image elements absorb and reflect incident light from an external source to form an image seen by jane . screen 103 shows some video , where this is assumed to include barcode 104 . this is typically a 2 dimensional barcode . often , the rest of the video can be something of semantic meaning to jane . ( though a degenerate case is where the video only consists of barcode 104 .) the meaning induces her to point the camera of the cellphone at barcode 104 and take a video recording . one instance of screen 103 might be the screen of a television . the video being shown could be that of a normal television channel that is being broadcast in the usual wireless manner . or it could be of a cable television channel , that is connected to the television in a wired manner . we will refer to screen 103 as the transmitter and cellphone 102 as the receiver . in this section of the invention , the website 106 and controller 105 should be ignored . [ these will be used later .] suppose for the moment that the barcode is static , even if the rest of the video varies over time . the current state of the art is where jane &# 39 ; s recorder has software installed that can isolate the barcode in the image , and decode it . in general , the barcode can encode arbitrary data . in practice , in the current deployment of static 2d barcodes , the data encoded is usually a url . an installed application on jane &# 39 ; s device will decode this url and then open a browser at that url . [ assuming that the device has wireless internet access .] in this invention , the type of data encoded can be arbitrary . it is not restricted to the de facto case of a url . but while the type of data is arbitrary , any given encoding has a finite capacity to the amount of data that can be encoded in a single barcode . in general , if we choose an encoding , like qr , the capacity can be increased , by having smaller regions [ usually rectangles ] of different colours . but for any given encoding , there is usually defined a maximum capacity . the resolution of the screen might also affect the maximum capacity image that can be shown . on the recorder , its angular resolution defines the smallest solid angle that can be subtended by an encoding image . so depending on jane &# 39 ; s distance from the screen , the recorder might or might not be able to decode the maximum capacity encoded image that the screen can produce . hence for a given recorder and transmitter and a given encoding , there is a maximum amount of data that can be decoded successfully by the recorder from a single barcode . one way around this constraint is to use the dynamic ability of the screen to show different encoded data over time . this is the essence of this invention . the first is on the transmitter screen . it now shows a series of images of different barcodes ( 107 , 108 , 109 , 110 , 111 ). where we assume a given choice of barcode encoding . the preferred implementation is where the barcode images appear at the same position in the screen , and where the barcodes are all the same size . while this is not strictly necessary , it can simplify the amount of processing that the recorder has to do to isolate and analyse each barcode . also , as a practical matter , if jane points her recorder &# 39 ; s camera at a subset of the screen , where the first barcode appears , then when subsequent barcodes appear in the same location , she does not have to move the camera . the second novel aspect is on the recorder . currently when the device is a cellphone , jane points its camera at a static image and then presses a button which triggers the decoding of a barcode in that image . the novel modification is now when she presses the button , the camera records the video and decodes the different barcodes and combines these into a single data set . since software exists that can decode a single image of a barcode , this modification is a straightforward extension of that software . below , we discuss some of the implications of how this is done . one case is where the video is recorded for some duration , and then recording is stopped , and decoding is commenced on the different barcode images . this can be considered a batch processing approach . another case is where as the video is recorded in one thread , another thread or threads runs to decode the completed images in the video . this can be considered a streaming mode of processing . when the images have been decoded , they might be deleted , which frees up space and lets the recorder potentially hold more decoded data than the previous case . the cost of this might be in the extra computational power and battery power consumption needed for the concurrent threads . note that the data flow goes from the transmitter to the receiver . the receiver is not assumed to have a transmitter subdevice that can directly communicate with the original transmitter . suppose the transmitter is repeatedly playing a finite , ordered set of barcodes . the recorder needs to know when this sequence starts and ends . one method is for special start and stop symbols to be defined . these symbols should be distinct from all possible images produced in that given encoding . the symbols might be defined by some public process that is separate from the official standard for that encoding . or the symbols might be approved by whatever entity owns , maintains or defines that encoding standard . in general , the start and stop symbols should have the same sizes as the barcodes . the sequence starts with the start symbol ( 107 ), followed by the barcodes , and ends with the stop symbol ( 111 ). also , the preferred implementation is where the start and stop symbols appear at the same place on the screen as the barcodes , so that jane does not have to shift the orientation of the camera . the recorder has an extension to the standard software , where the latter decodes the normal encoding , so that the start and stop symbols can now be detected . the information content in these 2 symbols will be typically much less than in a barcode . in one limit , the start and stop symbols are only 1 bit of information each . an extension is where the start symbol also encodes information about the incoming data stream of barcodes . perhaps the number of barcodes , or the frame rate of number of barcode images per second . but even in the case of extensions like these , it can be seen that the information content of the start symbol can be expected to be relatively small , compared to a typical barcode . thus , given the small information content of the start and stop symbols , whatever choice of symbols is made , the detection and decoding of these by the recorder can be expected to be computationally simpler than of each barcode . note that if the start symbol can contain information about the barcode stream , and if this information is needed during the recording of that stream , then the start symbol should be decoded before the first barcode is recorded . an example of this arises in the next point . another issue is the possibility of a repeated barcode . each barcode has to appear on the transmitter screen for a minimum amount of time , to let a recorder have enough time to at capture the image , and perhaps also to decode it . call this time x . different transmitters might have different values of x . how does the recorder know x ? one answer is that the start symbol encodes the amount of time a single barcode will appear . then if the recorder sees that a given barcode appears for twice this time , say , it knows that this means the decoded data correctly appears twice . it might be objected that instead of the start symbol defining the duration of a single barcode , how about just having the recorder deduce this from the incoming barcodes ? one problem is that if streaming decoding is done , and the first barcode appears 3 times , say , then the recorder does not know what is the duration of a single barcode . this complicates the overall decoding . an alternative to having the start symbol encode the barcode duration is to define a white space symbol ( 110 ). like the start and stop symbols , this would be of the same dimensions as a barcode , but as an image it would be different from any possible barcode . so imagine that we have a initial barcode stream of “ a b c c d e ”, where { a , b , c , d , e } are barcodes , all different from each other , and c is repeated . let w be the white space symbol . then the transmitter would display in this order —“ a b c w c d e ”. in turn , an alternative to the previous paragraph is a simple run length encoding . instead of w , imagine a repeat symbol r which contains a parameter indicating the number of times the next symbol , which is assumed to be a barcode , is repeated . then the previous example of the transmitter would output “ a b r ( 2 ) c d e ”, where the notation r ( 2 ) means that the r symbol has a 2 encoded in it . for the white space and repeat symbols , the preferred implementation has these located at the positions of the barcodes . above , we described the case where the start and repeat symbols encoded parameters . what encoding method should be used ? one case is where the method is an extension of that used for the barcodes . where now extra graphics are added to these special symbols so that they cannot be confused with the barcodes . another case is to devise a new encoding method , perhaps simpler than that used for barcodes , because the amount of data to be encoded is expected to be far less . suppose the data encoded in the barcodes is ascii or unicode . in turn , there could be an internal format to this data , where the format has been publicised so that the recorder &# 39 ; s software understands and uses it . for example , the simplest case could be where the data is written in a variable = value format , where these pairs are delimited by , say , a semicolon . or perhaps the data is written in xml . the latter might be circumspect because even though the use of multiple barcodes gets around the data limitation in a single barcode , xml can still be verbose , and this might be considered excessive in the context of this application . above , we discussed the case where a fixed set of barcodes is repeatedly shown on the transmitter screen , bracketed by start and stop symbols . so the original data is constant . another possibility is where the barcodes contain dynamic data , being shown in near real time . note the difference between the dynamic barcodes and dynamic data . for example , suppose the transmitter is connected to a set of sensors that measure parameters about the surroundings , like temperature , pressure , humidity and rainfall . then the current values of these are output in a given set of barcodes . the next set of barcodes will then have newer readings . this also leads into examining an instance of why this invention might be implemented . one case could be transducers or sensors that have data about the surroundings . these could have a display that shows the data or subsets of it in human readable format . for example , “ temperature = 35 celcius , high = 40 , humidity = 80 % [ etc ]”. jane can read this for herself . but suppose she has some application on her device that can use this information . even typing the limited amount of data in the above example can be error prone on her device , especially if it has a small form factor , like a cellphone . and of course the use of multiple barcodes lets her easily download a relatively large amount of data . why can &# 39 ; t the transmitter just use a wireless method like wifi or bluetooth ? it might also do that . but suppose that the transmitter has a screen , that perhaps is primarily for humans to view . then the incremental cost in software and memory to implement the transmitter side of this invention is relatively small . no extra hardware needed . this is especially germane if there are a lot of transmitter screens already deployed , without the means to also broadcast in some other wireless manner . like conventional televisions or electronic billboards or screens . hence the prior existence of the transmitter screen for human viewing can be a key reason for using this invention . likewise at the user level , the only main assumption is that the recorder have a camera . the invention piggybacks on existing hardware . another reason is to allow a second channel or modality for jane to get the data , assuming that the transmitter is also broadcasting it by other means . in case jane &# 39 ; s device is not able to receive by those means . also , in contrast to a wireless communication method that is not line of sight , the current invention minimises the chances of spoofing , where a false transmitter pretends to be the correct wireless transmitter . the line of sight nature of this invention means that jane can be assured that she is getting data directly from the screen . one possible usage is where jane is at an automated teller machine ( atm ) or some other type of kiosk with a computer screen . suppose she has a cellphone that can implement the receiver side of this invention , and there is a button on the atm that she can press to indicate this to the machine . the atm screen then might commence displaying some dynamic barcodes . prior to this , the atm could have a holder near the screen , into which jane places the cellphone . the holder aligns the cellphone so that its camera can focus on the barcodes . the holder might be designed to hold most common types of cellphones . optionally , jane might have to adjust the holder to best align the cellphone vis a vis the screen . or the holder / atm might have electronics that can do this , perhaps based on detecting the model of cellphone and thus having knowledge of the placement of the phone &# 39 ; s camera . the close distance between the cellphone and the screen means that a relatively high resolution encoding might be used , which increases the download bandwidth . currently with most atms , any data transfer is from the customer to the machine , via the pressing of buttons . this invention lets the atm send considerable data in the other direction . perhaps this data is specific to the customer , like her stock portfolio ; hence the desire for privacy against evesdropping . there is utility in jane getting this information in electronic form on her cellphone , rather than say as paper printout from the atm . it can be cheaper for the bank . also , having it electronically can be more convenient than a lot of bulky hardcopy . and the data might be in a format that can be used by other software packages , like a spreadsheet . analogous to how film cameras have been superseded by digital cameras . of course , there could be other means to download data . including bluetooth or near field communication . the method of this invention should not be seen as an exclusive means , but perhaps as a fallback if the cellphone cannot use other means . there could be specific implementations of this invention &# 39 ; s transmitter where jane might be able to manually affect the transmitter &# 39 ; s operation . for example , the transmitter &# 39 ; s screen might be turned off or in a low power mode , and jane can go to it and press a button to activate it , whereupon the screen displays the barcodes and perhaps some other information to be viewed manually . in a co - pending application ser . no . 13 / 068 , 782 , we discussed how the user could use a cellphone with a camera , view a barcode ( that encodes a url ) on an electronic screen , and where by the phone going to that url , a signal goes to the server that controls the screen . the server then causes a different image or video to appear on the screen . the server is a dual server , for it responds to general queries from the internet , and it controls (‘ serves ’) the screen . in that provisional , a bar code was considered static , even if it appeared in a video where other parts of the screen varied in time . in fig1 , this is shown as the objects website 106 and controller 105 . the server for the url can be envisaged as website 106 , and controller 105 can be considered as the computer that directly controls screen 103 . website 106 sends data and instructions to controller 106 via some type of wired or wireless connection . by combining that provisional with this invention , we have the following . one implementation is for the transmitter to show several static barcodes , each encoding a url . assume that all the urls go to the same server , but that the arguments in the url indicate which has been picked by jane . from a given choice , the server displays on the screen a set of dynamic barcodes , as described earlier in this invention . where each set corresponds to a given static barcode . the location of the dynamic barcodes might be different from any of those static barcodes . or it might be at the location of the picked static barcode . this makes it easier for jane , as she has already moved her camera to focus on the latter barcode . so simply holding the camera steady means that she can then download the new data . another implementation is where one or more of the static barcodes can affect the resolution settings on the dynamic barcodes . imagine perhaps that jane &# 39 ; s camera is having trouble decoding the latter because the resolution is too fine for the combination of her camera and the distance to the screen and the resolving power of the screen . hence there might be 2 static barcodes ; one that implements ‘ lower resolution ’ and one that implements ‘ higher resolution ’. these barcodes would appear on the screen while the dynamic barcodes are shown elsewhere on the screen . by picking the ‘ lower ’ barcode , jane triggers a redisplay of the dynamic barcodes . or she might pick ‘ higher ’ if her camera can read the smaller details . a variant is where there is a set of static barcodes , each corresponding to a given resolution . in general , having both static and dynamic barcodes on the screen lets the server offer arbitrarily complex choices to the user about the type of data and how it is shown in the latter barcodes . another implementation is where the data decoded from the dynamic barcodes contains one or more urls that go back to the server . the cellphone could have software that displays these in a browser or other application , where jane could click on one of these . it could tell the server various things , including changing the transmitter screen to show other video or to offer other data to download via barcodes . this use of embedded urls to close a feedback loop to the transmitter could be instead of or in addition to the use of static barcodes on the screen . a variant on the previous paragraph is where jane does not have to click on a decoded url . instead , the data is automatically decoded and sent to an application that uses it to perform some computations . one result could be that the application opens a connection on the internet to a decoded url . which could then cause the server to send more data via the barcodes . hence there is an automated feedback . an instance of a machine to machine [ m2m ] interaction . in the previous 2 paragraphs , the use of a url inside the downloaded data offers potentially more customised feedback to the server than via static barcodes . the ‘ internal ’ url could be picked out of many in the data . more than the number of static barcodes on the screen , since the size of the screen and the probable need to have space on the screen to show other video limits this . also , an internal url could be constructed not just using a url in the downloaded data , but also with extra arguments , where these are computed by the cellphone application , based on the data and on jane &# 39 ; s preferences and on any other parameters on the phone accessible to the application . so an internal url can be more flexible than a static url from a static barcode . thus far , we referred to the receiver as typically being a device like a cellphone , where jane manually points its camera at the portion of the transmitter screen that has the barcodes , dynamic or static . another possibility is for the receiver to be an automated device , with image recognition software that recognises the presence of barcodes in a possibly low resolution image . the receiver can then focus its camera directly on those barcodes . if the receiver is moving , it could have an electromechanical apparatus that automatically keeps the focus on the barcodes as much as possible , i . e . autotracking and image stabilisation . another extension refers to the earlier description of how a choice of a static barcode can determine what is shown in the dynamic barcodes . it was assumed that there was only one user doing this near the transmitter . this can be generalised to several users in the vicinity , each with a receiver device that can also access the internet . different users might choose different static barcodes . the transmitter could tally these up over some time interval , and use voting to determine which choice or choices it will implement in the encoding of a future set of dynamic barcodes . similarly , the users might choices from various urls inside the data decoded from the dynamic barcodes , where these choices go back to the transmitter . which can tally these up and use voting to determine a future set of dynamic barcodes . the ideas of the previous 2 paragraphs can be combined , so that users make choices from static barcodes and from urls inside the data decoded from the dynamic barcodes . the transmitter tallies these to determine a future set of dynamic barcodes . “ clock free two - dimensional barcode and method for printing and reading the same ” by d . lopresti et al , u . s . pat . no . 6 , 115 , 508 ( 2000 ). “ apparatus and method for printing two - dimensional barcode and articles incorporating such barcode ” by g . athens et al , u . s . pat . no . 6 , 631 , 012 ( 2003 ). “ two - dimensional color barcode and method of generating and decoding the same ” by p . cattrone , u . s . pat . no . 7 , 478 , 746 ( 2009 ). “ optimised messages containing barcode information for mobile receiving device ” by r . forbes , u . s . pat . no . 7 , 693 , 744 ( 2010 ). “ data transfer system using mobile terminal and two - dimensional barcode ” by t . ueno et al , us patent application 20010051915 ( 2001 ). “ three dimensional barcode ” by r . shoobridge , us patent application 20070125861 ( 2007 ). “ sensor - embedded barcodes ” by marc cohen et al , us patent application 20090020609 ( 2009 ). “ dynamic barcode system ” by g . bradford , us patent application 20100078482 ( 2010 ). “ cellphone changing an electronic display that contains a barcode ” by w . boudville , u . s . patent application ser . no . 13 / 068 , 782 ( 2011 ). | 6 |
please refer to fig2 and 3 of schematic views of assembly and function of the present invention . as shown in fig2 and 3 , the device 1 to motorize bladeset rotation angle of shutter of the present invention comprises a body 10 buried on one side of a frame 20 of the shutter , an output shaft 109 fitted with one end of one of the blades of the bladeset 21 through an end cover 212 for transmission . the body 10 can be controlled remotely with an input interface 61 by transmitting signals in a wired or wireless manner , and the wireless communication manner may be a radio frequency or an infrared signal manner . here , each of the blades of bladeset is pivotally connected to a corresponding spindle hole of the frame 20 in a smoothly - rotatable manner , such that the output of the device 1 is controlled to be sufficient to drive the bladeset 21 to rotate . the shutter includes a pull rod 22 joining each of the blades of bladeset 21 together for a linked - up control , and allows a manual operation by the user . during a motorizing operation , a plurality of keys of the given target angle on the input interface 61 , for example an upper origin point key 610 , a first target angle ( 45 degrees ) key 611 a second target angle ( 90 degrees ) key 612 , a third target angle ( 135 degrees ) key 613 , etc ., is used for outputting an angle instruction to the body 10 , such that the bladeset 21 of the shutter automatically rotates to the required upper origin point u , the first target angle a , the second target angle b , the third target angle c , etc . please refer to fig4 of an appearance and local exploded view of the body 10 of one embodiment of the present invention . the body 10 generally is a box buried and fixed in the frame of shutter ( not shown ), and an output shaft 109 is connected to an end cover 212 fitted with one end of one of the blades of bladeset 21 for transferring a rotary force . the power coming from a battery ( not shown ) in the body 10 is controlled to drive a motor 51 driven . a battery cover 101 may be taken off for replacing the battery . generally , the body 10 of the device to motorize bladeset rotation angle of shutter of the present invention comprises a receiver ( not shown ), for example an infrared signal receiving circuit , for receiving a control instruction ; a sense 40 for sensing at least one origin point position of the bladeset 21 , a driver 50 for driving the bladeset 21 to rotate , and a controller ( which contains a microprocessor and a circuit ) for calculating and controlling the operation of the driver 50 according to the origin point position . here , the sensor 40 includes an actuating piece 41 connected to the output shaft 109 and a switch 42 , and the driver 50 includes a motor 51 and a reduction gear set ( such as the gears 52 , 53 , 54 , 55 described below ), for driving the output shaft 109 . when the controller receives the instruction signal from the input interface , the driver 50 is controlled to determine the origin point position of the bladeset 21 by utilizing the sensor 40 , and then the bladeset 21 is further driven to the target angle . fig5 shows a local structure of one embodiment of the driver 50 , the sensor 40 , and the bladeset 21 ( represented by the end cover 212 ). the output shaft of the motor 51 is connected to a motor gear 52 , a big gear 53 is engaged with the motor gear 52 , a small gear 54 and the big gear 53 are set coaxially , which are connected with each other or have a moment restrictor , an output gear 55 is fixed to the output shaft 109 , and the above motor 51 , motor gear 52 , and coaxial gear set ( including the big gear 53 and the small gear 54 ) and output shaft 109 together form the driver 50 disposed in the body 10 , such that the coaxial gear set ( including the big gear 53 and the small gear 54 ) and the output shaft 109 may be positioned and rotated pivotally , and thereby the rotary force of the motor 51 is decreased in speed and increased in force and then transmitted to the output shaft 109 . the output shaft 109 forms a cross shaped ( or another suitable shape ) spindle hole 109 a to transfer the rotary force in combination with a protrusion 212 a corresponding to the end cover 212 of the blade . the motor 51 preferably is a stepping motor , by the driving pulse of which the rotation angle is controlled exactly . at least one actuating point is set on the output shaft 109 , and here two actuating protrusions 411 , 412 respectively correspond to the upper origin point u and lower origin point d of the bladeset 21 . the actuating protrusions 411 , 412 press a switch 42 for an actuation through a spring 413 , such that the switch 42 produces an on signal when the output shaft 109 and the bladeset 21 are rotated to near the positions of upper , lower limits of a rotatable range of the blade ( that is the upper origin point and the lower origin point ), while produces an off signal when they are at other intermediate angles . the controller ( not shown ) controls the bladeset 21 to be rotated and positioned according to the signals , and once the controller determines that the bladeset 21 has reached the upper or lower origin point u or d , the blades are accordingly controlled to be rotated to other positioning angles a , b , c etc . the above spring 413 and switch 42 ( fixed on a circuit board 62 ) are both fixed within the body 10 , and form the sensor 40 together with the actuating protrusions 411 , 412 . fig6 shows an embodiment of the input interface 61 of the present invention . the input interface preferably is a remote control , such that multiple shutters may be remotely controlled simultaneously with a radio frequency or an infrared signal . the input interface 61 is provided with a plurality of given target angle keys , for example the upper origin point key 610 , the first target angle key 611 , the second target angle key 612 , the third target angle key 613 , the lower origin key 614 and a stop key 615 . accordingly , the user only needs to choose to press any one of the target angle keys 610 , 611 , 612 , 613 , and 614 to send out the instruction signal , the device of the present invention automatically performs the angle control . during the performance , the user may change the target angle at any time or may press the stop key 615 to stop the rotation of the bladeset 21 . the control method of the present invention is illustrated by taking fig7 as an example ; fig7 is a schematic view of the rotation angle of the bladeset 21 . for example , when starting from an initial point s 1 , the blade first rotates upwards until reaching the upper origin point u ( the sensor is on ), and then the controller counts the angle ( with time or in pulse number ) inversely to rotate the blade to the target angle ti . during this period , for example being at the intermediate point m 1 before reaching the upper origin point u , even though the setting of the target angle is changed , the controller continues to perform an upward rotation to turn to the control of a new target angle after finding the upper origin point u ( if the target angle is the upper origin point u or the lower origin point d , the rotation proceeds upwards , downwards to the end at any time ). if the instruction of a new target angle is received when the upper origin point u is exceeded and an intermediate point m 2 is reached , the controller reckons a subsequent travel with the current position and continues to rotate the blade to the new target angle t 2 . for example , if again receiving the instruction of a new target angle at an intermediate point m 3 before t 2 is reached , the controller inversely rotates the blade to the new target angle t 3 since the position has been exceeded . another example on control is that , the blade 21 originally stops at the lower origin point d , the sensor being on , and when being restarted , the controller is incapable of determining whether the blade 21 is at the upper origin point u or at the lower origin point d ( since the blade may be moved manually - by the user when it is stopped ), so the controller still controls the blade to rotate upwards . the sensor 40 is checked at real time , and if it is found that the signal has changed from on to off , it is known that the blade 21 is at the lower origin point d originally , and the blade can be controlled to rotate towards the target angle ( that is the second target angle b ) accordingly . the method to motorize the bladeset rotation angle of the shutter of the present invention is still illustrated by referring to fig8 which is a flow diagram . when receiving a start instruction which causes the blade to start from a stop state , the state of sensor in a current position is checked and recorded ( step si 0 ). the blade rotates upwards by a certain rotation angle ( step s 20 ). the case on a change in the sensor is determined ( step s 30 ). if the sensor 40 changes from on to off , it represents that the blade originally is at the lower origin point , so a present angle equals to the lower origin point minus the rotation angle ( step s 40 ), the rotation continues to be controlled accordingly . if the sensor remains off or has changed from off to on just now , it represents that the upper origin point u has still not been reached ( or been entered just now ), the controller may continues to rotate the blade by a certain rotation angle for a re - determination , and when it is determined that the sensor remains on , it represents that the blade now is at the upper origin point , and a present angle equals to the upper origin point ( step s 50 ), and the blade may be rotated downwards to the target angle accordingly . during the operation , a difference between an up - to - date target angle and a present angel is viewed circularly ( step s 60 ). if the present angle is larger than the target angle , the blade is rotated upwards , that is the blade is rotated upwards by a rotation angle and the rotation angle is subtracted from the present angle ( step s 70 ). if the present angle is less than the target angle , the blade continues to be rotated downwards , that is the blade is rotated downwards by a rotation angle and the rotation angle is subtracted from the present angle ( step s 80 ). if the difference equals to 0 , the rotation is stopped . in this embodiment , the rotation angle modified each time is represented by 5 degrees , and practically other angle values may also be used for operation . in the present invention , the motor functions as a power which is slowed down by the reduction gear set , such that the output shaft generates a sufficient moment , correspondingly , when the pull rod or blade is rotated by manual operation , or a barrier is encountered or a dead point is reached during the blade rotation , an external force is input from the blade , which relatively drives an internal driver means to rotate instantly and rapidly , such that the driver means is easy to be damaged . therefore , in the present invention , a moment restrictor is designed on the transmitting path between the transmitting shaft and the motor output shaft , such that the transmitting force detaches when the external force or load exceeds a preset value , and thereby avoiding the driver means from being damaged by the external force . in the embodiment as shown in fig5 of the present invention , an elastic damping structure is designed on the coaxial reduction gear , and as shown the perspective and exploded view of fig9 a and 9 b , the big , small gears 53 , 54 are slidably arranged on the shaft rod 56 , and an elastic piece , for example colloidal silica or a rubber ring 59 , is clamped therebetween , which is firmly locked to an appropriate pressure by utilizing the shoulder region of one end of the shaft rod 56 or a snap ring 561 as well as a screw thread 562 , a washer 580 and dual lug nuts 581 , 582 at the other end , and thereby generating an appropriate friction rotation moment . thus a moment is set sufficient to be output from the inside to drive the blade to rotate , and is capable of protecting the internal driver means from being damaged by the undue moment input from the outside via an overload slip . the moment restrictor naturally may be designed between the output gear and the output shaft , or on the motor gear . the method and device to motorize bladeset rotation angle of the shutter of the present invention at least can achieve the following functions . 1 . the present invention enables the bladeset of the shutter to be rotated to the given angle under an instruction , and allows a remote control operation , and meanwhile controls the bladeset of multiple shutters to be rotated to the target angle ; 2 . the present invention enables the bladeset of the shutter to seek the origin point wisely , controls the rotation to the target angle accordingly , and allows updating of the requirement for the target angle during the process , thereby saving the time and power consumption and considering both the motorized and manual operations . the invention being thus described , it will be obvious that the same may be varied in many ways . such variations are not to be regarded as a departure from the spirit and scope of the invention , and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims . | 4 |
fig1 illustrates a device for the use in the non - surgical clipping of an aneurysm . the guiding catheter 1 encompasses a guiding needle 2 which encompasses a wire comprising a shape memory alloy 3 . the guiding catheter 1 is essentially any catheter known in the art capable of getting to the affected area ( i . e ., the lumen of a blood vessel or artery proximal to an aneurysm ) and allowing the passage of a guiding needle . the guiding needle 2 is a hollow tube with a needle tip at its distal end . the guiding needle can perforate the wall of the blood vessel thus allowing the properly shaped guiding needle to exit and re - enter the vessel lumen . the guiding needle can be made of any known material that can pass through the guiding catheter , and is shaped with the appropriate curvature such that it can exit and re - enter the vessel lumen , and that can deliver the wire comprising a shape memory alloy . such materials include , but are not limited to , metal or a reinforced polymer material . the wire comprising a shape memory alloy 3 is made from such metal alloy that allows it to be straight during deployment and then assume a pre - set twisted form that was thermo mechanically predetermined , this transformation being triggered by a temperature step . the temperature step may be affected by changing the temperature of the environment around the wire , e . g ., by hot fluid or body heat , or by passing current through the wire generating resistive heat . any shape memory alloy can be used to make the wire comprising a shape memory alloy . in specific embodiments , the shape memory alloy used is niti ( e . g ., nitinol ), cuznal , cualni , or a mixture thereof ( see , e . g ., shape memory materials , edited by otsuka and wayman , cambridge university press ; october 1999 and shape memory alloys , edited by youyi and otsuka , international academic publishers , june 1998 ). fig2 illustrates the device whose tip is shown in fig1 . the devise is positioned in the lumen 4 of a blood vessel proximal to an aneurysm 5 . the guiding catheter can be passed through the body lumen to the affected area by any method known in the art . the affected area is identified by diagnostic methods known in the art , e . g ., mri , angiogram , or the like . the location of the catheter can be monitored by any method known in the art . in one embodiment , the progress of the catheter through the lumen is monitored by a device that detects radiopacity of the catheter device such as angiographic equipment in x - ray . increased radiopacity can be provided to the catheter by manufacturing ( all or a part of ) or coating ( all or a part of ) the catheter with one or more radiopaque materials . the method of using the device to treat an aneurysm begins with the guiding needle 2 being deployed from the guiding catheter 1 . the guiding needle 2 perforates the vessel wall ( first perforation 6 ). the guiding needle is then passed through the first perforation 6 and leaves the vessel lumen 4 immediately proximal to the aneurysm 5 . the guiding needle is then tracked along the exterior vessel wall until it passes the aneurysm 5 on a first side of the aneurysm . the guiding needle 2 perforates the vessel wall ( second perforation 7 ) and passes through the perforation to re - enter the vessel lumen 4 immediately distal to the aneurysm 5 . the position of the guiding needle can be monitored by any method known in the art . in one embodiment , the guiding needle is monitored by angiography . increased radiopacity can be provided to the guiding needle by the means described supra . fig3 illustrates the next step in the method of the invention to treat an aneurysm . a first wire comprising a shape memory alloy 3 is fed through and deployed from the guiding needle 2 . fig4 illustrates the next step in the method of the invention to treat an aneurysm . the guiding needle is retracted back into the guiding catheter 1 though the first 6 and second 7 perforations leaving the first wire comprising a shape memory alloy 3 positioned around the first side of the aneurysm 5 . fig5 illustrates the next step in the method of the invention to treat an aneurysm . the guiding needle 2 is deployed from the guiding catheter 1 for a second time . the guiding needle 2 perforates the vessel wall ( third perforation 8 ). the guiding needle is then passed through the third perforation 8 and leaves the vessel lumen 4 immediately proximal to the aneurysm 5 . the guiding needle is then tracked along the exterior vessel wall until it passes the aneurysm 5 on a second side of the aneurysm ( the side of the aneurysm opposite the first wire comprising a shape memory alloy ). the guiding needle 2 perforates the vessel wall ( fourth perforation 9 ) and passes through the perforation to re - enter the vessel lumen 4 immediately distal to the aneurysm 5 . a second wire comprising a shape memory alloy 10 is fed through and deployed from the guiding needle 2 . perforations 1 and 3 may be separate perforations or they may overlap . perforations 2 and 4 may be separate perforations or they may overlap . fig6 illustrates the next step in the method of the invention to treat an aneurysm . the guiding needle is retracted back into the guiding catheter 1 through the third 8 and fourth 9 perforations leaving the second wire comprising a shape memory alloy 10 positioned around the second side of the aneurysm 5 ( i . e ., opposite that of the first wire ). the first wire 3 and the second wire 10 are now on either side of the neck of the aneurysm 5 . the first and second wires comprising a shape memory alloy have been pre - conditioned such that when heated they will revert to a mutually twisted configuration . this is accomplished by the first and second wires twisting around each other after heating them due to the pre - set twisted shape of the wires . fig7 illustrates the last step in the method of the invention to treat an aneurysm . the guiding catheter and the guiding needle are retracted through the vessel and removed from the patient leaving the twisted first 3 and second 10 wires . the first wire 3 and second wire 10 are twisted around each other by application of moderate heat . thus the neck of the aneurysm is pressed close by the twisted wires . the amount of heat necessary to cause the shape reversion of the wires will vary depending on , e . g ., the type of shape memory alloy used , the thickness of the wire , etc . in one embodiment , the heat necessary to cause shape reversion is body heat . in another embodiment , the heat necessary to cause shape reversion is higher than body heat . in such embodiments , any means of applying the moderate heat necessary to cause the shape reversion of the first and second wires can be used . in a specific embodiment , a mild electric current may be passed through the wires to heat them . in another specific embodiment , there is heating by a hot fluid in the region of the wires . by twisting wires 3 and 10 , the neck of the aneurysm 5 has been substantially clipped by twisted wires 3 , 10 and thus the blood flow from the lumen 4 of the vessel is reduced . this can be measured by methods known in the art . the reduction in blood flow would lead to thrombosis in the aneurysm and its further exclusion from blood circulation . as various changes can be made in the above - described subject matter without departing from the scope and spirit of the present invention , it is intended that all subject matter contained in the above description , or defined in the appended claims , be interpreted as descriptive and illustrative of the present invention . modifications and variations of the present invention are possible in light of the above teachings . | 0 |
an electronic system and corresponding methods , according to an embodiment of the present invention , facilitate and provide an automatic real time update system for controlling events of a mobile device in a communications network . the terms electronic services , services , network services and online services are used interchangeably herein . the services provided by the system of this invention , in one or more embodiments , are provided by a service provider . a service provider is an entity that operates and maintains the computing systems and environment , such as server systems and infrastructure that enable the delivery of information and services . typically , server architecture comprises of components ( e . g ., hardware , software , and communication lines ) that store and offer electronic or online data , text and voice communication services . in the following , numerous specific details are set forth to provide a thorough description of various embodiments of the invention . certain embodiments of the invention may be practiced without these specific details or with some variations in detail . in some instances , features not pertinent to the novelty of the system are described in less detail so as not to obscure other aspects of the invention . referring to the drawings , fig1 illustrates an exemplary communications environment in which the system of the present invention may operate . in accordance with one aspect of the system , the environment comprises plurality of mobile devices ( e . g . device 110 , device 120 , etc .) that communicate with a communications server 100 , via a base station 150 , for example . communications server 100 , in accordance with one embodiment , provides commands , requests , data or text messaging service ( e . g ., instant messaging , short messaging , etc . ), and may comprise or be coupled to one or more databases ( not shown ), for example , to control events or update data stored on mobile communication devices 110 , 120 . said data or events may be associated with or comprise one or more processes configured to update and store appointment data , phone numbers , alarm tones , special functions or other related configuration information on mobile devices 110 , 120 . the terms “ connected ,” “ coupled ,” or any variant thereof , mean any connection or coupling , either direct or indirect , between two or more elements . the coupling or connection between the elements can be physical , logical , or a combination thereof . communications server 100 , in accordance with one embodiment , may comprise or be connected or coupled to one or more computer systems or databases ( not shown ), for example , to receive configuration , command or update information for mobile device 110 , 120 . communication server 100 may communicate with mobile device 110 , 120 and the respective computing systems or databases via a direct point - to - point connection or a remote internet connection , for example . the communication protocol for establishing said communication connections and data transfer may be implemented over any wired or wireless telephony or communication protocol ( e . g ., internet protocol ( ip ), transmission control protocol over ip ( tcp / ip ), user datagram protocol over ip ( udp / ip ), short messaging service ( sms ), instant messaging service ( im )) or any combination thereof . referring back to fig1 , the exemplary communications network illustrated therein provides the medium and infrastructure ( i . e ., base station 150 ) for transmitting digital or analog voice and data signals between communications server 100 and mobile devices 110 , 120 . in certain embodiments , mobile devices 110 , 120 are cellular telephones communicating in a cellular telephone network with communication server 100 . communication server 100 as discussed may be connected to other databases or computing systems via the internet , for example . one of ordinary skill in the art will appreciate that the communications network of the invention may advantageously be comprised of one or a combination of various types of networks without departing from the scope of the invention . for example , in some embodiments , the communications network can comprise one or more local area networks ( lans ), wide area networks ( wans ), public , private or secure networks , value - added networks , interactive television networks , wireless communications networks , two - way cable networks , satellite networks , interactive kiosk networks , cellular networks , personal mobile gateways ( pmgs ) and / or any other suitable communications network or part of the world wide web ( i . e ., the internet ). in either context , mobile devices 110 or 120 can communicate with a service provider to send and receive electronic packets of information , in the form of electronic requests and responses . in one embodiment , the service provider is a wireless communications service provider ( e . g ., sprint , cingular , t - mobil or verizon ) to which a user may subscribe . some of the services provided by the system of the present invention may be implemented as application software 1122 installed and executed on mobile devices 110 , 120 , as provided in further detail below . in certain embodiments , the application software 1122 executed on mobile devices 110 or 120 can act as client software that is in communication with communications server 100 or a service provider , for example . alternatively , in some embodiments , mobile devices 110 or 120 may comprise a pmg device or communicate with a pmg device on which application software 1122 is executed . the pmg architecture comprises a pmg server that can wirelessly communicate with a number of pmg enabled devices within the personal area of the user , thus providing a personal area network ( pan ). in addition , the pmg server can wirelessly communicate with remote server systems , such as a service provider or communications server 100 , via a wireless system or communications network in a wan . thus , the pmg acts as an interface to seamlessly connect a pan to a wan , and as such the devices attached to the pan or wan can communicate with each other . a more detailed description of the pmg architecture is provided in u . s . patent application ser . no . 09 / 850 , 399 , filed on may 7 , 2001 , the entire content of which is hereby incorporated by reference here . as used herein , the terms service provider , communications server and communications network are to be viewed as designations of one or more computing environments that comprise application , client or server software for servicing requests submitted by respective software included in mobile devices 110 , 120 , or other computing systems connected thereto . these terms are not to be otherwise limiting in any manner . application software 1122 , for example , may be comprised of one or more modules that execute on one or more computing systems , as provided in further detail below . referring to fig1 and 3 a , in accordance with one aspect of the invention , application software 1122 may be implemented on a device or system other than mobile device 110 , 120 . for example , application software 1122 or its components may be implemented , installed , uploaded and executed either in a local or in a distributed environment that are inclusive or exclusive of mobile device 110 , 120 or communication server 100 . for example , certain components of the application software 1122 may be installed and executed on mobile devices 110 or 120 , while other components may be executed and installed on a pmg device , communications server 100 , internet portals , service provider server systems , a telephony switching system or other computer systems and networks attached thereto to update data or control occurrence of events on mobile device 110 , for example . the term “ event ” as used herein refers to one or more actions , functions , programs or processes that may be executed on mobile device 110 such as playing a ring tone , alarm or other audio at a designated time . other exemplary time triggered events may comprise displaying an image or video , activating the vibration mode of the mobile device 110 , initiating a call to a specific number , accessing content on a network server , and sending text , voice or data messages . certain events may be directly triggered by an action of a user or occurrence of another event , rather than expiration of a designated time . in one embodiment , the event constitutes a request or command to mobile device 110 to synchronize or update data stored in mobile device 110 with another computing system . the command or request may enable or disable specific functions on mobile device 110 , activate ring tones , correct time , or cause mobile device 110 to receive or transmit data ( e . g ., text , image , audio , video , html , xml , etc . ), for example . in certain embodiments , the command or request may be utilized to automatically set mobile device 110 in a particular mode ( e . g ., vibration mode , meeting mode , etc .) with or without informing the user of mobile device 110 . in other embodiments , the command or request can include a time or delay parameter t , such that the respective mode or function is activated at a set time or expiration of a threshold period . in the following , one embodiment of the invention is described , by way of example , as applicable to commands or requests implemented in form of a text message transmitted over the sms protocol . application software 1122 executed on mobile device 110 is configured to process the received text message and cause mobile device 110 to perform the respective function or trigger a particular event as indicated in the text message . it should be noted , however , that the scope of the invention is not limited to application software 1122 exclusively executed on mobile device 110 , or commands or requests implemented as text messages transmitted over the sms protocol . in other embodiments , commands may be sent over any type of data communication protocol in text format or otherwise , and may be processed by application software 1122 executed on communication server 100 , for example . referring to fig1 and 2 , in accordance with one aspect of the invention , a user may interact with a computing device ( e . g ., mobile device 120 ) to control and event on a mobile device 110 or group of devices ( s 210 ). in an exemplary embodiment , selection of mobile device 110 is performed by sending a text message via an sms protocol to a phone number or other address ( e . g ., ip address ) identifying mobile device 110 ( s 220 ). the text message comprises one or more commands that can be processed by application software 1122 to control an event ( e . g ., setting an alarm ) on mobile device 110 . as noted earlier , depending on implementation , application software 1122 may be executed on one or both of communication server 100 and mobile device 110 to receive and process the text message comprising the commands for controlling occurrence of an event on mobile device 110 . thus , in accordance with one embodiment , application software 1122 processes the text message and determines if the event can be controlled or triggered based on the current settings or configuration of mobile device 110 ( s 230 ). triggering an event may require performing or accessing a prerequisite functions or data . for example , activating the alarm with a specific tone may require uploading the tone first , or setting the correct time on mobile device 110 . if the event cannot be controlled due to the unavailability of a prerequisite function or data , then an error is generated to inform the user , for example ( s 260 ) and the generated error is logged in either communication server 100 or mobile device 110 ( s 270 ). the occurrence of the error may be displayed on the requesting system ( e . g ., mobile device 120 ). if application software 1122 determines that the requested event can be controlled on mobile device 110 , then the event is either triggered or scheduled for a future time in accordance with the content of the text message ( s 250 ). after verifying that the event has been successfully set or triggered , the application software 1122 updates the status information ( 250 ). the status information may , for example , be transmitted to mobile device 120 for confirmation . in one embodiment , application software 1122 processes the text message and causes the designated event to be triggered in real time . for example , in one implementation , the user may drag - and - drop a contact entry from his ms outlook into an interactive text messaging interface ( e . g ., a graphically displayed box ) to cause a text message to be sent to mobile device 110 to dial a number in the contact entry . once the text message is received by mobile device 110 , then the number is dialed in real time . some events , on the other hand , can be scheduled for future triggering . for example , a user may drag and drop a calendar entry into a graphic user interface to send a text message mobile device 110 . the text message as processed by mobile device 110 will result in calendaring a meeting and for the alarm to sound on mobile device 110 at the scheduled meeting time . in embodiments of the system , mobile devices , service provider servers , and communications servers comprise a controlled computing system environment that can be presented largely in terms of hardware components and software code executed to perform processes that achieve the results contemplated by the system of the present invention . a more detailed description of such system environment is provided below with reference to fig3 a and 3b . as shown , a computing system environment is composed of two environments , a hardware environment 1110 and a software environment 1120 . the hardware environment 1110 comprises the machinery and equipment that provide an execution environment for the software . the software provides the execution instructions for the hardware . it should be noted that certain hardware and software components may be interchangeably implemented in either form , in accordance with different embodiments of the invention . software environment 1120 is divided into two major classes comprising system software 1121 and application software 1122 . system software 1121 comprises control programs , such as the operating system ( os ) and information management systems that instruct the hardware how to function and process information . application software 1122 is a program that performs a specific task such as detecting changes in configuration data stored in mobile device 110 and reporting the updated data to the service provider . referring to fig3 a , an embodiment of the application software 1122 can be implemented as computer software in the form of computer readable code executed on a general purpose hardware environment 1110 that comprises a central processor unit ( cpu ) 1101 , a main memory 1102 , an input / output controller 1103 , optional cache memory 1104 , a user interface 1105 ( e . g ., keypad , pointing device , etc . ), storage media 1106 ( e . g ., hard drive , memory , etc . ), a display screen 1107 , a communication interface 1108 ( e . g ., a network card , a blue tooth port , a modem , or an integrated services digital network ( isdn ) card , etc . ), and a system synchronizer ( e . g ., a clock , not shown in fig3 a ). cache memory 1104 is utilized for storing frequently accessed information . a communication mechanism , such as a bidirectional data bus 1100 , can be utilized to provide for means of communication between system components . hardware environment 1110 is capable of communicating with local or remotes systems connected to a communications network ( e . g ., a pan or a wan ) through communication interface 1108 . in one or more embodiments , hardware environment 1110 may not include all the above components , or may include additional components for additional functionality or utility . for example , hardware environment 1110 can be a laptop computer or other portable computing device that can send messages and receive data through communication interface 1108 . hardware environment 1110 may also be embodied in an embedded system such as a set - top box , a personal data assistant ( pda ), a wireless mobile device ( e . g ., cellular phone ), or other similar hardware platforms that have information processing and / or data storage and communication capabilities . for example , in one or more embodiments of the system , hardware environment 1110 may comprise a pmg unit or an equivalent thereof . in embodiments of the system , communication interface 1108 can send and receive electrical , electromagnetic , or optical signals that carry digital data streams representing various types of information including program code . if communication is established via a communications network , hardware environment 1110 may transmit program code through the network connection . the program code can be executed by central processor unit 1101 or stored in storage media 1106 or other non - volatile storage for later execution . program code may be transmitted via a carrier wave or may be embodied in any other form of computer program product . a computer program product comprises a medium configured to store or transport computer readable code or a medium in which computer readable code may be embedded . some examples of computer program products are memory cards , cd - rom disks , rom cards , floppy disks , magnetic tapes , computer hard drives , and network server systems . in one or more embodiments of the invention , processor 1101 is a microprocessor manufactured by motorola , intel , or sun microsystems corporations , for example . the named processors are for the purpose of example only . any other suitable microprocessor , microcontroller , or microcomputer may be utilized . referring to fig3 b , software environment 1120 is stored in storage media 1106 and is loaded into memory 1102 prior to execution . software environment 1120 comprises system software 1121 and application software 1122 . depending on system implementation , certain aspects of software environment 1120 can be loaded on one or more hardware environments 1110 . system software 1121 comprises control software , such as an operating system that controls the low - level operations of hardware environment 1110 . low - level operations comprise the management of the system resources such as memory allocation , file swapping , and other core computing tasks . in one or more embodiments of the invention , the operating system can be nucleus , symbian , microsoft windows ce , microsoft windows nt , macintosh os , or ibm os / 2 . however , any other suitable operating system may be utilized . application software 1122 can comprise one or more computer programs that are executed on top of system software 1121 after being loaded from storage media 1106 into memory 1102 . in a client - server architecture , application software 1122 may comprise client software and server software . referring to fig1 for example , in one embodiment of the invention , client software is executed on mobile unit 110 and server software is executed on the service provider system ( not shown ) or communications server 100 . software environment 1120 may also comprise web browser software 1126 for accessing content on a remote server . further , software environment 1120 may comprise user interface software 1124 ( e . g ., a graphical user interface ( gui )) for receiving user commands and data . the received commands and data are processed by the software applications that run on the hardware environment 1110 . the hardware and software architectures and environments described above are for purposes of example only . embodiments of the invention may be implemented in any type of system architecture or processing environment . embodiments of the invention are described by way of example as applicable to systems and corresponding methods that facilitate remotely controlling events on a mobile communication device . in this exemplary embodiment , logic code for performing these methods is implemented in the form of , for example , application software 1122 . the logic code , in one embodiment , may be comprised of one or more modules that execute on one or more processors in a distributed or non - distributed communication model . it should also be understood that the programs , modules , processes , methods , and the like , described herein are but exemplary implementations and are not related , or limited , to any particular computer , apparatus , or computer programming language . rather , various types of general - purpose computing machines or customized devices may be used with logic code implemented in accordance with the teachings provided , herein . further , the order in which the methods of the present invention are performed is purely illustrative in nature . these methods can be performed in any order or in parallel , unless indicated otherwise in the present disclosure . the methods of the present invention may be performed in either hardware , software , or any combination thereof . in particular , some methods may be carried out by software , firmware , or macrocode operating on a computer or computers of any type . furthermore , such software may be transmitted in the form of a computer signal embodied in a carrier wave , and through communication networks by way of internet portals or websites , for example . accordingly , the present invention is not limited to any particular platform , unless specifically stated otherwise in the present disclosure . the present invention has been described above with reference to preferred embodiments . however , those skilled in the art will recognize that changes and modifications may be made in these preferred embodiments without departing from the scope of the present invention . other system architectures , platforms , and implementations that can support various aspects of the invention may be utilized without departing from the essential characteristics as described herein . these and various other adaptations and combinations of features of the embodiments disclosed are within the scope of the invention . the invention is defined by the claims and their full scope of equivalents . | 7 |
in one aspect of the present invention , an n - sulfoxyanhydride ( 15 ) is formed in - situ by reaction of n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ) with chlorosulfinyl imidazole ( 14 ) as shown in scheme iii : the preparation of chlorosulfinyl imidazole ( 14 ) is disclosed in , for example , ogata masaru and matsumoto hiroshi , “ n ( chlorosulfinyl )- imidazole as a new imidazole transfer reagent ” synthetic communications , 10 ( 10 ), pp . 733 - 742 ( 1980 ), and coll , alberto palomo , “ formation of new n - sulfoxyanhydrides as intermediates for the synthesis of ace inhibitors ” afinidad 57 ( 487 ), pp . 209 - 210 ( 2000 ), the contents of which are incorporated by reference herein . generally , chlorosulfinyl imidazole ( 14 ) may be prepared by reacting imidazole ( 12 ) with socl 2 in an about 1 : 4 ratio in dry methylene chloride yielding n , n ′- thionyldiimidazole hydrochloride ( 13 ). n , n ′- thionyldiimidazole hydrochloride ( 13 ) can then be filtered off and an equimolar amount of thionyl chloride is added to the filtrate to yield chlorosulfinyl imidazole ( 14 ). in accordance with the present invention , chlorosulfinyl imidazole ( 14 ) is reacted with n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ) to form nsa ( 15 ). the reaction can be carried out at a temperature ranging from about − 15 ° c . to about 25 ° c . for a time period ranging from about 60 minutes to about 90 minutes . the molar ratio of chlorosulfinyl imidazole to n - 1s - carboxyethylbutyl -( s )- alanine can vary widely , e . g ., a molar ratio of chlorosulfinyl imidazole to n - 1s - carboxyethylbutyl -( s )- alanine ranging from about 1 : 1 . 1 to about 1 : 1 . 2 . if desired , this reaction can take place in the presence of substantially dry organic solvents ( e . g ., solvents having a moisture content of less than about 0 . 04 %). suitable dry organic solvents include , but are not limited to , chlorinated organic solvents , non - chlorinated solvents and the like and mixtures thereof . the chlorinated organic solvents may be , for example , methylene chloride . the non - chlorinated solvents may be , for example , ethyl acetate , dimethyl carbonate , diethyl carbonate , and acetonitrile . the solvent is generally added in an amount of from about 0 to about 20 wt . percent . the organic solvent may be regenerated and recycled . any imidazole hydrochloride that is formed may be filtered off . after performing the reaction to form nsa , the nsa ( 15 ) can be left in the organic solvent , if used . the presence of the nsa in the solvent may be confirmed by the quantitative isolation of the hydrochloride form of chlorosulfinyl imidazole in two steps : ( 1 ) iodometric titration of the so 2 formed after hydrolysis of nsa ( ir spectroscopy of the solution having characteristic absorption bands at 1820 cm − 1 , 1750 cm − 1 , and 1030 cm − 1 ); and ( 2 ) reacting the nsa with silylated amino acids under release of so 2 . the nsa ( 15 ) is then reacted with a silylated ( 2s , 3as , 7as )- octahydoindole - 2 - carboxylic acid ( 2a ) to form perindopril . this reaction may be performed at a ph ranging from about 2 to about 6 . alternatively , the reaction may be performed at a ph over 7 in the presence of inorganic or organic salts of n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ). in one embodiment of the present invention , the inorganic salt of n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ) is selected from the potassium salts or sodium salts or combinations thereof . in another embodiment of the present invention , the organic salt of n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ) is selected from the group consisting of 1 , 8 - diazabicylo [ 5 . 4 . 0 . ] undec - 7 - ene ( dbu ), 1 , 5 - diazabicyclo [ 4 . 3 . 0 ] non - 5 - ene ( dbn ), triethylamine ( tea ), tetramethylguanidine , imidazole , and methylimidazole salts of n - 1s - carboxyethylbutyl -( s )- alanine . the reaction between nsa ( 15 ) and silylated octahydoindole - 2 - carboxylic acid ( 2a ) may also be performed in the presence of the free amino acid form of n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ). when the free amino acid form is used , n - 1s - carboxyethylbutyl -( s )- alanine ( 7 ) is activated with n - chlorosulfinyl imidazole to form n - ethoxycarbonylbutylalanine - n - sulfoxyanhydride ( 15 ). this nsa is reacted with a silylated 2s , 3as , 7as octahydro - 1h - indole - 2 - carboxylic acid ( 2 ) to form perindopril . during the reaction , gaseous so 2 is released , which may also be used to detect the nsa . generally , the reaction between nsa and silylated 2s , 3as , 7as octahydro - 1h - indole - 2 - carboxylic acid may be carried out at a temperature ranging from about − 20 ° c . to about 25 ° c . for a time period sufficient to form perindopril , e . g ., a time period of no more than about 90 minutes . the molar ratio of nsa to silylated 2s , 3as , 7as octahydro - 1h - indole - 2 - carboxylic acid can range from about 1 : 0 . 9 to about 1 : 1 . 1 . the perindopril is further reacted with tert - butylamine as known in the art to form perindopril erbumine . the reaction of perindopril and tert - butylamine may be performed in ethyl acetate at a temperature ranging from about 25 ° c . to about 35 ° c . the following examples are provided to enable one skilled in the art to practice the invention and are merely illustrative of the invention . the examples should not be read as limiting the scope of the invention as defined in the claims . trimethyl chlorosilane ( 10 . 86 g , 0 . 1m ) was added to a mixture of octahydroindole - 1h - 2 - carboxylic acid ( 15 . 2 g , 0 . 09m ), anhydrous methylene chloride ( 300 ml ) and triethylamine ( 10 . 1 g , 0 . 1m ) and the mixture was stirred for 2 hours until silylated octahydro - 1h - indole - 2 - carboxylic acid was formed . thionyl chloride ( 14 . 28 g , 0 . 120m ) was added to dry methylene chloride ( 150 ml ) and the mixture was cooled to a temperature of about − 5 ° c . imidazole ( 16 g , 0 . 22 ) was then added and the mixture was stirred for about 65 minutes at a temperature ranging from about − 5 ° c . to about 0 ° c . n - 1 ( s )- carboxyethylbutyl -( s )- alamine ( 19 . 95 g , 0 . 1m ) in methylene chloride ( 200 ml ) was added . the mixture was stirred for about 65 minutes while increasing the temperature to a range of from about 20 ° c . to about 25 ° c . until nsa was formed . the silylated ( 2s , 3as , 7as )- octahydro - 1h - indole - 2 - carboxylic acid in methylene chloride from step i was cooled to a temperature of about − 15 ° c . and was added to the reaction mixture containing nsa from step ii under stirring . the reaction was maintained for a few hours at a temperature of about 25 - 35 ° c . a slightly yellow solution was formed and was evaporated on a rota vapor . the solvent was removed and water ( 100 ml ), sodium chloride 25 g and ethyl acetate ( 200 ml ) were added to the residue . the ph was from about 2 . 5 to about 3 . 0 and was adjusted with a 10 % naoh solution to a ph ranging from about 4 . 2 to about 4 . 5 . the organic phase was separated and the aqueous phase was extracted with ethyl acetate ( 100 ml × 2 ). the combined ethyl acetate phases were dried with anhydrous sodium sulphate ( 50 g ). the dried organic layer was concentrated on a rotavapor bath at 40 ° c . under vacuum to get an oily residue . ( weight : 30 g , %- yield : 90 %, purity : 92 to 94 % by hplc ). the oily residue was dissolved in 300 ml ethyl acetate and tert - butylamine ( 6 g , 0 . 08 mol ) was added at room temperature under stirring for about 60 minutes to about 90 minutes . the precipitated product was filtered and further recrystallized in ethyl acetate ( 350 ml ) to get perindopril erbumine . ( weight : 28 g , %- yield : 65 %; purity : ˜ 99 . 5 %) specific optical rotation [ α ] n =− 66 ( c = 1 %, meoh ), ir ( kbr ) spectrum shows the following absorptions cm − 1 3300 , 2930 , 1744 , 1732 m 1644 m 1568 . the 1h - nmr ( cdcl 3 ) shows the following signals at δ 4 . 28 - 4 . 12 ( m , 1h ), 4 . 18 - 4 . 09 ( q , 2h ), 3 . 76 ( m , 2h ) 3 . 53 ( q , 1h ), 3 . 1 ( t , 1h ), 2 . 32 - 2 . 14 ( m , 2h ), 2 . 01 ( m , 1h ), 1 . 75 - 1 . 62 ( m , 4h ), 1 . 32 ( m , 2h ), 1 . 30 ( s , 9h ), 1 . 28 ( t , 3h ), 0 . 88 ( t , 3h ). ci mass shows m / z at 368 ( m +). it will be understood that various modifications may be made to the embodiments disclosed herein . therefore the above description should not be construed as limiting , but merely as exemplifications of preferred embodiments . for example , the functions described above and implemented as the best mode for operating the present invention are for illustration purposes only . other arrangements and methods may be implemented by those skilled in the art without departing from the scope and spirit of this invention . moreover , those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto . | 8 |
referring to the drawings and more particularly fig2 and fig3 there is shown a bedpan 10 of a generally pear shape made of any suitable material such as stainless steel or polypropylene . the design of the bedpan may also be of any of the various types presently on the market , including the fracture bedpan . the pan 10 includes an upper shoulder 12 that extends inwardly around the inner periphery of the pan 10 and is contoured in a manner that will comfortably support the buttocks of a patient , and which defines a bowling pinlike continuous opening having a back portion 14 and a narrower foward portion 16 . the opening communicates with the interior of the pan 10 which provides a basin for accepting and holding human waste . the free edge of the shoulder 12 is concave and slightly sloping downwardly to provide a contoured seat for the individual using the pan 10 . it is important to note that most pans are comparatively shallow to reduce the amount of room needed for stacking , storage and to provide stability when in use . for many years the use of a bedpan by male individuals caused their genital organs to partially rest in the waste . this required that the genitals of the individual be cleaned after every use of the pan . it also presented the danger of skin infection in the genital area , as well as the danger of urethral infection if the head of the penis was located in the waste . obviously such positioning of the genitalia was extremely uncomfortable for the patient . to prevent male genitalia from immersion in the waste while a patient is using a bedpan , the inventor has created the disposable bedpan guard 18 . the guard comprises a generally rectalinear , flexible , substantially flat body portion 20 ( trapazoidal in the embodiment shown ) having a forward or first edge 22 and a rear or second edge 24 spaced from and in parallel relation to the forward edge 22 . the rear edge 24 is longer than the forward edge 22 for a purpose to be described hereinafter . the forward and rear edges 22 , 24 are connected at their ends by side edges 26 so that the guard 18 in top plan view has the configuration of a trapazoid . as can be seen in the drawings , the side edges 26 are angled or biased to somewhat conform to the increased width of the pan 10 from front to back . the guard 18 is formed of a soft , flexible material or combination of a waterproof material such as thin polyvinal chloride attached to a soft , absorbent material such as guaze or tissue . in the embodiment shown , the upper surface 27 of the guard 18 is a tissue material in supra - abutting relation to the lower surface 28 which is formed of pvc . the upper surface 27 material may be adhered by a convenient method , such as glueing , to the water impermiable material 28 . the water impermiable material 28 can be made longer and wider than the upper surface 27 ( i . e . tissue ) and its edges folded over the edges of the superposed tissue and adhered in place . one side of a double faced tape 30 is adhered to the lower surface 28 along and adjacent to each side edge 26 . the other adherent surface of the tape 30 is protected by a removeable covering until the guard 18 is ready to be used . the tape can be single faced with the non - adhesive face permanently bonded or adhered to the guard 18 . if desired , strips or single faced adherent tape could be attached to the guard 18 extending beyond its side edges to provide a means of adherent engagement between the guard 18 and the bedpan . the bedpan guard 18 may have other configurations , for example , oval or rectangular , when seen in plan view . in these cases , the strips of double faced tape could be cut or made to conform to the shape of the &# 34 ; side edge &# 34 ; along which they are positioned . other means of removeably attaching the bedpan guard 18 to the bedpan could be utilized if desired , for example , by snap fasteners with the sockets positioned on the bedpan and the studs on the bedpan guard . a cover 32 is attached to the upper surface 27 of the guard 18 adjacent the rear edge 24 . the cover 32 is folded in accordian fashion on top of the upper surface , has a width equal to or greater than the rear edge 24 , and is formed of a soft , flexible material such as tissue paper . the top layer of the folded cover 32 includes a free end 34 having a double sided tape 36 on its top surface extending beyond the free edge 34 for a purpose to be described hereinafter . the lowest folded layer of the cover 32 is attached by an adhesive or the like to the upper surface 27 . the cover 32 is prefolded on the bedpan guard 18 prior to use . to use the guard 18 , the patient 38 is seated on the bedpan 10 , the guard is then passed under the scrotum of the patient , rear edge 24 first with the upper surface 27 and the folded cover 32 facing the genitalia . the scrotum is positioned on the cover 32 and the tapes 30 are pressed into adherence with the shoulder 12 of the bedpan 10 . in this position , the guard 18 transversely divides the opening of the bedpan leaving a portion of the forward portion 16 available for patient urination and the back portion 14 available for defecation . if desired , the guard 18 could first be placed on the bedpan 10 in the approximate position shown in fig2 and 3 and the patient 38 could then seat himself on the pan 10 with his genitalia superposed on the guard 18 and its folded cover 32 . after the patient has used the bedpan 10 and it is removed from under him , the cover 34 is pulled out and over the bedpan opening and the tape 36 is engaged with the bedpan 10 . the bedpan 10 , with the wastes concealed by the attached cover 32 can now be carried to the waste disposal area where the guard 18 and cover 32 are stripped from the bedpan 10 and thrown away . the contents of the bedpan 10 can now be disposed of and the bedpan 10 can be cleaned in preparation for its next use . | 0 |
a method for manufacturing a cylindrical winding in accordance with the present invention will now be described together with an apparatus with which the invention is concerned . fig1 is a view showing essential parts of means for manufacturing a cylindrical winding in accordance with the present invention . reference numeral 1 denotes a base ; 2 , a cylindrical winding core or spindle ; 3 , a winding head and 4 , 5 denote posts . the post 4 is fixed to the base 1 . the other post 5 passing through a u - shaped guide cylinder 6 is detachably fixed to the base 1 . the guide cylinder 6 is also detachably mounted to the base 1 . the cylindrical winding core or spindle 2 is supported by the guide cylinder 6 to be rotated by a motor ( not shown ). rollers 7 , 8 made of elastic materials such as rubber , plastics and the like are rotatably supported on the posts 4 , 5 , respectively . these elastic rollers 7 , 8 function as members for preventing the wound wire from sliding and dropping off . they are pushed against the cylindrical winding core 2 with suitable deformation . the posts 4 , 5 are subjected to spring resiliency so that the elastic rollers 7 , 8 are pushed against the core 2 . there are formed shoulder portions 9 , 10 at both ends of the winding core 2 . a coated conductive wire 11 which preferably has a diameter less than 0 . 25 mm , is guided through the winding head 3 and is wound around these shoulder portions . the slant angle of the shoulder portion 10 is made greater than that of the shoulder portion 9 . the elastic rollers 7 , 8 are pushed against the peripheral surface 12 of the core 2 in confronting relation with the shoulder portions 9 , 10 , respectively . the winding head 3 is adapted to rotate in the direction indicated by the arrow a around the rotational axis line l , so that the wire is wound obliquely with respect to the rotary axis of the cylindrical winding core 2 . it is preferable that the extension of the axis line l to adapted to intersect with the rotary axis at the center of the core 2 in order that the wire may be wound smoothly . in fig1 the cylindrical winding core 2 has a small diameter in comparison with its axial length , and the winding head 3 is not displaced in the axial direction l . in this case , the wire 11 which is wound along the roller 8 slides down in turn towards the shoulder portion 10 while being given a tensile force . referring to fig1 a illustrating the winding turn order , this tendency will be explained more in detail . reference numerals ○ 1 , ○ 2 , ○ 3 denote the order in accordance with which the wire 11 is arranged on the shoulder portion 10 , which reference numerals ○ 1 &# 39 ;, ○ 2 &# 39 ;, ○ 3 &# 39 ; denote the order in accordance with which the wire 11 is arranged on the shoulder portion 9 . since the elastic rollers 7 , 8 are deformed in elastic contact with the winding core 2 , the projection contour of the turn of wire is substantially in the form of a hexagonal shape as shown in fig1 b . the hexagonal shape is preferable for the winding because it approaches the rectangular shape which is most preferable for the maximum output shaft torque . in other words , the turns of the wire wound around the shoulder portions 9 , 10 of the cylindrical winding core 2 slidingly move in the directions indicated by the arrows b , c , respectively , along the portions of the elastic rollers 7 , 8 which are pushed against the cylindrical winding core 2 . thus , the configuration of the winding which conforms to these portions of the elastic rollers 7 , 8 which are pushed against the cylindrical winding core 2 may be obtained . the above - described winding operation is repeated while rotating the winding core 2 to thereby obtain a full winding . then , the cylindrical winding core 2 and the post 5 are removed from the base 1 together with the guide cylinder 6 . the guide cylinder 6 is detached from the core 2 . the portion , located on the shoulder portion 10 , of the winding is opened outside . the winding is separated apart from the cylindrical core 2 in its axial direction . in accordance with the method for manufacturing a cup - shaped winding of the invention , it is also possible to effect a continuous winding or a step winding . if the winding head is rotated while the core is being rotated at a constant speed , it becomes possible to effect the continuous winding . if the cylindrical core is rotated at a predetermined angle and thereafter , the rotation of the cylindrical core is brought to a halt , and the winding head 3 is rotated predetermined times so that the wire 11 is wound around the core 2 and the rotation of the winding head 3 is brought to a halt , and this operation is repeated alternately , it is possible to effect the step winding . it is possible to use a fusible - adhesive wire to adhere together turns of wire with alcohol or heat . there are provided pins 13 in the vicinity of the shoulder portion 9 . the pins 13 are used for tapping . the winding head 3 is moved back and forth along the axis line l by drive means such as a solenoid , so that the wire is hooked on the pins 13 . in the above - described embodiment , a roller technique is used for attaining a rotary winding . however , it is possible to carry out a zigzag winding method by applying elastic rollers as shown in fig1 c . in the zigzag winding , the rollers are fixed to the shaft of the rotary core and the wire is fed reciprocatingly in right and left directions and the wire is obliquely laid around the winding core as indicated by phantom line . it is obvious that the winding core is rotatingly displaced step by step corresponding to a turn of wire in accordance with a diameter of the wire . fig2 is a developed view illustrating a twisted cross - over band of wire in accordance with the method described above with reference to fig1 a and 1b . as shown in fig2 each of the cross - over portions c is formed in the vicinity of the shoulder portion on the trailing side . the cross - over portions are formed if the cup - shaped winding is long in the axial direction relative to its diameter . such a winding manner will be hereinafter referred to as the twisted cross - over winding method . fig3 is an enlarged view showing the cross - over portion . the reference numerals ○ 1 , ○ 2 and ○ 3 denote turns of wire in this order . as can be seen in fig2 each successive turn of wire , e . g ., turn 3 , extends further in the axial direction of the cylindrical shape , which corresponds to the vertical direction in fig2 than a previous turn of wire , e . g ., turn 2 . further , as shown at the bottom of fig2 which corresponds to the peripheral portion of the cylindrical shape , each successive turn of wire will extend in the circumferential direction , e . g ., horizontally in fig2 for a greater distance than a previous turn of wire . still further , since the wires in any given band cross one another as shown in fig2 each successive turn of wire in the shoulder portion at the top of fig2 will be closer to the center axis of the cylindrical shape than a previous turn of wire in the same band , so that each successive turn of wire will extend for a greater distance in the shoulder portion that a previous turn of wire in the same band . as shown in fig3 the cross - over portion c tends to develop toward the shoulder portion on the trailing side of the wire turn . in fig4 the aligned cylindrical winding is provided with a wire band 22 . this wire band 22 is formed with a predetermined pitch around the periphery of the core 2 . one portion of the wire is in engagement with the shoulder portion 9 so as to constitute the bowstring portion 23 as shown in fig5 and 6 . in addition , there is formed the peripheral portion 24 of the wire band 22 at the side of the shoulder portion 10 as shown in fig4 . in fig4 reference numeral 25 denotes the terminal line for tapping . the peripheral portion 24 forms an opening . the winding is taken away from the side of the shoulder portion 9 of the core 2 . in case the winding core 2 has a short axial length in comparison with a diameter , an aligned winding without any twisted cross - over portion explained above may be obtained as shown in fig6 . as can be see in fig6 since the wires in each band do not cross one another in the inclined portion but are instead substantially parallel with one another , each wire in any given band will extend for a greater distance in the peripheral portion 24 than a previous wire in the same band , but each wire and the bow string portion 23 will extend for a shorter distance than a previous wire in the same band . this is due to the fact that , as shown in fig5 each successive wire in the bow string portion will be displaced further from the central axis of the cylindrical shape than a previous wire in the same band , so that it need traverse a smaller chord of the bow string portion . it can also be seen that each band of wire in the peripheral portion 24 extends for a distance which is at least equal to the width of the band . referring again to fig4 explanation will be made as to the cup - shaped winding which is produced in accordance with the step winding method . this winding is provided with wire bands 22 in which the wire is wound stepwise . this wire band 22 is formed with a predetermined pitch around the periphery of the cylindrical winding core 2 . a part of the wire 21 is laid around the shoulder portion 9 so as to constitute the bowstring portion 23 of the wire band 22 as shown in fig4 . in addition , there is formed a peripheral portion 24 of the wire band 22 at the side of the shoulder portion 10 . in this case , the bowstring portion 23 approaches the axis center as the winding of wire is formed depending upon a relationship between the diameter and the axial length of the core . therefore , the length of the bowstring portion 23 decreases gradually . on the other hand , the peripheral portion 24 formed at the side of the shoulder portion 10 is wound along the peripheral slant surface of the shouldered portion 10 far from the shoulder portion 9 . as a result , the peripheral length thereof gradually becomes long . the portion between the bowstring portion 23 and the peripheral portion 24 is inclined as shown in fig5 . the inclined portion is aligned as shown . as can be seen in fig4 and 5 , the bands forming the cup - shaped winding will be substantially symmetrical with respect to the center axis of the cylindrical shape . fig7 is a longitudinal cross sectional view illustrating a cylindrical winding in accordance with another embodiment of the invention with the embodiment being collectively illustrated in fig7 - 10 . in fig7 - 10 , reference numeral 101 denotes a winding core . this cylindrical core 101 is composed of an inner cylinder 102 and an outer cylinder 103 , so that the outer cylinder 103 may rotate together with the inner cylinder 102 around its own axis . there is formed an insertion hole 104 which extends in the axial direction at the center of the inner cylinder 102 . a bobbin 105 is mounted on the outer cylinder 103 . a film sheet is subjected to a hot pressing so as to produce the bobbin 105 in order to make small an air gap . a rotary shaft 106 and a commutator 107 are formed in integral with this bobbin 105 in accordance with a molding method . this rotary shaft 106 is inserted into the insertion hole 104 . there is mounted the commutator 107 as well as riser 108 on the bobbin 105 . the wire which is prepared for tapping is soldered to the risers 108 . the bobbin 105 is provided with a shoulder portion 109 and an opening end surface 110 . in this case , the bobbin 105 is formed so that its axial length is long in comparison with its diameter . the wire 111 is aligned and wound obliquely with respect to the axis line of the bobbin 105 on the peripheral surface 112 of the bobbin between the shoulder portion 109 and the opening end face 110 . fig8 shows a wire band 113 in accordance with the aligning winding method . the wire 111 is aligned so as to engage the shoulder portion 109 from the inner side towards the outer side in the order indicated by reference numerals ○ 1 , ○ 2 , ○ 3 . . . . the wire 111 is aligned with the opening end face 110 in the vicinity of the opening edge 114 . in fig9 reference numerals ○ 1 , ○ 2 , ○ 3 denote the order in accordance with which the wire 111 is aligned and wound . an elastic roller 115 made or rubber or the like is pushed against the peripheral surface 112 in the vicinity of the opening end face 110 as shown in fig7 so that the winding may not drop from the opening end 110 as the wire 111 is being wound . the elastic roller 115 is supported rotatably on a support shaft 115a . in a winding operation , there may be employed a zigzag winding or a fly winding using a winding head . fig1 is a top view showing the order in accordance with which the wire bands i , ii , iii , iv and v are formed over the shoulder surface of the bobbin 105 around the periphery thereof . the wire band i in fig1 and the wire 111 is drawn out for tapping as shown in fig8 . therefore , the roller 115 is rotated by a predetermined angle with respect to the bobbin 105 in the direction indicated by the arrow e and then stopped . as indicated by the reference numeral ii , the wire 111 is aligned and wound in the direction indicated by the arrow d so as to form the wire band 113 . as indicated by the reference characters iii to v , the wire band 113 is formed over the surface , as shown in fig4 around the periphery of the bobbin 105 . the inner cylinder 102 is pushed in the direction indicated by the arrow f in fig7 so that the bobbin 105 is removed from the outer cylinder 103 . since the present invention resides in the cylindrical winding in which the wire is wound around the bobbin as mentioned above , the wire is prevented from being injured when the cylindrical winding is dismounted from the cylindrical core . in addition , since one portion of the coil wire band is aligned on the opening end surface of the bobbin at the side of the opening end surface of the bobbin in the cylindrical winding , the portion which the wire engages reduces the increase of the thickness in the direction of the diameter of the bobbin at the side of the opening end surface of the bobbin , thereby making it possible to form the well balanced cylindrical winding . fig1 - 16 show another embodiment of the invention , in which a flat shaped winding is attained . in fig1 , reference numeral 201 denotes a winding core which includes an inner cylinder 202 and an outer cylinder 203 . the inner cylinder 202 is provided with an insertion hole 204 . the inner cylinder 202 can be reciprocated with respect to the outer cylinder 203 in its axial direction so that , after producing a cup - shaped winding , the core can be dismounted from the core 201 . the outer cylinder 203 rotates together with the inner cylinder 202 . on the outer cylinder 203 , there is mounted a bobbin 205 as the core . a rotary shaft 206 and a commutator 207 are formed integral with the bobbin 205 through molding . the rotary shaft 206 is inserted into the insertion hole 204 . the bobbin 205 is formed of a flat type cylinder of which the diameter is long in comparison with the axial length thereof . the risers 207 &# 39 ; are projected radially outwardly . the bobbin 205 is provided with a shoulder portion 208 and an opening end face 209 at ends thereof , respectively . the commutator 207 axially extends the opening end face 209 of the bobbin 205 . the wire 210 is aligned and wound on the peripheral surface 211 of the bobbin 205 obliquely between the shoulder portion 208 and the opening end face 209 . there are provided a pair of elastic rollers 212 , 213 as shown in fig1 at the side of the shoulder portion 208 of the bobbin 205 . the elastic rollers 212 , 213 are rotatably supported on support shafts 214 , 215 , respectively . the elastic rollers 212 , 213 can be reciprocated in the direction in which the support shafts 214 , 215 extend . there is provided an elastic roller 216 on the opening end face 209 side of the bobbin 205 so as to rotate about its support shaft 217 . the elastic rollers 212 , 213 are formed like truncated cones to have tapered surfaces 212a , 213a . the tapered surfaces 212a , 213a are pushed against the corner edge of the shoulder portion 208 . as shown in fig1 , the elastic roller 216 is pushed against the peripheral surface 211 of the bobbin 205 on the circumference between the pair of elastic rollers 212 , 213 . the elastic rollers 212 , 213 have in combination a function to cause the wire 210 to be aligned and wound on the surface of the shoulder portion 208 for producing a wire band like a bowstring . on the other hand , the elastic roller 216 has a function to cause the wire to be located in alignment with opening end face 209 of the bobbin 205 . the wire 210 is aligned and wound to form a wire band 218 as shown in fig1 to 14 . in this case , the elastic rollers 212 , 213 and 216 are arranged so that the wire 210 is retained in engagement with the opening end face 209 . in fig1 , the arrows denote the wire winding direction . a well known method in accordance with a zigzag winding or a fly winding using a winding head may be used when the wire 210 is wound around the bobbin 205 . explanation will be made as to the order for winding the wire with reference to fig1 and 13 . in order that the wire 210 is aligned and wound , the wire 210 is wound along the surface of the shoulder portion 208 and the surface of the outer cylinder 203 . hence , the wire 210 is rendered to engage with the shoulder portion 208 from the vicinity of the rotary shaft 206 as indicated by reference numeral ○ 1 in fig1 . the wire 210 is oriented to the opening end face 209 as indicated by reference numeral ○ 1 &# 39 ; while keeping the wire 210 in contact with the elastic roller 212 . the wire 210 is guided along the peripheral surface 211 of the bobbin 205 as indicated by the reference numeral ○ 1 &# 39 ; in fig1 so as to extend obliquely across its axis line , so that the wire 210 is made to engage with one portion of the opening end face 209 where the elastic roller 216 exists . then , the wire 210 is directed to the shoulder portion 208 at the portion where the elastic roller 213 exists by the elastic roller 216 and is brought into contact with the elastic roller 213 , and hence , this wire 210 is made to engage with the shoulder portion 208 . the series of these operations are performed as indicated by the reference numerals ○ 2 to ○ 4 and ○ 2 &# 39 ; to ○ 4 &# 39 ;, thereby producing wire bands 218 as a split coil . the wire 210 is drawn out for tapping , and thereafter , the bobbin 205 is rotated together with the core 201 by a predetermined angle with respect to the elastic rollers 212 , 213 and 216 . this operation is repeated predetermined times corresponding to the number of the divided coils , so that a plurality of wire bands 218 around the periphery of the bobbin 215 may be formed as shown in fig1 . fig1 is a perspective view showing the wire winding order . the inner cylinder 202 and the elastic rollers 212 , 213 are moved in the directions as indicated by the arrows in fig1 and the core 201 is dismounted from the bobbin 205 , thereby producing the winding like a bottomed cup cylinder . the wire 210 is aligned to form the band as shown in fig1 when the wire 210 is made to engage with the opening end face 209 . the thickness in the radial direction is not so much increased at this engaging portion to form a well balanced cup - shaped winding 219 . on the upper surface at the side of the shoulder portion 208 , the wire 210 is aligned in parallel and wound by the assistance of elastic rollers 212 , 213 so that the winding will not be at a high level with respect to the bobbin 205 . after the wire bands 218 are formed over the peripheral surface of the bobbin 205 , the wire 210 for tapping is soldered to the risers 207 &# 39 ;. after the wire bands 218 are formed over the peripheral surface of the bobbin 205 , the commutators 207 are held in a cylindrical space formed in the wire 218 . fig1 shows the state in which a motor is assembled using the thus formed winding 219 . in fig1 , 220 denotes a case , 221 denotes a case cover , 222 denotes permanent magnets and 223 denotes a brush . fig1 and 19 show other embodiments of the method and the apparatus for manufacturing a cup - shaped winding in accordance with the invention . fig1 shows an embodiment in which the support shafts 214 , 215 of the pair of elastic rollers are horizontally arranged . in the embodiment which is shown in fig1 , the pair of elastic rollers 212 , 213 are made cylindrical , so that their peripheral surfaces are obliquely pushed against the corner edge of the shoulder portion 208 . in fig1 and 19 , the like components and members are designated by the same reference numerals as used in the embodiment shown in fig1 . fig2 and 21 show still another embodiment of the winding method . the pair of elastic rollers 212 , 213 and the elastic roller 216 are arranged close to each other with the rotary shaft 206 as the boundary . in fig2 , reference numerals ○ 1 , ○ 2 , ○ 3 denote the order in which the wire 210 is wound . as can be seen in fig2 and 28 , the rotary shaft passes outside of the area circumscribed by each band . as a consequence , each wire in any given band , as shown most clearly in fig2 , will pass in the bow string portion somewhat closer to the rotary shaft than a previous turn of wire in the same band , thus necessitating that each wire traverse a larger chord in the bow string portion than a previous turn of wire in the same band . as can be seen most clearly in fig2 , the bands of wire forming the cup - shape winding will be substantially symmetrical with respect to the center axis of the cylindrical shape . in fig2 , the distance of the engaging portion from the shoulder portion 208 to the opening end face 209 is made short , so that the length of the wire 210 required for forming one wire band 218 is decreased . as a result , the resistance loss is made small and the overlapping of the wire band 218 on the peripheral surface is also made small . in addition , advantageously , the inertia of the cup - shaped winding is also made small . in the foregoing embodiments , the wire 210 is wound around the bobbin 205 to form the cup - shaped winding 219 . however , the wire 210 can be wound directly around the winding core 201 to manufacture the cup - shaped winding 219 in case of the wire having a diameter more than 0 . 1 mm . however , in case of the wire 210 having a diameter smaller than 0 . 1 mm , it is preferable that the wire 210 be wound around the bobbin 205 in order to prevent the wire 210 from being damaged or cut . in addition , also , the elastic rollers 212 , 213 , 216 can be rotated along the peripheral surface of the bobbin 205 while they rotate on their own axes . in accordance with the invention , since the pair of engaging roller members are pushed against the shoulder portion of the core having the shoulder portion at the end thereof so that the winding engages the shoulder portion as the aligned wire band like a bowstring , it is possible to provide the cup - shaped winding having the aligned and wound wire with the short axial length in comparison with its diameter , thereby obtaining the well balanced cup - shaped winding . in accordance with the apparatus for manufacturing a cup - shaped winding of the invention , since the peripheral surfaces of the pair of elastic rollers are obliquely pushed against the corner edge of the shoulder portion of the bobbin , the peripheral surfaces of the elastic rollers come into contact with only the corner edge of the shoulder portion , whereby the wire may be obliquely oriented on the peripheral surface of the winding core from the shoulder portion . fig2 to 28 show another embodiment of the invention , in which the like winding apparatus in fig1 is used . a pair of elastic rollers 312 , 313 are provided as shown in fig2 at the side of the shoulder portion 308 of the bobbin 305 on both sides of a rotary shaft 306 to be symmetrical with the rotary shaft 306 as the boundary . reference numerals 314 , 315 denote the support shafts thereof . a pair of elastic rollers 316 , 317 are provided on both sides of the rotary shaft 306 with the rotary shaft 306 as the boundary . reference numerals 318 , 319 denote the support shafts thereof . one of the pair of elastic rollers 316 , 317 is positioned apart from the peripheral surface 311 of the bobbin 305 so as not to become an obstacle at the time when the wire 310 is wound in case the other of them is pushed against the peripheral surfce 311 of the bobbin 305 as shown in fig2 . since the wire 310 is made adhere onto the bobbin 305 , for example , by a thermal fusing or sticking means , there is caused no trouble even if the pair of elastic rollers 316 , 317 are alternately positioned away from or close to each other . the elastic rollers 312 , 313 , 316 , 317 are arranged such that the straight line connecting the pair of elastic rollers 312 , 313 is perpendicular to the straight line connecting the pair of elastic rollers 316 , 317 , and the elastic rollers 312 , 313 , 316 and 317 are rotatable with respect to the support shafts 314 , 315 , 318 and 139 respectively . the tapered surfaces 312a , 313a of the rollers 312 , 313 are pushed against the edge of the shoulder portion 308 . the peripheral surface of the rollers 316 , 317 are pushed against the peripheral surface 311 of the bobbin 305 over the surface thereof in the axial direction as shown in fig2 . each of the elastic rollers 312 , 313 , 316 , 317 has a function as a member which the wire 310 engages so that the wire 310 may not be slid . the wire 310 is aligned and wound so as to form wire bands 320 as shown in fig2 . the wire 310 is made to laid from the shoulder portion 308 to the opening end face 309 which is distant therefrom with the rotary shaft 306 as the boundary . an explanation will be given in respect to this with reference to fig2 . the wire 310 is directed to the elastic roller 313 along the surface of the shoulder portion so that the wire 310 may be aligned as indicated by reference numeral ○ 1 , thereby aligning the wire 310 like a bowstring by the assistance of the elastic roller 313 . this is made engage the shoulder portion 308 , and the wire 310 is directed in the direction in which the elastic roller 316 exists along the peripheral surface towards the opening end face 309 , and this elastic roller 316 is utilized to prevent the wire 310 from being slid and dropped and the wire 310 is laid by the surface of the elastic roller 316 and the surface of the outer cylinder 303 beyond the opening end so that the wire 310 is aligned on the opening end surface 309 . after the wire 310 is passed by way of the elastic roller 316 , the wire 310 is directed in direction in which the elastic roller 312 exists towards the side of the shoulder portion 308 , so that the wire 310 is again made to engage the shoulder portion 308 as indicated by reference numeral ○ 2 . this operation is repeated so that the wire bands 320 are formed at one side only . therefore , the wire 310 is directed towards the elastic roller 13 as indicated by reference numeral ○ 3 , so that the wire 310 is made to engage the elastic roller 13 . the wire 310 is directed to the rotary shaft 306 as indicated by reference numeral ○ 4 so that the wire 310 engages the rotary shaft 306 . then , the wire 310 is again directed to the elastic roller 313 as indicated by reference numeral ○ 4 , so as to invert the winding direction . thereafter , the wire 310 is directed in the direction in which the elastic roller 317 exists and in which the opening end face 309 exists as indicated by reference numeral ○ 5 so that the wire 310 is made to engage with the opening end face 309 utilizing this elastic roller 217 . the wire 310 is passed by this elastic roller 317 and directed in the direction in which the elastic roller 312 exists towards the shoulder portion 308 . the wire 310 is made to engage the shoulder portion 308 as indicated by reference numeral ○ 5 while the wire 310 is being aligned like a bowstring utilizing this elastic roller 312 . this operation is repeated so that wire bands 320 may be symmetrically arranged on both sides of the rotary shaft 306 with the rotary shaft 306 as the boundary as shown in fig2 . fig2 is a perspective view showing the winding thereof . in accordance with the winding method , a pair of wire bands 320 , 320 are made to cross each other on the peripheral surface of the bobbin 305 as shown in fig2 . the wire 310 is aligned and laminated so as to engage the surface as shown in fig2 at the side of the opening end surface 309 , and this engaged portion reduces the increase of the thickness in the radial direction . hence , after the symmetrical wire bands 320 , 320 are formed as the set , the wire 310 is drawn out for tapping . then , the bobbin 305 is rotated through a predetermined angle with respect to the elastic rollers 312 , 313 , 316 , 317 so that the sets of symmetrical wire bands are repeatedly formed . the bobbin 305 is rotated for every 120 ° together with the rotary cylinder so as to form the sets of symmetrical wire bands . fig2 shows three sets of symmetrical wire bands . fig2 shows another embodiment of the cup - shaped winding in accordance with the present invention . in accordance with the embodiment , the wire 310 is made to engage the surface from the shoulder portion 308 which the wire 310 engages to the opening end surface 309 at the side which is close thereto with the rotary shaft 306 as the boundary . after the wire 310 is wound as indicated by reference character k in the drawing , the wire 310 is wound as indicated by reference character l so as to form a set of symmetrical wire bands 320 . in accordance with the winding method , the set of wire bands 320 do not cross each other . in this embodiment , the angle that the wire 310 is pulled around becomes small so that the length of the engaging portion from the shoulder portion 308 to the opening end face 309 is made short . as a result , ( 1 ) the resistance loss is reduced , ( 2 ) the overlapping of the peripheral wire bands is reduced and ( 3 ) the inertia is also reduced . as explained above , since the invention resides in the cup - shaped winding in which the wire bands are symmetrically formed on both sides of the rotary shaft with the rotary shaft as the boundary , it is possible to form the well balanced cup - shaped winding , in particular , as required in case the winding is like a short or flat cylinder . this brings about the effects as follows in case this winding is used as an armature . even if the diameter is small as the flat armature like a short cylinder , the torque is rather large . another embodiment of the invention will now be described . a bobbin 401 is mounted onto a cylindrical core 406 as shown in fig2 . a winding core 406 is composed of axially displacable inner cylinder 407 and outer cylinder 408 . in the inner cylinder 407 , there is formed a hole 409 into which is inserted the rotary shaft 404 . the outer cylinder 408 is rotated together with the inner cylinder 407 . there is provided a shaft 410 above the winding core 406 so that the axis of the rotary shaft 410 is aligned with the axis of the cylindrical core 406 as shown in fig3 and 31 . the shaft 410 is provided with aligning plate 411 and guide plate 412 which are adapted to cooperate with each other for aligning the wire . the interval 412 &# 39 ; between the aligning plate 411 and guide plate 412 is suitably selected so as to align the wire in a plurality of turns of wire as well as a single turn . the aligning plate 411 is slightly obliquely supported by the shaft 410 . it is desired that the aligning plate 411 be made somewhat larger than a half circular disc in case of a winding for two poles and be made larger than a three - fourths circular poles in case of the winding for four poles . in addition , the size of the guide plate 412 is made equal to or larger than that of the aligning plate 411 . three elastic rollers 414 , 415 , 416 supported by support shafts 417 , 418 , 419 are pushed against a peripheral surface 413 of the bobbin 401 as shown in fig3 and 33 . the elastic rollers 414 and 415 are formed like cones . reference numeral 414a in fig3 denotes the tapered surface of the elastic roller 414 . the elastic roller 416 is formed like a cylinder . the wire 420 is aligned so as to engage the shoulder portion . each of the elastic rollers 414 , 415 , 416 has a function to align and engage the wire 420 when the wire 420 is wound and press the wire bands so as to be in contact with each other and made flat by its movement while rotating on its own axis in contact with the wire . as shown in fig3 and 33 , the aligning plate 411 and the guide plate 412 are , respectively , of a semicircular configuration . when the wire 420 is wound around the bobbin 401 , the elastic rollers 414 , 415 are utilized so that the wire 420 is laid on the shoulder portion 402 and is pushed against and retained at the surface of the aligning plate 411 . in addition , the elastic roller 416 is used for retaining the wire at the opening end face 403 . this operation is repeated a plurality of times . the wire is laid on the aligning plate 411 as indicated by reference numerals ○ 1 , ○ 2 , ○ 3 , ○ 4 , ○ 5 at the shoulder portion side . the wire band 421 formed on the aligning plate 11 is aligned . the turns of wire of the wire band 420 are prevented from overlapping one on another . as can be clearly seen in fig3 and 33 , which are views from the axial direction of the winding , each band in the bow string portion will form a substantially curved shape . after the wire bands 422 are formed as mentioned above , the rotary shaft 410 is rotated in the direction indicated by the arrow h with respect to the bobbin 401 as shown in fig3 to 35 . when only the aligning plate 411 is rotated through 360 ° while the rollers 417 , 418 , 419 are kept in this state , the wire band 421 laid on the aligning plate 411 fall down out of the trailing edge 423 of the aligning plate 411 and is brought into contact with the shoulder surface of the bobbin . after the aligning plate 411 is rotated through 360 °, the leading edge 424 comes just above the wire band 421 on the surface of the bobbin . then , lead wires 425 for tapping are drawn out as shown in fig3 , and after the wire bands are fully wound over the surface of the bobbin , the lead wires are connected and soldered onto the risers . in case the cup - shaped winding is used in the brushless motor , they are used as input lead wires as they are . the winding core 406 and the bobbin 403 are rotated through a predetermined unit angle with respect to the shaft 410 and the elastic rollers 414 , 415 , 416 . this operation is repeated so that a plurality of wire bands 422 are formed over the peripheral surface of the bobbin 401 . the bobbin 401 can be dismounted by moving the inner cylinder , the roller shafts 417 , 418 and the aligning plate shaft 410 respectively , as indicated by the arrows in fig2 . fig3 shows a cylindrical coil winding 426 which is thus produced . fig3 shows the winding method for producing a winding for four poles in the same manner as described above . in fig3 , the angle defined by the leading edge 424 and the trailing edge 423 of the aligning plate 411 is below 90 °. | 7 |
fig4 a is a section view of a cased wellbore 10 having a liner 15 disposed therein and a mill / drill 20 disposed at the end thereof . a shearable connection 25 between the mill / drill and a diverter , in this case a whipstock 30 , therebelow allows the entire assembly , including an anchor 35 , to be run into the wellbore at once . the anchor 35 is located below the whipstock and fixes the whipstock in place allowing the mill / drill 20 to form a window at a predetermined point in the wall of the casing 40 as it rotates along a concave portion 42 of the whipstock 30 . after the assembly is run into the wellbore and the whipstock 30 and anchor 35 are fixed in place , a downward force is applied to the liner 15 and mill / drill 20 to cause the shearable connection 25 between the mill / drill and the whipstock to fail . the mill / drill can then be rotated and formation of the window can begin . in the embodiment shown in fig4 a , the mill / drill 20 is rotationally fixed to the end of the liner 15 and rotational force is applied to the liner at the well surface . fig4 b is a section view of the wellbore illustrating a window 45 that has been formed in the casing wall 40 by the rotating mill / drill 20 . fig4 b also illustrates the liner 15 having advanced through the window 45 and into the lateral wellbore . fig4 c , a section view of the wellbore 10 , shows the lateral wellbore 50 formed and lined with the liner 15 which was inserted into the lateral wellbore as it was formed . in the embodiment illustrated , the mill / drill 20 remains at the end of the liner 15 after the lateral wellbore 50 is formed and can be subsequently destroyed by additional drilling . to complete the lateral wellbore , portions of the liner extending into the central wellbore from the window may be removed . techniques for cutting off that portion of a liner extending into and blocking a vertical wellbore are described in u . s . pat . nos . 5 , 301 , 760 and 5 , 322 , 127 and those patents are incorporated herein by reference in their entirety . in an alternative embodiment of the arrangement depicted in fig4 a - c , the liner 15 with the mill / drill disposed thereupon can be non - rotating and a two - piece drill / mill 55 rotates independently of the liner 15 with rotational forces supplied by a downhole motor within the liner or by a rotational device located at the surface of the well . for example , fig5 a is a section view of a two - piece mill / drill 55 with rotational force provided thereto by a downhole motor 60 and fig5 b is a view of the two - piece mill / drill 55 with rotational force provided from the well surface ( not shown ). a first portion 65 of the two - piece mill / drill 55 has an outer diameter smaller than the inside diameter of the liner and a second portion 70 of the mill / drill 55 extends around the perimeter of the liner and is rotationably coupled to the first portion 65 . after the lateral wellbore has been formed , the portions 65 , 70 of the mill / drill 55 can be disconnected from each other and the first portion 65 may be removed from the lateral wellbore with a wireline or any other well - known technique for recovering downhole devices from a wellbore . when drilling a lateral wellbore with liner , undersized liner may be used during the formation of the lateral wellbore to facilitate the operation and thereafter , when the wellbore is formed , the liner can be expanded to increase its diameter to more closely match the inside diameter of the lateral wellbore . enlargement of the liner is typically accomplished by insertion of a selective expansion device into the lateral wellbore and subsequent actuation of the device which places an outward force on the wall of the liner . moving the actuated device axially in the liner creates a section of enlarged liner . fig6 a is a section view of a lateral wellbore 10 drilled with liner 300 and having a selective expansion tool 310 inserted therein on a separate tubular string 312 for enlarging the diameter of the liner . in the figure , the selective expansion tool 310 is run into the lateral wellbore where it is then actuated and urged towards the window 315 of the wellbore , enlarging the liner to a size adequate to line the lateral wellbore for cementing therein . compliant rollers 116 ( fig1 ) of the expansion tool 310 may alternatively be cone - shaped to facilitate a gradual enlargement of the liner as the expansion tool moves therethrough . in fig6 b , another section view of a lateral wellbore 10 , the undersized liner 300 has been expanded up to and through the window in the vertical casing in a manner that has sealed an annular area 320 between the exterior of the liner and the window opening . after removal of the selective expansion tool 310 , the liner 300 can be severed at the window leaving a sealed lateral wellbore extending from the central wellbore . fig7 a is a section view of a wellbore 10 having a conventional drill stem 75 for providing rotational force to a mill / drill 78 disposed at the end thereof . a rotary steerable mechanism 80 is installed above the mill / drill and includes selectively radially extendable pads 85 which can transmit a force against the casing wall causing the mill / drill therebelow to be diverted towards the opposite wall of the casing . a measurement while drilling device ( mwd ) 90 is installed within the tubular string to provide orientation . as illustrated in fig7 b , the assembly including the mwd 90 , steerable mechanism 80 and mill / drill 78 is run into the wellbore 10 to a predetermined depth and , thereafter , at least one pad 85 of the rotary steerable mechanism 80 is actuated to urge the mill / drill 78 against that area of the casing wall 87 where the window will be formed . after the window has been formed by the mill / drill 78 , the assembly extends into the window and the lateral wellbore is formed . upon completion of the lateral wellbore the assembly is removed from the well and the new lateral wellbore may be lined with tubular liner in a conventional manner well known in the art . fig8 is a section view of a wellbore 10 wherein a liner 200 is provided with a two - piece mill / drill 205 disposed at the end thereof , the liner having a bent portion 215 at the lower end which directs the mill / drill 205 to a predetermined area of the wellbore casing 220 where a window will be formed . in this embodiment , the liner is non - rotating and the mill / drill 205 rotates independently thereof , powered by either a downhole motor 210 thereabove or a rotary unit located at the surface of the well ( not shown ). to cooperate with the bent liner portion , downhole motor 210 may have a bent housing . as described herein , the mill / drill is a two - piece assembly with a center portion 207 that can be removed when the formation of the lateral wellbore is complete . in another embodiment depicted in fig9 , a rotating straight liner 400 is provided with a rotary steerable mechanism 405 and a mill / drill 410 disposed at a lower end thereof . the rotary steerable mechanism 405 , like those described herein has selectively extendable pads 407 which exert a force against the casing wall 420 , of the central wellbore , biasing the mill / drill 410 therebelow in a direction where the window is to be formed in the casing wall and formation of the lateral wellbore is to begin . in this embodiment , the assembly is lowered into the well to a predetermined depth and thereafter , the 400 liner and mill / drill 410 rotate as the mill / drill 410 is urged against the wall of the casing 420 biased by the rotary steerable mechanism 405 . the mill / drill 410 forms a window in the casing and then the assembly , including the rotating liner 400 , is urged through the window and the lateral wellbore is formed . after the wellbore is formed , an mwd device ( not shown ) which is located on a separate tubular string within the liner is removed and the fixed mill / drill is left in the lateral wellbore . while foregoing is directed to the preferred embodiment of the present invention , other and further embodiments of the invention may be devised without departing from the basic scope thereof , and the scope thereof is determined by the claims that follow . | 4 |
a sufficient amount of pure and undegraded nucleic acids is the precondition for sensitive detection of a target nucleic acid from a whole blood sample . the inventors surprisingly found rapid stabilization after sampling with chaotrope in combination with shock - freezing thereafter provide the means for isolating nucleic acids of high quality . in addition , the method of the invention allows to store the frozen stabilized sample for at least 2 years . thus , a first embodiment of the invention is a method for purifying nucleic acids from a whole blood sample , comprising the steps of ( a ) providing a whole blood sample from a mammal , whereby the sample is not older than 5 minutes ; ( b ) subsequently mixing the sample with anticoagulant ; ( c ) mixing the composition of ( b ) with an aequous stabilization reagent comprising a non - ionic detergent and a guanidinium salt , whereby the final concentration of the guanidinium salt in the resulting mixture is between 15 % and 35 % weight by volume , and the final concentration of the non - ionic detergent in the resulting mixture is between 3 % and 10 % volume by volume ; ( d ) incubating the composition of ( c ); ( e ) subsequently shock - freezing the composition , thereby solidifying the composition homogeneously ; ( f ) optionally storing the composition of step ( e ) in a frozen , solidified state ; ( g ) thawing the frozen composition of step ( e ) in the presence of an aequous lysis reagent comprising a guanidinium salt , whereby the volume of the lysis buffer adjusts the final concentration of the guanidinium salt in the resulting mixture after thawing to a concentration of between 3 . 5 m and 4 . 2 m ; ( h ) adsorbing the nucleic acids contained in the composition of step ( g ) ( liquid phase ) to a solid phase , separating the solid phase from the liquid phase , optionally washing the solid phase with the adsorbed nucleic acids and subsequently desorbing the nucleic acids from the solid phase with an elution buffer , thereby purifying said nucleic acids . preferably , the anticoagulant of step ( b ) is an agent capable of forming complexes with divalent cations . citrate , heparin or edta are very much preferred . it is also preferred that the incubation of step ( d ) is performed at a temperature between 15 ° c . and 25 ° c ., more preferred at room temperature . it is also advantageous that the incubation of step ( d ) is performed under constant agitation , for example on a laboratory roller device or a shaker . preferably the final concentration of the guanidinium salt in the resulting mixture of step ( c ) is between 15 % and 25 % weight by volume , more preferred between 17 % and 22 % weight by volume , even more preferred 20 %. preferably the final concentration of the non - ionic detergent in the resulting mixture of step ( c ) is between 5 % and 7 % volume by volume , even more preferred about 6 . 5 %. a very much preferred non - ionic detergent is triton x - 100 . the incubation step ( d ) is preferably performed for 5 to 20 minutes , more preferred for about 10 minutes . it is further preferred that in step ( g ) prior to thawing dithiothreitol ( dtt ) is added to the frozen composition of step ( e ) whereby the concentration of dtt in the resulting mixture after thawing is between 0 . 01 % and 0 . 1 % weight by volume . very much preferred is a concentration of between 0 . 03 % and 0 . 07 % weight by volume . even more preferred is 0 . 06 % weight by volume . also preferred in step ( g ) the final concentration of the guanidinium salt in the mixture is between 3 . 5 m and 4 . 2 m after thawing . furthermore preferred , the thawing process of step ( g ) is performed under constant agitation . the elution buffer of step ( h ) is a low salt buffer capable of desorbing nucleic acids from the solid phase . the volume of the elution buffer is chosen such that a concentration of nucleic acids in the range of between 1 . 5 and 15 ng / μl results . another embodiment of the invention is a composition comprising whole blood , an anticoagulant , a guanidinium salt , and a non - ionic detergent in a frozen and homogeneously solid state of aggregation . yet , another embodiment of the invention is a method of determining the presence of a target nucleic acid in a whole blood sample , comprising the steps of ( a ) purifying nucleic acids from the whole blood sample according to the method of any of the claims 1 to 5 ; ( b ) detecting among the purified nucleic acids of step ( a ) the presence of the target nucleic acid , thereby determining the presence of the target nucleic acid . in a preferred embodiment of the invention the target nucleic acid is rna or dna . as a consequence of tse the expression of certain rnas is changed in several cell types . detection of such changes can be used for diagnosing tse , thereby offering an alternative to immunological assays for prion protein , e . g . prp sc . to this end , amplification of nucleic acid sequences by means of the polymerase chain reaction ( also referred to as pcr ; u . s . pat . nos . 4 , 683 , 202 , 4 , 683 , 195 , 4 , 800 , 159 , and 4 , 965 , 188 ) provides a sensitive detection means which is amenable to high - throughput testing . pcr typically employs two oligonucleotide primers that bind to a selected nucleic acid template ( e . g . a dna or a cdna ). primers useful in the present invention include oligonucleotides capable of acting as a point of initiation of nucleic acid synthesis within l1 , l3 or l4 . a primer can be purified from a restriction digest by conventional methods , or it can be produced synthetically . the primer is preferably single - stranded for maximum efficiency in amplification , but the primer can be double - stranded . double - stranded primers are first denatured , i . e ., treated to separate the strands . one method of denaturing double stranded nucleic acids is by heating . the term “ thermostable polymerase ” refers to a polymerase enzyme that is heat stable , i . e ., the enzyme catalyzes the formation of primer extension products complementary to a template and does not irreversibly denature when subjected to the elevated temperatures for the time necessary to effect denaturation of double - stranded template nucleic acids . generally , the synthesis is initiated at the 3 ′ end of each primer and proceeds in the 5 ′ to 3 ′ direction along the template strand . thermostable polymerases have been isolated from thermus flavus , t . ruber , t . thermophilus , t . aquaticus , t . lacteus , t . rubens , bacillus stearothermophilus , and methanothermus fervidus . nonetheless , polymerases that are not thermostable also can be employed in pcr assays provided the enzyme is replenished . if the target nucleic acid is double - stranded , it is necessary to separate the two strands before it can be used as a template in pcr . strand separation can be accomplished by any suitable denaturing method including physical , chemical or enzymatic means . one method of separating the nucleic acid strands involves heating the nucleic acid until it is predominately denatured ( e . g ., greater than 50 %, 60 %, 70 %, 80 %, 90 % or 95 % denatured ). the heating conditions necessary for denaturing template nucleic acid will depend , e . g ., on the buffer salt concentration and the length and nucleotide composition of the nucleic acids being denatured , but typically range from about 90 ° c . to about 105 ° c . for a time depending on features of the reaction such as temperature and the nucleic acid length . denaturation is typically performed for about 30 sec to 4 min . if the double - stranded nucleic acid is denatured by heat , the reaction mixture is allowed to cool to a temperature that promotes annealing of each primer to its target sequence on the target nucleic acid . the temperature for annealing is usually from about 35 ° c . to about 65 ° c . annealing times can be from about 10 secs to about 1 min . the reaction mixture is then adjusted to a temperature at which the activity of the polymerase is promoted or optimized , i . e ., a temperature sufficient for extension to occur from the annealed primer to generate products complementary to the template nucleic acid . the temperature should be sufficient to synthesize an extension product from each primer that is annealed to a nucleic acid template , but should not be so high as to denature an extension product from its complementary template ( e . g ., the temperature for extension generally ranges from about 40 ° to 80 ° c .). extension times can be from about 10 secs to about 5 mins . in a very much preferred embodiment of the invention the target nucleic acid is rna and step ( b ) of the method of determining the presence of a target nucleic acid in a whole blood sample comprises ( i ) reverse transcribing the rna to form a cdna , ( ii ) subsequently amplifying , by means of the polymerase chain reaction , the cdna , ( iii ) detecting the presence of the cdna , thereby determining the presence of the target nucleic acid . also very much preferred , prior to step ( i ) the rna concentration is adjusted to a standard value . the newly synthesized strands form a double - stranded molecule that can be used in the succeeding steps of the reaction . the steps of strand separation , annealing , and elongation can be repeated as often as needed to produce the desired quantity of amplification products corresponding to the target nucleic acid molecule . the limiting factors in the reaction are the amounts of primers , thermostable enzyme , and nucleoside triphosphates present in the reaction . the cycling steps ( i . e ., denaturation , annealing , and extension ) are preferably repeated at least once . for use in detection , the number of cycling steps will depend , e . g ., on the nature of the sample . if the sample is a complex mixture of nucleic acids , more cycling steps will be required to amplify the target sequence sufficient for detection . generally , the cycling steps are repeated at least about 20 times , but may be repeated as many as 40 , 60 , or even 100 times . studies using the datas approach ( wo2005 / 049863 ) have identified five bovine nucleic acid sequences as markers for tse in rna isolates from whole blood ( target nucleotide sequences ). surprisingly it has been found that seq id nos : 1 , 6 , and 11 are particularly advantageous since in an experimental setting using the preparation method for nucleic acids according to the invention and real time pcr they are able to discriminate between tse - infected and non - infected animals . therefore , the present invention is used for assessing tse in cattle . in a further preferred embodiment of the invention a whole blood sample is taken from a living bovine animal . even more preferred , the whole blood sample is obtained from an animal which is to proceed to the abattoir and to be processed for the human food chain later on . in this regard , the method of the invention can also be performed in combination with an immunological test detecting infectious prion protein ( prp sc ) or protease - resistant prion protein ( prp res ). according to the method of the invention , rna from whole blood samples is analyzed . in a further preferred embodiment of the invention the whole blood sample is taken from a living bovine animal . even more preferred , the bovine animal is asymptomatic with respect to tse . an example therefor is a bovine animal which is to proceed to the abattoir and about to enter the human food chain . when assessing tse in a bovine animal the target nucleic acid is preferably selected from the group consisting of seq id no : 1 , seq id no : 6 , and seq id no : 11 or a subfragment of any of said sequences . very much preferred , the amplified cdna is detected using a fluorescent signal . even more preferred , the amplified cdna is detected by monitoring the amplification in real time and determining the amount of amplification product after each cycle . detection of the amplified target nucleic acid is possible by several means . in a preferred embodiment of the invention , the amplified target nucleic acid is detected using a fluorescent signal . several detection formats based on target nucleic acid dependent fluorescent signaling have been disclosed , which enable continuous monitoring of the generation of amplification products ( reviewed in wittwer , et al ., biotechniques , 22 , ( 1997 ) 130 - 138 ). these detection formats include but are not limited to ( 1 ) to ( 4 ): ( 1 ) use of fluorescent double - stranded dna recognizing compounds : since the amount of double stranded amplification product usually exceeds the amount of nucleic acid originally present in the sample to be analyzed , double - stranded dna specific dyes may be used , which upon excitation with an appropriate wavelength show enhanced fluorescence only if they are bound to double - stranded dna . preferably , only those dyes may be used which like sybr green i ( molecular probes ), for example , do not affect the efficiency of the pcr reaction . in a very much preferred embodiment of the invention , the target nucleic acid is detected by monitoring the amplification in real time and determining the amount of amplification product after each cycle . the fluorescent signal generated by the incorporated dye can be quantified . signal strength correlates with the amount of pcr product formed and thus allows quantification of the target nucleic acid after each circle . therefore , in an even more preferred embodiment of the invention the target nucleic acid is detected by monitoring the amplification in real time and determining the amount of amplification product after each cycle . ( 2 ) increased fluorescence resonance energy transfer ( fret ) upon hybridization : for this detection format , two oligonucleotide hybridization probes each labeled with a fluorescent moiety are used which are capable of hybridizing to adjacent but non overlapping regions of one strand of the amplification product . preferably , one oligonucleotide is labeled at the 5 ′ end and the second oligonucleotide is labeled at the 3 ′ end . when hybridized to the target dna , the two fluorescent labels are brought into close contact , such that fluorescence resonance energy transfer between the two fluorescent moieties can take place . as a consequence , the hybridization can be monitored through excitation of the donor moiety and subsequent measurement of fluorescence emission of the second acceptor moiety . in a similar embodiment , only one fluorescently labeled probe is used , which together with one appropriately labeled primer may also serve as a specific fret pair ( bernard , p . s ., et al ., anal . biochem . 255 ( 1998 ) 101 - 107 ). in a very much preferred embodiment of the invention , the target nucleic acid is detected with fret hybridization probes . independent from the detection format or fluorescent label , hybridization probes are always polynucleotides having sequences which are completely identical with or exactly complementary to the sequence of the target nucleic acid . yet , it is also within the scope of the invention if the probes contain one or several mismatches , as long as they are capable of hybridizing to the amplification product under appropriate hybridization conditions . in any case , it has been proven to be particular advantageous , if the sequence identity or complementarity is 100 % over a range of at least 10 contiguous residues . taking onto account the length of the amplified fragments in the method of the invention , the length of the probe does not exceed 40 nucleotides , preferably not more than 30 nucleotides . however , hybridization probes may have 5 ′ or 3 ′ overhangs which do not hybridize to the target nucleic acid . ( 3 ) hydrolysis probes used in taqman instruments : in order to detect the amplification product , a single - stranded hybridization probe is used , which is labeled with a fluorescent entity , the fluorescence emission of which is quenched by a second label on the same probe which may act as a quenching compound . during the annealing step of the pcr reaction , the probe hybridizes to its target sequence , and , subsequently , during the extension of the primer , the dna polymerase having a 5 ′- 3 ′- exonuclease activity hydrolyzes the hybridization probe , such that the fluorescent entity is separated from the quencher compound . after appropriate excitation , fluorescence emission can be monitored as an indicator of accumulating amplification product . ( 4 ) molecular beacons : similar to hydrolysis probes , a molecular beacon oligonucleotide is labeled with a fluorescent compound and a quencher compound , which due to the secondary structure of the molecule are in dose vicinity to each other . upon binding to the target dna , the intramolecular hydrogen bonding is broken , and the fluorescent compound located at one end of the probe is separated from the quencher compound , which is located at the opposite end of the probe ( u . s . pat . no . 5 , 118 , 801 ). a very much preferred embodiment of the invention is a method of assessing tse in a bovine animal by way of determining the presence of a target nucleic acid in a preparation of nucleic acids from whole blood sample comprising the steps of performing at least one cycling step , wherein a cycling step comprises an amplifying step and hybridizing step , wherein said amplifying step comprises contacting said sample with a pair of lt1 , lt3 or lt4 primers to produce lt1 , lt3 or lt4 amplification product if a target nucleic acid lt1 ( seq id no : 1 ), lt3 ( seq id no : 6 ), or lt4 ( seq id no : 11 ) is present in said sample , wherein said hybridizing step comprises contacting said sample with a pair of lt1 , lt3 or lt4 probes , wherein the members of said pair of lt1 , lt3 or lt4 probes hybridize within no more than five nucleotides of each other , wherein a first lt1 , lt3 or lt4 probe of said pair of lt1 , lt3 or lt4 probes is labelled with a donor fluorescent moiety and said second lt1 , lt3 or lt4 probe of said pair of lt1 , lt3 or lt4 probes is labelled with a corresponding acceptor fluorescent moiety ; and detecting the presence or absence of fluorescence resonance energy transfer ( fret ) between said donor fluorescent moiety of said first lt1 , lt3 or lt4 probe and said acceptor fluorescent moiety of said second lt1 , lt3 or lt4 probe , wherein the presence of fret is indicative of the presence of transmissible spongiform encephalopathy ( tse ) in the individual from which said sample , derives and wherein the absence of fret in indicative of the absence of tse in said individual . preferably , the lt1 primer pair consists of the oligonucleotides according to seq id no : 2 . and seq id no : 3 ; the lt3 primer pair consists of the oligonucleotides according to seq id no : 7 and seq id no : 8 ; and lt4 primer pair consists of the oligonucleotides according to seq id no : 12 . and seq id no : 13 . also preferred , the pair of lt1 probes consists of the oligonucleotides according to seq id no : 4 and seq id no : 5 ; the pair of lt3 probes consists of the oligonucleotides according to seq id no : 9 and seq id no : 10 ; and the pair of lt4 probes consists of the oligonucleotides according to seq id no : 14 and seq id no : 15 . the oligonucleotide primers are combined with pcr reagents under reaction conditions that induce primer extension . for example , chain extension reactions typically include 3 . 25 mm manganese acetate , 0 . 5 μm forward primer , 0 . 5 μm reverse primer , 0 . 2 μm fluorescein probe , and 0 . 2 μm lcred640 probe . the reactions usually contain 150 to 320 μm each of datp , dctp , dttp , dgtp , or one or more analogs thereof . the amplification products generated during this process can be visualized using gel electrophoresis or by way of hybridization using specific probes . in addition , methods are known to the art which allow to monitor the amplification of a target nucleic acid in real time ( wo 97 / 46707 , wo 97 / 4671 ., wo 97 / 46714 ). most preferred in this regard is monitoring the amplification by way of detecting fluorescence resonance energy transfer ( fret ). fret technology ( see , for example , u . s . pat . nos . 4 , 996 , 143 , 5 , 565 , 322 , 5 , 849 , 489 , and 6 , 162 , 603 ) is based on a concept that when a donor and a corresponding acceptor fluorescent moiety are positioned within a certain distance of each other , energy transfer takes place between the two fluorescent moieties that can be visualized or otherwise detected and / or quantitated . two oligonucleotide probes , each containing a fluorescent moiety , can hybridize to an amplification product at particular positions determined by the complementarity of the oligonucleotide probes to the target nucleic acid sequence . upon hybridization of the oligonucleotide probes to the amplification product nucleic acid at the appropriate positions , a fret signal is generated . hybridization temperatures can range from about 35 to about 65 ° c . for about 10 secs to about 1 min . fluorescent analysis can be carried out using , for example , a photon counting epifluorescent microscope system ( containing the appropriate dichroic mirror and filters for monitoring fluorescent emission at the particular range ), a photon counting photomultiplier system or a fluorometer . excitation to initiate energy transfer can be carried out with an argon ion laser , a high intensity mercury ( hg ) arc lamp , a fiber optic light source , or other high intensity light source appropriately filtered for excitation in the desired range . as used herein with respect to donor and corresponding acceptor fluorescent moieties “ corresponding ” refers to an acceptor fluorescent moiety having an emission spectrum that overlaps the excitation spectrum of the donor fluorescent moiety . the wavelength maximum of the emission spectrum of the acceptor fluorescent moiety should be at least 100 nm greater than the wavelength maximum of the excitation spectrum of the donor fluorescent moiety . accordingly , efficient non - radiative energy transfer can be produced therebetween . fluorescent donor and corresponding acceptor moieties are generally chosen for ( a ) high efficiency förster energy transfer ; ( b ) a large final stokes shift (& gt ; 100 nm ); ( c ) shift of the emission as far as possible into the red portion of the visible spectrum (& gt ; 600 nm ); and ( d ) shift of the emission to a higher wavelength than the raman water fluorescent emission produced by excitation at the donor excitation wavelength . for example , a donor fluorescent moiety can be chosen that has its excitation maximum near a laser line ( for example , helium - cadmium 44 . nm or argon 488 nm ), a high extinction coefficient , a high quantum yield , and a good overlap of its fluorescent emission with the excitation spectrum of the corresponding acceptor fluorescent moiety . a corresponding acceptor fluorescent moiety can be chosen that has a high extinction coefficient , a high quantum yield , a good overlap of its excitation with the emission of the donor fluorescent moiety , and emission in the red part of the visible spectrum (& gt ; 600 nm ). representative donor fluorescent moieties that can be used with various acceptor fluorescent moieties in fret technology include fluorescein , lucifer yellow , b - phycoerythrin , 9 - acridineisothiocyanate , lucifer yellow vs , 4 - acetamido - 4 ′- isothiocyanatostilbene - 2 , 2 ′- disulfonic acid , 7 - diethylamino - 3 -( 4 ′- isothiocyanatophenyl )- 4 - methylcoumarin , succinimdyl 1 - pyrenebutyrate , and 4 - acetamido - 4 ′- isothiocyanatostilbene - 2 , 2 ′- disulfonic acid derivatives . representative acceptor fluorescent moieties , depending upon the donor fluorescent moiety used , include lc ™- red 640 , lc ™- red 705 , cy5 , cy5 . 5 , lissamine rhodamine b sulfonyl chloride , tetramethyl rhodamine isothiocyanate , rhodamine x isothiocyanate , erythrosine isothiocyanate , fluorescein , diethylenetriamine pentaacetate or other chelates of lanthanide ions ( e . g ., europium , or terbium ). donor and acceptor fluorescent moieties can be obtained , for example , from molecular probes ( junction city , usa ) or sigma chemical co . ( st . louis , usa ). the donor and acceptor fluorescent moieties can be attached to the appropriate probe oligonucleotide via a linker arm . the length of each linker arm is important , as the linker arms will affect the distance between the donor and acceptor fluorescent moieties . the length of a linker arm for the purpose of the present invention is the distance in angstroms ( å ) from the nucleotide base to the fluorescent moiety . in general , a linker arm is from about 10 to about 25 å . the linker arm may be of the kind described in wo 84 / 03285 . wo 84 / 03285 also discloses methods for attaching linker arms to a particular nucleotide base , and also for attaching fluorescent moieties to a linker arm . an acceptor fluorescent moiety such as an lc ™- red 640 - nhs - ester can be combined with c6 - phosphoramidites ( available from abi ( foster city , usa ) or glen research ( sterling , usa )) to produce , for example , lc ™- red 640 - phosphoramidite . frequently used linkers to couple a donor fluorescent moiety such as fluorescein to an oligonucleotide include thiourea linkers ( fitc - derived , for example , fluorescein - cpg &# 39 ; s from glen research or chemgene ( ashland , mass . )), amide - linkers ( fluorescein - nhs - ester - derived , such as fluorescein - cpg from biogenex ( san ramon , usa )), or 3 ′- amino - cpg &# 39 ; s that require coupling of a fluorescein - nhs - ester after oligonucleotide synthesis . before detection of the target nucleic acid , the fraction encompassing all nucleic acids ( dna and rna ) is purified from the sample which is a complex mixture of different components . often , for the first steps , processes are used which allow the enrichment of the nucleic acids . to release the contents of cells , they may be treated with enzymes or with chemicals to dissolve , degrade or denature the cellular walls . this process is commonly referred to as lysis . the resulting solution containing such lysed material is referred to as lysate . a problem often encountered during the lysis is that other enzymes degrading the component of interest , e . g . ribonucleases degrading rna , come into contact with the component of interest during lysis . these degrading enzymes may also be present outside the cells or may have been spatially separated in different cellular compartiments before the lysis and come now into contact with the component of interest . it is common to use chaotropic agents as e . g . guanidinium thiocyanate or anionic , cationic , zwitterionic or non - ionic detergents when nucleic acids are intended to be set free . it is also an advantage to use proteases which rapidly degrade these enzymes or unwanted proteins . however , this may produce another problem as the said substances or enzymes can interfere with reagents or components in subsequent steps . proteases ( see walsh , enzymatic reaction mechanisms . w . h . freeman and company , san francisco , chapter 3 ( 1979 ) which are commonly known to the are e . g . alkaline proteases ( wo 98 / 04730 ) or acid proteases ( u . s . pat . no . 5 , 386 , 024 ). the protease which is widely used in the prior art for sample preparation for the isolation of nucleic acids is proteinase k from tritirachium album l ( see e . g . sambrook , j . et al ., molecular cloning : a laboratory manual , cold spring harbor laboratory press , cold spring harbor , n . y ., 1989 ) which is active around neutral ph and belongs to a family of proteases known as subtilisins . in the next steps of the sample preparation which follow on the lysis step , the nucleic acids are further enriched . there are several methods for the extraction of nucleic acids : ( a ) sequence - dependent or biospecific methods such as e . g . : affinity chromatography and hybridisation to immobilised probes ; ( b ) sequence - independent or physico - chemical methods such as e . g . : liquid - liquid extraction ( e . g . with phenol - chloroform ), precipitation ( e . g . with pure ethanol ), extraction with filter paper , extraction with micelle - forming agents ( e . g . cetyl - trimethyl - ammonium - bromide ), binding to immobilised intercalating dyes ( e . g . acridine derivatives ), adsorption to silica gel or diatomic earths , and adsorption to magnetic glass particles ( mgp ) or organo silane particles under chaotropic conditions . particularly interesting for extraction purposes is the adsorption of nucleic acids to a glass surface although other surfaces are possible . many procedures for isolating nucleic acids from their natural environment have been proposed in recent years by the use of their binding behavior to glass surfaces . if unmodified nucleic acids are the target , a direct binding of the nucleic acids to a material with a silica surface or glass is preferred because among other reasons the nucleic acids do not have to be modified and even native nucleic acids can be bound . to separate the particles from the contaminants , the particles may be either centrifuged or fluids are drawn through glass fiber filters . this is a limiting step , however , that prevents the procedure from being used to process large quantities of samples . the use of magnetic particles to immobilize nucleic acids after precipitation by adding salt and ethanol is more advantageous and described e . g . in alderton , r . p ., et al ., anal . biochem . 201 ( 1992 ) 166 - 169 and wo 91 / 12079 . in this procedure , the nucleic acids are agglutinated along with the magnetic particles . the agglutinate is separated from the original solvent by applying a magnetic field and performing a washing step . after one or more washing steps , the nucleic acids are dissolved in a tris buffer . magnetizable particular adsorbents proved to be very efficient and suitable for automatic sample preparation . ferrimagnetic and ferromagnetic as well as superparamagnetic pigments are used for this purpose . the most preferred magnetic glass particles and methods using these are described in wo 01 / 37291 . after the purification or isolation of the nucleic acids including the target nucleic acid from their natural surroundings , the target nucleic acid may be detected . before detection , however , in an additional step the nucleic acids are incubated with rnase - free dnase , thereby allowing to specifically purify the rnas which were present in the sample . example 2 describes a preferred method of sample preparation using the magna pure lc instrument and an rna isolation kit ( roche diagnostics gmbh , mannheim , germany ). the target nucleic acid is detected by way of specific amplification using rt - pcr ( rt = reverse transcriptase ; pcr = polymerase chain reaction ). the target rna is first reverse - transcribed to form a complementary single - stranded cdna . the cdna in turn serves as a template for dna amplification using suitable primers . the amplification product is also referred to as the “ target nucleic acid ”. in the method of the invention , a preferred target sequence selected from the group consisting of seq id nos : 1 , 6 , and 11 or a partial sequence thereof or a combination of the sequences of seq id nos : 1 , 6 , and 11 or partial sequences thereof or all three sequences or partial sequences thereof are amplified by means of pcr using specific primer pairs . a primer pair consisting of one forward primer and one reverse primer is used in the method of the invention . in the amplification reaction mixture the preferred initial concentration of each primer is 0 . 5 ° μm . the forward primer is an oligonucleotide with a preferred length of between 15 and 25 nucleotides . preferably , the sequence of the primer is a contiguous partial sequence of the respective preferred target nucleotide sequence selected from the group consisting of seq id nos : 1 , 6 , and 11 . the reverse primer is an oligonucleotide with a preferred length of between 15 and 25 nucleotides . also preferred , the sequence of the primer is a contiguous partial sequence of the complement of the respective preferred target nucleotide sequence selected from the group consisting of seq id nos : 1 , 6 , and 11 . although there are numerous possibilities to design such primers , there are preferred primer sequences according to the invention . preferably , the lt1 primer pair consists of the oligonucleotides according to seq id no : 2 . and seq id no : 3 ; the lt3 primer pair consists of the oligonucleotides according to seq id no : 7 and seq id no : 8 ; and lt4 primer pair consists of the oligonucleotides according to seq id no : 12 . and seq id no : 13 . it is noted that the terms “ oligonucleotide ” and also “ polynucleotide ” in the context of the present invention summarizes not only ( desoxy )- oligo - ribonucleotides , but also all dna - or rna - derivatives known in the art like e . g . methyl - phosphonates , phosphothioates , 2 ′- o - alkyl - derivatives as well as peptide nucleic acids , and analoga comprising modified bases like 7 - deaza - purines . it is also noted that a primer oligo - or polynucleotide is understood as being capable of serving as a substrate for template - dependent dna - or rna - polymerases . by virtue of polymerase activity a primer can be elongated by the addition of nucleoside phosphates or analogues thereof . the present invention provides methods for detecting the presence or absence of tse - specific differentially spliced transcripts in a whole blood sample from a bovine individual . methods provided by the invention avoid problems of sample contamination , false negatives , and false positives . the methods include performing at least one cycling step that includes amplifying a target nucleic acid portion of a lt1 , lt3 , and / or lt4 nucleic acid molecule from a sample using a pair of lt1 , lt3 , and / or lt4 primers , respectively . each of the lt1 , lt3 , or lt4 primers anneals to a target within or adjacent to a lt1 , lt3 , or lt4 nucleic acid molecule , respectively , such that at least a portion of each amplification product contains nucleic acid sequence corresponding to lt1 , lt3 , or lt4 , respectively . more importantly , the amplification product should contain the nucleic acid sequences that are complementary to the lt1 , lt3 , or lt4 probes , respectively . the lt1 , lt3 , and / or lt4 amplification product is produced provided that target nucleic acid ( tse - specific and differentially spliced mrna ) is present . each cycling step further includes contacting the sample with a pair of lt1 , lt3 , and / or lt4 probes . according to the invention , one member of each pair of the lt1 , lt3 , and / or lt4 probes is labeled with a donor fluorescent moiety and the other is labeled with a corresponding acceptor fluorescent moiety . the presence or absence of fret between the donor fluorescent moiety of the first lt1 , lt3 , or lt4 probe and the corresponding acceptor fluorescent moiety of the second lt1 , lt3 , or lt4 probe , respectively , is detected upon hybridization of the lt1 , lt3 , or lt4 probes to the respective amplification product . each cycling step includes an amplification step and a hybridization step , and each cycling step is usually followed by a fret detecting step . multiple cycling steps are performed , preferably in a thermocycler . methods of the invention can be performed using one or more of the lt1 , lt3 , and / or lt4 primer and probe sets to detect the presence of the respective target nucleic acid ( s ). alternatively , methods of the invention can be performed simultaneously with each of the lt1 , lt3 , and lt4 primer and probe sets to detect the respective target sequences in whole blood samples . as used herein , “ amplifying ” refers to the process of synthesizing nucleic acid molecules that are complementary to one or both strands of a template nucleic acid molecule ( e . g ., lt1 , lt3 , or lt4 nucleic acid molecules ). amplifying a nucleic acid molecule typically includes denaturing the template nucleic acid , annealing primers to the template nucleic acid at a temperature that is below the melting temperatures of the primers , and enzymatically elongating from the primers to generate an amplification product . amplification typically requires the presence of deoxyribonucleoside triphosphates , a dna polymerase enzyme ( e . g ., platinum taq ) and an appropriate buffer and / or co - factors for optimal activity of the polymerase enzyme ( e . g ., mgcl 2 . and / or kcl ). if amplification of a target nucleic acid occurs and an amplification product is produced , the step of hybridizing results in a detectable signal based upon fret between the members of the pair of probes . as used herein , “ hybridizing ” refers to the annealing of probes to an amplification product . hybridization conditions typically include a temperature that is below the melting temperature of the probes but that avoids non - specific hybridization of the probes . generally , the presence of fret indicates tse infection of the bovine individual from which the respective blood sample was taken ; the absence of fret indicates the absence of tse . inadequate specimen collection , transportation delays , inappropriate transportation conditions , among other factors can affect the success and / or accuracy of a test result , however . using the methods disclosed herein , detection of fret within 45 cycling steps is indicative of tse infection . in a most preferred embodiment of the invention , the amplification product is detected with fret hybridization probes . independent from the detection format or fluorescent label , hybridization probes are always polynucleotides having sequences which are completely identical with or exactly complementary to the sequence of the target nucleic acid . yet , it is also within the scope of the invention if the probes contain one or several mismatches , as long as they are capable of hybridizing to the amplification product under appropriate hybridization conditions . in any case , it has been proven to be particular advantageous , if the sequence identity or complementarity is 100 % over a range of at least 10 contiguous residues . taking onto account the length of the amplified fragments in the method of the invention , the length of a probe does not exceed 40 nucleotides , preferably not more than 30 nucleotides . however , hybridization probes may have 5 ′ or 3 ′ overhangs which do not hybridize to the target nucleic acid . preferably , the pair of lt1 probes consists of the oligonucleotides according to seq id no : 4 and seq id no : 5 ; the pair of lt3 probes consists of the oligonucleotides according to seq id no : 9 and seq id no : 10 ; and the pair of lt4 probes consists of the oligonucleotides according to seq id no : 14 and seq id no : 15 . according to the invention , it is furthermore preferred that a first and the second target sequence are amplified and detected in one tube . this is possible in a multiplex approach , wherein differentially labeled hybridization probes for each sequence are used for detection of the respective amplification products . the assays of the invention may be performed on a lightcycler instrument ( roche diagnostics gmbh , mannheim , germany ) using a pair of fret hybridization probes labeled with fluorescein at the 3 ′ end of the first hybridization probe and with lc - red - 640 ( roche diagnostics gmbh , mannheim , germany ) at the 5 ′ end of the second hybridization probe . when performing multiplex analysis with two different target sequences , a second pair of fret hybridization probes labeled with fluorescein at the 3 ′ end of the first oligonucleotide and with lc - red - 705 ( roche diagnostics gmbh , mannheim , germany ) at the 5 ′ end of the second oligonucleotide are preferably used . principally , any kind of quantification method can be applied , however , it has been proven to be advantageous , if methods using an external standard are applied . the external standard itself may be a plasmid or a linearized template with one or more target sequences to be amplified . in case of quantification of a nucleic acid using external standards , a calibration curve has to be generated . for this calibration curve , known amounts of the target nucleic acid are amplified and the intensity of fluorescent signal is determined as a function of cycle number . after smoothening of the kinetics by a mathematical fit , the first or second maximum of the derivative are calculated . this enables a correlation between the original target concentration and the fractional cycle number of a determined maximum . subsequently , determination of unknown analyte concentrations may be performed . in order to eliminate quantification errors originating from different detection sensitivities , it has been proven to be particular advantageous , if the same batch of hybridization probe ( s ) is used for the sample to be analyzed and for the calibration samples . melting curve analysis is an additional step that can be included in a cycling profile . melting curve analysis is based on the fact that dna melts at a characteristic temperature called the melting temperature ( tm ), which is defined as the temperature at which half of the dna duplexes have separated into single strands . the melting temperature of a dna depends primarily upon its nucleotide composition . thus , dna molecules rich in g and c nucleotides have a higher tm than those having an abundance of a and t nucleotides . by detecting the temperature at which signal is lost , the melting temperature of probes can be determined . similarly , by detecting the temperature at which signal is generated , the annealing temperature of probes can be determined . the melting temperature ( s ) of the lt1 , lt3 , or lt4 probes from the respective amplification product can confirm the presence or absence of the respective target nucleic acid in the sample . within each thermocycler run , control samples are cycled as well . positive control samples can amplify a control template ( other than lt1 , lt3 , or lt4 ) using , for example , control primers and control probes . positive control samples can also amplify , for example , a plasmid construct containing lt1 , lt3 , or lt4 nucleic acid molecule . such a plasmid control can be amplified internally ( e . g ., within the sample ) or in a separate sample run side - by - side with the individuals &# 39 ; samples . each thermocycler run should also include a negative control that , for example , lacks target template dna . such controls are indicators of the success or failure of the amplification , hybridization and / or fret reaction . therefore , control reactions can readily determine , for example , the ability of primers to anneal with sequence - specificity and to initiate elongation , as well as the ability of probes to hybridize with sequence - specificity and for fret to occur . conventional pcr methods in conjunction with fret technology can be used to practice the methods of the invention . in one embodiment , a lightcycler instrument is used . a detailed description of the lightcycler system and real - time and on - line monitoring of pcr can be found at http :// biochem . roche . com / lightcycler . the following patent applications describe real - time pcr as used in the lightcycler technology : wo 97 / 46707 , wo 97 / 46714 and wo 97 / 46712 . the lightcycler instrument is a rapid thermal cycler combined with a microvolume fluorometer utilizing high quality optics . this rapid thermocycling technique uses thin glass cuvettes as reaction vessels . heating and cooling of the reaction chamber are controlled by alternating heated and ambient air . due to the low mass of air and the high ratio of surface area to volume of the cuvettes , very rapid temperature exchange rates can be achieved within the lightcycler thermal chamber . addition of selected fluorescent dyes to the reaction components allows the pcr to be monitored in real time and on - line . furthermore , the cuvettes serve as an optical element for signal collection ( similar to glass fiber optics ), concentrating the signal at the tip of the cuvette . the effect is efficient illumination and fluorescent monitoring of microvolume samples . the lightcycler carousel that houses the cuvettes can be removed from the instrument . therefore , samples can be loaded outside of the instrument ( in a pcr clean room , for example ). in addition , this feature allows for the sample carousel to be easily cleaned and sterilized . the fluorometer , as part of the lightcycler apparatus , houses the light source . the emitted light is filtered and focused by an epi - illumination lens onto the top of the cuvette . fluorescent light emitted from the sample is then focused by the same lens , passed through a dichroic mirror , filtered appropriately , and focused onto data - collecting photohybrids . the optical unit available in the lightcycler 1 . 2 instrument ( roche applied science , catalog no . 2011468 ) includes three band - pass filters ( 530 nm , 640 nm , and 710 nm ), providing three - color detection and several fluorescence acquisition options . data collection options include once per cycling step monitoring , fully continuous single - sample acquisition for melting curve analysis , continuous sampling ( in which sampling frequency is dependent on sample number ) and / or stepwise measurement of all samples after defined temperature interval . the lightcycler can be operated using a pc workstation and can utilize a windows operating system . signals from the samples are obtained as the machine positions the capillaries sequentially over the optical unit . the software can display the fluorescence signals in real - time immediately after each measurement . fluorescent acquisition time is 10 - 100 milliseconds ( msec ). after each cycling step , a quantitative display of fluorescence vs . cycle number can be continually updated for all samples . the data generated can be stored for further analysis . the following examples , sequence listing and figures are provided to aid the understanding of the present invention , the true scope of which is set forth in the appended claims . it is understood that modifications can be made in the procedures set forth without departing from the spirit of the invention . a first set of whole blood samples came from 10 animals which were shown to be infected with bse by means of a post mortem test which immunologically detects prp res . a second set of whole blood samples came from 14 healthy animals . they were tested negative using commercially available post - mortem tests . workflow , rna preparation , also see legend to fig1 . blood was drawn from test animals and immediately mixed with anticoagulant . a typical blood sample had a volume of 50 ml . using a volume ratio of 2 : 1 stabilization reagent was added to the blood samples ( to result in a final volume of 150 ml ) which were subsequently snap - frozen in liquid nitrogen . frozen samples were transferred to the laboratory on dry ice and stored at − 80 ° c . if necessary . before thawing the stabilized samples 150 mg solid dtt were added onto the solid frozen block , followed by 100 ml lysis reagent . thawing was accomplished at room temperature under constant agitation ( laboratory roller ). the final concentration of guanidinium salt in the lysed sample was 3 . 9 m . aliquots of 900 μl of the lysed sample were subjected to rna preparation using the magna pure lc instrument and commercial rna isolation kits ( e . g . catalogue no . 03542394001 ) according to the instructions of the supplier ( roche diagnostics gmbh , mannheim , germany ). for setting up the rt - pcr 5 μl of rna eluate was used in a total reaction volume of 20 μl . a typical rt - pcr consists of 3 . 25 mm mn ( oac ) 2 , 0 . 5 μm of each primer ( forward , reverse primer ) and 0 . 2 μm of each lightcycler hybprobe ( fluorescein , lcred640 hybprobe ). the pcr specific components were added according to package insert of lightcycler rna master hybridization probes ( roche diagnostics catalogue no . 03 018 954 001 ). after pcr amplification melting curve analysis was performed . for analysis of pcr product size agarose ( 1 . 5 %) gel electrophoresis was performed . pcr was performed on a lightcycler instrument using the protocol as given in fig4 . results are depicted in fig5 ( lt1 ), fig8 ( lt3 ), and fig1 ( lt4 ). in a pcr amplification reaction , the cycle at which the fluorescence , i . e . in the present case the fret fluorescence of the detection probes hybridized to the amplified dna , rises above the background fluorescence is called the “ crossing point ” of the sample . the crossing point of a sample appears as a sharp upward curve on the experiment &# 39 ; s fluorescence chart . the crossing point is the point at which the concentration of the target nucleic acid in the sample . table 2 sample status crossing point h 2 o negative run control no cp 1 infected , confirmed by post - mortem test 24 . 57 2 infected , confirmed by post - mortem test 24 . 25 3 infected , confirmed by post - mortem test 24 . 89 4 infected , confirmed by post - mortem test 25 . 07 5 infected , confirmed by post - mortem test 24 . 69 6 infected , confirmed by post - mortem test 24 . 74 7 infected , confirmed by post - mortem test 24 . 68 8 infected , confirmed by post - mortem test 24 . 54 9 infected , confirmed by post - mortem test 25 . 51 10 infected , confirmed by post - mortem test 24 . 88 bse , average 24 . 78 11 healthy , not infected , negative post - mortem test 24 . 12 12 healthy , not infected , negative post - mortem test 23 . 91 13 healthy , not infected , negative post - mortem test 23 . 25 14 healthy , not infected , negative post - mortem test 23 . 89 15 healthy , not infected , negative post - mortem test 23 . 71 16 healthy , not infected , negative post - mortem test 24 . 08 17 healthy , not infected , negative post - mortem test 23 . 96 18 healthy , not infected , negative post - mortem test 23 . 24 19 healthy , not infected , negative post - mortem test 23 . 76 20 healthy , not infected , negative post - mortem test 23 . 33 healthy , average 23 . 73 | 2 |
this invention is described in preferred embodiments in the following description with reference to the figures , in which like numbers represent the same or similar elements . while this invention is described in terms of the best mode for achieving this invention &# 39 ; s objectives , it will be appreciated by those skilled in the art that variations may be accomplished in view of these teachings without deviating from the spirit or scope of the invention . referring to fig1 , an example of a data storage cartridge 10 comprising a longitudinal tape 11 , such as magnetic tape , is illustrated wherein the rewritable magnetic tape 11 is wound on a hub 12 of reel 13 . a cartridge memory 14 may store information regarding the data storage cartridge and , for example , comprises a transponder having a contactless interface . the illustrated magnetic tape cartridge is a single reel cartridge . magnetic tape cartridges may also comprise dual reel cartridges in which the tape is fed between reels of the cartridge . referring to fig2 , a magnetic tape drive 15 is illustrated . an example of a magnetic tape drive is the ibm ® lto ( linear tape open ) magnetic tape drive 15 , with microcode , etc ., to perform desired operations with respect to the magnetic tape cartridge 10 . another example of a magnetic tape drive is the ibm ® totalstorage enterprise magnetic tape drive . both the above examples of magnetic tape drives employ single reel tape cartridges 10 . an alternative magnetic tape drive and magnetic tape cartridge is a dual reel cartridge and drive in which both reels 13 and 16 are contained in the cartridge . in the instant example , the magnetic tape 11 is wound on a reel 13 in the cartridge 10 , and , when loaded in the magnetic tape drive 15 , is fed between the cartridge reel and a take up reel 16 in the magnetic tape drive . alternatively , both reels of a dual reel cartridge are driven to feed the magnetic tape between the reels . the magnetic tape drive comprises a memory interface 17 for reading information from , and writing information to , the cartridge memory 14 of the magnetic tape cartridge 10 . a read / write system is provided for reading and writing information to the magnetic tape , and , for example , may comprise a read / write and servo head system 18 with a servo system for moving the head laterally of the magnetic tape 11 , a read / write servo control 19 , and a drive motor system 20 which moves the magnetic tape 11 between the cartridge reel 13 and the take up reel 16 and across the read / write and servo head system 18 . the read / write and servo control 19 controls the operation of the drive motor system 20 to move the magnetic tape 11 across the read / write and servo head system 18 at a desired velocity , and , in one example , determines the lateral location of the read / write and servo head system with respect to the magnetic tape 11 , and , in another example , determines the longitudinal position of the tape 11 by reading the tape servo tracks . in one example , the read / write and servo head system 18 and read / write and servo control 19 employ servo signals on the magnetic tape 11 to determine the location of the read / write and servo head system , and in another example , the read / write and servo control 19 employs at least one of the reels , such as by means of a tachometer , to determine the location of the read / write and servo head system with respect to the magnetic tape 11 . the read / write and servo head system 18 and read / write and servo control 19 may comprise hardware elements and may comprise any suitable form of logic , including a processor operated by software , or microcode , or firmware , or may comprise hardware logic , or a combination . an interface 23 provides communication with respect to one or more host systems or processors 25 , and is configured to receive and to send information externally of the data storage drive . alternatively , the magnetic tape drive 15 may form part of a subsystem , such as a library , and may also receive commands from the subsystem , also at interface 23 . a control 24 communicates with the host interface 23 , with memory interface 17 , and communicates with the read / write system , e . g ., at read / write and servo control 19 . the control 24 may comprise any suitable form of logic , including one or more processors operated by software , or microcode , or firmware , or may comprise hardware logic , or a combination . the illustrated and alternative embodiments of magnetic tape drives are known to those of skill in the art , including those which employ dual reel cartridges . other types of removable data storage cartridges and data storage drives are known to those of skill in the art . examples comprise optical disk cartridges and drives , optical tape cartridges and drives , removable computer diskettes and drives , rigid magnetic disk cartridges and drives , etc . the control 24 typically communicates with the one or more host systems 25 or subsystems via interface 23 , and operates the magnetic tape drive 15 in accordance with commands originating at the host or subsystem . as illustrated , the magnetic tape drive 15 provides information to the magnetic tape 11 of the magnetic tape cartridge 10 . the magnetic tape is a serial data storage means where the data may be stored as various blocks or sections of data , arranged in a serial string . referring to fig3 , a magnetic tape 11 is illustrated with several parallel wraps of groups of parallel tracks . in the example , the magnetic tape is moved longitudinally in a first direction from the leading end of the tape while the head system reads and / or writes data with respect to one linear path of the wrap , and is reversed at the other end of the tape to be moved in the opposite direction and the head system is shifted to another linear path of the wrap , and the paths are termed “ serpentine ” paths . in the illustration , only one path is shown for each wrap , whereas in a physical tape a number of read and write elements are arranged to trace parallel paths within the linear path . the serpentine paths may be arranged in at least two patterns . in fig3 , in one pattern , a wrap comprises laterally offset adjacent linear paths 50 and 51 . in another pattern , the wraps are arranged in an inward spiral so that a wrap comprises laterally offset paths 50 and 52 . the wrap comprising adjacent linear paths 50 and 51 has the advantage of the paths being closer together , reducing the time to translate between the paths at the ends of the tape . the wrap comprising an inward spiral of linear paths 50 and 52 is typically used when adjacent linear paths are “ shingled ” as shown in fig5 . shingling is employed to increase the number of tracks that can be recorded without reducing the size of the tape write elements . as can be seen in fig5 , track 55 partially overwrites track 53 . again , a single linear path is illustrated , while the individual write elements shingle each of the parallel paths making up the linear path . the end of the string of data may be called the “ end of data ” and may also be called the “ end of tape ”. subsequent additions of data begin at the previous “ end of tape ”, and continue , ultimately ending with a new “ end of tape ”. data that has been stored and subsequently modified is typically not modified in place . rather , typically , the updated data is stored separately at the end of the string of data and the host system identifies the superseded data as expired . referring to fig2 and 4 , a block 60 of data has been marked as expired by a host ( as shown by the “ x ” s ). in accordance with the present invention , the control 24 identifies expired portions of the data stored on the tape 11 . the control further determines whether data of a complete linear path 63 of the longitudinal tape has been expired ; and allows reuse of any determined complete linear path 63 for storage of data . alternatively , the determination may be of expiration of a complete wrap 63 , 64 and the control 24 allows reuse of the determined complete wrap . the lateral translation between paths normally occurs at each end of the physical tape . when the end of tape or end of data reaches an end of the physical tape , the control 24 operates the read / write and servo 19 to translate the head 18 laterally to the next path in the sequence . in accordance with the present invention , the control , in allowing the reuse of a complete linear path or a complete wrap , when the end of tape or end of data reaches an end of the physical tape , similarly operates the read / write and servo to translate the head 18 laterally , but not to the next linear path in the sequence , but instead back to the complete linear path or wrap that has been determined to have been expired , thereby reusing the linear path or wrap . referring additionally to fig6 , in step 80 , the control 24 operates the longitudinal tape data storage drive 15 to store data received from a host or hosts 25 as directed by the host ( s ), storing the data as a sequence of serpentine wraps of two laterally offset linear paths on longitudinal tape 11 . the host ( s ) may also update the data or indicate that the data is no longer needed , and the updated data is stored in the continuing sequence of serpentine wraps , while the superseded and unneeded data is expired by the host ( s ). in step 83 , the control identifies the expired data 60 , 63 , 64 , storing the identification , for example , in memory . the control prevents reuse of small segments of free space represented by the small expired blocks 60 thereby avoiding a performance impact that would be incurred due to the linear tape motion associated with finding an empty segment . although one of the key functions that is typical of an enterprise class tape drive is the ability to do a high speed locate operation to the beginning of the expired data , doing so for a large number of small segments causes a performance impact . in step 87 , the control 24 determines whether data of a complete linear path 63 or 64 of the longitudinal tape has been expired . a complete linear path allows translation to the linear path in a similar manner as a normal translation to continue the sequence of serpentine paths . thus , if the end of tape or end of data was positioned at the physical end of tape position 89 , the normal translation would be laterally to path 52 and is instead made in the opposite direction to path 64 . alternatively , the user may prefer to operate only with wraps , and in that case , the control 24 , in step 87 , determines whether data of a complete wrap 63 , 64 of the longitudinal tape has been expired . a complete wrap allows translation to the linear path in a similar manner as a normal translation to continue the sequence of serpentine wraps . thus , if the end of tape or end of data was positioned at the physical end of tape position 90 , the normal translation would be laterally to path 92 and is instead made in the opposite direction to path 63 . referring additionally to fig5 , if the linear paths are shingled , as are paths 1 , 2 , 3 , a different scenario is conducted . step 95 determines whether the linear paths are shingled , a determination that may be made by accessing the cartridge memory 14 where an indication is stored , as is known in the art . in the event that the longitudinal tape comprises shingled data , not only must a complete path 100 or 101 , or wrap 100 , 101 be determined to be expired in step 87 , but in step 105 , the complete path 53 or 103 or wrap 53 , 103 overlying the complete path 100 or 101 , or wrap 100 , 101 must also be determined to be expired . this is because to overwrite the complete path 100 or 101 , or wrap 100 , 101 would destroy the overlying complete path 53 or 103 or wrap 53 , 103 . if either step 87 or step 105 indicates insufficient data has been expired , the process returns to step 80 to continue to store and expire data . if step 87 indicates that sufficient data has been expired to comprise a complete linear path or wrap and , if not shingled , step 110 allows the complete linear path 63 or 64 to be available for reuse , or alternatively , allows the complete wrap 63 , 64 to be available for reuse . if step 95 indicates that the linear paths are shingled , and step 87 indicates that sufficient data has been expired to comprise a complete linear path or wrap , and step 105 additionally indicates that the complete path 53 or 103 or wrap 53 , 103 overlying the complete path 100 or 101 , or wrap 100 , 101 has been determined to be expired , step 110 allows the complete linear path 100 or 101 , or wrap 100 , 101 to be available for reuse , limiting the reuse to exclude reuse of a linear path which is shingled by an adjacent linear path whose data is at least partially unexpired . the allowing step 110 makes the complete linear path ( s ) available for reuse from the beginning of the complete linear path where lateral translation to the linear path normally occurs , such as at point 112 for linear path 64 . if a serpentine wrap is expired and available , the allowing step 110 makes the complete linear path ( s ) available for reuse from the beginning of the complete wrap where lateral translation to the first linear path of the wrap normally occurs , such as at point 113 for linear path 63 . in another way of stating the requirement , the allowing step comprises allowing the reuse upon an end of data position of another linear path reaching a point wherein the normal lateral translation occurrence is aligned with the beginning of the allowed complete linear path . thus , allowing step 110 makes the complete linear path ( s ) available for reuse from the end of the complete linear path where lateral translation to another linear path normally occurs , such as at point 89 for linear path 92 . the translation becomes a lateral translation to point 112 for linear path 64 rather than to linear path 52 . similarly , if the allowing step is to a complete wrap for reuse , allowing step 110 makes the complete wrap ( s ) available for reuse from the beginning of the first complete linear path of the wrap where lateral translation to the wrap normally occurs , such as at point 113 for linear path 63 rather than to linear path 92 . the same holds true for shingled paths in that the allowing step 110 makes the complete linear paths available for reuse from the end of the complete linear path where lateral translation to another linear path normally occurs , such as from point 118 of linear path 100 to a point 119 for linear path 101 . similarly , if the allowing step is to a complete wrap for reuse , allowing step 110 makes the complete wrap ( s ) available for reuse from the beginning of the first complete linear path of the wrap where lateral translation to the wrap normally occurs , such as at point 120 from linear path 53 to point 121 of linear path 53 . in step 115 , the control 24 maps the sequence of lateral repositioning upon completion of tracing the linear paths . the mapping indicates the new sequence of the lateral positions after reuse . the present invention is of importance if the host ( s ) is writing multiple backups on a single volume . as old backups expire , large contiguous sections of the tape can be reclaimed . when data has been expired and reuse allowed of a complete linear path or complete wrap and a host has overwritten the expired data , a host may attempt to access the expired data . for example , if in fig4 , assume linear paths 63 and 64 contain logical blocks 2000 through 3999 . then assume the complete linear paths 63 and 64 are expired , made available for reuse , and then overwritten with logical blocks 8000 through 9999 . referring to fig6 , if the host ( s ) attempt to read any of the expired and overwritten data blocks 2000 through 3999 at a later time , in step 118 , the control instead returns “ dummy ” data blocks . an example of “ dummy ” data is a 1 kb x “ 00 ” pattern . in the specific example , if a host application attempts to read any logical block in the range 2000 to 3999 , “ dummy ” data is returned until the host reaches block 4000 ( which is located at the beginning of the linear path following path 64 ). thus , the control ensures that unexpired data on the tape is always found at the same logical block offset independent of linear paths that may have been overwritten . the implementations may involve software , firmware , micro - code , hardware and / or any combination thereof . the implementation may take the form of code or logic implemented in a medium , such as memory , storage and / or circuitry of control 24 where the medium may comprise hardware logic ( e . g . an integrated circuit chip , programmable gate array [ pga ], application specific integrated circuit [ asic ], or other circuit , logic or device ), or a computer readable storage medium , such as a magnetic storage medium ( e . g . an electronic , magnetic , optical , electromagnetic , infrared , or semiconductor system , semiconductor or solid state memory , magnetic tape , a removable computer diskette , and random access memory [ ram ], a read - only memory [ rom ], a rigid magnetic disk and an optical disk , compact disk - read only memory [ cd - rom ], compact disk - read / write [ cd - r / w ] and dvd ). those of skill in the art will understand that changes may be made with respect to the methods discussed above , including changes to the ordering of the steps . further , those of skill in the art will understand that differing specific component arrangements may be employed than those illustrated herein . while the preferred embodiments of the present invention have been illustrated in detail , it should be apparent that modifications and adaptations to those embodiments may occur to one skilled in the art without departing from the scope of the present invention as set forth in the following claims . | 6 |
turning now to the drawing , and in particular to fig1 there is shown an arrangement which essentially includes a mounting device 2 and a flat monitor 3 . the flat monitor 3 may be a commercially available plasma monitor with a 42 ″ screen and has a compartment 4 which has arranged at its underside connections and adjustment devices 5 to 12 . the connection point 12 has a cable 13 attached to connect the monitor 3 with a computer ( not shown ) located in the mounting device 2 . the mounting device 2 has a main body with a side 14 which , for a wall - mounted monitor , attaches to the wall , and a side 15 which provides the attachment surface for the monitor 3 . the flat monitor 3 has a casing with a rear wall which defines a circumferential line 16 to correspond in its shape and position to a circumferential line 17 of the monitor - facing side 15 of the mounting device 2 . the depth of the mounting device 2 between the side 14 adjacent to a wall and the side 15 adjacent to the monitor 3 corresponds approximately to the depth of the flat monitor 3 between its side adjacent to the mounting device 2 and the visual display surface of the monitor 3 . the monitor 3 as well as the mounting device 2 have a frustoconical shape whereby the mounting device 2 has side surfaces 18 , 19 which are in line with side surfaces 20 , 21 of the flat monitor 3 . the opposite side of the mounting device 2 shown in fig2 depicts a compartment 22 with a computer connection point 23 . furthermore , cable entries 24 , 25 and 26 are located in the compartment 22 . the compartment 22 is designed such that a computer can be slid into this compartment . the computer couples thereby with connection point 23 on the base plate 27 of the compartment 22 . the connection point 23 is connected with a cable 13 which is located on the side of the base plate 27 of compartment 22 being opposite to compartment 22 , whereby the cable 13 connects the computer ( not shown ) with the flat monitor 3 . a plug 28 is part of a power supply line for connection to a power supply 29 of the box - like mounting device 2 . the power supply 29 is indicated here by a phantom line . turning now to fig3 there is shown an exploded , perspective view of an assembly , generally designated by reference numeral 40 and including a flat monitor 41 , a drawer compartment 42 and a computer 43 . the flat monitor 41 may be a commercially available lcd monitor with a particularly large screen and a housing tapering inward behind the screen . the rear side 44 of the monitor 41 thus has a smaller area than the front side 45 of the monitor . at the rear side 44 of monitor 41 , four fixing elements 46 , 47 , 48 and 49 in the shape of nailheads are provided . these fixing elements 46 to 49 enable the monitor 41 to be fixed to pear - shaped recesses 50 , 51 , 52 and 53 at the front side 54 of the drawer compartment 42 . to that end , the nailhead - shaped fixing elements 46 to 49 can be inserted into the larger end of the pear - shaped recesses 50 to 53 . the monitor 41 then slides down to a level where the nail - headshaped holding elements are retained within the narrow area of the pear - shaped recesses 50 to 53 . the drawer compartment 42 has two mounting attachments 55 and 56 with which it can be attached to a wall , a ceiling or a stand ( not shown ). apart from that , the drawer compartment 42 has a box - like recess 57 ( drawn in dashed lines ) with an opening 58 which allows the computer 43 to be slid into the drawer compartment 42 like a drawer . when the computer 43 is slid into the drawer compartment 42 , socket 59 ( drawn in dashed lines ) engages with plug 60 such that , with the computer 43 pushed home properly , an electrical contact is closed between plug 60 and socket 59 . naturally , a socket can be provided at the drawer compartment 42 and a plug at the computer 43 . the same applies to socket 61 ( also drawn in dashed lines ) which engages with plug 62 . a handle 63 makes it easier to properly slide the computer 43 into drawer compartment 42 . in the embodiment shown in fig3 the plug 62 connects to the power supply and plug 60 to the data input . on the top side of the computer 43 , an on / off switch 64 is provided . next to it , there are two pci slots 65 , 66 and a slot for a cd / dvd drive 67 . furthermore , on this top side of computer 43 , there are network interfaces 68 and interfaces for peripheral units such as a mouse or a printer . in order to avoid overheating of computer 43 , ventilation slots 70 are provided in the drawer compartment 42 , which allow air movement to the built - in fan in the computer . the arrangement shown in fig1 essentially comprises the mounting device 2 and the flat monitor 3 . the flat monitor is a commercially available plasma monitor with a 42 ″ screen . this monitor has a compartment 4 at its underside in which the connections and adjustment devices 5 to 12 are placed . the connection point 12 has a cable 13 attached that connects the monitor 3 with a computer ( not shown ) located in the mounting device 2 . the mounting device 2 has a side 14 which , for a wall - mounted monitor , attaches to the wall , and a side 15 which provides the attaching surface for the monitor 3 . the circumferential line 16 at the rear of flat monitor 3 corresponds in its shape and position to the circumferential line 17 of the side 15 of mounting device 2 , which attaches to monitor 3 . the depth of the mounting device between the side 14 adjacent to the wall and the side 15 adjacent to monitor 3 corresponds approximately to the depth of the flat monitor between its side adjacent to the mounting device and the screen surface . the shape of monitor 3 is that of a truncated pyramid and the shape of mounting device 2 is also that of a truncated pyramid whereby the side surfaces 18 , 19 of the mounting device are in line with the side surfaces 20 , 21 of flat monitor 3 . the opposite side of the mounting device 2 shown in fig2 shows the compartment 22 with the computer connection point 23 . furthermore , cable entries 24 , 25 and 26 are located in compartment 22 . the compartment 22 is designed such that a computer can be slid into this compartment . then , the computer couples with connection point 23 on the base plate 27 of compartment 22 . the connection point 23 is connected with a cable 13 which is located on the side of base plate 27 of compartment 22 being opposite compartment 22 , said cable 13 connecting the computer ( not shown ) with the flat monitor 3 . a plug 28 is part of the power supply line into the box - like mounting device 2 in which space is provided for a power supply 29 shown in a phantom line . the assembly 40 shown in fig3 consists of the flat monitor 41 , the drawer compartment 42 and the computer 43 . the flat monitor 41 is a commercially available lcd monitor with a particularly large screen and a housing tapering inward behind the screen . the rear side 44 of the monitor 41 thus has a smaller area than the front side 45 of the monitor . at the rear side 44 of monitor 41 , four fixing elements 46 , 47 , 48 and 49 in the shape of nailheads are provided . these fixing elements 46 to 49 enable the monitor 41 to be fixed to pear - shaped recesses 50 , 51 , 52 and 53 at the front side 54 of the drawer compartment 42 . to that end , the nailhead - shaped fixing elements 46 to 49 can be inserted into the larger end of the pear - shaped recesses 50 to 53 . the monitor 41 then slides down to a level where the nailhead - shaped holding elements are retained within the narrow area of the pear - shaped recesses 50 to 53 . the drawer compartment 42 has two mounting attachments 55 and 56 with which it can be attached to a wall , a ceiling or a stand ( not shown ). apart from that , the drawer compartment 42 has a box - like recess 57 ( drawn in dashed lines ) with an opening 58 which allows the computer 43 to be slid into the drawer compartment 42 like a drawer . when the computer 43 is slid into the drawer compartment 42 , socket 59 ( drawn in dashed lines ) engages with plug 60 such that , with the computer 43 pushed home properly , an electrical contact is closed between plug 60 and socket 59 . naturally , a socket can be provided at the drawer compartment 42 and a plug at the computer 43 . the same applies to socket 61 ( also drawn in dashed lines ) which engages with plug 62 . a handle 63 makes it easier to properly slide the computer 43 into drawer compartment 42 . in the embodiment shown in fig3 the plug 62 connects to the power supply and plug 60 to the data input . on the top side of the computer 43 , an on / off switch 64 is provided . next to it , there are two pci slots 65 , 66 and a slot for a cd / dvd drive 67 . furthermore , on this top side of computer 43 , there are network interfaces 68 and interfaces for peripheral units such as a mouse or a printer . in order to avoid overheating of computer 43 , ventilation slots 70 are provided in the drawer compartment 42 , which allow air movement to the built - in fan in the computer . while the invention has been illustrated and described as embodied in a mounting device for a monitor , a flat monitor with such a mounting device , and an assembly of a flat monitor , a drawer and a computer , it is not intended to be limited to the details shown since various modifications and structural changes may be made without departing in any way from the spirit of the present invention . the embodiments were chosen and described in order to best explain the principles of the invention and practical application to thereby enable a person skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated . what is claimed as new and desired to be protected by letters patent is set forth in the appended claims and their equivalents : | 8 |
fig1 shows the coiled tubing operation of the invention in a typical configuration of a horizontal wellbore ; fig2 snows a more detailed view of the above ground components used to facilitate the coiled tubing operations ; fig3 reveals provides a more detailed observation of the components that directly drive coiled tubing into a well and also the configuration that results in bending events upon the coiled tubing ; fig4 demonstrates the drive mechanism and how it operatively connects to the tubing in such a way that buckling of coiled tubing may occur inside the casing of a wellbore ; fig5 b depicts a cross - sectional view of that shown in fig5 a of the casing containing sinusoidally buckled coiled tubing ; fig5 d is a cross - sectional view of fig5 c or the casing containing the helically buckled coiled tubing ; fig6 a shows a preferred embodiment of the invention of the composite coiled tubing with a solid liner inner layer and several different fiber layers overlaying the solid liner inner layer ; fig6 b demonstrates an alternate embodiment of the composite coiled tubing which uses a weave without an inner mandrel ; fig6 c presents yet another alternate embodiment of the composite coiled tubing invention ; fig6 d shows a further alternate embodiment of the composite coiled tubing invention ; fig6 e depicts a cross section of composite coiled tubing containing conductive wires ; fig7 depicts a sketch of an automated circular braiding machine configuration of the type used to manufacture composite coiled tubing ; fig8 shows a three dimensional solid finite element model of a composite coiled tubing laminate ; fig9 shows a three dimensional solid finite element model of regular steel containing one element ; fig1 depicts axial stress in composite coiled tubing that is wound ( and therefore deformed ) on an 84 inch circular reel ; fig1 shows axial stress in composite coiled tubing that is wound upon ( i . e . deformed ) on a 96 inch circular reel ; fig1 demonstrates the axial stress load for case b ( case scenario &# 34 ; b &# 34 ; is presented later in the specification ); fig1 demonstrates the axial stress load for hoop stresses for load case b ; fig1 depicts axial stress for load case c ( case scenario &# 34 ; c &# 34 ; is presented later in the specification ); fig1 presents hoop stress for load case d ( load case scenario &# 34 ; d &# 34 ; is presented later in the specification ); fig2 presents axial stress for load case e ( load case scenario &# 34 ; e &# 34 ; is presented later herein ); fig2 presents hoop stress for load case f ( load case &# 34 ; f &# 34 ; is presented later herein ); fig2 shows a typical prior art configuration for a downhole connection means to connect coiled tubing to a downhole tool ; fig2 shows one embodiment of the invention of the composite disconnect of this invention ; fig2 reveals a magnetic marking depth calculating configuration of the present invention that serves to calculate depth using magnetic marker materials embedded within the composite laminate of the coiled tubing ; fig2 shows a detailed view of the magnetic nodes that operate to provide depth data in the configuration of fig2 ; fig2 depicts an alternate configuration of this invention in which the magnetic detector is located underground and acts to relay depth information to the surface . in fig1 the operating environment of this invention is shown . coiled tubing operation 10 is comprised of a truck 11 which supports power supply 12 and tubing reel 13 . an injector head unit 15 feeds and directs composite coiled tubing 16 from the tubing reel into the subterranean formation . the configuration of fig1 shows a horizontal wellbore configuration which supports a coiled tubing well trajectory 18 into a horizontal wellbore 19 . this invention is not limited to a horizontal wellbore configuration , but is advantageously applied to that configuration . downhole tool 20 is connected to the coiled tubing , as for example , to conduct flow or measurements , or perhaps to provide diverting fluids . fig2 represents a coiled tubing unit 26 having a hydraulic operated tubing reel 27 which feeds tubing 29 by way of levelwind 39 and past a depth counter 28 . tubing guide 30 directs the tubing downward into hydraulic ( or electric ) drive tubing injector 31 and past stripper rubber 32 . a depth detector 40 is shown , which may be of the magnetic mark type detector . a tubing monitor 38 , which measures the ovality and outer diameter of coiled tubing is provided . the tubing 29 is pushed into the well through blowout preventor stack 33 and through flow tee 35 . injector support 34 supports the injector over the wellbore . a power pack 41 supplies power to control console 37 for operation of the coiled tubing unit . the forces and strain placed upon coiled tubing when it is used in a coiled tubing unit 44 is apparent from viewing fig3 . coiled tubing undergoes numerous bending events each time it is run into and out of a wellbore . the tubing is plastically deformed on the reel . first , coiled tubing 46 is bent when it emerges from the reel 45 . then , it is bent as it passes over tubing guide 47 , and is straightened as it goes into tubing injector 48 for entry into the wellbore . of course , each bending event is repeated in reverse when the tubing is later extracted from the wellbore . these bending events weaken the tubing each time it is used , and tubing use must be counted and tabulated , and tubing discarded , when it has been used beyond an acceptable safety limit . the composite tubing of this invention is designed to monitor tubing condition and even report data to the operator to show the condition of the tubing in real time during use . cost savings can be achieved by knowing the exact condition of the tubing , and instances of catastrophic tubing failure can be substantially reduced or even eliminated by use of this invention . cost savings can be realized since the fatigue life of composite coiled tubing will be substantially longer than that of steel . a more detailed description of the use of this invention is set forth below . tubing often buckles when it is places in deep wellbores , causing problems . buckling is especially pronounced in horizontal and long reach wellbores because the tubing is subject to gravitational forces that cause large amounts of friction between the tubing and the wellbore . when this friction overcomes the forces pulling or pushing the tubing into the wellbore , buckling occurs . first , buckling is of the sinusoidal type , which is akin to a two dimensional wave in the tubing , as seen in fig5 a and 5b . later , as the tubing proceeds further into the wellbore , helical buckling occurs . helical buckling is shown in fig5 c . helical buckling is a more serious problem , and it is a &# 34 ; corkscrew &# 34 ; effect represented as three dimensional buckling , which eventually leads to total lock - up of the tubing . helical buckling causes the tubing to be in contact with the inner surface of the wellbore at many ( or even all points ) which greatly increases the friction encountered by the tubing . sensors embedded in the wall of the coiled tubing can be used to ascertain when this occurs . when total lock - up is reached , the tubing no longer can be pushed further into the wellbore , and further coiled tubing operations cannot be performed . fig5 a shows a section 64 of sinusoidally buckled coiled tubing 65 . within wellbore casing 66 the tubing is in a sine - wave two dimensional form wherein it touches the casing at its peaks . cross section shown in fig5 b shows wellbore casing 66 in contact with tubing 65 at its high and low points a two dimensional sinusoidal buckling is seen in fig5 b . helical buckling is seen in fig5 c , wherein the helically buckled tubing section 68 is characterized by helically buckled tubing 69 in a spiral or &# 34 ; corkscrew &# 34 ; three dimensional configuration within wellbore casing 70 . fig6 a - 6e shows various configurations of composite coiled tubing that may be employed in the practice of this invention , although other embodiments are possible . in fig6 a , first embodiment composite tubing 75 comprises solid liner 76 upon which is placed longitudinal fiber layer 77 . circumferential fiber layer 78 overlays the longitudinal layer , and weaved fiber layer 79 provides a weave of composite fibers at an angle of preferably about 45 degrees in each direction . however , other angles and orientations are possible to achieve different strength properties of the composite fibers . the composite fiber is formed on an apparatus as seen in fig7 although it is anticipated that there may numerous methods and apparatus capable of forming such a composite tube which are known by those skilled in the art of composites . a suitable resin , such as epoxy resin , is impregnated into the fiber layers as they are formed , as seen later in fig7 . fig6 b shows a second embodiment composite tubing 82 which does not have the solid liner , but instead contains an inner weaved layer 83 which contains an overlay of longitudinal fiber layer 84 . on top of that layer , a circumferential fiber layer 85 is placed , and finally an outer weaved layer 86 provides the outer protective coating . a third embodiment in fig6 c shows a different arrangement of fiber layers . third embodiment composite tubing 90 is made of solid liner 91 upon which is placed longitudinal fiber layer 92 . first circumferential fiber layer 93 is next , and longitudinal fiber layer 94 provides the next layer . finally , second circumferential fiber layer 95 provides the outermost layer . fig6 d shows fourth embodiment composite tubing 98 containing solid liner 99 with longitudinal fiber layer 100 on top of said solid liner . circumferential fiber layer 101 is the next outermost layer , followed by longitudinal fiber layer 103 , then circumferential fiber layer 109 , followed by weaved fiber layer 102 . there are thousands of different laminates depending on the number of laminas ( individual layers ), materials and orientation of each lamina . in the specific use of coiled tubing , the desirable traits are contradictory in the two different load conditions ( spooled and downhole ). the bending stiffness of the tube is determined by the number of axial fibers , the fibers modulus of elasticity and the location of the fibers in the cross - section . adding more fibers and / or fibers with high moduli will result in a stiffer tube . more fibers can be used by either increasing the thickness of each lamina or adding more laminas . placing fibers closer to the outer diameter results in a stiffer tube . these factors are considered in the design process . since composite materials typically do not yield before failure , the tubing must remain elastic when spooled on the reel . therefore , a low bending modulus is desirable in this situation . however , when downhole , the buckling characteristics of the tubing are the controlling factors as to how far the tubing can be pushed downhole . the stiffer the tube , the farther it can be pushed downhole . therefore , different designs are beneficial depending on the job requirements . for example , if a large reel can be used the tubing can be extremely stiff and thus treat deeper wells . if small reels are required ( imposed by transportation limitations ) then only shallower wells can be treated . fig6 a and 6b illustrate tubing with virtually the same mechanical properties . the only difference is the liner . the inner provides two functions . the first is a mandrel for manufacturing and the second is to prevent leakage through the composite wall . the drawback is that it uses a substantial amount of space which limits the flow area of the tubing . through experimental testing and manufacturing development it may be possible to replace the plastic liner with another composite lamina , as in fig6 b . both of these tubes have axially stiff laminas which are close to the inner diameter . these tubes would be ideal for spooling on small reels and treating moderate death wells . the tubes illustrated in fig6 c and 6d are ideal for treating deeper wells using larger diameter reels . additional axially stiff laminas are included which are located closer to the outer diameter , thus increasing the tubing stiffness . fig6 c is shown without the outer +/- 45 degree lamina which is purely used as a damage reduction or sacrificial lamina . it does not significantly affect the overall mechanical properties , but it instead prevents damage to the load bearing laminas . fig6 e shows the coiled tubing arrangement 104 using a solid liner 105 surrounded by composite layer ( s ) 106 . included is conductive wires 107 and 108 located outside the inner solid liner layer . any conductive wire may be used , but copper is preferable due to conductivity and low price . alternate conductors would be inserted depending on the application . these would be thermal couple wires such as iron constantan , chrome alumel , graphite , aluminum , nickel cobalt ( mp35n ) and other types of metals could also be used . fibers which are magnetic due to proprietary processes or iron impregnation could also serve as a conductive medium . attaching the wires in a straight axial line is easiest from a manufacturing standpoint . however , the wires will yield when the tubing is spooled onto a reel . this will result in an elongation of the copper wires . when the tubing is unspooled , the wires will be longer than the tubing . the wires will either buckle inside the tubing or protrude from the ends . either case is undesirable . it would be preferential to attach the wires in a helix to prevent them from yielding . the wires may be used to either communicate with downhole tools or to receive data from downhole tools , such as pressure gages or to communicate at one or various places in the coiled tubing . the inner solid layer or any other layer could also include a circuit board with processing capability . fig7 shows a schematic arrangement of the automated circular braider machine 120 that may be used to manufacture the composite tubing of this invention . braiding machines and methods are known in the art , and the making of composite tubes has been accomplished for purposes other than coiled tubing . for example , composite tubes are known to be made and used for missile silos for ballistic missiles and other applications . mandrel 121 provides a form for construction of the composite . the composite fiber is wound or spun onto the mandrel from bobbins 122 , 123 , 124 , and 125 . bobbin spools contain the fiber and prevent fiber entanglement or slippage . the mandrel forms the composite in pulling direction 135 , and resin applicator 134 provides a continuous stream of resin impregnation to fill the matrix space existing within the fiber weave once it is formed . first axial 126 , second axial 127 and first axial tube 128 and second axial tube 129 cooperate to construct fiber weave 137 . the braiding plane 137 is actually circular and rotates as the mandrel proceeds towards the top of fig7 during composite tube manufacture . fibers 130 , 131 132 , and 133 are weaved upon the mandrel by the rotation of the circular braider along braider plane 136 . typically three different types of manufacturing processes are used to manufacture composite tubes . they are pultrusion , continuous filament winding and braiding . pultrusion is similar to the extrusion of plastics and nonferrous metals . the fibers are drawn through a die which has the desired final shape . in pultrusion , the fibers are pulled through the die ; conversely , in extrusion , the material is pushed through the die . the resin can be impregnated into the fibers either prior to entering the die or after entering the die under pressure . the resin is rapidly cured in the die using head . a post - cure module can be added after the curing / forming die . continuous filament winding is similar to forming wireline or cables . spools of fiber are mounted or ring wonders which rotate about the workpiece . as the spools rotate , the mandrel moves at a specified speed forming the desired fiber orientation with the axial axis . multiple winders are used to form the individual laminas with either different materials or different fiber orientations . resin can be applied by running the fibers through a resin bath prior to winding . alternatively , prepregged fibers can be used . the resin can then be cured on - line or off - line . braiding is similar to filament winding , except the fibers are interwoven onto the mandrel . this is accomplished with a braiding ring which contains spools moving in both a clock - wise and counterclockwise direction as well as moving radially which forms the over / under braiding sequence . the resin is cured in the same manner as the continuous filament winding technique . the steps of the manufacturing process are largely dependent upon the complexity of the machinery . typically , it is ideal to form all of the laminas in one run . however , this may require several winders / braiding heads which is expensive . alternatively , multiple runs may be made in which one or two laminas are deposited each time . this method takes more time , but is significantly less expensive . the type of resin is dependent on the design parameters and the cure time for the resin is more dependent on the manufacturing process . fig8 - 24 reveal finite element analysis test results that indicate the advantages of composite tubing in different load scenarios , as set forth below . detailed discussion of those figures will accompany the discussion of test methodology and finite element analysis , including examples 1 - 7 set forth in that portion of this specification . fig2 - 29 relate to downhole composite connection means and apparatus . fig2 shows a typical prior art configuration , while fig2 - 29 reveal the invention . in the prior art , it is known generally to provide disconnecting apparatus to disconnect coiled tubing from downhole tools and the like by separation of shear screws , for example . prior art downhole connection means 200 is arranged with coiled tubing 201 attached to locking sub 202 . upper screws 203 and 205 , and lower screws 204 and 206 provide connection . threaded connection 208 is screwed onto sleeve 209 , and o - ring 210 provides sealing engagement on the coiled tubing . mandrel 211 connects to threaded hub 212 , and lower unit 215 is adjacent to upper body 213 . threaded connection 218 provides connection between downhole tool 219 and the lower body 215 . a space 214 is within the string . shear screws 210 and 217 shear upon receiving a predetermined degree of force , thereby separating the downhole tool 219 from the coiled tubing . the range of this force sometimes is quite wide , and it is usually not possible to provide a narrow range of force at which such mechanical failure means will separate , releasing the coiled tubing . the invention shown in . fig2 is a composite disconnecting apparatus 231 which shows threaded sub 220 with internal space 222 , and upper joinder threads 221 as part of upper threaded joinder 223 . upper threaded joinder 223 connects to the composite fiber pack 224 by a sealing engagement that is made to maximize the surface area of the composite threaded pack upon the upper threaded joinder to increase strength of the connection . the fiber pack 224 is made so as to provide failure characteristics that are over a relatively narrow load range so that failure may be predetermined at a specific load . fibers provide a more definite failure mechanism at specific loads than that afforded by metal shearing failure mechanisms . composite fiber pack 226 is similarly connected to lower threaded joinder 228 which is threadedly or by other means connected by lower threaded joinder threads 229 to downhole tool 230 . fig2 shows one embodiment of the invention of this application including a magnetic marking depth or other means of detecting a specific location on a ct string calculating configuration 235 which uses magnetic mark detector or other type of location detector , gamma ray , light , etc . detector 236 to assist in determining depth of coiled tubing . wellbore 238 disposed below ground surface 237 contains casing 239 or can be open hole . coiled tubing 240 is disposed within the casing and is passed along into the wellbore past the detector 236 which serves to record the length or location of tubing that has descended into the well by magnetic or other measurement means . magnetic or other type of detectable nodes 241 , 242 , 243 , 244 , 245 , and 240 each sequentially are recognized as they pass the detector 236 . in fig2 , a close up view of detection node 244 is shown wherein magnetically active fibers 247 are detectable by detector 236 . such fibers preferably are of the type inco vaporfab nickel coated fibers , manufactured by inco spp at 681 lawlins road , wyckoff , n . j . 07481 . however , it is recognized that any number of fibers that are magnetically active , or radioactive or can give signal at a certain location in the coiled tubing could achieve the function of marking tubing depth . a . microprocessor also optionally may be provided within the layers of the coiled tubing , in the configuration of fig2 or 29 . an alternate configuration for determining coiled tubing depth is shown in fig2 . subterranean depth calculating configuration 250 uses magnetic mark or other detectable nodes like radioaction indicator 251 ( which may also be a relayer of information ) to determine more accurately the depth of coiled tubing in a well . in this configuration , accuracy is improved because the &# 34 ; zero &# 34 ; point for depth calculation is advantageously located hundreds or thousands of feet below the ground surface , facilitating a much more accurate measurement of exact depth of coiled tubing , or perhaps a determination when the tool is exactly adjacent or above a particular subterranean structure that is intended to be modified by the downhole operation . magnetic or other detectable nodes 253 , 254 , 255 , 250 , 257 , 258 , and 259 operate to provide a detectable signal when they pass the mark indicator 251 , which itself is incorporated into locking hub 260 downhole . this locking hub can be retrievable or permanently attached downhole . the mark indicator can also be part of the tubing , attaching to the outside . further , a transmitter 252 may relay information uphole in real time manner by inductively sending pulses or other means , acoustic for transmission by conductors or fibers in the cct wall . the transmitter downhole could also relay information via a conductor attached from the surface to the transmitter . alternatively , an ultrasonic source could provide high energy pulses that change the property of a fiber optic conductor , which would be detectable at the surface and readable by a coiled tubing operator in real time during a job . other conductive or detection methods and means are possible using specialized composite coiled tubing with magnetic mark or other indicators and conductive and / or other like acoustic means within the tubing . further it would be possible to use a subterranean receptor attached different ways downhole and send data up the borehole through a conductor in the casing wall or tubing , rather than using a conductor or fiber in the coiled tubing . composite coiled tubing manufactured as set forth above offers several advantages over traditional tubing such as lower weight , better fatigue characteristics , low ovality , and data transmission by way of intrinsic conductors built into the tubing ( no more cables in the inside diameter ). composite coiled tubing (&# 34 ; composite coiled tubing sometimes is abbreviated as &# 34 ; cct &# 34 ;&# 34 ;) has been studied to determine how cct could be designed with better properties than steel coiled tubing (&# 34 ; coiled tubing sometimes is abbreviated herein as &# 34 ; ct &# 34 ;). the results reveal that composite coiled tubing is more advantageous than steel , especially in terms of its strength characteristics . the ` final ` preliminary design outperformed steel ct in terms of pressure and axial strength , but at the sacrifice of flow area within the interior of the tubing . the results of the study show that cct is feasible based upon analytical models , limited environmental testing and production of short ( 10 foot ) samples . various environmental conditions must be considered in the design of the composite laminate for coiled tubing . specifically , exposure to both low and high temperatures (- 50 ° f . and 400 ° f ., respectively ) in naturally occurring wellbore fluids is required , including for example selected acid solutions and organic solvents . other important functional considerations include incorporation of a cct field splicing technique and end - coupling designs as well as the incorporation of communications capability along the cct length . composite laminate design and analysis was performed to create an optimum composite construction which satisfies all the load cases . the design was based on an optimizing routine and classical laminate plate theory . since the ` plate ` is relatively thick , finite element analysis was used to verify / improve the design , as further shown in the fig8 - 24 . the various hostile environmental conditions currently experienced by the steel coiled tubing during service were considered . after completion o ; the design and analysis of the composite structure , fabrication of reduced scale tubular sections was completed to support mechanical and environmental testing . in addition , fabrication of full scale , nominal 1 . 50 &# 34 ; od ct sections were completed to investigate : 1 ) incorporating a cct coupling mechanism , 2 ) intrinsic communication lines and 3 ) the fatigue life of the proposed cct design . advantages of composite coiled tubing include the ability to treat deeper wells , more buoyancy and improved buckling characteristics , better fatigue characteristics , little increase in ovality during the tubing lifetime , lower fluid friction and less pressure drop for a specified inner diameter . intrinsic conductors ( wire , fiber optics , etc .) in cct wall are possibilities that provide distinct communication advantages . composite coiled tubing has several advantages over steel or alloy coiled tubing for oilfield service . the composite coiled tubing weighs considerably less which allows treatment of deeper wells and also is more buoyant which improves the buckling characteristics . steel tubing suffers from severe fatigue limits . typically the tubing is scrapped because the fatigue limits have been reached . the steel is plastically deformed every time it is spooled off the reel , over the gooseneck , through the chains and the reverse process . it is known that the fatigue resistance of steel is severely degraded when it is plastically deformed . a main advantage of composite coiled tubing , other than the improved fatigue properties of composite materials compared to steel , is that typically it is not plastically deformed , thus its fatigue failure resistance remains high . steel coiled tubing also suffers from ovality and ballooning both of which are attributed to cyclic fatigue and result in severely degraded properties . for example , perfectly round 1 . 5 &# 34 ;, 0 . 095 &# 34 ; thick steel coiled tubing has a collapse pressure of approximately 10 , 000 psi . tubing with a 5 % ovality ratio , typically the allowable maximum , has a collapse pressure of about 6 , 000 psi . composite tubing does not plastically deform , hence its ovality will be small . steel coiled tubing exhibits a fluid resistance coefficient , friction , that approximates &# 34 ; smooth &# 34 ; tubing . as the tubing is used , this value increases which results in a larger pressure drop . the proposed cct utilizes a plastic liner which should not change appreciably with use . initially , the steel ct has a 10 % to 20 % higher pressure drop for a given flow diameter . the pressure drop of the steel ct will increase with time . the final advantage of composite coiled tubing is related to the utilization within coiled tubing of an intercommunication or &# 34 ; smart &# 34 ; coiled tubing . conductors , fiber and / or microprocessors , may be intrinsically manufactured in the composite coiled tubing eliminating many of the problems associated with &# 34 ; smart tubing &# 34 ; ( i . e . cable in the inside diameter of ct ). another property of composite tubing , which could be advantageous or disadvantageous depending on the situation , is that the tubing would be virtually non - conductive . disadvantages of coiled tubing include lower buckling load in ` dry ` wells , more stored energy on the reel , higher initial cost , smaller inner diameter for a specified outer diameter , and larger diameter reels ( 8 &# 39 ; minimum drum diameter for 1 . 5 &# 34 ; cct ). also , a microprocessor could be incorporated into the layers of the coiled tubing facilitating &# 34 ; smart &# 34 ; operations . the only performance disadvantage currently known in use of composite coiled tubing as compared to steel is the lower bending stiffness of composite materials . one of the major operational characteristics of coiled tubing is the distance it can be run in the hole before the onset of helical buckling and thus lockup . lockup is defined as the point at which the tubing cannot be pushed farther in the hole . helical buckling is a function of the tubing modulus of elasticity and the moment of inertia . since the composite tubing has a lower modulus , but similar moment of inertia , earlier lockup will occur than steel tubing when running in a dry well . one unknown is the friction of composite coiled tubing . it is feasible to coat the tubing with a low friction coefficient material to improve the lockup properties . however , since the composite tubing is less dense than steel , the tubing will have less effective weight in fluid packed wells which decreases the frictional force and thus increases the distance to lockup . currently known cct designs require a liner to prevent leakage through the wall of the ct . the liner serves no structural purpose , but uses valuable space ( approximately 20 % of the flow area ). the liner also aids in manufacturing by providing a ` mandrel ` on which to wind the composite material . several fibers and matrix materials were considered based on temperature limits and chemical compatibility genetic algorithm was used to determine ` ideal ` laminate properties for various design cases ( 1000 &# 39 ; s of lamina combinations ) laminate design and analyses were performed using three distinct load cases , table 1 , which were based on the design criteria . loads were converted into curvatures and / or stress resultants as required for a general laminated plate analysis . the computer program used was provided in conjunction with a combinatorial optimization routine . this program searched for an optimum design given up to ten laminas ( layers , plies , etc .). in a single run , thousands of material , stacking sequence and ply angle combinations were evaluated . four fiber materials , e glass , s - 2 glass , kevlar 29 , kevlar 49 , and three matrix materials , epoxy , polycyanate and siloxirane , were considered . table 1__________________________________________________________________________design cases for laminate design &# 34 ; easy &# 34 ; &# 34 ; medium &# 34 ; &# 34 ; hard &# 34 ; load axial pressure axial pressure axial pressurecase ( psi ) ( lbf ) ( psi ) ( psi ) __________________________________________________________________________1 x 0 0 x 0 0 x 0 02 x 7 , 500 x 0 11 , 250 0 14 , 0003 -- 7 , 500 -- 11 , 250 -- 14 , 000 7 , 500 7 , 500 7 , 5004 25 , 000 7 , 500 27 , 500 11 , 250 30 , 000 14 , 0005 -- -- -- -- -- -- 7 , 500 5 , 750 7 , 500 5 , 750 7 , 500 5 , 7506 25 , 000 -- 27 , 500 -- 30 , 000 -- 5 , 750 5 , 750 5 , 750__________________________________________________________________________ in each load set , the spool diameter was varied to study the trade - off between stresses due to spooling and the other loading conditions . a curvature term for the laminated plate analysis was calculated as follows : k = e / y where e = y / r y = distance from neutral axis r = radius of curvature of neutral axis ( 1 ) based on the results of the optimization analysis , a hybrid construction with kevlar 49 at approximately 85 ° and s - 2 glass at 0 ° with a matrix of either epoxy or siloxirane was selected for prototype fabrication . this design , the lay - up for which is shown in fig8 and tabulated in table 2 , met all three load case sets with a 7 &# 39 ; diameter spool . using a 6 &# 39 ; diameter spool , the kevlar just begins to reach compression failure under the more extreme loading conditions . the predicted longitudinal and transverse stiffness levels for the laminate are 3 msi and 9 . 6 msi , respectively . for comparison , the cct samples made previously by us composites corporation (&# 34 ; us composites &# 34 ;) for conoco oil company (&# 34 ; conoco &# 34 ;) had a longitudinal and transverse modulus of 1 . 09 msi . us composites developed alternate designs , using axial carbon fiber , which have longitudinal moduli values of up to 9 msi , if required to control buckling . temperature differences were not considered in the optimization analysis . when taken into account ( to represent thermal residual stresses ) in the optimized design , transverse failures , or micro - cracking , were indicated . although these are not necessarily critical , they do suggest the need for an impermeable liner and / or layer . fig8 shows composite coiled tubing laminate 110 containing finite elements 111 with a twelve layer finite element matrix ( circumferential layers ) containing depth lines 113 . the ply or layers are numbered as seen in fig1 , counting the plies or layers from the outermost to the innermost layers , from outside to inside , and the innermost being layer 12 . ( see table 2 below ). two full size cross section cct samples , approximately 10 &# 39 ; long , were fabricated . fabrication of the 10 &# 39 ; long sections was completed using the standard epoxy matrix utilized on the first set of 1 / 4 &# 34 ; cct samples discussed further herein . to facilitate fabrication of the limited length of full size cct , commercially available stock materials were selected for the mandrel and liner materials . specifically , standard 13 / 16 &# 34 ; steel tubing was selected for the mandrel and a stock 7 / 8 &# 34 ; id × 1 . 0 &# 34 ; od pvdf tubing was used as a liner . fig6 a shows the liner construction utilized on the these sections . table 2______________________________________composite coiled tubing laminate design ply angle compositeply number material thickness layer ( 1 - 12 ) ______________________________________1 85 kevlar 49 0 . 015 first ( outer ) 2 s - 2 glass 0 . 015 second3 kevlar 49 0 . 015 third4 s - 2 glass 0 . 015 fourth5 kevlar 49 0 . 015 fifth6 kevlar 49 0 . 015 sixth7 kevlar 49 0 . 015 seventh8 kevlar 49 0 . 015 eighth9 s - 2 glass 0 . 015 ninth10 - 85 kevlar 49 0 . 015 tenth11 0 s - 2 glass 0 . 015 eleventh12 85 kevlar 49 0 . 015 twelfth ( inner ) ______________________________________ using a scale up of the 1 / 4 &# 34 ; cct sample construction , and additional dry fiber wrapping trials over the fall size mandrel , the following construction was utilized in fabrication of the full size cct sections . two 10 &# 39 ; cct sections were fabricated , ( see fig6 a ), using the above fiber construction and on - line resin impregnation with the epoxy system . to demonstrate the ability to include communications capability in the cct , four individual 28 gauge insulated copper wires were installed in the laminate concurrent with the application of the first ply . these conductors were installed longitudinally in the full scale samples for demonstration purposes only and alternate incorporation techniques are being considered for the production cct . as discussed above , the resulting outside diameter , using the predicted 12 ply design construction and the undersized stock liner , was expected to fall short of the 1 . 5 &# 34 ; nominal outside diameter . therefore , to provide a configuration more representative of the desired 1 . 5 &# 34 ; nominal od , a sample of cct section was fabricated using a 14 ply construction of alternating unidirectional fiberglass and high angle kevlar . the average outside diameter of this cured sample was determined to be 1 . 395 &# 34 ; which approaches the predicted 1 . 410 &# 34 ; outsider diameter per the computer generated laminate design over the 1 . 050 &# 34 ; ideal liner . the second 10 &# 39 ; section , sample # 2 was fabricated using a 12 ply construction of the same alternating fiber plies and had a resulting average outside diameter of 1 . 340 &# 34 ;. accordingly , a sample section is more representative of the actual 12 ply design laminate construction tabulated earlier in this report . table 3______________________________________composite coiled tubing laminate design ply angleply number ( degrees ) material thickness______________________________________1 0 s - 2 glass 0 . 0121 s - 2 glass 0 . 0122 kevlar 49 0 . 0163 s - 2 glass 0 . 0124 kevlar 49 0 . 0165 s - 2 glass 0 . 0126 kevlar 49 0 . 0167 s - 2 glass 0 . 0128 kevlar 49 0 . 0169 s - 2 glass 0 . 01210 - 81 kevlar 49 0 . 01611 s - 2 glass 0 . 01212 81 kevlar 49 0 . 01613 . sup . 1 0 s - 2 glass 0 . 01214 . sup . 1 - 81 kevlar 49 0 . 016______________________________________ 1 plies 13 and 14 apply to sample # 1 only . s - 2 glass is believed to be a registered trademark of owens - corning and this material may be obtained from owens corning . kevlar 49 is believed to be a registered trademark of dupont company , and this material may be obtained from dupont . it is also noted that an ` on - line ` resin curing system is planned for the production cct cell . this curing method , however , could not be practically incorporated in the prototype manufacturing cell utilized in fabrication of the 10 &# 39 ; cct sections . alternatively , the 10 &# 39 ; sample sections were overwrapped with conventional heat shrink materials and then rotisserie cured in a conventional oven . the heat shrink materials were utilized to provide both laminate consolidation and an acceptable exterior surface appearance . during design and fabrication phases , it was considered that interim staging of the various cct plies may become necessary to ensure adequate cure and to maintain dimensional stability of the relatively thick wall section . sample # 1 cct section was fabricated by applying several layers of wet wrapped fiber , staging of the partial build - up , application of the remaining plies , and , subsequent shrink wrap and curing of the laminate . for comparative purposes , samples # 2 was fabricated by applying all wet wrapped plies to the mandrel , an overwrap of heat shrink tape , and final cure of the laminate . as expected , irregularities of the sample section surface finish resulted from the relatively thick , compliant laminate being over consolidated in localized regions by the heat shrink wrap during cure . as a result , it is anticipated that on - line staging of the production cct , at select layers in the multiply wall thickness will be required . if cct friction = ct friction then cct lockups at 60 % of ct lockup length if cct friction = 1 / 2 ct friction then cct lockups at 120 % of ct lockup length if cct friction = ct friction then cct lockups at 100 % of ct lockup length if cct friction = 1 / 2 ct friction then cct lockups at 200 % of ct lockup length buckling is one of the controlling parameters in coiled tubing operations . the ct buckles downhole as shown in fig4 . a cursory buckling analysis was performed based on industry recognized technology . the controlling parameters for a buckling problem ( sinusoidal buckling , fig5 a and 5b ) are the section modulus ( linear relation ), weight ( linear relation ) and length ( nonlinear relation ). however , for helical buckling , fig5 c and 5d , only the section modulus and weight are of consequence . the section modulus of the proposed composite coiled tubing is approximately 1 / 10 that of steel coiled tubing , and the weight of the tubing per foot is approximately 1 / 2 . both of these parameters are comparable to other companies &# 39 ; cct designs . the lower section modulus reduces the buckling length but is somewhat offset by the lower cct weight . the effective weight is dependent on the fluid in the well ( buoyancy of the ct string ). a simple governing equation for helical buckling [ 1 ] is ## equ1 ## where e = modules of elasticity lockup occurs when the friction force required to push the pipe downhole is equivalent to the helical buckling load , thus the tubing can no longer be pushed down hole . the friction force can be calculated using [ 2 ] ## equ2 ## where f 1 = loading force b = angle from bottom of outer tubing / casing the first term is the normal force exerted by the helical buckling , and the second term is the coiled tubing weight . therefore , the total frictional force can be written as ## equ3 ## where f = friction coefficient the depth the ct can be pushed before lockup can thus be approximated as ## equ4 ## the results shown in table 4 are for a horizontal section only . a casing radius of 4 &# 34 ; is assumed . two different composite moduli are used . the first is the proposed design and the second is the maximum value determined by the design procedure . also , two different friction coefficients are assumed . the first case uses the same friction as steel ct and the latter assumes 1 / 2 the friction coefficient . actual values will have to be determined , but handbooks show plastic laminate / steel friction coefficients as low as 1 / 2 steel / steel values . column 4 of table 4 shows the ratio of the lockup distance of cct to steel ct . obviously , the results can be construed to match any viewpoint . the worst case is that cct will only be pushed half as far as steel ct in horizontal applications and the best scenario is that cct can be pushed twice as far . realistically , cct will exhibit similar lockup distances as steel ct . table 4______________________________________comparison of lockup depth for cct versus ctcomposite axial friction lockup ratio , modulus ( msi ) wellbore fluid coefficient , f . sub . c / f . sub . st l . sub . c / l . sub . st______________________________________3 × 10 . sup . 6 dry 1 . 0 0 . 573 × 10 . sup . 6 water 1 . 0 0 . 633 × 10 . sup . 6 dry 0 . 5 1 . 163 × 10 . sup . 6 water 0 . 5 1 . 259 × 10 . sup . 6 dry 1 . 0 1 . 009 × 10 . sup . 6 water 1 . 0 1 . 089 × 10 . sup . 6 dry 0 . 5 2 . 009 × 10 . sup . 6 water 0 . 5 2 . 16______________________________________ limited modifications are required to meet &# 34 ; hard &# 34 ; specification except for 300 ° f . temperature limit the finite element analysis was conducted using ansys , which is a computer program written by swanson analysis system incorporated of p . o box 65 johnson road , houston , pa . 15342 . normally , pressurized tubes are modeled using axisymmetric shell or solid elements , depending on the thickness . however , since the problem contains non - axisymmetric loading ( bending ), these types cannot be used . the next logical choice would be plane stress or plane strain elements . again , most planar elements , including ansys &# 39 ; s elements , do not allow this type of loading due to the bending loads , as well as the axial loads . therefore , three dimensional solid elements must be used . the coiled tubing is constructed of three - dimensional solid elements with one element along the length and numerous elements radially and circumferentially . a typical model is shown in fig9 the length is greatly exaggerated for a clearer picture . only one element through the thickness is required since the strain field is constant . the length of the ` slice ` should be approximately equal to the element length in the radial and hoop directions for well shaped elements . a special layered composite element was used ; however , the elements are not easy to use ( the orientation of the elements was tedious to construct ). in fig9 a composite coiled tubing finite element model 115 with depth lines 116 and a twelve layer matrix 117 is shown . the elements were formulated to allow several laminas per element , but one element per lamina was used for improved results , as seen in fig1 - 24 . better results could be obtained by using more than one element per lamina , the need of which will be demonstrated later . for this preliminary analysis , however , one element per layer suffices . the basic element is an eight node ( linear ) formulation but allows higher order ( parabolic ) displacement shapes . there are 12 laminas . the other laminas are +/- 85 degrees from the axial ( stiff in the circumferential direction ). as discussed previously , only one element is along the length , which is constant strain . symmetry is not used for two reasons . the first is that 1 / 4 symmetry cannot be used because of the bending loads ( 1 / 2 would have to be used ). the second is that since the circumferential laminas are not symmetric , the 1 / 2 model symmetry is destroyed . pressure loads are applied by either pressure applied to the internal surface or external surface . axial loads are applied by displacing the axial direction a prescribed amount thus providing the applied axial load . the difficulty in defining the loading parameters arises from the debate of plane strain versus plane stress . if the coiled tubing is allowed to move freely in the well ( assuming negligible friction ) then plane stress occurs ; however , if the coiled tubing is fixed at the end ( by a tool ) and tension is applied , then plane strain occurs . in most cases the plane stain condition is most severe , so that is what is modeled . one end of the tubing is completely constrained while the other end is given a displacement based on the stress level . the problem with this technique is that as external pressure is applied to the tubing , the tubing elongates due to poisson &# 39 ; s ratio thus reducing the effective axial load . failure criteria for this analysis are believed to be at levels of about the following : ______________________________________axially stiff laminalongitudinal stress - tension : 360 ksilongitudinal stress - compression : 124 ksitransverse stress - tension : ksitransverse stress - compression 24 ksihoop stiff laminalongitudinal stress - tension : 315 ksilongitudinal stress - compression : 45 ksitransverse stress - tension : ksitransverse stress - compression 27 ksi______________________________________ fig1 shows axial stress model 140 with coiled tubing which is spooled and deformed on an 84 inch reel . the layers of this model , and for explanatory purposes , layers generally in this modeling , are numbered , for example here , as first finite element layer 141 , second finite element layer 142 , third finite element layer 143 , fourth finite element layer 144 , fifth finite element layer 145 , sixth finite element layer 146 , seventh finite element layer 147 , eighth finite element layer 148 , ninth finite element layer 149 , tenth finite element layer 150 , eleventh finite element layer 151 , and twelfth finite element layer 152 . fig1 shows particularly high tension levels in high tension zone 155 , while showing high compression levels in high compression zones 153 and 154 . in the axially stiff laminas ( layers 2 , 4 , 9 , 11 ) the axial stress corresponds to the longitudinal strength ad the hoop and radial stresses to the transverse stress . for the hoop stiff laminas ( 1 , 3 , 5 , 6 , 7 , 8 , 10 , 12 ) the fibers are oriented at 85 degrees to the axial . therefore , the radial stress closely corresponds to the longitudinal strength , but the strength at 90 degrees will be lower . the hoop and axial stresses closely correspond to the transverse stress , but the strength will be slightly higher at 0 degrees . the failure properties for the laminas can be specified in ansys using either a default failure criteria or a user defined criteria . for this preliminary analysis , neither was used . twenty - one different load cases were evaluated for the finite element analysis . the axial loading varied from spooled tubing to tubing in both tension and compression . internal pressure was varied from 0 psi to 22 , 500 psi . external ( hydrostatic ) pressure was varied from 0 psi to 15 , 000 psi . safety factors of 2 and 1 . 5 were used for surface and downhole conditions respectively . the six most severe cases are documented below . load case a . 1 : cct spooled on an 84 &# 34 ; drum without pressure . increasing the pressure reduces the minimum stress and increases the maximum stress which is a less severe case . this case will fail in axial compression . axial stress is plotted in fig1 . note the low stress in the hoop ( circumferential ) laminas and the overall bending behavior of the section . load case a . 2 : cct spooled on a 94 &# 34 ; drum without pressure . axial stresses are plotted in fig1 , which shows axial stress model 158 as existing on a spooled reel . high tension finite element 156 and high compression finite element 157 are visible . in this case axial stresses are close to failure ( compression ), but manageable through material modifications and / or design modifications . load case b : cct downhole with 15000 psi internal pressure and 30000 lb .. axial load . axial stress , fig1 , in a downhole ( unspooled ) condition with only internal pressure ( safety factor of 1 . 5 on 10 , 000 psi ) along with 30 , 000 lb . axial load ( low safety factor on axial load is generally used ). axial stress model 161 reveals second finite element layer 163 and ninth finite element layer 164 that show axial stresses ( pulling ) due primarily to gravity since the tubing is in the unspooled state . fig1 shows the hoop stress for load case b , including hoop stress model 165 ( showing internal pressure effects ) and twelfth finite element layer 166 , which shows high pressure . note the very low stress states -- approximately 1 / 2 of failure in the hoop laminas and 1 / 3 in the axial laminas . the hoop ( circumferential ) stress is shown in fig1 . the stress in the hoop - stiff laminas are low compared to failure ; however , the stress in the axial - stiff laminas are at failure ( low strength transverse to fiber orientation ). fig1 shows the radial stress , the pressure gradient through the element . radial stress model 168 discloses first finite element layer 169 and second finite element layer 170 and twelfth finite element layer 171 . the minimum stress should be 15 , 000 psi and the maximum stress 0 psi . the actual is 13655 and 133 psi which is an error in mesh refinement . better refinement will provide better results at the expense of time . for a final design , the analysis would be better refined . the compressive transverse strength of the laminas is twice the tensile , hence this stress is well below failure ( approximately 1 / 2 ). load case c : cct downhole with 7500 psi external pressure and - 7500 lb .. axial load axial stress are plotted in fig1 for tubing in a downhole condition with external pressure and - 7500 lb .. axial load . axial stress model 173 , as expected shows that the axial stresses are very low . hoop stress are shown in fig1 , in hoop stress model diagram 175 . stresses as shown in fig1 are well within maximum and minimum stresses should be 0 and - 7500 but are actually - 541 and - 7374 respectively for the reasons discussed above . load case d : cct downhole wits 20 , 000 psi internal pressure hoop stress for downhole condition with 0 axial load and 20 , 000 psi internal pressure is plotted in fig1 . fig1 contains hoop stress diagram 178 , and one may note the stress levels in twelfth finite element layer 179 . this loading condition would occur between the gooseneck and reel in high pressure situations , 10000 psi with a safety factor of 2 ( surface ). the axial stiff laminas would crack in this case , but the hoop stiff laminas are well below ( 1 / 3 ) their failure strength . fig1 shows the radial stress . radial stress diagram 180 in fig1 further reveal eleventh finite element layer 181 and twelfth finite element layer 182 . note that stresses are not very close to the pressure at the od and id . all stresses are well below the failure stress . load case e : cct downhole with 22 , 500 psi internal pressure , 15 , 000 external pressure and 30 , 000 lb .. axial load axial stress are plotted in fig2 for the most severe downhole case with maximum internal pressure , wellbore pressure and axial load . fig2 reveals axial stress condition 184 with areas of relatively high stress shown at fifth finite element layer 185 , sixth finite element layer 186 , seventh finite element layer 187 and eighth finite element layer 188 . axial stresses are well within limits , again approximately 1 / 2 or less of failure . fig2 shows the hoop stress . as in fig1 , the axial stiff laminas would crack , but both the hoop stiff laminas are approximately 1 / 4 of their failure stress . radial stresses are plotted in fig2 , as shown by radial stress condition 192 . first finite element layer 193 and twelfth finite element layer 194 show that pressures are suite low on the outer layer but relatively higher on the inner layer . extreme stresses match applied pressure fairly well . load case f : cct downhole with 22 , 500 psi internal pressure , 15 , 000 external pressure similar loading as the previous case but without the axial load . the hoop stress , fig2 , is slightly lower , but not much indicating that axial load does not significantly affect this particular cct design when considering stresses in the hoop direction . hoop stress condition 196 is shown in fig2 . radial stresses are shown in fig2 ( showing radial stress condition 198 ) which are not much different than fig2 . the finite element analysis load cases were more severe than those used in the computer program . the design load cases are realistic service conditions while the fea are the most rigorous including 10 , 000 psi tubing pressure and 7 , 500 psi hydrostatic pressure with high safety factors . in general the finite element results verify the results from the software program . the cct design meets the minimum requirements and with some modifications will likely meet the maximum requirements . 1 . dawson , r ., and paslay , p . r ., ` drill pipe buckling in inclined holes `, journal of petroleum technology , pp . 1734 - 1738 , 1984 2 . chen , y . c ., and cheatham , j . b ., ` wall contact forces on helically buckled tubulars in inclined wells `, transactions of the asme , pp . 142 - 144 , vol . 112 , 1990 . the invention has been described in the more limited aspects of preferred embodiments hereof , including numerous examples . other embodiments have been suggested and still others may occur to those skilled in the art upon a reading and understanding of the this specification . it is intended that all such embodiments be included within the scope of this invention . | 4 |
unless otherwise indicated , the following terms as used throughout this specification have the following meanings : “ pharmaceutically acceptable salt ” refers to those salts which retain the biological effectiveness and properties of the free bases and which are obtained by reaction with inorganic acids such as hydrochloric acid , hydrobromic acid , sulfuric acid , nitric acid , phosphoric acid , methanesulfonic acid , ethanesulfonic acid , p - toluenesulfonic acid , salicylic acid and the like . “ alkyl ” refers to a straight - chain , branched or cyclic saturated aliphatic hydrocarbon . preferably , the alkyl group has 1 to 12 carbons . more preferably , it is a lower alkyl of from 1 to 7 carbons , most preferably 1 to 4 carbons . typical alkyl groups include methyl , ethyl , propyl , isopropyl , butyl , isobutyl , tertiary butyl , pentyl , hexyl and the like . the alkyl group may be optionally substituted with one or more substituents are selected from the group consisting of hydroxyl , cyano , alkoxy , ═ o , ═ s , no 2 , halogen , dimethyl amino and sh . “ alkenyl ” refers to a straight - chain , branched or cyclic unsaturated hydrocarbon group containing at least one carbon - carbon double bond . preferably , the alkenyl group has 2 to 12 carbons . more preferably it is a lower alkenyl of from 2 to 7 carbons , most preferably 2 to 4 carbons . the alkenyl group may be optionally substituted with one or more substituents selected from the group consisting of hydroxyl , cyano , alkoxy , o , s , no 2 , halogen , dimethyl amino and sh . “ alkynyl ” refers to a straight - chain , branched or cyclic unsaturated hydrocarbon containing at least one carbon - carbon triple bond . preferably , the alkynyl group has 2 to 12 carbons . more preferably it is a lower alkynyl of from 2 to 7 carbons , most preferably 2 to 4 carbons . the alkynyl group may be optionally substituted with one or more substituents selected from the group consisting of hydroxyl , cyano , alkoxy , o , s , no 2 , halogen , dimethyl amino and sh . “ aryl ” refers to an aromatic group which has at least one ring having a conjugated pi electron system and includes carbocyclic aryl , heterocyclic aryl and biaryl groups . the aryl group may be optionally substituted with one or more substituents selected from the group consisting of halogen , trihalomethyl , hydroxyl , sh , oh , no 2 , amine , thioether , cyano , alkoxy , alkyl , and amino . “ alkaryl ” refers to an alkyl that is covalently joined to an aryl group . preferably , the alkyl is a lower alkyl . “ carbocyclic ” refers to cyclic saturated or unsaturated aliphatic hydrocarbon and aryl hydrocarbon groups wherein the ring atoms are exclusively carbons , and comprises from 6 to 20 carbon atoms , including said ring atoms . “ carbocyclic aryl ” refers to an aryl group wherein the ring atoms are carbon . “ heterocyclic ” refers to cyclic groups wherein the ring atoms comprise carbon atoms and at least one oxygen , nitrogen , and / or sulfur atom and may be saturated , unsaturated , i . e . have one or more double bonds , or aryl , and comprises up to 20 carbon atoms and from 1 to 5 of the above heteroatoms . “ heterocyclic aryl ” refers to an aryl group having from 1 to 3 heteroatoms as ring atoms , the remainder of the ring atoms being carbon . heteroatoms include oxygen , sulfur , and nitrogen . “ hydrocarbyl ” refers to a hydrocarbon radical having only carbon and hydrogen atoms . preferably , the hydrocarbyl radical has from 1 to 20 carbon atoms , more preferably from 1 to 12 carbon atoms and most preferably from 1 to 7 carbon atoms . “ substituted hydrocarbyl ” refers to a hydrocarbyl radical wherein one or more , but not all , of the hydrogen and / or the carbon atoms are replaced by a halogen , nitrogen , oxygen , sulfur or phosphorus atom or a radical including a halogen , nitrogen , oxygen , sulfur or phosphorus atom , e . g . fluoro , chloro , cyano , nitro , hydroxyl , phosphate , thiol , etc . “ amide ” refers to — c ( o )— nh — r ′, wherein r ′ is alkyl , aryl , alkylaryl or hydrogen . “ ester ” refers to — c ( o )— o — r ′, wherein r ′ is alkyl , aryl or alkylaryl . “ thioamide ” refers to — c ( s )— nh — r ′, wherein r ′ is alkyl , aryl , alkylaryl or hydrogen . “ thiol ester ” refers to — c ( o )— s — r ′, wherein r ′ is alkyl , aryl , alkylaryl or hydrogen . “ amine ” refers to a — n ( r ″) r ′″ group , wherein r ″ and r ′″ are independently selected from the group consisting of alkyl , aryl , and alkylaryl . “ thioether ” refers to — s — r ″, wherein r ″ is alkyl , aryl , or alkylaryl . “ sulfonyl ” refers to — s ( o ) 2 — r ″″, where r ″″ is aryl , c ( cn )═ c - aryl , ch 2 cn , alkyaryl , sulfonamide , nh - alkyl , nh - alkylaryl , or nh - aryl . also , alternatively the substituent on the phenyl moiety , as shown below , is referred to as an o , m or p substituent or a 2 , 3 or 4 substituent , respectively . ( obviously , the 5 substituent is also a m substituent and the 6 substituent is an o substituent .) specific compounds of the invention , that are prepared according to example 2 through 199 and / or schemes 1 through 16 , are able to inhibit the activity of sphingosine - 1 - phosphate receptors reported in table i , below . compounds were assessed for their ability to activate or block activation of the human s1p3 receptor in t24 cells stably expressing the human s1p3 receptor . ten thousand cells / well were plated into 384 - well poly - d - lysine coated plates one day prior to use . the growth media for the s1p3 receptor expressing cell line was mccoy &# 39 ; s 5a medium supplemented with 10 % charcoal - treated fetal bovine serum ( fbs ), 1 % antibiotic - antimycotic and 400 μg / ml geneticin . on the day of the experiment , the cells were washed twice with hank &# 39 ; s balanced salt solution supplemented with 20 mm hepes ( hbss / hepes buffer ). the cells were then dye loaded with 2 um fluo - 4 diluted in the hbss / hepes buffer with 1 . 25 mm probenecid and incubated at 37 ° c . for 40 minutes . extracellular dye was removed by washing the cell plates four times prior to placing the plates in the flipr ( fluorometric imaging plate reader , molecular devices ). ligands were diluted in hbss / hepes buffer and prepared in 384 - well microplates . the positive control , sphingosine - 1 - phosphate ( s1p ), was diluted in hbss / hepes buffer with 4 mg / ml fatty acid free bovine serum albumin . the flipr transferred 12 . 5 μl from the ligand microplate to the cell plate and took fluorescent measurements for 75 seconds , taking readings every second , and then for 2 . 5 minutes , taking readings every 10 seconds . drugs were tested over the concentration range of 0 . 61 nm to 10 , 000 nm . data for ca + 2 responses were obtained in arbitrary fluorescence units and not translated into ca + 2 concentrations . ic 50 values were determined through a linear regression analysis using the levenburg marquardt algorithm . the compounds of table 1b are prepared according to procedures analogous to the procedures of schemes 1 through 19 and / or examples 2 through 226 . these compounds are also tested for ability to inhibit the activity of the s1p3 receptor . as a result of the above activity of the compounds utilized in the method of the present invention , it is clear that such compounds may be used in treating the following diseases and conditions for the following reasons . s1p3 subtypes are expressed in primary human trabecular meshwork cells and s1p decreases outflow facility & gt ; 30 % in perfused porcine eyes ( see iovs 45 , 2263 ; 2004 ) by altering paracellular permeability . s1p3 receptor subtype is expressed in vascular endothelial cells and sirna knockdown of s1p1 and s1p3 inhibits angiogenesis . s1p also promotes vascular endothelial cell migration and promotes barrier assembly and integrity . the invention is further illustrated by the following examples which are illustrative of a specific mode of practicing the invention and are not intended as limiting the scope of the claims . unless otherwise indicated , the following chemical abbreviations are used in the examples : acetyl chloride , benzyl bromide , 2 - bromoethyl methyl ether , cyclopentyl iodide , diisopropylethylamine , 2 - dimethylaminoethyl chloride hydrochloride , dimethylcarbamyl chloride , 1 - iodobutane , 2 - iodobutane , iodoethane , 1 - iodohexane , 1 - iodopropane , 2 - iodopropane , 4 - methylbenzene - 1sulfonyl chloride , pivaloyl chloride , pyridinium p - toluenesufonate and tetrahydrofuran - 3 - ol were purchased from aldrich chemical company . methyl 1 - benzyl - 6 - methoxy - 1h - indole - 2 - carboxylate ( compound 2 ). to a solution of methyl6 - methoxy - 1h - indole - 2 - carboxylate ( compound 1 , 1 . 0 g , 4 . 9 mmol ) in dmf ( 10 ml ) was added k 2 co 3 ( 2 . 0 g , 14 . 6 mmol ) and benzyl bromide ( 0 . 87 ml , 7 . 3 mmol ). the mixture was stirred at room temperature for 40 h and was diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by crystallization from et 2 o to yield the title compound as an off - white solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 3 . 81 ( s , 3 h ), 3 . 85 ( s , 3 h ), 5 . 81 ( s , 2 h ), 6 . 73 ( d , j = 2 . 0 hz , 1 h ), 6 . 84 ( dd , j = 8 . 8 , 2 . 0 hz , 1 h ), 7 . 07 ( d , j = 6 . 8 hz , 2 h ), 7 . 19 - 7 . 29 ( m , 3 h ), 7 . 33 ( s , 1 h ), 7 . 58 ( d , j = 8 . 8 hz , 1 h ). 2 -( 1 - benzyl - 6 - methoxy - 1h - indol - 2 - yl ) propan - 2 - ol ( compound 3 ). to a solution of methyl1 - benzyl - 6 - methoxy - 1h - indole - 2 - carboxylate ( compound 2 , 4 . 33 g , 14 . 7 mmol ) in thf ( 50 ml ) at 0 ° c . under argon was added meli ( 3 . 0 m in diethoxymethane , 19 . 6 ml , 58 . 7 mmol ) slowly . after 1 h , the ice - water bath was removed and the reaction was stirred at room temperature for 1 h , cooled to − 78 ° c ., quenched with dry ice , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 , concentrated in vacuo to yield the crude title compound as a yellow solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 69 ( s , 6 h ), 3 . 73 ( s , 3 h ), 5 . 76 ( s , 2 h ), 6 . 42 ( s , 1 h ), 6 . 55 ( d , j = 2 . 4 hz , 1 h ), 6 . 75 - 6 . 81 ( m , 1 h ), 6 . 96 ( d , j = 7 . 3 hz , 2 h ), 7 . 22 ( d , j = 7 . 3 hz , 1 h ), 7 . 25 - 7 . 30 ( m , 2 h ), 7 . 49 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - 2 - isopropyl - 6 - methoxy - 1h - indole ( compound 4 ). to a solution of 2 -( 1 - benzyl - 6 - methoxy - 1h - indol - 2 - yl ) propan - 2 - ol ( compound 3 , 1 . 05 g , 3 . 57 mmol ) in etoac ( 35 ml ) and etoh ( 15 ml ) was added 10 % pd — c ( 190 mg , 0 . 18 mmol ) and hcl - et 2 o ( 1 . 0 m , 1 . 25 ml , 1 . 25 mmol ). the mixture was stirred under hydrogen gas ( atmospheric pressure ) for 1 h and was filtered . to the filtrate was added nahco 3 ( 0 . 5 g ) and h 2 o ( 0 . 5 ml ), followed by na 2 so 4 and mgso 4 . this was then filtered and concentrated in vacuo to yield the crude title compound as a yellow solid . 1 h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 31 ( d , j = 6 . 7 hz , 6 h ), 2 . 90 - 3 . 10 ( m , 1 h ), 3 . 79 ( s , 3 h ), 5 . 33 ( s , 2 h ), 6 . 33 ( s , 1 h ), 6 . 68 ( d , j = 2 . 1 hz , 1 h ), 6 . 79 ( dd , j = 8 . 5 , 2 . 3 hz , 1 h ), 6 . 94 - 7 . 04 ( m , 2 h ), 7 . 20 - 7 . 37 ( m , 2 h ), 7 . 49 ( d , j = 8 . 5 hz , 1 h ). 1 - benzyl - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 5 ). pocl 3 ( 0 . 48 ml , 5 . 23 mmol ) was added dropwise to anhydrous dmf ( 2 ml ) at 0 ° c . under argon . after stirred for 30 min , this solution was added dropwise to a solution of 1 - benzyl - 2 - isopropyl - 6 - methoxy - 1h - indole ( compound 4 , 583 mg , 2 . 09 mmol ) in anhydrous dmf ( 8 ml ) at 0 ° c . under argon . the reaction was stirred for 1 h at 0 ° c . and 30 min at room temperature , diluted with etoac , washed with aqueous nahco 3 , brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound as a light yellow syrup . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 45 ( d , j = 7 . 3 hz , 6 h ), 3 . 40 - 3 . 52 ( m , 1 h ), 3 . 79 ( s , 3 h ), 5 . 40 ( s , 2 h ), 6 . 69 ( d , j = 2 . 4 hz , 1 h ), 6 . 94 ( dd , j = 8 . 8 , 2 . 0 hz , 1 h ), 7 . 01 ( d , j = 7 . 3 hz , 2 h ), 7 . 25 - 7 . 35 ( m , 3 h ), 8 . 28 ( d , j = 8 . 8 hz , 1 h ), 10 . 45 ( s , 1 h ). 1 - benzyl - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxylic acid ( compound 6 ). to a solution of 1 - benzyl - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 5 , 608 mg , 1 . 98 mmol ) in t - buoh ( 15 ml ), ch 3 cn ( 15 ml ), and 2 - methyl - 2 - butene ( 10 ml ) was added a solution of kh 2 po 4 ( 5 . 4 g , 39 . 6 mmol ) and naclo 2 ( 80 %, 4 . 5 g , 39 . 6 mmol ) in h 2 o ( 50 ml ). the mixture was stirred at room temperature and additional 2 - methyl - 2 - butene , kh 2 po 4 , and naclo 2 were added at the above ratio every 16 - 24 h until the starting material was consumed . the reaction mixture was extracted with etoac (× 3 ) and the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound as a yellow solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 39 ( d , j = 7 . 3 hz , 6 h ), 3 . 75 ( s , 3 h ), 3 . 99 - 4 . 17 ( m , 1 h ), 5 . 45 ( s , 2 h ), 6 . 62 ( d , j = 2 . 4 hz , 1 h ), 6 . 90 ( dd , j = 8 . 8 , 2 . 4 hz , 1 h ), 6 . 99 ( d , j = 7 . 3 hz , 2 h ), 7 . 22 - 7 . 34 ( m , 3 h ), 8 . 18 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxamide ( compound 7 ). to a solution of 1 - benzyl - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxylic acid ( compound 6 , 226 mg , 0 . 70 mmol ) in ch 2 cl 2 ( 7 . 0 ml ) was added edc ( 202 mg , 1 . 05 mmol ) and dmap ( 128 mg , 1 . 05 mmol ) followed by 3 , 4 - difluorobenzylamine ( 0 . 25 ml , 2 . 1 mmol ). the reaction was stirred at room temperature for 18 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound as a yellow solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 3 hz , 6 h ), 3 . 65 - 3 . 73 ( m , 1 h ), 3 . 74 ( s , 3 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 40 ( s , 2 h ), 6 . 30 ( t , j = 6 . 3 hz , 1 h ), 6 . 63 ( d , j = 2 . 0 hz , 1 h ), 6 . 82 ( dd , j = 8 . 8 , 2 . 4 hz , 1 h ), 6 . 96 ( d , j = 6 . 8 hz , 2 h ), 7 . 11 - 7 . 17 ( m , 2 h ), 7 . 21 - 7 . 31 ( m , 4 h ), 7 . 51 ( d , j = 8 . 3 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxamide ( compound 7 , 452 mg , 1 . 0 mmol ) in ch 2 cl 2 ( 20 ml ) at 0 ° c . was added bbr 3 ( 1 . 0 m in ch 2 cl 2 , 3 . 0 ml , 3 . 0 mmol ) dropwise . the reaction was stirred for 1 h at 0 ° c . and 1 h at room temperature , quenched with ice , extracted with etoac , the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a yellow solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 3 hz , 6 h ), 3 . 65 - 3 . 74 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 4 . 78 ( s , 1 h ), 5 . 37 ( s , 2 h ), 6 . 27 ( t , j = 5 . 6 hz , 1 h ), 6 . 60 ( d , j = 2 . 4 hz , 1 h ), 6 . 71 ( dd , j = 8 . 5 , 2 . 2 hz , 1 h ), 6 . 95 ( d , j = 6 . 8 hz , 2 h ), 7 . 11 - 7 . 17 ( m , 2 h ), 7 . 21 - 7 . 32 ( m , 4 h ), 7 . 46 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - ethoxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 9 ). general procedure a . to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 40 mg , 0 . 092 mmol ) in dmf ( 2 . 0 ml ) was added k 2 co 3 ( 39 mg , 0 . 28 mmol ) and iodoethane ( 22 μl , 0 . 28 mmol ). the reaction was stirred at room temperature for 48 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by ptlc on silica gel ( 30 % etoac - hexanes ) to yield the title compound as an off - white solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 37 ( t , j = 7 . 0 hz , 3 h ), 1 . 38 ( d , j = 7 . 3 hz , 6 h ), 3 . 68 - 3 . 75 ( m , 1 h ), 3 . 96 ( q , j = 7 . 0 hz , 2 h ), 4 . 67 ( d , j = 6 . 3 hz , 2 h ), 5 . 40 ( s , 2 h ), 6 . 31 ( t , j = 5 . 4 hz , 1 h ), 6 . 64 ( d , j = 2 . 4 hz , 1 h ), 6 . 82 ( dd , j = 8 . 8 , 2 . 0 hz , 1 h ), 6 . 97 ( d , j = 6 . 8 hz , 2 h ), 7 . 13 - 7 . 17 ( m , 2 h ), 7 . 23 - 7 . 31 ( m , 4 h ), 7 . 52 ( d , j = 8 . 3 hz , 1 h ) 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - propoxy - 1h - indole - 3 - carboxamide ( compound 10 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 8 . 0 mg , 0 . 018 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 8 . 0 mg , 0 . 055 mmol ) and 1 - iodopropane ( 9 . 0 μl , 0 . 092 mmol ) to yield the title compound as a white solid . 1 h nmr ( 500 mhz , methanol - d 4 ) δ ppm 0 . 99 ( t , j = 7 . 6 hz , 3 h ), 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 1 . 67 - 1 . 77 ( m , 2 h ), 3 . 42 - 3 . 53 ( m , 1 h ), 3 . 84 ( t , j = 6 . 6 hz , 2 h ), 4 . 57 ( s , 2 h ), 5 . 46 ( s , 2 h ), 6 . 73 ( d , j = 2 . 0 hz , 1 h ), 6 . 78 ( dd , j = 8 . 8 , 2 . 4 hz , 1 h ), 6 . 95 ( d , j = 6 . 8 hz , 2 h ), 7 . 19 - 7 . 29 ( m , 5 h ), 7 . 30 - 7 . 36 ( m , 1 h ), 7 . 49 ( d , j = 8 . 3 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 11 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 8 . 0 mg , 0 . 018 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 8 . 0 mg , 0 . 055 mmol ) and 2 - iodopropane ( 9 . 0 μl , 0 . 092 mmol ) to yield the title compound as a white solid . 1 h nmr ( 500 mhz , methanol - d 4 ) δ ppm 1 . 21 ( d , j = 5 . 9 hz , 6 h ), 1 . 33 ( d , j = 7 . 3 hz , 6 h ), 3 . 45 - 3 . 55 ( m , 1 h ), 4 . 41 - 4 . 50 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 46 ( s , 2 h ), 6 . 72 ( d , j = 2 . 0 hz , 1 h ), 6 . 74 - 6 . 79 ( m , 1 h ), 6 . 96 ( d , j = 7 . 3 hz , 2 h ), 7 . 18 - 7 . 29 ( m , 5 h ), 7 . 30 - 7 . 37 ( m , 1 h ), 7 . 49 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - 6 - butoxy - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 12 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 10 . 7 mg , 0 . 025 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 10 . 0 mg , 0 . 074 mmol ) and 1 - iodobutane ( 14 . 0 μl , 0 . 12 mmol ) to yield the title compound as a white solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 0 . 93 ( t , j = 7 . 3 hz , 3 h ), 1 . 37 ( d , j = 7 . 3 hz , 6 h ), 1 . 40 - 1 . 50 ( m , 2 h ), 1 . 66 - 1 . 74 ( m , 2 h ), 3 . 61 - 3 . 75 ( m , 1 h ), 3 . 88 ( t , j = 6 . 6 hz , 2 h ), 4 . 66 ( d , j = 6 . 3 hz , 2 h ), 5 . 39 ( s , 2 h ), 6 . 30 ( t , j = 5 . 9 hz , 1 h ), 6 . 63 ( d , j = 2 . 0 hz , 1 h ), 6 . 81 ( dd , j = 8 . 5 , 2 . 2 hz , 1 h ), 6 . 96 ( d , j = 6 . 8 hz , 2 h ), 7 . 10 - 7 . 17 ( m , 2 h ), 7 . 21 - 7 . 32 ( m , 4 h ), 7 . 50 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - isobutoxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 13 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 10 . 7 mg , 0 . 025 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 10 . 0 mg , 0 . 074 mmol ) and 2 - iodobutane ( 14 . 0 μl , 0 . 12 mmol ) to yield the title compound as a white solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 0 . 98 ( d , j = 6 . 8 hz , 6 h ), 1 . 36 ( d , j = 7 . 3 hz , 6 h ), 1 . 96 - 2 . 08 ( m , 1 h ), 3 . 65 ( d , j = 6 . 8 hz , 2 h ), 3 . 65 - 3 . 72 ( m , 1 h ), 4 . 66 ( d , j = 6 . 3 hz , 2 h ), 5 . 39 ( s , 2 h ), 6 . 29 ( t , j = 5 . 6 hz , 1 h ), 6 . 63 ( d , j = 2 . 0 hz , 1 h ), 6 . 82 ( dd , j = 8 . 8 , 2 . 0 hz , 1 h ), 6 . 96 ( d , j = 6 . 8 hz , 2h ), 7 . 11 - 7 . 16 ( m , 2h ), 7 . 21 - 7 . 31 ( m , 4 h ), 7 . 50 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( hexoxy )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 14 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 10 . 7 mg , 0 . 025 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 10 . 0 mg , 0 . 074 mmol ) and 1 - iodohexane ( 18 . 0 μl , 0 . 12 mmol ) to yield the title compound as a white solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 0 . 85 - 0 . 93 ( m , 3 h ), 1 . 24 - 1 . 33 ( m , 4 h ), 1 . 37 ( d , j = 6 . 8 hz , 6 h ), 1 . 38 - 1 . 46 ( m , 2 h ), 1 . 66 - 1 . 77 ( m , 2 h ), 3 . 63 - 3 . 75 ( m , 1 h ), 3 . 87 ( t , j = 6 . 6 hz , 2 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 39 ( s , 2 h ), 6 . 30 ( t , j = 5 . 6 hz , 1 h ), 6 . 63 ( d , j = 2 . 4 hz , 1 h ), 6 . 81 ( dd , j = 8 . 8 , 2 . 4 hz , 1 h ), 6 . 96 ( d , j = 6 . 8 hz , 2 h ), 7 . 10 - 7 . 16 ( m , 2 h ), 7 . 21 - 7 . 31 ( m , 4 h ), 7 . 50 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - 6 -( benzyloxy )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 15 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 10 . 7 mg , 0 . 025 mmol ) in dmf ( 1 . 0 ml ) and acetone ( 1 . 0 ml ) was reacted with k 2 co 3 ( 10 . 0 mg , 0 . 074 mmol ), benzyl bromide ( 14 . 0 μl , 0 . 12 mmol ), and catalytic amount of nai to yield the title compound as an off - white solid . 1 h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 3 hz , 6 h ), 3 . 65 - 3 . 75 ( m , 1 h ), 4 . 66 ( d , j = 6 . 3 hz , 2 h ), 4 . 99 ( s , 2 h ), 5 . 37 ( s , 2 h ), 6 . 28 ( t , j = 6 . 3 hz , 1 h ), 6 . 71 ( d , j = 2 . 0 hz , 1 h ), 6 . 89 ( dd , j = 8 . 8 , 2 . 0 hz , 1 h ), 6 . 95 ( d , j = 6 . 8 hz , 2 h ), 7 . 11 - 7 . 18 ( m , 2 h ), 7 . 22 - 7 . 30 ( m , 5 h ), 7 . 31 - 7 . 39 ( m , 4 h ), 7 . 51 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - 6 -( cyclopentoxy )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 16 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 40 mg , 0 . 092 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 38 mg , 0 . 28 mmol ), cyclopentyl iodide ( 53 μl , 0 . 46 mmol ) to yield the title compound as a white solid . 1 h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 1 . 48 - 1 . 60 ( m , 2 h ), 1 . 66 - 1 . 86 ( m , 6 h ), 3 . 62 - 3 . 83 ( m , 1 h ), 4 . 56 - 4 . 77 ( m , 3 h ), 5 . 38 ( s , 2 h ), 6 . 32 ( t , j = 5 . 9 hz , 1 h ), 6 . 61 ( d , j = 2 . 1 hz , 1 h ), 6 . 78 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 6 . 91 - 7 . 02 ( m , 2 h ), 7 . 08 - 7 . 17 ( m , 2 h ), 7 . 17 - 7 . 36 ( m , 4 h ), 7 . 49 ( d , j = 8 . 5 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 2 - methoxyethoxy )- 1h - indole - 3 - carboxamide ( compound 17 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 17 mg , 0 . 039 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 28 mg , 0 . 20 mmol ), 2 - bromoethyl methyl ether ( 18 μl , 0 . 20 mmol ) to yield the title compound ( 9 mg , 49 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 1 . 37 ( d , j = 7 . 04 hz , 6 h ), 3 . 40 ( s , 3 h ), 3 . 60 - 3 . 78 ( m , 3 h ), 4 . 04 ( dd , j = 5 . 42 , 3 . 96 hz , 2 h ), 4 . 66 ( d , j = 5 . 86 hz , 2 h ), 5 . 39 ( s , 2 h ), 6 . 30 ( t , j = 5 . 86 hz , 1 h ), 6 . 68 ( d , j = 2 . 35 hz , 1 h ), 6 . 85 ( dd , j = 8 . 65 , 2 . 20 hz , 1 h ), 6 . 89 - 7 . 01 ( m , 2 h ), 7 . 10 - 7 . 18 ( m , 2 h ), 7 . 17 - 7 . 35 ( m , 4 h ), 7 . 51 ( d , j = 8 . 79 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 2 -( dimethylamino ) ethoxy )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 18 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 17 mg , 0 . 039 mmol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 28 mg , 0 . 20 mmol ), 2 - dimethylamino ethyl chloride hydrochloride ( 20 mg , 0 . 20 mmol ) to yield the title compound ( 10 mg , 53 %). 1 h nmr ( 300 mhz , cd 3 od ) δ ppm 1 . 32 ( d , j = 7 . 04 hz , 6 h ), 2 . 30 ( s , 6 h ), 2 . 71 ( t , j = 5 . 42 hz , 2 h ), 3 . 37 - 3 . 59 ( m , 1 h ), 4 . 02 ( t , j = 5 . 42 hz , 2 h ), 4 . 57 ( s , 2 h ), 5 . 48 ( s , 2 h ), 6 . 73 - 6 . 88 ( m , 2 h ), 6 . 89 - 7 . 02 ( m , 2 h ), 7 . 12 - 7 . 40 ( m , 6 h ), 7 . 50 ( d , j = 8 . 50 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( tetrahydrofuran - 3 - yloxy )- 1h - indole - 3 - carboxamide ( compound 19 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 8 mg , 0 . 039 mmol ) in dmf ( 1 . 0 ml ) was added k 2 co 3 ( 13 mg , 0 . 092 mmol ) and catalytic amount of naoh , 3 - iodotetrahydrofuran ( compound 29 , 120 mg , crude ). the reaction was stirred at room temperature for 2 days , and purified by a short silica gel column to yield the title compound ( 8 mg , 86 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 1 . 38 ( d , j = 7 . 04 hz , 6 h ), 1 . 95 - 2 . 14 ( m , 2 h ), 3 . 59 - 4 . 01 ( m , 5 h ), 4 . 66 ( d , j = 6 . 16 hz , 2 h ), 4 . 74 - 4 . 88 ( m , 1 h ), 5 . 39 ( s , 2 h ), 6 . 29 ( t , j = 4 . 40 hz , 1 h ), 6 . 57 ( d , j = 2 . 05 hz , 1 h ), 6 . 69 - 6 . 83 ( m , 1 h ), 6 . 96 ( d , j = 7 . 62 hz , 2 h ), 7 . 08 - 7 . 19 ( m , 2 h ), 7 . 18 - 7 . 35 ( m , 4 h ), 7 . 51 ( d , j = 8 . 79 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 2 - oxotetrahydrofuran - 3 - yloxy )- 1h - indole - 3 - carboxamide ( compound 20 ). following general procedure a , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 h - indole - 3 - carboxamide ( compound 8 , 19mg , 0 . 044 mol ) in dmf ( 1 . 0 ml ) was reacted with k 2 co 3 ( 30 g , 0 . 22 mmol ), 3 - bromodihydrofuran - 2 ( 3h )- one ( 20 mg , 0 . 22 mmol ) to yield the title compound ( 16mg , 71 %). 1 h nmr ( 300 mhz , acetone - d 6 ) δ ppm 1 . 33 ( d , j = 5 . 57 hz , 6 h ), 2 . 21 - 2 . 42 ( m , 1 h ), 2 . 68 - 2 . 88 ( m , 1 h ), 3 . 43 - 3 . 65 ( m , 1 h ), 4 . 21 - 4 . 53 ( m , 2 h ), 4 . 66 ( d , j = 6 . 16 hz , 2 h ), 5 . 10 - 5 . 24 ( m , 1 h ), 5 . 54 ( s , 2 h ), 6 . 90 ( dd , j = 8 . 65 , 2 . 20 hz , 1 h ), 6 . 97 - 7 . 08 ( m , 2 h ), 7 . 11 ( d , j = 2 . 35 hz , 1 h ), 7 . 17 - 7 . 35 ( m , 5 h ), 7 . 42 ( dd , j = 12 . 31 , 8 . 50 hz , 1 h ), 7 . 62 ( d , j = 8 . 79 hz , 1 h ), 7 . 68 - 7 . 78 ( m , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl dimethylcarbamate ( compound 21 ). general procedure b . to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 18mg , 0 . 041mol ) in pyridine ( 1 ml ) was added dimethylcarbamyl chloride ( 40 μl , 0 . 41 mmol ) and stirred at room temperature overnight . the reaction was quenched with water , extracted with ethyl acetate . the combined organic layer was washed with water , brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a white solid ( 17 mg , 82 %). 1 h nmr ( 300 mhz , cd 3 od ) δ ppm 1 . 32 ( d , j = 7 . 04 hz , 6 h ), 2 . 96 ( s , 3 h ), 3 . 09 ( s , 3 h ), 3 . 37 - 3 . 55 ( m , 1 h ), 4 . 58 ( s , 2 h ), 5 . 48 ( s , 2 h ), 6 . 87 ( dd , j = 8 . 65 , 1 . 91 hz , 1 h ), 6 . 91 - 6 . 99 ( m , 2 h ), 7 . 02 ( d , j = 2 . 05 hz , 1 h ), 7 . 16 - 7 . 39 ( m , 6 h ), 7 . 58 ( d , j = 8 . 79 hz , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl pivalate ( compound 22 ). following general procedure b , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 18 mg , 0 . 041 mol ) in pyridine ( 1 ml ) was reacted with pivaloyl chloride ( 5 . 1 μl , 0 . 41 mmol ) to yield the title compound ( 16 mg , 74 %). 1 h nmr ( 300 mhz , cd 3 od ) δ ppm 1 . 25 - 1 . 40 ( m , 15 h ), 3 . 34 - 3 . 55 ( m , 1 h ), 4 . 58 ( d , j = 5 . 86 hz , 2 h ), 5 . 49 ( s , 2 h ), 6 . 73 - 6 . 88 ( m , 1 h ), 6 . 89 - 6 . 99 ( m , 2 h ), 7 . 00 ( d , j = 1 . 76 hz , 1 h ), 7 . 14 - 7 . 41 ( m , 6 h ), 7 . 60 ( d , j = 8 . 50 hz , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl acetate ( compound 23 ). following general procedure b , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 7 mg , 0 . 016 mol ) in pyridine ( 1 ml ) was reacted with acetyl chloride ( 1 . 0 μl , 0 . 16 mmol ) to yield the title compound ( 8 mg , 100 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 1 . 37 ( d , j = 7 . 04 hz , 6 h ), 2 . 26 ( s , 3 h ), 3 . 54 - 3 . 76 ( m , 1 h ), 4 . 66 ( d , j = 6 . 16 hz , 2 h ), 5 . 41 ( s , 2 h ), 6 . 28 ( t , j = 6 . 01 hz , 1 h ), 6 . 81 - 7 . 01 ( m , 4 h ), 7 . 06 - 7 . 19 ( m , 2 h ), 7 . 18 - 7 . 35 ( m , 4 h ), 7 . 61 ( d , j = 9 . 09 hz , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl propionate ( compound 24 ). following general procedure b , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 7 mg , 0 . 016 mol ) in pyridine ( 1 ml ) was reacted with propionyl chloride ( 1 . 4 μl , 0 . 16 mmol ) to yield the title compound ( 8 mg , 100 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 1 . 23 ( t , j = 7 . 48 hz , 3 h ), 1 . 37 ( d , j = 7 . 33 hz , 6 h ), 2 . 55 ( q , j = 7 . 43 hz , 2 h ), 3 . 53 - 3 . 73 ( m , 1 h ), 4 . 66 ( d , j = 5 . 86 hz , 2 h ), 5 . 41 ( s , 2 h ), 6 . 30 ( t , j = 5 . 72 hz , 1 h ), 6 . 83 - 7 . 00 ( m , 4 h ), 7 . 06 - 7 . 18 ( m , 2 h ), 7 . 18 - 7 . 35 ( m , 4 h ), 7 . 60 ( d , j = 8 . 50 hz , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl isobutyrate ( compound 25 ). following general procedure b , 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 9 mg , 0 . 021 mol ) in pyridine ( 1 ml ) was reacted with isobutyryl chloride ( 4 . 1 μl , 0 . 21 mmol ) to yield the title compound ( 8 mg , 80 %). 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 1 . 13 - 1 . 42 ( m , 12 h ), 2 . 47 - 2 . 85 ( m , 1 h ), 3 . 50 - 3 . 74 ( m , 1 h ), 4 . 66 ( d , j = 6 . 16 hz , 2 h ), 5 . 41 ( s , 2 h ), 6 . 20 - 6 . 44 ( m , 1 h ), 6 . 74 - 7 . 00 ( m , 4 h ), 7 . 07 - 7 . 18 ( m , 2 h ), 7 . 17 - 7 . 35 ( m , 4 h ), 7 . 60 ( d , j = 8 . 50 hz , 1h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( methoxymethoxy )- 1h - indole - 3 - carboxamide ( compound 26 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 39 mg , 0 . 090 mmol ) in ch 2 cl 2 ( 2 . 0 ml ) was added i - pr 2 net ( 47 μl , 0 . 27 mmol ) and momcl ( 35 μl , 0 . 45 mmol ). the reaction was stirred at room temperature for 4 h , and was purified directly by ptlc on silica gel ( 30 % etoac - hexanes ) to yield the title compound as a white solid . 1 h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 3 . 42 ( s , 3 h ), 3 . 59 - 3 . 78 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 10 ( s , 2 h ), 5 . 40 ( s , 2 h ), 6 . 29 ( t , j = 5 . 7 hz , 1 h ), 6 . 85 ( d , j = 2 . 1 hz , 1 h ), 6 . 89 - 7 . 01 ( m , 3 h ), 7 . 10 - 7 . 17 ( m , 2 h ), 7 . 20 - 7 . 34 ( m , 4 h ), 7 . 52 ( d , j = 8 . 5 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( tetrahydrofuran - 2 - yloxy )- 1h - indole - 3 - carboxamide ( compound 27 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 39 mg , 0 . 090 mmol ) in ch 2 cl 2 ( 2 . 0 ml ) was added 2 , 3 - dihydrofuran ( 68 μl , 0 . 90 mmol ) and catalytic amount of ppts . the reaction was stirred at room temperature for 4 h , and was purified directly by ptlc on silica gel ( 30 % etoac - hexanes ) to yield the title compound as a white solid . 1 h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 36 ( d , j = 7 . 3 hz , 6 h ), 1 . 85 - 1 . 98 ( m , 1 h ), 2 . 01 - 2 . 19 ( m , 3 h ), 3 . 58 - 3 . 73 ( m , 1 h ), 3 . 85 - 3 . 95 ( m , 1 h ), 3 . 96 - 4 . 07 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 40 ( s , 2 h ), 5 . 70 ( d , j = 4 . 7 hz , 1 h ), 6 . 29 ( t , j = 5 . 7 hz , 1 h ), 6 . 86 ( d , j = 2 . 1 hz , 1 h ), 6 . 89 - 6 . 99 ( m , 3 h ), 7 . 11 - 7 . 17 ( m , 2 h ), 7 . 19 - 7 . 32 ( m , 4 h ), 7 . 51 ( d , j = 8 . 5 hz , 1 h ). tetrahydrofuran - 3 - yl4 - methylbenzenesulfonate ( compound 28 ). to a solution of tetrahydrofuran - 3 - ol ( 500 mg , 5 . 67 mmol ) in pyridine ( 10 ml ) at 0 ° c . was added 4 - methylbenzene - 1 - sulfonyl chloride ( 1 . 08 g , 5 . 67 mmol ). the reaction was stirred at room temperature overnight . the reaction was quenched with water , extracted with ethyl acetate . the organic layer was washed with water , brine , dried over na 2 so 4 and concentrated in vacuo to yield crude oil ( 1 . 2 g ). 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 1 . 91 - 2 . 23 ( m , 2 h ), 3 . 61 - 4 . 05 ( m , 4 h ), 4 . 95 - 5 . 24 ( m , 1 h ), 7 . 36 ( d , j = 7 . 92 hz , 2 h ), 7 . 80 ( d , j = 8 . 50 hz , 2 h ). 3 - iodotetrahydrofuran ( compound 29 ). to a solution of crude tetrahydrofuran - 3 - yl4 - methylbenzenesulfonate ( compound 28 , 1 . 2 g , 4 . 96 mmol ) in dry acetone ( 50 ml ) was added nai ( 1 . 1 g , 7 . 44 mmol ). the reacted was heated at 60 ° c . for 2 days . the mixture was diluted with water and extracted with diethyl ether . the organic layer was washed with water , brine , dried over na 2 so 4 and concentrated in vacuo to yield crude oil which was used directly without purification . 1 h nmr ( 300 mhz , cdcl 3 ) δ ppm 2 . 23 - 2 . 55 ( m , 2 h ), 3 . 81 - 4 . 08 ( m , 3 h ), 4 . 08 - 4 . 43 ( m , 2 h ). ethyl 4 - iodo - 3 - nitrobenzoate ( compound 30 ). to a solution of ethyl - 4 - iodobenzoate ( 10 . 0 g , 36 . 2 mmol ) in h 2 so 4 ( 20 ml ) at 0 ° c . was added dropwise hno 3 ( 4 . 7 ml , 72 . 4 mmol ). reaction was stirred at room temperature for 1 h , cooled to 0 ° c ., quenched with ice , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 , concentrated in vacuo to yield the crude title compound as a yellow solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 41 ( t , j = 7 . 09 hz , 3 h ), 4 . 40 ( q , j = 7 . 09 hz , 2 h ), 7 . 89 ( dd , j = 6 . 11 , 1 . 96 hz , 1 h ), 8 . 19 ( d , j = 7 . 62 hz , 1 h ), 8 . 45 ( s , 1 h ). ethyl 3 - amino - 4 - iodobenzoate ( compound 31 ). to a solution of ethyl4 - iodo - 3nitrobenzoate ( compound 30 , 9 . 45 g , 29 . 4 mmol ) in ethyl acetate ( 200 ml ) and tin ( ii ) chloride dehydrate ( 33 . 1 g , 147 mmol ). reaction was heated to 85 ° c . for 1 h , cooled to 25 ° c ., quenched with nahco 3 ( s ), filtered off white solid , and then organic layer was concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 38 ( t , j = 7 . 09 hz , 3 h ), 4 . 34 ( q , j = 7 . 18 hz , 2 h ), 7 . 11 ( dd , j = 8 . 21 , 2 . 05 hz , 1 h ), 7 . 39 ( d , j = 2 . 05 hz , 1 h ), 7 . 71 ( d , j = 8 . 06 hz , 1h ). ethyl 3 - amino - 4 -( 3 - methylbut - 1 - ynyl ) benzoate ( compound 32 ). to a solution of ethyl3 - amino - 4 - iodobenzoate ( compound 31 , 6 . 87 g , 23 . 1 mmol ) in triethylamine ( 50 ml ) at 25 ° c . under argon then added cui ( 22 mg , 1 . 16 mmol ), pd ( pph 3 ) 2 cl 2 ( 82 mg , 1 . 16 mmol ), and 3 - methyl - 1 - butyne ( 3 . 18 g , 46 . 2 mmol ). the reaction was stirred for 20 h at 25 ° c ., filtered off brown solid , and then rinsed solid with etoac , organic layer was concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 29 ( s , 3 h ), 1 . 31 ( s , 3 h ), 1 . 38 ( t , j = 7 . 11 hz , 3 h ), 2 . 86 ( dt , j = 13 . 67 , 6 . 87 hz , 1 h ), 4 . 25 ( br . s ., 2 h ), 4 . 34 ( q , j = 7 . 08 hz , 2 h ), 7 . 29 ( s , 1 h ), 7 . 32 ( d , j = 1 . 47 hz , 1 h ), 7 . 33 - 7 . 38 ( m , 1 h ). ethyl 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 33 ). to a solution of ethyl3 - amino - 4 -( 3 - methylbut - 1 - ynyl ) benzoate ( compound 32 , 5 . 30 g , 22 . 9 mmol ) in dmf ( 50 ml ) at 25 ° c . under argon then added cui ( 218 mg , 11 . 5 mmol ). the reaction was heated for 2 h at 160 ° c ., filtered off black solid , and then rinsed solid with etoac , organic layer was concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 20 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , chloroform - d ) 6 ppm 1 . 37 ( s , 3 h ), 1 . 39 ( s , 3 h ), 1 . 40 - 1 . 44 ( m , 3 h ), 1 . 42 ( t , j = 7 . 09 hz , 3 h ), 3 . 11 ( ddd , j = 13 . 71 , 6 . 74 , 6 . 52 hz , 1 h ), 4 . 39 ( q , j = 7 . 08 hz , 2 h ), 6 . 30 ( ddd , j = 2 . 09 , 0 . 99 , 0 . 88 hz , 1 h ), 7 . 53 ( d , j = 8 . 21 hz , 1 h ), 7 . 78 ( dd , j = 8 . 36 , 1 . 47 hz , 1 h ), 8 . 08 ( d , j = 0 . 73 hz , 1 h ), 8 . 17 ( br . s ., 1 h ). ethyl 3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 34 ). to a solution of ethyl 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 33 , 2 . 00 g , 8 . 66 mmol ) in dmf ( 12 ml ) at 0 ° c . under argon then added dropwise pocl 3 ( 1 . 58 ml , 17 . 3 mmol ) was added dropwise . the reaction was stirred for 30 minutes at 25 ° c . then cooled to 0 ° c ., quenched with saturated nahco 3 , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a light tan solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 43 ( t , j = 7 . 18 hz , 3 h ), 1 . 48 ( s , 3 h ), 1 . 50 ( s , 3 h ), 3 . 84 ( dt , j = 14 . 00 , 6 . 93 hz , 1 h ), 4 . 42 ( q , j = 7 . 18 hz , 2 h ), 7 . 97 ( dd , j = 8 . 28 , 1 . 39 hz , 1 h ), 8 . 18 ( d , j = 0 . 73 hz , 1 h ), 8 . 28 ( d , j = 8 . 21 hz , 1 h ), 8 . 95 ( br . s ., 1 h ), 10 . 29 ( s , 1 h ). ethyl 1 - benzyl - 3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 35 ). general procedure c . to a solution of ethyl3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 34 , 2 . 08 g , 8 . 04 mmol ) in dmf ( 15 ml ) was added k 2 co 3 ( 3 . 32 g , 24 . 1 mmol ) and benzyl bromide ( 1 . 91 ml , 16 . 1 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 35 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 37 ( t , j = 7 . 11 hz , 3 h ), 1 . 44 ( s , 3 h ), 1 . 47 ( s , 3 h ), 3 . 54 - 3 . 76 ( m , 0 h ), 4 . 35 ( q , j = 7 . 18 hz , 2 h ), 5 . 67 ( s , 2 h ), 7 . 02 ( d , j = 7 . 18 hz , 1 h ), 7 . 18 - 7 . 42 ( m , 4 h ), 7 . 93 ( d , j = 8 . 36 hz , 1 h ), 8 . 08 ( s , 1 h ), 8 . 33 ( d , j = 8 . 65 hz , 1 h ), 10 . 41 ( s , 1 h ). ethyl 3 - formyl - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 36 ). following general procedure c , ethyl3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 34 , 278 mg , 1 . 07 mmol ) in dmf ( 15 ml ) was added k 2 co 3 ( 590 mg , 4 . 28 mmol ) and 2 -( bromomethyl ) pyridine ( 914 mg , 5 . 35 mmol ). the reaction was stirred at 60 ° c . for 5 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 35 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 36 ( t , j = 7 . 17 hz , 3 h ), 1 . 47 ( s , 3 h ), 1 . 50 ( s , 3 h ), 3 . 62 - 3 . 72 ( m , 1 h ), 4 . 34 ( d , j = 7 . 18 hz , 2 h ), 5 . 74 ( s , 2 h ), 7 . 01 ( d , j = 7 . 77 hz , 1 h ), 7 . 32 ( d , j = 7 . 48 hz , 1 h ), 7 . 75 ( td , j = 7 . 70 , 1 . 76 hz , 1 h ), 7 . 93 ( td , j = 4 . 14 , 1 . 39 hz , 1 h ), 8 . 07 ( d , j = 0 . 73 hz , 1 h ), 8 . 34 ( t , j = 4 . 18 hz , 1 h ), 8 . 52 ( ddd , j = 4 . 87 , 1 . 72 , 0 . 88 hz , 1 h ), 10 . 42 ( s , 1 h ). ethyl 3 - formyl - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 37 ). to a solution of ethyl3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 34 , 1 . 00 g , 3 . 86 mmol ) in dmf ( 50 ml ) was added nah ( 463 mg , 19 . 3 mmol ) and and 3 -( bromomethyl ) pyridine ( 2 . 62 g , 15 . 4 mmol ). the reaction was stirred at 60 ° c . for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 70 % etoac - hexanes ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 36 ( t , j = 7 . 11 hz , 3 h ), 1 . 46 ( s , 3 h ), 1 . 49 ( s , 3 h ), 3 . 66 ( dt , j = 14 . 37 , 7 . 18 hz , 1 h ), 4 . 35 ( q , j = 7 . 08 hz , 2 h ), 5 . 78 ( s , 2 h ), 7 . 40 ( qd , j = 3 . 81 , 3 . 66 hz , 3 h ), 7 . 94 ( dd , j = 8 . 36 , 1 . 47 hz , 1 h ), 8 . 10 ( d , j = 0 . 73 hz , 1 h ), 8 . 30 - 8 . 40 ( m , 1 h ), 8 . 47 ( dd , j = 4 . 47 , 1 . 98 hz , 1 h ), 10 . 43 ( s , 1 h ). ethyl 3 - formyl - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 38 ). to a solution of ethyl3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 34 , 1 . 22 g , 4 . 72 mmol ) in dmf ( 10 ml ) was added nah ( 170 mg , 7 . 08 mmol ) and 2 -( chloromethyl ) oxazole ( 1 . 10 g , 9 . 44 mmol ). the reaction was stirred at 25 ° c . for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 40 ( t , j = 7 . 11 hz , 3 h ), 1 . 54 ( s , 3 h ), 1 . 56 ( s , 3 h ), 3 . 77 ( dt , j = 14 . 33 , 7 . 13 hz , 1 h ), 4 . 38 ( q , j = 7 . 04 hz , 2 h ), 5 . 80 ( s , 2 h ), 7 . 15 ( d , j = 0 . 73 hz , 1 h ), 7 . 80 - 8 . 11 ( m , 2 h ), 8 . 11 - 8 . 52 ( m , 2 h ), 10 . 42 ( s , 1 h ). 1 - benzyl - 6 -( ethoxylcarbonyl )- 2 - isopropyl - 1h - indole - 3 - carboxylic acid ( compound 39 ). general procedure d . to a solution of ethyl1 - benzyl - 3 - formyl - 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 35 , 220 mg , 0 . 63 mmol ) in t - buoh ( 6 ml ), ch 3 cn ( 1 ml ), and 2 - methyl - 2 - butene ( 1 . 76 ml ) was added a solution of nah 2 po 4 ( 1 . 51 g , 12 . 6 mmol ) and naclo 2 ( 80 %, 1 . 13 g , 12 . 6 mmol ) in h 2 o ( 6 ml ). the mixture was stirred at room temperature fro 12 h . the reaction mixture was extracted with etoac (× 3 ) and the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 20 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 35 ( t , j = 7 . 11 hz , 3 h ), 1 . 37 ( s , 3 h ), 1 . 40 ( s , 3 h ), 3 . 80 - 4 . 08 ( m , 1 h ), 4 . 33 ( q , j = 7 . 13 hz , 2 h ), 5 . 67 ( s , 2 h ), 6 . 96 ( d , j = 9 . 23 hz , 2 h ), 7 . 20 - 7 . 38 ( m , 3 h ), 7 . 84 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 7 . 98 ( s , 1 h ), 8 . 21 ( dd , j = 8 . 50 , 0 . 59 hz , 1 h ). 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 40 ). following general procedure d , ethyl3 - formyl - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 36 , 287 mg , 0 . 82 mmol ) in t - buoh ( 6 ml ), 2 - methyl - 2 - butene ( 2 . 29 ml ) was added a solution of nah 2 po 4 ( 1 . 97 g , 16 . 4mmol ) and naclo 2 ( 80 %, 1 . 48 g , 16 . 4 mmol ) in h 2 o ( 6 ml ). the mixture was stirred at room temperature for 12 h . the reaction mixture was extracted with etoac (× 3 ) and the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 - 1 . 47 ( m , 9 h ), 3 . 94 - 4 . 13 ( m , 1 h ), 4 . 33 ( q , j = 7 . 13 hz , 2 h ), 5 . 74 ( s , 2 h ), 6 . 76 ( d , j = 8 . 06 hz , 1 h ), 7 . 26 - 7 . 37 ( m , 1 h ), 7 . 65 - 7 . 77 ( m , 1 h ), 7 . 85 ( d , j = 7 . 04 hz , 1 h ), 7 . 98 ( d , j = 0 . 73 hz , 1 h ), 8 . 21 ( d , j = 8 . 50 hz , 1 h ), 8 . 55 ( dd , j = 6 . 23 , 1 . 25 hz , 1 h ). 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 41 ). following general procedure d , ethyl3 - formyl - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 37 , 754 mg , 1 . 54 mmol ) in t - buoh ( 30 ml ), 2 - methyl - 2 - butene ( 6 . 0 ml ) was added a solution of nah 2 po 4 ( 5 . 17 g , 30 . 8 mmol ) and naclo 2 ( 80 %, 3 . 88 g , 30 . 8 mmol ) in h 2 o ( 12 ml ). the mixture was stirred at room temperature for 12 h . the reaction mixture was extracted with etoac (× 3 ) and the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 60 % etoac - hexanes ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 36 ( t , j = 7 . 11 hz , 3 h ), 1 . 39 ( s , 3 h ), 1 . 42 ( s , 3 h ), 3 . 85 - 4 . 13 ( m , 1 h ), 4 . 33 ( q , j = 7 . 08 hz , 2 h ), 5 . 77 ( s , 2 h ), 7 . 36 ( t , j = 2 . 05 hz , 2 h ), 7 . 86 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 8 . 00 ( d , j = 0 . 88 hz , 1 h ), 8 . 22 ( dd , j = 8 . 50 , 0 . 73 hz , 1 h ), 8 . 27 ( d , j = 1 . 76 hz , 1 h ), 8 . 45 ( dd , j = 4 . 03 , 2 . 42 hz , 1 h ). 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 42 ). following general procedure d , ethyl3 - formyl - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 38 , 240 mg , 0 . 70 mmol ) in t - buoh ( 20 ml ), 2 - methyl - 2 - butene ( 2 . 0 ml ) was added a solution of nah 2 po 4 ( 1 . 69 g , 14 . 0 mmol ) and naclo 2 ( 80 %, 1 . 27 g , 14 . 0 mmol ) in h 2 o ( 4 ml ). the mixture was stirred at room temperature for 12 h . the reaction mixture was extracted with etoac (× 3 ) and the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 55 % etoac - hexanes ) to yield the title compound as a light tan solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 40 ( t , j = 7 . 11 hz , 3 h ), 1 . 46 ( s , 3 h ), 1 . 48 ( s , 3 h ), 3 . 94 - 4 . 15 ( m , 1 h ), 4 . 38 ( q , j = 7 . 18 hz , 2 h ), 5 . 78 ( s , 2 h ), 7 . 14 ( d , j = 0 . 73 hz , 1 h ), 7 . 76 - 7 . 93 ( m , 2 h ), 8 . 17 ( d , j = 2 . 05 hz , 2 h ). ethyl 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 43 ). general procedure e . to a solution of 1 - benzyl - 6 -( ethoxylcarbonyl )- 2 - isopropyl - 1h - indole - 3 - carboxylic acid ( compound 39 , 1 . 00 g , 2 . 74 mmol ) in ch 2 cl 2 ( 10 ml ) was added edc ( 1 . 04 g , 5 . 84 mmol ) and dmap ( 500 mg , 4 . 11 mmol ), followed by 3 , 4 - difluorobenzylamine ( 589 mg , 4 . 11 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 35 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 - 1 . 39 ( m , 9 h ), 3 . 47 ( m , 1 h ), 4 . 33 ( q , j = 7 . 18 hz , 2 h ), 4 . 59 ( s , 2 h ), 5 . 60 ( s , 2 h ), 6 . 96 ( d , j = 8 . 21 hz , 1 h ), 7 . 22 - 7 . 40 ( m , 6 h ), 7 . 67 ( d , j = 8 . 36 hz , 1 h ), 7 . 82 ( d , j = 1 . 47 hz , 1 h ), 8 . 00 ( d , j = 0 . 59 hz , 1 h ). ethyl 1 - benzyl - 3 -(( 5 - fluoropyridin - 3 - yl ) methylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 44 ). following general procedure e , 1 - benzyl - 6 -( ethoxylcarbonyl )- 2 - isopropyl - 1h - indole - 3 - carboxylic acid ( compound 39 , 93 mg , 0 . 254 mmol ) in ch 2 cl 2 ( 6 ml ) was added edc ( 97 mg , 0 . 508 mmol ) and dmap ( 46 mg , 0 . 381mmol ), followed by ( 5 - fluoropyridin - 3 - yl ) methanamine ( 81 mg , 0 . 63 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 80 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 27 - 1 . 43 ( m , 9 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 33 ( q , j = 7 . 18 hz , 2 h ), 4 . 69 ( s , 2 h ), 5 . 61 ( s , 2 h ), 6 . 95 ( dd , j = 7 . 48 , 1 . 03 hz , 2 h ), 7 . 19 - 7 . 34 ( m , 3 h ), 7 . 65 - 7 . 76 ( m , 2 h ), 7 . 82 ( dd , j = 8 . 36 , 1 . 47 hz , 1 h ), 8 . 00 ( d , j = 1 . 47 hz , 1 h ), 8 . 39 ( d , j = 2 . 64 hz , 1 h ), 8 . 52 ( s , 1 h ). ethyl 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 45 ). following general procedure e , 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 40 , 150 mg , 0 . 409 mmol ) in ch 2 cl 2 ( 6 ml ) was added edc ( 157 mg , 0 . 81 mmol ) and dmap ( 75 mg , 0 . 60 mmol ), followed by ( 5 - fluoropyridin - 3 - yl ) methanamine ( 88 mg , 0 . 63 mmol ). the crude material was purified by chromatography on silica gel ( 0 → 40 % etoac - hexanes ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 25 - 1 . 45 ( m , 9 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 33 ( t , j = 7 . 04 hz , 2 h ), 4 . 60 ( s , 2 h ), 5 . 68 ( s , 2 h ), 6 . 74 ( d , j = 6 . 89 hz , 1 h ), 7 . 18 - 7 . 43 ( m , 4 h ), 7 . 61 - 7 . 76 ( m , 2 h ), 7 . 82 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 8 . 00 ( d , j = 0 . 73 hz , 1 h ), 8 . 54 ( dt , j = 5 . 42 , 0 . 95 hz , 1 h ). ethyl 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 46 ). following general procedure e , 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 41 , 365 mg , 0 . 997 mmol ) in ch 2 cl 2 ( 12 ml ) was added edc ( 288 mg , 2 . 00 mmol ) and dmap ( 146 mg , 1 . 50 mmol ), followed by 3 , 4 - difluorobenzyl amine ( 171 mg , 1 . 50 mmol ). the crude material was purified by chromatography on silica gel ( 0 → 70 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 35 ( dt , j = 7 . 18 , 3 . 59 hz , 9 h ), 3 . 47 ( m , 1 h ), 4 . 33 ( q , j = 7 . 18 hz , 2 h ), 4 . 59 ( s , 2 h ), 5 . 70 ( s , 2 h ), 7 . 15 - 7 . 41 ( m , 5 h ), 7 . 68 ( dd , j = 8 . 36 , 0 . 59 hz , 1 h ), 7 . 82 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 8 . 01 ( d , j = 0 . 73 hz , 1 h ), 8 . 22 ( d , j = 1 . 91 hz , 1 h ), 8 . 43 ( dd , j = 3 . 81 , 2 . 64 hz , 1 h ). ethyl 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 47 ). following general procedure e , 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 42 , 244 mg , 0 . 685 mmol ) in ch 2 cl 2 ( 12 ml ) was added edc ( 262 mg , 1 . 37 mmol ) and dmap ( 125 mg , 1 . 03 mmol ), followed by 3 , 4 - difluorobenzyl amine ( 197 mg , 1 . 03 mmol ). the crude material was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 33 - 1 . 52 ( m , 9 h ), 3 . 59 ( m , 1 h ), 4 . 37 ( q , j = 7 . 18 hz , 2 h ), 4 . 57 ( s , 2 h ), 5 . 70 ( s , 2 h ), 7 . 12 ( d , j = 0 . 88 hz , 1 h ), 7 . 18 - 7 . 42 ( m , 3 h ), 7 . 63 ( s , 1 h ), 7 . 81 ( dd , j = 8 . 43 , 1 . 39 hz , 2 h ), 7 . 85 ( d , j = 0 . 88 hz , 1 h ), 8 . 18 ( s , 1 h ). ethyl 3 -( 3 , 5 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 48 ). following general procedure e , 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 40 , 80 mg , 0 . 22 mmol ) in ch 2 cl 2 ( 5 ml ) was added edc ( 84 mg , 0 . 42 mmol ) and dmap ( 40 mg , 0 . 32 mmol ), followed by 3 , 5 - difluorobenzyl amine ( 47 mg , 0 . 32mmol ). the crude material was purified by chromatography on silica gel ( 0 → 40 % etoac - hexanes ) to yield the title compound as an off white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 28 - 1 . 41 ( m , 9 h ), 3 . 51 ( m , 1 h ), 4 . 32 ( q , j = 7 . 03 hz , 2 h ), 4 . 62 ( s , 2 h ), 5 . 68 ( s , 2 h ), 6 . 74 ( d , j = 7 . 91 hz , 1 h ), 6 . 85 ( tt , j = 9 . 08 , 2 . 34 hz , 1 h ), 7 . 04 ( dd , j = 8 . 50 , 2 . 34 hz , 2 h ), 7 . 30 ( dd , j = 6 . 74 , 4 . 98 hz , 1 h ), 7 . 59 - 7 . 75 ( m , 2 h ), 7 . 74 - 7 . 88 ( m , 1 h ), 8 . 00 ( s , 1 h ), 8 . 53 ( d , j = 4 . 10 hz , 1 h ). ethyl 3 -(( 5 - fluoropyridin - 3 - yl ) methylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 49 ). following general procedure e , 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 40 , 150 mg , 0 . 41 mmol ) in ch 2 cl 2 ( 25 ml ) was added edc ( 236 mg , 0 . 82 mmol ) and dmap ( 75 mg , 0 . 60 mmol ), followed by ( 5 - fluoropyridin - 3 - yl ) methanamine ( 94 mg , 0 . 82 mmol ). the crude material was purified by chromatography on silica gel ( 0 → 80 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 25 - 1 . 45 ( m , 9 h ), 3 . 42 - 3 . 62 ( m , 1 h ), 4 . 33 ( q , j = 7 . 04 hz , 2 h ), 4 . 69 ( s , 2 h ), 5 . 68 ( s , 2 h ), 6 . 69 - 6 . 80 ( m , 1 h ), 7 . 26 - 7 . 36 ( m , 1 h ), 7 . 63 - 7 . 76 ( m , 3 h ), 7 . 79 - 7 . 86 ( m , 1 h ), 8 . 00 ( s , 1 h ), 8 . 39 ( s , 1 h ), 8 . 52 ( d , j = 1 . 61 hz , 2 h ). ethyl 3 -( 4 - fluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 50 ). following general procedure e , 6 -( ethoxycarbonyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 40 , 80 mg , 0 . 22 mmol ) in ch 2 cl 2 ( 5 ml ) was added edc ( 84 mg , 0 . 42 mmol ) and dmap ( 40 mg , 0 . 32 mmol ), followed by 4 - fluorobenzyl amine ( 47 mg , 0 . 32 mmol ). the crude material was purified by chromatography on silica gel ( 0 → 45 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 27 - 1 . 44 ( m , 9 h ), 3 . 48 ( quin , j = 7 . 25 hz , 1 h ), 4 . 32 ( q , j = 7 . 13 hz , 2 h ), 4 . 60 ( s , 2 h ), 5 . 66 ( s , 2 h ), 6 . 72 ( d , j = 7 . 91 hz , 1 h ), 7 . 09 ( dd , j = 8 . 79 , 4 . 40 hz , 2 h ), 7 . 31 ( d , j = 5 . 86 hz , 1 h ), 7 . 47 ( dd , j = 8 . 79 , 5 . 27 hz , 2 h ), 7 . 61 - 7 . 72 ( m , 2 h ), 7 . 74 - 7 . 84 ( m , 1 h ), 7 . 98 ( s , 1 h ), 8 . 53 ( d , j = 4 . 10 hz , 1 h ). 3 , 4 - difluorobenzyl 1 - benzyl - 6 -( ethoxycarbonyl )-- 2 - isopropyl - 1h - indole - 3 - carboxylate ( compound 51 ). following general procedure e , 1 - benzyl - 6 -( ethoxylcarbonyl )- 2 - isopropyl - 1h - indole - 3 - carboxylic acid ( compound 39 , 39 mg , 0 . 1 1 mmol ) in ch 2 cl 2 ( 4 ml ) was added edc ( 35 mg , 0 . 22 mmol ) and dmap ( 16 mg , 0 . 15 mmol ), followed by 3 , 4 - difluorobenzyl alcohol ( 20 mg , 0 . 15 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 21 - 1 . 44 ( m , 9 h ), 3 . 74 - 4 . 03 ( m , 1 h ), 4 . 32 ( q , j = 7 . 04 hz , 2 h ), 5 . 39 ( s , 2 h ), 5 . 66 ( s , 2 h ), 6 . 96 ( d , j = 6 . 74 hz , 2 h ), 7 . 21 - 7 . 37 ( m , 5 h ), 7 . 38 - 7 . 56 ( m , 1 h ), 7 . 83 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 8 . 01 ( s , 1 h ), 8 . 12 ( d , j = 8 . 50 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( hydroxymethyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 52 ). to a solution of ethyl1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 43 , 200 mg , 0 . 408 mmol ) in ch 2 cl 2 ( 10 ml ) at − 78 ° c . under argon was added dibal - h ( 1 . 0 m in ch 2 cl 2 , 1 . 6 ml , 1 . 63 mmol ) slowly . the reaction was stirred for 3 h , quenched with methanol , celite , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 , concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( s , 3 h ), 1 . 33 ( s , 3 h ), 3 . 41 ( m , 1 h ), 4 . 58 ( s , 2 h ), 4 . 62 ( s , 2 h ), 5 . 53 ( s , 2 h ), 5 . 66 ( s , 2 h ), 6 . 96 ( dd , j = 6 . 16 , 1 . 76 hz , 2 h ), 7 . 14 ( d , j = 8 . 50 hz , 1 h ), 7 . 30 ( m , 6 h ), 7 . 39 ( m , 1 h ), 7 . 60 ( d , j = 7 . 91 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - formyl - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 53 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( hydroxymethyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 52 , 340 mg , 0 . 759 mmol ) in ch 2 cl 2 ( 10 ml ) at 25 ° c . under argon was added molecular sieve powder ( 300 mg ), nmo ( 267 mg , 2 . 28 mmol ), tpap ( 26 mg , 0 . 08 mmol ). the reaction was stirred for 10 minutes , then concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 33 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 64 ( s , 2 h ), 6 . 86 - 7 . 06 ( m , 2 h ), 7 . 19 - 7 . 44 ( m , 6 h ), 7 . 61 - 7 . 78 ( m , 2 h ), 7 . 91 ( d , j = 0 . 73 hz , 1 h ), 9 . 91 ( s , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 5 - dihydro - 1h - imidazol - 2 - yl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 54 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - formyl - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 53 , 18 mg , 0 . 040 mmol ) in ch 2 cl 2 ( 1 ml ) at 0 ° c . under argon was added ethylene diamine ( 2 . 5 mg , 0 . 042 mmol ). the mixture was stirred at 0 ° c . for 30 minutes , and then added nbs ( 8 mg , 0 . 042 mmol ). the reaction was stirred at 25 ° c . for 12 h , quenched with nahco 3 ( aqueous ), diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 , concentrated in vacuo . the residue was purified by chromatography on silica gel ( 100 % etoac ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( s , 3 h ), 1 . 33 ( s , 3 h ), 3 . 38 - 3 . 52 ( m , 1 h ), 3 . 73 ( s , 4 h ), 4 . 58 ( s , 2 h ), 5 . 57 ( s , 2 h ), 6 . 94 ( dd , j = 7 . 77 , 1 . 47 hz , 2 h ), 7 . 15 - 7 . 41 ( m , 6 h ), 7 . 56 - 7 . 60 ( m , 1 h ), 7 . 64 - 7 . 67 ( m , 1 h ), 7 . 82 ( d , j = 0 . 73 hz , 1 h ). ( e )- 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -(( hydroxyimino ) methyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 55 ). to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - formyl - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 53 , 12 mg , 0 . 027 mmol ) in meoh ( 6 ml ) was hydroxylamine hydrochloride ( 6 . 0 mg , 0 . 081 mmol ) and pyridine ( 3 mg , 0 . 16 mmol ). the mixture was stirred at 65 ° c . for 12 h , and then added concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 40 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( s , 3 h ), 1 . 33 ( s , 3 h ), 3 . 36 - 3 . 52 ( m , 1 h ), 4 . 58 ( s , 2 h ), 5 . 54 ( s , 2 h ), 6 . 95 ( dd , j = 7 . 99 , 1 . 54 hz , 2 h ), 7 . 17 - 7 . 38 ( m , 5 h ), 7 . 42 ( dd , j = 8 . 36 , 1 . 32 hz , 1 h ), 7 . 49 ( s , 1 h ), 7 . 61 ( d , j = 8 . 36 hz , 1 h ), 8 . 10 ( s , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 ). general procedure f . to a solution of ethyl1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 43 , 609 mg , 1 . 24 mmol ) in etoh ( 15 ml ) was added naoh ( 248 mg , 6 . 21 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 50 ° c . for 12 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 38 - 3 . 59 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 59 ( s , 2 h ), 6 . 96 ( d , j = 9 . 38 hz , 2 h ), 7 . 18 - 7 . 44 ( m , 6 h ), 7 . 63 ( d , j = 8 . 36 hz , 1 h ), 7 . 80 ( dd , j = 8 . 36 , 1 . 32 hz , 1 h ), 8 . 00 ( d , j = 0 . 88 hz , 1 h ). 1 - benzyl - 3 -( 5 - fluoropyridin - 3 - yl ) methylcarbamoyl )- 2 - isopropyl - 1 - indole - 6 - carboxylic acid ( compound 57 ). following general procedure f , ethyl1 - benzyl - 3 -(( 5 - fluoropyridin - 3 - yl ) methylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylate ( compound 44 , 94 mg , 0 . 90 mmol ) in etoh ( 12 ml ) was added naoh ( 42 mg , 4 . 5 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 50 ° c . for 12 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 62 ( s , 2 h ), 6 . 95 ( dd , j = 7 . 48 , 1 . 03 hz , 2 h ), 7 . 19 - 7 . 34 ( m , 3 h ), 7 . 65 - 7 . 76 ( m , 2 h ), 7 . 82 ( dd , j = 8 . 36 , 1 . 47 hz , 1 h ), 8 . 00 ( d , j = 1 . 47 hz , 1 h ), 8 . 39 ( d , j = 2 . 64 hz , 1 h ), 8 . 52 ( s , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylic acid ( compound 58 ). following general procedure f , ethyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1 h - indole - 6 - carboxylate ( compound 45 , 117 mg , 0 . 238 mmol ) in etoh ( 10 ml ) was added naoh ( 47 mg , 1 . 20 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 50 ° c . for 12 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 67 ( s , 2 h ), 6 . 74 ( d , j = 6 . 89 hz , 1 h ), 7 . 18 - 7 . 43 ( m , 4 h ), 7 . 61 - 7 . 76 ( m , 2 h ), 7 . 82 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 8 . 00 ( d , j = 0 . 73 hz , 1 h ), 8 . 54 ( dt , j = 5 . 42 , 0 . 95 hz , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 6 - carboxylic acid ( compound 59 ). following general procedure f , ethyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 46 , 439 mg , 0 . 896 mmol ) ) in etoh ( 12 ml ) was added naoh ( 179 mg , 4 . 48 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 25 ° c . for 12 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 70 ( s , 2 h ), 7 . 15 - 7 . 41 ( m , 5 h ), 7 . 68 ( dd , j = 8 . 36 , 0 . 59 hz , 1 h ), 7 . 82 ( dd , j = 8 . 50 , 1 . 47 hz , 1 h ), 8 . 01 ( d , j = 0 . 73 hz , 1 h ), 8 . 22 ( d , j = 1 . 91 hz , 1 h ), 8 . 43 ( dd , j = 3 . 81 , 2 . 64 hz , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 6 - carboxylic acid ( compound 60 ). following general procedure f , ethyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 47 , 197 mg , 0 . 414 mmol ) in etoh ( 12 ml ) was added naoh ( 82 mg , 2 . 07 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 25 ° c . for 12 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 59 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 70 ( s , 2 h ), 7 . 12 ( d , j = 0 . 88 hz , 1 h ), 7 . 18 - 7 . 42 ( m , 3 h ), 7 . 63 ( s , 1 h ), 7 . 81 ( dd , j = 8 . 43 , 1 . 39 hz , 2 h ), 7 . 85 ( d , j = 0 . 88 hz , 1 h ), 8 . 18 ( s , 1 h ). 3 -( 3 , 5 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylic acid ( compound 61 ). following general procedure f , ethyl3 -( 3 , 5 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 48 , 92 mg , 0 . 187 mmol ) in etoh ( 10 ml ) was added naoh ( 40 mg , 0 . 94 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 55 ° c . for 4 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 51 ( m , 1 h ), 4 . 62 ( s , 2 h ), 5 . 68 ( s , 2 h ), 6 . 74 ( d , j = 7 . 91 hz , 1 h ), 6 . 85 ( tt , j = 9 . 08 , 2 . 34 hz , 1 h ), 7 . 04 ( dd , j = 8 . 50 , 2 . 34 hz , 2 h ), 7 . 30 ( dd , j = 6 . 74 , 4 . 98 hz , 1 h ), 7 . 59 - 7 . 75 ( m , 2 h ), 7 . 74 - 7 . 88 ( m , 1 h ), 8 . 00 ( s , 1 h ), 8 . 53 ( d , j = 4 . 10 hz , 1 h ). 3 -( 4 - fluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylic acid ( compound 62 ). following general procedure f , ethyl3 -( 4 - fluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 6 - carboxylate ( compound 50 , 90 mg , 0 . 18 mmol ) in etoh ( 6 ml ) was added naoh ( 39 mg , 0 . 90 mmol ) and h 2 o ( 1 ml ). the reaction was stirred at 55 ° c . for 12 h , concentrated in vacuo to an oil then acidified to ph = 5 with 10 % hcl , diluted with etoac , washed organic with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 48 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 66 ( s , 2 h ), 6 . 72 ( d , j = 7 . 91 hz , 1 h ), 7 . 09 ( dd , j = 8 . 79 , 4 . 40 hz , 2 h ), 7 . 31 ( d , j = 5 . 86 hz , 1 h ), 7 . 47 ( dd , j = 8 . 79 , 5 . 27 hz , 2 h ), 7 . 61 - 7 . 72 ( m , 2 h ), 7 . 74 - 7 . 84 ( m , 1 h ), 7 . 98 ( s , 1 h ), 8 . 53 ( d , j = 4 . 10 hz , 1 h ). 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 2 - hydroxyethyl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 63 ). general procedure g . to a solution of 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 30 mg , 0 . 065 mmol ) in dmf ( 3 ml ) was added bop ( 35 mg , 0 . 090 mmol ) and dipea ( 17 mg , 0 . 098 mmol ), followed by ethanolamine ( 6 mg , 0 . 098 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 37 - 3 . 46 ( m , 1 h ), 3 . 49 ( t , j = 5 . 86 hz , 2 h ), 3 . 65 - 3 . 74 ( m , 2 h ), 4 . 59 ( s , 2 h ), 5 . 60 ( s , 2 h ), 6 . 94 ( dd , j = 7 . 92 , 1 . 61 hz , 2 h ), 7 . 17 - 7 . 42 ( m , 6 h ), 7 . 65 ( dd , j = 2 . 35 , 1 . 03 hz , 2 h ), 7 . 91 ( s , 1 h ). 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxy - 2 - methylpropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 64 ). following general procedure g , 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 35 mg , 0 . 076 mmol ) in dmf ( 3 ml ) was added bop ( 40 mg , 0 . 091 mmol ) and dipea ( 20 mg , 0 . 10 mmol ), followed by 2 - amino - 2 - methylpropan - 1 - ol ( 15 mg , 0 . 15 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( s , 3 h ), 1 . 34 ( s , 3 h ), 1 . 39 ( s , 6 h ), 3 . 43 ( dt , j = 14 . 18 , 7 . 05 hz , 1 h ), 3 . 66 ( s , 2 h ), 4 . 58 ( s , 2 h ), 5 . 59 ( s , 2 h ), 6 . 96 ( d , j = 1 . 61 hz , 2 h ), 7 . 16 - 7 . 49 ( m , 5 h ), 7 . 52 - 7 . 60 ( m , 1 h ), 7 . 60 - 7 . 68 ( m , 1 h ), 7 . 84 ( s , 1 h ), 7 . 97 ( s , 1 h ). ( s )- 1 - benzyl - n3 -(( 5 - fluoropyridin - 3 - yl ) methyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 65 ). following general procedure g , 1 - benzyl - 3 -( 5 - fluoropyridin - 3 - yl ) methylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 57 , 104 mg , 0 . 237 mmol ) in dmf ( 6 ml ) was added bop ( 124 mg , 0 . 284 mmol ) and dipea ( 61 mg , 0 . 355 mmol ), followed by l - alanol ( 26 mg , 0 . 355 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 23 ( s , 3 h ), 1 . 30 ( s , 3 h ), 1 . 32 ( s , 3 h ), 3 . 37 - 3 . 48 ( m , 1 h ), 3 . 54 - 3 . 61 ( m , 2 h ), 4 . 12 - 4 . 23 ( m , 1 h ), 4 . 69 ( s , 2 h ), 5 . 60 ( s , 2 h ), 6 . 95 ( dd , j = 7 . 62 , 1 . 03 hz , 2 h ), 7 . 19 - 7 . 31 ( m , 3 h ), 7 . 63 - 7 . 76 ( m , 4 h ), 7 . 93 ( s , 1 h ), 8 . 39 ( d , j = 2 . 35 hz , 1 h ). ( r )- 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 66 ). following general procedure g , 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 37 mg , 0 . 08 mmol ) in dmf ( 3 ml ) was added bop ( 42 mg , 0 . 10 mmol ) and dipea ( 16 mg , 0 . 10 mmol ), followed by d - alanol ( 16 mg , 0 . 10 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 22 ( d , j = 6 . 89 hz , 3 h ), 1 . 31 ( s , 3 h ), 1 . 33 ( s , 3 h ), 3 . 38 - 3 . 48 ( m , 1 h ), 3 . 58 ( d , j = 5 . 57 hz , 2 h ), 4 . 17 ( q , j = 6 . 89 hz , 1 h ), 4 . 59 ( s , 2 h ), 5 . 59 ( s , 2 h ), 6 . 94 ( dd , j = 7 . 92 , 1 . 61 hz , 2 h ), 7 . 18 - 7 . 41 ( m , 6 h ), 7 . 65 ( s , 2 h ), 7 . 91 ( s , 1 h ). ( s )- 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxybutan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 67 ). following general procedure g , 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 42 mg , 0 . 089 mmol ) in dmf ( 4 ml ) was added bop ( 48 mg , 0 . 11 mmol ) and dipea ( 23 mg , 0 . 10 mmol ), followed by ( s )- 2 - aminobutan - 1 - ol ( 16 mg , 0 . 10 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as a light yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 0 . 97 ( t , j = 7 . 16 hz 3 h ), 1 . 24 ( t , j = 7 . 11 hz , 4 h ), 1 . 32 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 38 - 3 . 52 ( m , 1 h ), 3 . 61 - 3 . 78 ( m , 2 h ), 3 . 83 - 3 . 95 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 61 ( s , 2 h ), 6 . 96 ( d , j = 8 . 21 hz , 2 h ), 7 . 18 - 7 . 43 ( m , 6 h ), 7 . 66 ( s , 2 h ), 7 . 92 ( d , j = 1 . 03 hz , 1 h ). 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 2 - hydroxy - 2 - methylpropyl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 68 ). following general procedure g , 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 35 mg , 0 . 080 mmol ) in dmf ( 4 ml ) was added bop ( 40 mg , 0 . 10 mmol ) and dipea ( 20 mg , 0 . 11 mmol ), followed by 1 - amino - 2 - methylpropan - 2 - ol ( 10 mg , 0 . 10 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 21 ( s , 6 h ), 1 . 31 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 39 ( s , 2 h ), 3 . 40 - 3 . 51 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 59 ( s , 2 h ), 6 . 96 ( d , j = 1 . 76 hz , 2 h ), 7 . 16 - 7 . 40 ( m , 6 h ), 7 . 66 ( dd , j = 3 . 30 , 1 . 10 hz , 2 h ), 7 . 91 ( s , 1 h ). 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - n6 -( prop - 2 - ynyl )- 1h - indole - 3 , 6 - dicarboxamide ( compound 69 ). following general procedure g , 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 35 mg , 0 . 080 mmol ) in in ch 2 cl 2 ( 3 ml ) was added edc ( 25 mg , 0 . 15 mmol ) and dmap ( 15 mg , 0 . 09 mmol ), followed by propargyl amine ( 7 mg , 0 . 09 mmol ). the crude material was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as an oil . 1h nmr ( 500 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 33 ( s , 3 h ), 2 . 55 ( t , j = 2 . 57 hz , 1 h ), 3 . 44 ( dt , j = 14 . 27 , 7 . 11 hz , 1 h ), 4 . 13 ( s , 2 h ), 4 . 58 ( s , 2 h ), 5 . 58 ( s , 2 h ), 6 . 94 ( d , j = 6 . 97 hz , 2 h ), 7 . 18 - 7 . 30 ( m , 5 h ), 7 . 31 - 7 . 41 ( m , 1 h ), 7 . 59 - 7 . 70 ( m , 2 h ), 7 . 89 ( d , j = 0 . 73 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 5 - dihydrooxazol - 2 - yl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 70 ). general procedure h . to a solution of 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 2 - hydroxyethyl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 63 , 17 mg , 0 . 033 mmol ) in ch 2 cl 2 ( 2 ml ) at 0 ° c under argon was added et 3 n ( 0 . 03 ml , 0 . 2 mmol ), and then added mscl ( 7 mg , 0 . 066 mmol ). the reaction was stirred at 25 ° c . for 3 h , quenched with h 2 o diluted with etoac , washed with brine , dried over na 2 so 4 , concentrated in vacuo . the residue was purified by chromatography on silica gel ( 100 % etoac ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 3 . 41 - 3 . 56 ( m , 1 h ), 3 . 98 ( t , j = 9 . 38 hz , 2 h ), 4 . 45 ( t , j = 9 . 53 hz , 2 h ), 4 . 59 ( d , j = 4 . 10 hz , 2 h ), 5 . 57 ( s , 2 h ), 6 . 94 ( d , j = 6 . 16 hz , 2 h ), 7 . 13 - 7 . 43 ( m , 6 h ), 7 . 55 - 7 . 79 ( m , 2 h ), 7 . 87 ( s , 1 h ), 8 . 71 ( t , j = 5 . 13 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 4 - dimethyl - 4 , 5 - dihydrooxazol - 2 - yl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 71 ). the title compound was prepared from 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxy - 2 - methylpropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 64 ) by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 18 - 1 . 47 ( m , 12 h ), 3 . 37 - 3 . 53 ( m , 1 h ), 4 . 20 - 4 . 46 ( m , 2 h ), 4 . 59 ( d , j = 5 . 57 hz , 2 h ), 5 . 59 ( s , 2 h ), 6 . 94 ( d , j = 3 . 96 hz , 2 h ), 7 . 06 - 7 . 43 ( m , 6 h ), 7 . 55 - 7 . 84 ( m , 2 h ), 7 . 89 - 7 . 96 ( m , 1 h ), 8 . 78 ( d , j = 1 . 17 hz , 1 h ). ( s )- 1 - benzyl - n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1h - indole - 3 - carboxamide ( compound 72 ). the title compound was prepared from ( s )- 1 - benzyl - n3 -(( 5 - fluoropyridin - 3 - yl ) methyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 65 ) by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 26 - 1 . 36 ( m , 9 h ), 3 . 39 - 3 . 53 ( m , 1 h ), 4 . 04 ( t , j = 7 . 99 hz , 1 h ), 4 . 27 - 4 . 46 ( m , 1 h ), 4 . 61 ( d , j = 8 . 36 hz , 1 h ), 4 . 69 ( d , j = 5 . 72 hz , 2 h ), 5 . 59 ( s , 2 h ), 6 . 89 - 7 . 03 ( m , 2 h ), 7 . 12 - 7 . 35 ( m , 3 h ), 7 . 56 - 7 . 78 ( m , 3 h ), 7 . 91 ( s , 1 h ), 8 . 39 ( d , j = 2 . 64 hz , 1 h ), 8 . 51 ( s , 1 h ), 8 . 82 ( t , j = 7 . 84 hz , 1 h ). ( s )- 1 - benzyl - 6 -( 4 - ethyl - 4 , 5 - dihydrooxazol - 2 - yl )- n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 73 ). the title compound was prepared from ( s )- 1 - benzyl - n3 -(( 5 - fluoropyridin - 3 - yl ) methyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 65 ) by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 0 . 96 ( t , j = 7 . 40 hz , 3 h ), 1 . 31 ( s , 3 h ), 1 . 33 ( s , 3 h ), 1 . 51 - 1 . 81 ( m , 2 h ), 3 . 39 - 3 . 57 ( m , 1 h ), 4 . 11 ( dd , j = 7 . 48 , 6 . 45 hz , 2 h ), 4 . 50 ( dd , j = 8 . 94 , 7 . 92 hz , 1 h ), 4 . 68 ( s , 2 h ), 5 . 58 ( s , 2 h ), 6 . 94 ( dd , j = 7 . 77 , 1 . 47 hz , 2 h ), 7 . 14 - 7 . 35 ( m , 4 h ), 7 . 62 - 7 . 81 ( m , 3 h ), 7 . 90 ( s , 1 h ), 8 . 39 ( d , j = 2 . 64 hz , 1 h ), 8 . 51 ( s , 1 h ). ( r )- 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1h - indole - 3 - carboxamide ( compound 74 ). the title compound was prepared from ( r )- 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 66 ) by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 26 ( s , 3 h ), 1 . 37 ( s , 3 h ), 3 . 36 - 3 . 51 ( m , 1 h ), 4 . 09 ( t , j = 7 . 11 hz , 1 h ), 4 . 26 - 4 . 42 ( m , 1 h ), 4 . 59 ( s , 2 h ), 4 . 71 ( m , 1h ), 5 . 60 ( s , 2 h ), 6 . 89 - 7 . 02 ( m , 2 h ), 7 . 16 - 7 . 44 ( m , 6 h ), 7 . 59 - 7 . 75 ( m , 2 h ), 7 . 90 ( s , 1 h ). ( s )- 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 4 - ethyl - 4 , 5 - dihydrooxazol - 2 - yl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 75 ). the title compound was prepared from ( s )- 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxybutan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide ( compound 67 ) by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 0 . 96 ( t , j = 7 . 40 hz , 3 h ), 1 . 32 ( s , 3 h ), 1 . 34 ( s , 3 h ), 1 . 52 - 1 . 81 ( m , 2 h ), 3 . 38 - 3 . 52 ( m , 1h ), 4 . 12 ( d , j = 7 . 62 hz , 1h ), 4 . 15 - 4 . 29 ( m , 1 h ), 4 . 51 ( dd , j = 8 . 94 , 7 . 92 hz , 1h ), 4 . 57 - 4 . 62 ( m , 2 h ), 5 . 58 ( s , 2 h ), 6 . 95 ( d , j = 1 . 76 hz , 2 h ), 7 . 08 - 7 . 45 ( m , 6 h ), 7 . 51 - 7 . 82 ( m , 2 h ), 7 . 89 ( d , j = 0 . 59 hz , 1h ), 8 . 72 ( t , j = 7 . 84 hz , 1h ). ( s )- 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1h - indole - 3 - carboxamide ( compound 76 ). the title compound was prepared from ( s )- 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 21 - 1 . 41 ( m , 9 h ), 3 . 39 - 3 . 56 ( m , 1h ), 4 . 12 ( t , j = 8 . 21 hz , 1h ), 4 . 59 ( s , 2 h ), 4 . 65 ( d , j = 8 . 50 hz , 1h ), 5 . 60 ( s , 2 h ), 6 . 88 - 6 . 99 ( m , 2 h ), 7 . 15 - 7 . 41 ( m , 6 h ), 7 . 63 - 7 . 78 ( m , 2 h ), 7 . 93 ( s , 1h ). ( s )- 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 -( methoxymethyl )- 4 , 5 - dihydrooxazol - 2 - yl )- 1h - indole - 3 - carboxamide ( compound 77 ). the title compound was prepared from ( r )- 1 - benzyl - n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxy - 3 - methoxypropan - 2 - yl )- 2 - isopropyl - 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( s , 3 h ), 1 . 36 ( s , 3 h ), 3 . 37 ( s , 3 h ), 3 . 44 - 3 . 61 ( m , 2 h ), 4 . 31 - 4 . 57 ( m , 2 h ), 4 . 60 ( d , j = 5 . 57 hz , 2 h ), 5 . 60 ( s , 2 h ), 6 . 97 ( d , j = 1 . 76 hz , 2 h ), 7 . 17 - 7 . 45 ( m , 6 h ), 7 . 63 - 7 . 80 ( m , 2 h ), 7 . 93 ( s , 1h ), 8 . 74 ( s , 1h ). ( r )— n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 78 ). the title compound was prepared from ( r )— n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( m , 9 h ), 3 . 43 - 3 . 55 ( m , 1h ), 4 . 00 ( t , j = 8 . 06 hz , 1h ), 4 . 28 - 4 . 38 ( m , 1h ), 4 . 52 - 4 . 64 ( m , 3 h ), 5 . 65 ( s , 1h ), 6 . 71 ( d , j = 7 . 62 hz , 1 h ), 7 . 20 - 7 . 40 ( m , 4 h ), 7 . 63 - 7 . 75 ( m , 3 h ), 7 . 88 ( s , 1h ), 8 . 53 ( d , j = 4 . 10 hz , 1h ), 8 . 72 ( t , 1 h ). ( s )— n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 79 ). the title compound was prepared from ( s )— n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 24 - 1 . 39 ( m , 9 h ), 3 . 42 - 3 . 60 ( m , 1h ), 4 . 00 ( t , j = 8 . 06 hz , 1 h ), 4 . 25 ( m , 1 h ), 4 . 38 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 70 ( d , j = 7 . 62 hz , 1 h ), 7 . 18 - 7 . 40 ( m , 4 h ), 7 . 60 - 7 . 77 ( m , 3 h ), 7 . 88 ( d , j = 0 . 73 hz , 1 h ), 8 . 54 ( d , j = 5 . 57 hz , 1 h ). ( s )— n -( 3 , 4 - difluorobenzyl )- 6 -( 4 - ethyl - 4 , 5 - dihydrooxazol - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 80 ). the title compound was prepared from ( s )— n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxybutan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 0 . 96 ( t , j = 7 . 61 hz , 3 h ), 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 1 . 49 - 1 . 85 ( m , 2 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 02 - 4 . 11 ( m , 1 h ), 4 . 49 ( t , j = 8 . 79 hz , 1 h ), 4 . 56 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 70 ( d , j = 7 . 62 hz , 1 h ), 7 . 18 - 7 . 40 ( m , 4 h ), 7 . 60 - 7 . 77 ( m , 3 h ), 7 . 88 ( d , j = 0 . 73 hz , 1 h ), 8 . 54 ( d , j = 5 . 57 hz , 1 h ). following general procedure h , ( s )- 6 -( 4 -( benzyloxymethyl )- 4 , 5 - dihydrooxazol - 2 - yl )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide was prepared ( 10 mg , 0 . 015 mmol ), was then reacted with bbr 3 ( 1m in ch 2 cl 2 , 0 . 05 ml , 0 . 05 mmol ) in ch 2 cl 2 ( 2 ml ) at − 78 ° c . for 1 h , quenched with water , diluted with etoac , washed organic with brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 5 : 95 meoh — ch 2 cl 2 ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 41 - 3 . 57 ( m , 1 h ), 3 . 59 - 3 . 76 ( m , 2 h ), 4 . 27 - 4 . 43 ( m , 1 h ), 4 . 50 ( t , j = 8 . 28 hz , 1 h ), 4 . 59 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 70 ( d , j = 7 . 92 hz , 1 h ), 7 . 18 - 7 . 42 ( m , 4 h ), 7 . 61 - 7 . 79 ( m , 3 h ), 7 . 91 ( s , 1 h ), 8 . 53 ( d , j = 4 . 98 hz , 1 h ). ( s )— n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 82 ). the title compound was prepared from ( s )— n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 22 - 1 . 42 ( m , 9 h ), 3 . 41 - 3 . 62 ( m , 1 h ), 3 . 99 ( t , j = 8 . 06 hz , 1 h ), 4 . 31 ( dd , j = 9 . 52 , 6 . 89 hz , 1 h ), 4 . 54 ( d , j = 8 . 20 hz , 1 h ), 4 . 59 ( s , 2 h ), 5 . 67 ( s , 2 h ), 7 . 08 - 7 . 31 ( m , 2 h ), 7 . 29 - 7 . 49 ( m , 3 h ), 7 . 56 - 7 . 80 ( m , 2 h ), 7 . 89 ( s , 1h ), 8 . 21 ( s , 1 h ), 8 . 43 ( d , j = 3 . 52 hz , 1 h ). ( s )— n -( 3 , 4 - difluorobenzyl )- 6 -( 4 - ethyl - 4 , 5 - dihydrooxazol - 2 - yl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 83 ). the title compound was prepared from ( s )— n3 -( 3 , 4 - difluorobenzyl )- n6 -( 1 - hydroxybutan - 2 - yl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 500 mhz , methanol - d 4 ) δ ppm 1 . 00 ( t , j = 7 . 46 hz , 3 h ), 1 . 38 ( s , 3 h ), 1 . 40 ( s , 3 h ), 1 . 55 - 1 . 87 ( m , 2 h ), 3 . 57 ( dt , j = 14 . 18 , 7 . 09 hz , 1 h ), 4 . 17 ( t , j = 7 . 83 hz , 1h ), 4 . 25 ( ddd , j = 14 . 73 , 7 . 27 , 7 . 09 hz , 1 h ), 4 . 57 ( s , 2 h ), 5 . 67 ( s , 2 h ), 7 . 11 ( s , 1 h ), 7 . 19 - 7 . 28 ( m , 2 h ), 7 . 34 ( d , j = 7 . 82 hz , 1 h ), 7 . 61 ( d , j = 8 . 31 hz , 1 h ), 7 . 73 ( d , j = 8 . 56 hz , 1 h ), 7 . 84 ( s , 1 h ), 8 . 05 ( s , 1 h ), 8 . 71 ( br . s ., 1 h ). ( s )— n -( 3 , 5 - difluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 84 ). the title compound was prepared from ( s )— n3 -( 3 , 5 - difluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 23 - 1 . 42 ( m , 9 h ), 3 . 41 - 3 . 58 ( m , 1 h ), 3 . 98 ( t , 1 h ), 4 . 23 - 4 . 38 ( m , 1 h ), 4 . 47 - 4 . 58 ( m , 1 h ), 4 . 62 ( m , 1 h ), 5 . 65 ( s , 2 h ), 6 . 76 ( d , j = 7 . 91 , hz , 1 h ), 6 . 76 - 6 . 91 ( m , 1 h ), 7 . 00 - 7 . 11 ( m , 1 h ), 7 . 21 - 7 . 36 ( m , 1 h ), 7 . 61 - 7 . 79 ( m , 4 h ), 7 . 88 ( s , 1 h ), 8 . 44 - 8 . 58 ( m , 1 h ). ( s )— n -( 3 , 5 - difluorobenzyl )- 6 -( 4 - ethyl - 4 , 5 - dihydrooxazol - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 85 ). the title compound was prepared from ( s )— n3 -( 3 , 5 - difluorobenzyl )- n6 -( 1 - hydroxybutan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 0 . 96 ( t , j = 7 . 61 hz , 3 h ), 1 . 32 ( s , 3 h ), 1 . 35 ( s , 3 h ), 1 . 49 - 1 . 85 ( m , 2 h ), 3 . 40 - 3 . 59 ( m , 1 h ), 4 . 12 ( t , j = 7 . 61 hz , 2 h ), 4 . 14 - 4 . 30 ( m , 1 h ), 4 . 49 ( t , j = 8 . 79 hz , 1 h ), 4 . 63 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 71 ( d , j = 7 . 91 hz , 1 h ), 6 . 79 - 6 . 90 ( m , 1 h ), 6 . 99 - 7 . 10 ( m , 1 h ), 7 . 25 - 7 . 33 ( m , 1 h ), 7 . 62 - 7 . 78 ( m , 4 h ), 7 . 89 ( s , 1 h ), 8 . 52 ( d , j = 5 . 57 hz , 1 h ). ( s )— n -( 4 - fluorobenzyl )- 2 - isopropyl - 6 -( 4 - methyl - 4 , 5 - dihydrooxazol - 2 - yl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 86 ). the title compound was prepared from ( s )— n3 -( 4 - fluorobenzyl )- n6 -( 1 - hydroxypropan - 2 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide by general procedure h . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( m , 9 h ), 3 . 41 - 3 . 61 ( m , 1 h ), 3 . 95 ( t , j = 7 . 91 hz , 1 h ), 4 . 25 - 4 . 43 ( m , 1 h ), 4 . 54 ( t , j = 8 . 79 hz , 1 h ), 4 . 63 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 63 ( d , j = 7 . 91 hz , 1 h ), 7 . 01 - 7 . 14 ( m , 2 h ), 7 . 23 - 7 . 33 ( m , 1 h ), 7 . 40 - 7 . 54 ( m , 2 h ), 7 . 61 - 7 . 76 ( m , 3 h ), 7 . 90 ( s , 1 h ), 8 . 53 ( d , j = 5 . 57 hz , 1 h ). 6 -( 5 , 5 - dimethyl - 4 , 5 - dihydrooxazol - 2 - yl )- n -( 4 - fluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 87 ). to a solution of n3 -( 4 - fluorobenzyl )- n6 -( 2 - hydroxy - 2 - methylpropyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 , 6 - dicarboxamide ( compound 68 , 23 mg , 0 . 043 mmol ) in benzene ( 6 ml ) at 25 ° c . was added p 2 o 5 ( 120 mg , 0 . 86 mmol ). the mixture was stirred at 50 ° c . for 4 h , quenched with 6n naoh ( 1 ml ), extracted several times with etoac , washed with h 2 o , brine , dried over na 2 so 4 , concentrated in vacuo . the residue was purified by chromatography on silica gel ( 100 % etoac ) to yield the title compound as yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( s , 3 h ), 1 . 34 ( s , 3 h ), 1 . 46 ( s , 6 h ), 3 . 35 - 3 . 54 ( m , 1 h ), 3 . 71 ( s , 2 h ), 4 . 58 ( s , 2 h ), 5 . 57 ( s , 2 h ), 6 . 94 ( d , j = 6 . 16 hz , 2 h ), 7 . 24 ( dd , j = 3 . 59 , 1 . 39 hz , 6 h ), 7 . 67 ( dd , j = 2 . 05 , 1 . 03 hz , 2 h ), 7 . 85 ( s , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( hydrazinecarbonyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 88 ). following general procedure e , 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indole - 6 - carboxylic acid ( compound 56 , 82 mg , 0 . 176 mmol ) in ch 2 cl 2 ( 8 ml ) was added edc ( 51 mg , 0 . 264 mmol ) and dmap ( 26 mg , 0 . 256 mmol ), followed by hydrazine ( 7 mg , 0 . 264 mmol ). the reaction was stirred at room temperature for 12 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 29 - 1 . 41 ( m , 6 h ), 3 . 38 - 3 . 54 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 59 ( s , 2 h ), 6 . 88 - 7 . 02 ( m , 2 h ), 7 . 14 - 7 . 43 ( m , 6 h ), 7 . 52 - 7 . 73 ( m , 2 h ), 7 . 73 - 7 . 88 ( m , 1 h ), 8 . 00 ( br . s ., 1 h ), 8 . 71 ( d , j = 2 . 93 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 1 , 3 , 4 - oxadiazol - 2 - yl )- 1h - indole - 3 - carboxamide ( compound 89 ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( hydrazinecarbonyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 88 , 21 mg , 0 . 044 mmol ) in triethyl orthoformate ( 5 ml ) was heated to 145 ° c . for 5 h , then concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 55 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( s , 3 h ), 1 . 36 ( s , 3 h ), 3 . 39 - 3 . 59 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 63 ( s , 2 h ), 6 . 98 ( d , j = 8 . 06 hz , 2 h ), 7 . 15 - 7 . 47 ( m , 6 h ), 7 . 70 - 7 . 90 ( m , 2 h ), 8 . 02 ( d , j = 0 . 59 hz , 1 h ), 8 . 90 ( s , 1 h ). methyl 3 - formyl - 6 - methoxy - 1h - indole - 2 - carboxylate ( compound 90 ). general procedure i . pocl 3 ( 2 . 94 ml , 32 . 2 mmol ) was added dropwise to anhydrous dmf ( 10 ml ) at 0 ° c . under argon . after stirred for 30 min , this solution was added dropwise to a solution of methyl6 - methoxy - 1h - indole - 2 - carboxylate ( aldrich , 2 . 2 g , 10 . 7 mmol ) in anhydrous dmf ( 20 ml ) at 0 ° c . under argon . the reaction was stirred for 20 h at room temperature , quenched with ice , diluted with etoac , a precipitate formed and was filtered and washed with h 2 o (× 3 ) to give the title compound as an off - white solid . 1h nmr ( 300 mhz , dmso - d 6 ) δ ppm 3 . 81 ( s , 3 h ), 3 . 97 ( s , 3 h ), 6 . 79 - 7 . 09 ( m , 2 h ), 8 . 09 ( d , j = 9 . 1 hz , 1 h ), 10 . 57 ( s , 1 h ), 12 . 66 ( s , 1 h ). methyl 3 - formyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 91 ). general procedure j . 2 - bromomethylpyridine . hbr salt ( 7 . 0 g , 27 . 7 mmol ) was treated with naoh ( 4m , 6 . 9 ml , 27 . 6 mmol ) in et 2 o ( 20 ml ). the ether layer was separated , washed with brine , and dried over mgso 4 , filtered into a flask containing a suspension of methyl3 - formyl - 6 - methoxy - 1h - indole - 2 - carboxylate ( compound 90 , 1 . 29 g , 5 . 54 mmol ) and k 2 co 3 ( 2 . 3 g , 16 . 6 mmol ) in dmf ( 25 ml ). the reaction was stirred at 60 ° c . for 3 h , cooled to room temperature , quenched with h 2 o and extracted with etoac (× 2 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by washing with h 2 o (× 3 ) and filtration to yield the title compound as a golden brown solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 3 . 80 ( s , 3 h ), 3 . 99 ( s , 3 h ), 5 . 89 ( s , 2 h ), 6 . 82 ( d , j = 2 . 3 hz , 1 h ), 6 . 86 ( d , j = 7 . 9 hz , 1 h ), 7 . 00 ( dd , j = 8 . 8 , 2 . 3 hz , 1 h ), 7 . 19 ( ddd , j = 7 . 5 , 4 . 8 , 1 . 2 hz , 1 h ), 7 . 57 ( td , j = 7 . 7 , 1 . 9 hz , 1 h ), 8 . 40 ( d , j = 9 . 1 hz , 1 h ), 8 . 59 ( ddd , j = 4 . 7 , 1 . 8 , 0 . 9 hz , 1 h ), 10 . 65 ( s , 1 h ). 6 - methoxy - 2 -( methoxycarbonyl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 92 ). general procedure k . to a suspension of methyl3 - formyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 91 , 1 . 64 g , 5 . 07 mmol ) in t - buoh ( 120 ml ) and dioxane ( 20 ml ) was added 2 - methyl - 2 - butene ( 25 ml ) and a solution of nah 2 po 4 ( 7 . 3 g , 61 mmol ) and naclo 2 ( 80 %, 5 . 7 g , 50 . 7 mmol ) in h 2 o ( 100 ml ). the reaction was stirred at room temperature for 6 h , extracted with etoac (× 2 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as an off - white solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 3 . 82 ( s , 3 h ), 3 . 92 ( s , 3 h ), 5 . 76 ( s , 2 h ), 6 . 66 - 6 . 79 ( m , 2 h ), 7 . 02 ( dd , j = 9 . 1 , 2 . 1 hz , 1 h ), 7 . 22 ( dd , j = 7 . 3 , 5 . 3 hz , 1 h ), 7 . 59 ( td , j = 7 . 8 , 1 . 8 hz , 1 h ), 8 . 52 ( d , j = 8 . 8 hz , 1 h ), 8 . 62 ( d , j = 5 . 0 hz , 1 h ). methyl 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 93 ). to a solution of 6 - methoxy - 2 -( methoxycarbonyl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 92 , 1 . 59 g , 4 . 7 mmol ) in anhydrous ch 2 cl 2 ( 50 ml ) was added dmf ( 3 drops , catalytic amount ) and ( cocl ) 2 ( 2m in ch 2 cl 2 , 5 . 9 ml , 11 . 8 mmol ). the resulting mixture was stirred at room temperature for 1 h , and was concentrated in vacuo . to a solution of the crude product in ch 2 cl 2 ( 50 ml ) was added 3 , 4 - difluorobenzylamine ( 0 . 84 ml , 7 . 05 mmol ), followed by et 3 n ( 2 . 0 ml , 14 . 1 mmol ). the reaction was stirred at room temperature for 1 h , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 3 . 78 ( s , 3 h ), 3 . 80 ( s , 3 h ), 4 . 64 ( d , j = 5 . 9 hz , 2 h ), 5 . 73 ( s , 2 h ), 6 . 71 ( d , j = 2 . 1 hz , 1 h ), 6 . 77 ( d , j = 7 . 9 hz , 1 h ), 6 . 93 ( dd , j = 8 . 9 , 2 . 2 hz , 1 h ), 7 . 09 - 7 . 22 ( m , 3 h ), 7 . 22 - 7 . 32 ( m , 1 h ), 7 . 55 ( td , j = 7 . 6 , 1 . 8 hz , 1 h ), 8 . 14 ( d , j = 9 . 1 hz , 2 h ), 8 . 58 ( d , j = 4 . 1 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - formyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 94 ). general procedure o . to a solution of methyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 93 , 515 mg , 1 . 11 mmol ) in ch 2 cl 2 ( 20 ml ) at − 78 ° c . was added dibal ( 1 m in ch 2 cl 2 , 4 . 4 ml , 4 . 44 mmol ) slowly . the reaction was stirred at − 78 ° c . for 2 h , quenched with h 2 o , diluted with etoac , washed with naoh and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a beige solid . 1h nmr ( 500 mhz , methanol - d 4 ) δ ppm 3 . 81 ( s , 3 h ), 4 . 62 ( s , 2 h ), 5 . 98 ( s , 2 h ), 6 . 89 - 6 . 96 ( m , 3 h ), 7 . 22 - 7 . 30 ( m , 3 h ), 7 . 31 - 7 . 37 ( m , 1 h ), 7 . 65 - 7 . 72 ( m , 1 h ), 7 . 80 ( d , j = 9 . 8 hz , 1 h ), 8 . 48 ( d , j = 5 . 1 hz , 1 h ), 10 . 15 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -( hydroxymethyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 95 ). the title compound was also isolated in the synthesis of compound 94 . 1h nmr ( 500 mhz , methanol - d 4 ) δ ppm 3 . 75 ( s , 3 h ), 4 . 60 ( s , 2 h ), 4 . 95 ( s , 2 h ), 5 . 62 ( s , 2 h ), 6 . 80 - 6 . 88 ( m , 2 h ), 7 . 01 ( d , j = 8 . 3 hz , 1 h ), 7 . 20 - 7 . 26 ( m , 2 h ), 7 . 26 - 7 . 37 ( m , 2 h ), 7 . 71 ( td , j = 7 . 8 , 1 . 6 hz , 1 h ), 7 . 75 ( d , j = 8 . 8 hz , 1 h ), 8 . 51 ( d , j = 4 . 6 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -(( dimethylamino ) methyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 96 ). general procedure p . to a solution of n -( 3 , 4 - difluorobenzyl )- 2 - formyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 94 , 70 mg , 0 . 16 mmol ) in clch 2 ch 2 cl ( 10 ml ) at room temperature was added dimethylamine ( 2 m in thf , 0 . 24 ml , 0 . 48 mmol ), hoac ( 14 μl , 0 . 24 mmol ), and nabh ( oac ) 3 ( 102 mg , 0 . 48 mmol ). the reaction was stirred at room temperature for 16 h , diluted with etoac , washed with aqueous na 2 co 3 and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( etoac , then 9 : 1 etoac - et 3 n , then 7 : 2 : 1 ch 2 cl 2 - meoh - et 3 n ) to yield the title compound as an off - white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 2 . 07 ( s , 6 h ), 3 . 70 ( s , 2 h ), 3 . 76 ( s , 3 h ), 4 . 54 ( s , 2 h ), 5 . 61 ( s , 2 h ), 6 . 76 - 6 . 93 ( m , 3 h ), 7 . 15 - 7 . 37 ( m , 4 h ), 7 . 66 ( td , j = 7 . 6 , 1 . 8 hz , 1 h ), 8 . 01 ( d , j = 8 . 8 hz , 1 h ), 8 . 51 ( d , j = 5 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -(( dimethylamino ) methyl )- 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 97 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 2 -(( dimethylamino ) methyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 96 ) by general procedure m . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 2 . 06 ( s , 6 h ), 3 . 56 ( s , 2 h ), 4 . 57 ( d , j = 5 . 3 hz , 2 h ), 5 . 41 ( s , 2 h ), 6 . 50 ( d , j = 7 . 9 hz , 1 h ), 6 . 70 ( d , j = 2 . 1 hz , 1 h ), 6 . 85 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 03 - 7 . 24 ( m , 4 h ), 7 . 42 - 7 . 53 ( m , 1 h ), 8 . 20 ( d , j = 8 . 5 hz , 1 h ), 8 . 53 ( d , j = 5 . 0 hz , 1 h ), 9 . 96 - 10 . 14 ( m , j = 5 . 6 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -(( dimethylamino ) methyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 98 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 2 -(( dimethylamino ) methyl )- 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 97 ) by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 30 ( d , j = 6 . 2 hz , 6 h ), 2 . 09 ( s , 6 h ), 3 . 57 ( s , 2 h ), 4 . 42 - 4 . 63 ( m , 3 h ), 5 . 49 ( s , 2 h ), 6 . 51 ( d , j = 6 . 4 hz , 1 h ), 6 . 75 ( d , j = 2 . 1 hz , 1 h ), 6 . 92 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 04 - 7 . 25 ( m , 4 h ), 7 . 43 - 7 . 57 ( m , 1 h ), 8 . 27 ( d , j = 9 . 4 hz , 1 h ), 8 . 59 ( d , j = 4 . 4 hz , 1 h ), 9 . 96 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -( ethylthiomethyl )- 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 99 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 2 -( hydroxymethyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 95 ) by general procedure m . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 09 ( t , j = 7 . 3 hz , 3 h ), 2 . 41 ( q , j = 7 . 3 hz , 2 h ), 4 . 24 ( s , 2 h ), 4 . 58 ( s , 2 h ), 5 . 54 ( s , 2 h ), 6 . 62 ( d , j = 1 . 8 hz , 1 h ), 6 . 69 - 6 . 83 ( m , 2 h ), 7 . 17 - 7 . 40 ( m , 4 h ), 7 . 61 ( d , j = 8 . 2 hz , 1 h ), 7 . 63 - 7 . 72 ( m , 1 h ), 8 . 52 ( d , j = 5 . 6 hz , 1 h ). 6 -( cyclopentyloxy )- n -( 3 , 4 - difluorobenzyl )- 2 -( ethylthiomethyl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 100 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 2 -( ethylthiomethyl )- 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 99 ) by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 19 ( t , j = 7 . 5 hz , 3 h ), 1 . 47 - 1 . 65 ( m , 4 h ), 1 . 69 - 1 . 87 ( m , 4 h ), 2 . 55 ( q , j = 7 . 3 hz , 2 h ), 4 . 28 ( s , 2 h ), 4 . 61 - 4 . 75 ( m , 3 h ), 5 . 54 ( s , 2 h ), 6 . 61 - 6 . 72 ( m , 2 h ), 6 . 84 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 09 - 7 . 31 ( m , 4 h ), 7 . 48 - 7 . 58 ( m , 1 h ), 7 . 67 ( d , j = 9 . 4 hz , 1 h ), 8 . 60 ( d , j = 5 . 0 hz , 1 h ). isopropyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 101 ). the title compound was prepared from methyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 93 ) by general procedure m and general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 17 ( d , j = 6 . 4 hz , 6 h ), 1 . 25 ( d , j = 6 . 2 hz , 6 h ), 4 . 51 - 4 . 64 ( m , 3 h ), 5 . 05 - 5 . 18 ( m , 1 h ), 5 . 84 ( s , 2 h ), 6 . 80 - 6 . 89 ( m , 3 h ), 7 . 16 - 7 . 29 ( m , 3 h ), 7 . 30 - 7 . 40 ( m , 1 h ), 7 . 56 - 7 . 71 ( m , 2 h ), 8 . 49 ( d , j = 5 . 0 hz , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylic acid ( compound 102 ). a solution of isopropyl 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 101 , 551 mg , 1 . 06 mmol ) in meoh ( 15 ml ) and naoh ( 1 m , 5 . 3 ml , 5 . 3 mmol ) was stirred at room temperature for 4 h . the reaction was quenched cautiously with 6 m hcl at 0 ° c ., extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( etoac , then 8 : 2 etoac - meoh , then 7 : 2 : 1 etoac - meoh - et 3 n ) to yield the title compound as its et 3 n salt . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 22 ( d , j = 5 . 9 hz , 6 h ), 4 . 43 - 4 . 55 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 86 ( s , 2 h ), 6 . 72 ( d , j = 2 . 1 hz , 1 h ), 6 . 79 ( dd , j = 8 . 8 , 2 . 3 hz , 1 h ), 6 . 88 ( d , j = 7 . 9 hz , 1 h ), 7 . 15 - 7 . 36 ( m , 4 h ), 7 . 58 - 7 . 69 ( m , 1 h ), 8 . 23 ( d , j = 8 . 8 hz , 1 h ), 8 . 49 ( d , j = 5 . 0 hz , 1 h ). n 3 -( 3 , 4 - difluorobenzyl )- n 2 -( 2 - hydroxyethyl )- 6 - isopropoxy - l -( pyridin - 2 - ylmethyl )- 1h - indole - 2 , 3 - dicarboxamide ( compound 103 ). to a solution of 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylic acid ( compound 102 , 73 mg , 0 . 12 mmol ) in dmf ( 2 ml ) was added 2 - aminoethanol ( 11 μl , 0 . 17 mmol ), bop ( 64 mg , 0 . 14 mmol ), and i - pr 2 net 30 μl , 0 . 17 mmol ). the reaction was stirred at room temperature for 16 h , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a yellow syrup . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 29 ( d , j = 5 . 9 hz , 6 h ), 3 . 55 - 3 . 69 ( m , 2 h ), 3 . 74 - 3 . 85 ( m , 2 h ), 4 . 45 - 4 . 58 ( m , 1 h ), 4 . 63 ( d , j = 5 . 9 hz , 2 h ), 5 . 63 ( s , 2 h ), 6 . 77 ( d , j = 2 . 1 hz , 1 h ), 6 . 87 ( dd , j = 8 . 9 , 2 . 2 hz , 1 h ), 7 . 06 - 7 . 28 ( m , 4 h ), 7 . 32 ( d , j = 7 . 9 hz , 1 h ), 7 . 63 - 7 . 74 ( m , 1 h ), 7 . 80 - 7 . 96 ( m , 2 h ), 8 . 52 ( d , j = 4 . 1 hz , 1 h ), 9 . 93 - 10 . 08 ( m , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -( 4 , 5 - dihydrooxazol - 2 - yl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 104 ). to a solution of n 3 -( 3 , 4 - difluorobenzyl )- n 2 -( 2 - hydroxyethyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 , 3 - dicarboxamide ( compound 103 , 36 mg , 0 . 069 mmol ) in ch 2 cl 2 ( 3 ml ) at 0 ° c was added et 3 n ( 58 μl , 0 . 41 mmol ) and methanesulfonyl chloride ( 11 μl , 0 . 14 mmol ). the reaction was stirred at room temperature for 0 . 5 h , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a yellow film . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 25 ( d , j = 6 . 2 hz , 6 h ), 3 . 94 ( t , j = 10 . 0 hz , 2 h ), 4 . 31 ( t , j = 9 . 8 hz , 2 h ), 4 . 47 - 4 . 64 ( m , 3 h ), 5 . 85 ( s , 2 h ), 6 . 79 - 6 . 92 ( m , 3 h ), 7 . 16 - 7 . 42 ( m , 4 h ), 7 . 61 - 7 . 73 ( m , 1 h ), 7 . 85 ( d , j = 9 . 4 hz , 1 h ), 8 . 49 ( d , j = 5 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - formyl - 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 105 ). the title compound was prepared from methyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 96 ) by general procedure o . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 27 ( d , j = 6 . 2 hz , 6 h ), 4 . 51 - 4 . 70 ( m , 3 h ), 5 . 96 ( s , 2 h ), 6 . 86 - 7 . 00 ( m , 3 h ), 7 . 19 - 7 . 41 ( m , 4 h ), 7 . 63 - 7 . 74 ( m , 1 h ), 7 . 78 ( d , j = 9 . 7 hz , 1 h ), 8 . 48 ( d , j = 5 . 0 hz , 1 h ), 10 . 16 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -( hydroxymethyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 106 ). the title compound was also isolated in the synthesis of compound 105 . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 32 ( d , j = 5 . 9 hz , 6 h ), 4 . 47 - 4 . 60 ( m , 1 h ), 4 . 64 ( d , j = 5 . 9 hz , 2 h ), 4 . 95 ( s , 2 h ), 5 . 38 ( s , 2 h ), 6 . 02 ( s , 1 h ), 6 . 79 - 6 . 91 ( m , 3 h ), 7 . 07 - 7 . 32 ( m , 4 h ), 7 . 68 ( td , j = 7 . 8 , 1 . 8 hz , 1 h ), 7 . 85 ( d , j = 8 . 5 hz , 1 h ), 8 . 48 ( d , j = 4 . 4 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -( 4 , 5 - dihydro - 1h - imidazol - 2 - yl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 107 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 2 - formyl - 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 105 , 27 mg , 0 . 058 mmol ) in ch 2 cl 2 ( 2 ml ) was added 1 , 2 - ethylene - diamine ( 5 μl , 0 . 070 mmol ). the reaction was stirred at room temperature for 1 h and nbs ( 13 mg , 0 . 070 mmol ) was added . the reaction was stirred for 16 h and the solvent was removed in vacuo . the residue was purified by chromatography on silica gel ( 9 : 1 etoac - et 3 n , then 8 : 2 : 1 etoac - meoh - et 3 n ) followed by ptlc eluted with etoac to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 30 ( d , j = 6 . 2 hz , 6 h ), 3 . 78 ( s , 4 h ), 4 . 43 - 4 . 58 ( m , 1 h ), 4 . 62 ( s , 2 h ), 5 . 51 ( s , 2 h ), 6 . 66 ( d , j = 2 . 1 hz , 1 h ), 6 . 87 ( dd , j = 8 . 9 , 2 . 2 hz , 1 h ), 7 . 06 - 7 . 32 ( m , 4 h ), 7 . 38 ( d , j = 7 . 9 hz , 1 h ), 7 . 68 - 7 . 82 ( m , 1 h ), 8 . 24 ( d , j = 8 . 8 hz , 1 h ), 8 . 53 ( d , j = 5 . 0 hz , 1 h ), 9 . 95 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 -( 1 - hydroxyethyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 108 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 2 - formyl - 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 105 , 102 mg , 0 . 23 mmol ) in 1 , 2 - dimethoxy - ethane ( 15 ml ) was added memgbr ( 1 . 4 m in toluene - thf , 0 . 5 ml , 0 . 70 mmol ) at 0 ° c . the reaction was stirred at room temperature for 2 h and more memgbr ( 1 . 0 ml , 1 . 4 mmol ) was added . the reaction was stirred at room temperature for another 2 h and was quenched with ice , extracted with etoac . the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 23 ( dd , j = 6 . 0 , 1 . 3 hz , 6 h ), 1 . 44 ( d , j = 6 . 7 hz , 3 h ), 4 . 41 - 4 . 67 ( m , 3 h ), 5 . 43 ( q , j = 6 . 9 hz , 1 h ), 5 . 56 - 5 . 76 ( m , 2 h ), 6 . 75 - 6 . 91 ( m , 3 h ), 7 . 15 - 7 . 39 ( m , 4 h ), 7 . 61 - 7 . 74 ( m , 1 h ), 7 . 79 ( d , j = 8 . 8 hz , 1 h ), 8 . 52 ( d , j = 4 . 7 hz , 1 h ). 2 - acetyl - n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 109 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 2 -( 1 - hydroxyethyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 108 , 8 . 0 mg , 0 . 017 mmol ) in ch 2 cl 2 ( 1 ml ) was added nmo ( 6 . 0 mg , 0 . 051 mmol ) and tpap ( 0 . 6 mg , 0 . 0017 mmol ). the reaction was stirred at room temperature for 1 h and was purified directly by ptlc ( 75 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 29 ( dd , j = 6 . 0 , 0 . 7 hz , 6 h ), 2 . 59 ( s , 3 h ), 4 . 46 - 4 . 60 ( m , 1 h ), 4 . 67 ( d , j = 5 . 9 hz , 2 h ), 5 . 67 ( s , 2 h ), 6 . 55 ( t , j = 6 . 3 hz , 1 h ), 6 . 79 ( d , j = 2 . 1 hz , 1 h ), 6 . 83 - 6 . 89 ( m , 1 h ), 6 . 94 ( d , j = 7 . 6 hz , 1 h ), 7 . 07 - 7 . 35 ( m , 4 h ), 7 . 48 - 7 . 63 ( m , 2 h ), 8 . 54 ( d , j = 4 . 7 hz , 1 h ). ( e )- n -( 3 , 4 - difluorobenzyl )- 2 -( 1 -( hydroxyimino ) ethyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 110 ). general procedure q . to a solution of 2 - acetyl - n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 109 , 18 mg , 0 . 038 mmol ) in meoh ( 3 ml ) was added honh 2 . hcl ( 8 . 0 mg , 0 . 11 mmol ) and pyridine ( 30 μl , 0 . 38 mmol ). the reaction was stirred at 65 ° c . for 20 h and the solvent was removed in vacuo . the residue was purified by ptlc ( 75 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 26 ( d , j = 5 . 9 hz , 6 h ), 2 . 08 ( s , 3 h ), 4 . 40 - 4 . 53 ( m , 1 h ), 4 . 58 ( d , j = 5 . 9 hz , 2 h ), 5 . 46 ( s , 2 h ), 6 . 59 - 6 . 71 ( m , 3 h ), 6 . 89 ( dd , j = 8 . 8 , 2 . 2 hz , 1 h ), 7 . 03 - 7 . 24 ( m , 4 h ), 7 . 41 - 7 . 55 ( m , 1 h ), 7 . 92 ( d , j = 8 . 8 hz , 1 h ), 8 . 50 ( d , j = 4 . 1 hz , 1 h ), 10 . 61 ( s , 1 h ). ( e )- n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 2 -( 1 -( methoxyimino ) ethyl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 111 ). the title compound was prepared from 2 - acetyl - n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 109 ) and meonh 2 . hcl by general procedure q . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 27 ( d , j = 6 . 2 hz , 6 h ), 2 . 12 ( s , 3 h ), 3 . 82 ( s , 3 h ), 4 . 42 - 4 . 56 ( m , 1 h ), 4 . 61 ( d , j = 5 . 6 hz , 2 h ), 5 . 40 ( s , 2 h ), 6 . 69 ( d , j = 2 . 1 hz , 1 h ), 6 . 37 - 6 . 85 ( m , 2 h ), 6 . 89 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 03 - 7 . 25 ( m , 4 h ), 7 . 49 - 7 . 59 ( m , 1 h ), 7 . 94 ( d , j = 8 . 8 hz , 1 h ), 8 . 58 ( d , j = 4 . 4 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 4 , 4 - dimethyl - 3 - oxopentanamide ( compound 112 ). a solution of ethyl4 , 4 - dimethyl - 3 - oxopentanoate ( alfa aesar , 2 . 4 g , 14 mmol ) and 3 , 4 - difluorobenzylamine ( aldrich , 2 . 0 g , 14 mmol ) in toluene ( 15 ml ) was refluxed for 24 h . the solvent was removed to yield the title compound as an off - white wax . used without further purification . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 18 ( s , 9 h ), 3 . 55 ( s , 2 h ), 4 . 42 ( d , j = 6 . 2 hz , 2 h ), 6 . 95 - 7 . 31 ( m , 3 h ), 7 . 57 ( s , 1 h ). ethyl 4 - fluoro - 3 - nitrobenzoate ( compound 113 ). a solution of 4 - fluoro - 3 - nitrobenzoic acid ( alfa aesar , 10 . 0 g , 54 mmol ) and concentrated h 2 so 4 ( 0 . 2 ml , 4 . 1 mmol ) in etoh ( 200 ml ) was refluxed for 40 h . the mixture was cooled to 0 ° c ., solid nahco 3 and mgso 4 was added , and the suspension was filtered and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound as an off - white solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 43 ( t , j = 7 . 0 hz , 3 h ), 4 . 44 ( q , j = 7 . 2 hz , 2 h ), 7 . 39 ( dd , j = 10 . 3 , 8 . 8 hz , 1 h ), 8 . 33 ( ddd , j = 8 . 6 , 4 . 2 , 2 . 1 hz , 1 h ), 8 . 74 ( dd , j = 7 . 2 , 2 . 2 hz , 1 h ). ethyl 4 -( 1 -( 3 , 4 - difluorobenzylamino )- 4 , 4 - dimethyl - 1 , 3 - dioxopentan - 2 - yl )- 3 - nitrobenzoate ( compound 114 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 4 , 4 - dimethyl - 3 - oxopentanamide ( compound 112 , 126 mg , 0 . 47 mmol ) and ethyl4 - fluoro - 3 - nitrobenzoate ( compound 113 , 100 mg , 0 . 47 mmol ) in dmso ( 1 ml ) was added k 2 co 3 ( 130 mg , 0 . 94 mmol ). the mixture was stirred at room temperature for 16 h , diluted with etoac , washed with 1 m hcl , h 2 o , and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 17 ( s , 9 h ), 1 . 41 ( t , j = 7 . 2 hz , 3 h ), 4 . 35 ( dd , j = 5 . 9 , 1 . 8 hz , 2 h ), 4 . 42 ( q , j = 7 . 0 hz , 2 h ), 5 . 86 ( s , 1 h ), 6 . 63 ( t , j = 5 . 9 hz , 1 h ), 6 . 86 - 7 . 14 ( m , 3 h ), 7 . 77 ( d , j = 8 . 2 hz , 1 h ), 8 . 21 ( dd , j = 8 . 2 , 1 . 8 hz , 1 h ), 8 . 50 ( d , j = 1 . 8 hz , 1 h ). ethyl 2 - tert - butyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 1h - indole - 6 - carboxylate ( compound 115 ). general procedure r . to a solution of ethyl4 -( 1 -( 3 , 4 - difluorobenzylamino )- 4 , 4 - dimethyl - 1 , 3 - dioxopentan - 2 - yl )- 3 - nitrobenzoate ( compound 114 , 91 mg , 0 . 20 mmol ) in meoh ( 10 ml ) and saturated aqueous nh 4 cl ( 5 ml ) was added zinc dust ( 320 mg , 4 . 9 mmol ). the mixture was stirred at room temperature for 0 . 5 h , filtered and concentrated . the remaining aqueous suspension was extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 39 ( t , j = 7 . 2 hz , 3 h ), 1 . 53 ( s , 9 h ), 4 . 37 ( q , j = 7 . 1 hz , 2 h ), 4 . 64 ( d , j = 6 . 2 hz , 2 h ), 6 . 39 ( t , j = 6 . 0 hz , 1 h ), 7 . 07 - 7 . 29 ( m , 3 h ), 7 . 53 ( d , j = 8 . 5 hz , 1 h ), 7 . 79 ( dd , j = 8 . 5 , 1 . 5 hz , 1 h ), 8 . 12 ( d , j = 1 . 2 hz , 1 h ), 8 . 89 ( s , 1 h ). ethyl 1 - benzyl - 2 - tert - butyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 1h - indole - 6 - carboxylate ( compound 116 ). to a solution of ethyl2 - tert - butyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 1h - indole - 6 - carboxylate ( compound 115 , 33 mg , 0 . 080 mmol ) in dmf ( 1 ml ) was added benzyl bromide ( 47 μl , 0 . 40 mmol ) and k 2 co 3 ( 33 mg , 0 . 24 mmol ). the mixture was stirred at room temperature for 24 h , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) followed by ptlc ( 5 % meoh — ch 2 cl 2 ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 33 ( t , j = 7 . 2 hz , 3 h ), 1 . 49 ( s , 9 h ), 4 . 30 ( q , j = 7 . 0 hz , 2 h ), 4 . 65 ( d , j = 5 . 9 hz , 2 h ), 5 . 67 ( s , 2 h ), 6 . 26 ( t , j = 6 . 0 hz , 1 h ), 6 . 87 ( dd , j = 7 . 9 , 1 . 8 hz , 2 h ), 7 . 12 - 7 . 35 ( m , 6 h ), 7 . 45 ( d , j = 9 . 1 hz , 1 h ), 7 . 72 - 7 . 82 ( m , 2 h ). n -( 2 - hydroxy - 5 - nitrophenyl ) butyramide ( compound 117 ). to a solution of 2 - amino - 4 - nitrophenol ( aldrich , 1 . 0 g , 6 . 5 mmol ) in thf ( 25 ml ) was added n - prcocl ( 694 mg , 6 . 5 mmol ) and pyridine ( 2 . 6 ml , 32 . 4 mmol ). the reaction was refluxed for 5 days , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a brown solid . 1h nmr ( 300 mhz , acetone ) δ ppm 0 . 99 ( t , j = 7 . 5 hz , 3 h ), 1 . 60 - 1 . 89 ( m , 2 h ), 2 . 54 ( t , j = 7 . 5 hz , 2 h ), 7 . 07 ( d , j = 8 . 8 hz , 1 h ), 7 . 92 ( dd , j = 8 . 9 , 2 . 8 hz , 1 h ), 8 . 83 ( d , j = 2 . 9 hz , 1 h ), 9 . 10 ( s , 1 h ), 10 . 68 ( s , 1 h ). 2 - butyramido - 4 - nitrophenyl trifluoromethanesulfonate ( compound 118 ). to a solution of n -( 2 - hydroxy - 5 - nitrophenyl ) butyramide ( compound 117 , 1 . 75 g , 7 . 8 mmol ) in ch 2 cl 2 ( 40 ml ) at 0 ° c . was added et 3 n ( 1 . 4 ml , 10 . 1 mmol ) and tf 2 o ( 1 . 7 ml , 10 . 2 mmol ). after 10 min , the reaction was diluted with ch 2 cl 2 , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 05 ( t , j = 7 . 5 hz , 3 h ), 1 . 73 - 1 . 89 ( m , 2 h ), 2 . 46 ( t , j = 7 . 5 hz , 2 h ), 7 . 44 ( s , 1 h ), 7 . 49 ( d , j = 9 . 1 hz , 1 h ), 8 . 05 ( dd , j = 9 . 1 , 2 . 6 hz , 1 h ), 9 . 34 ( d , j = 2 . 6 hz , 1 h ). n -( 2 -( 3 - methylbut - 1 - ynyl )- 5 - nitrophenyl ) butyramide ( compound 119 ). a mixture of 2 - butyramido - 4 - nitrophenyl trifluoromethanesulfonate ( compound 118 , 200 mg , 0 . 56 mmol ), cui ( 32 mg , 0 . 17 mmol ), and n - bu 4 ni ( 311 mg , 0 . 84 mmol ) in ch 3 cn ( 5 ml ) and et 3 n ( 1 ml ) was purged with n 2 for 10 min and pd ( pph 3 ) 4 ( 64 mg , 0 . 056 mmol ) was added and the mixture was purged with n 2 for another 5 min . the mixture was then cooled to 0 ° c . and 3 - methyl - 1 - butyne ( 76 mg , 1 . 12 mmol ) was added . after 5 min , the reaction was quenched with aqueous nahco 3 , extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 20 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 06 ( t , j = 7 . 5 hz , 3 h ), 1 . 36 ( d , j = 6 . 7 hz , 6 h ), 1 . 72 - 1 . 92 ( m , 2 h ), 2 . 44 ( t , j = 7 . 5 hz , 2 h ), 2 . 85 - 3 . 01 ( m , 1 h ), 7 . 49 ( d , j = 8 . 5 hz , 1 h ), 7 . 88 ( dd , j = 8 . 8 , 2 . 3 hz , 1 h ), 8 . 04 ( s , 1 h ), 9 . 33 ( d , j = 2 . 3 hz , 1 h ). 2 - isopropyl - 6 - nitro - 1h - indole ( compound 120 ). to a solution of n -( 2 -( 3 - methylbut - 1 - ynyl )- 5 - nitrophenyl ) butyramide ( compound 119 , 900 mg , 3 . 29 mmol ) in nmp ( 10 ml ) was added kot - bu ( 552 mg , 4 . 94 mmol ) and the mixture was stirred at 70 ° c . for 16 h , cooled to room temperature , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 41 ( d , j = 7 . 0 hz , 6 h ), 3 . 07 - 3 . 22 ( m , 1 h ), 6 . 38 ( d , j = 2 . 3 hz , 1 h ), 7 . 56 ( d , j = 8 . 8 hz , 1 h ), 8 . 00 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 8 . 28 ( d , j = 2 . 1 hz , 1 h ). 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carbaldehyde ( compound 121 ). pocl 3 ( 0 . 12 ml , 1 . 4 mmol ) was added dropwise to anhydrous dmf ( 1 . 5 ml ) at 0 ° c . under argon . after stirred for 20 min , a solution of 2 - isopropyl - 6 - nitro - 1h - indole ( compound 120 , 115 mg , 0 . 56 mmol ) in anhydrous dmf ( 1 . 5 ml ) was added slowly to the above reaction and stirred for 1 h at 0 ° c . and 2 h at room temperature . the reaction was diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 44 ( d , j = 7 . 0 hz , 6 h ), 3 . 65 - 3 . 84 ( m , 1 h ), 7 . 38 ( s , 1 h ), 8 . 04 - 8 . 12 ( m , 1 h ), 8 . 18 - 8 . 32 ( m , 2 h ), 10 . 13 ( s , 1 h ). 1 - benzyl - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carbaldehyde ( compound 122 ). to a solution of 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carbaldehyde ( compound 121 , 244 mg , 1 . 05 mmol ) in dmf ( 10 ml ) was added benzyl bromide ( 0 . 62 ml , 5 . 26 mmol ) and k 2 co 3 ( 726 mg , 5 . 26 mmol ). the reaction was stirred at room temperature for 16 h , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 49 ( d , j = 7 . 0 hz , 6 h ), 3 . 45 - 3 . 60 ( m , 1 h ), 5 . 54 ( s , 2 h ), 6 . 94 - 7 . 02 ( m , 2 h ), 7 . 29 - 7 . 41 ( m , 3 h ), 8 . 16 - 8 . 24 ( m , 2 h ), 8 . 49 ( d , j = 8 . 5 hz , 1 h ), 10 . 51 ( s , 1 h ). 1 - benzyl - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylic acid ( compound 123 ). the title compound was prepared from 1 - benzyl - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carbaldehyde ( compound 122 ) by general procedure k . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 40 ( d , j = 7 . 3 hz , 6 h ), 3 . 87 - 4 . 10 ( m , 1 h ), 5 . 72 ( s , 2 h ), 6 . 98 ( dd , j = 7 . 3 , 1 . 5 hz , 2 h ), 7 . 22 - 7 . 41 ( m , 3 h ), 8 . 07 ( dd , j = 8 . 9 , 2 . 2 hz , 1 h ), 8 . 22 - 8 . 35 ( m , 2 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxamide ( compound 124 ). the title compound was prepared from 1 - benzyl - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylic acid ( compound 123 ) by general procedure c . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 42 ( d , j = 7 . 3 hz , 6 h ), 3 . 51 - 3 . 67 ( m , 1 h ), 4 . 70 ( d , j = 6 . 2 hz , 2 h ), 5 . 53 ( s , 2 h ), 6 . 28 ( t , j = 6 . 9 hz , 1 h ), 6 . 94 ( dd , j = 7 . 2 , 1 . 9 hz , 2 h ), 7 . 12 - 7 . 19 ( m , 2 h ), 7 . 19 - 7 . 37 ( m , 4 h ), 7 . 69 ( d , j = 8 . 8 hz , 1 h ), 8 . 08 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 8 . 18 ( d , j = 1 . 8 hz , 1 h ). 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 125 ). general procedure s . a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxamide ( compound 124 , 300 mg , 0 . 65 mmol ) in etoac ( 5 ml ) was treated with 10 % pd — c ( 6 . 8 mg , 0 . 065 mmol ) and hydrogen gas under atmospheric pressure at room temperature for 16 h . the mixture was filtered and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 3 hz , 6 h ), 3 . 38 - 3 . 58 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 41 ( s , 2 h ), 6 . 58 - 6 . 73 ( m , 2 h ), 6 . 89 - 7 . 01 ( m , 2 h ), 7 . 16 - 7 . 37 ( m , 6 h ), 7 . 39 ( d , j = 8 . 5 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( tetrahydrofuran - 3 - ylamino )- 1h - indole - 3 - carboxamide ( compound 126 ). general procedure t . to a solution of 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 125 , 15 mg , 0 . 035 mmol ) in meoh ( 1 ml ) was added dihydrofuran - 3 ( 2h )- one ( compound 129 , 6 . 0 mg , 0 . 069 mmol ), nabh 3 cn ( 2 . 2 mg , 0 . 035 mmol ), and hoac ( 1 drop ). the reaction was stirred at room temperature for 3 h , diluted with etoac , washed with aqueous na 2 co 3 and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 38 ( d , j = 7 . 0 hz , 6 h ), 1 . 69 - 1 . 83 ( m , 1 h ), 2 . 08 - 2 . 23 ( m , 1 h ), 3 . 61 ( dd , j = 9 . 4 , 2 . 9 hz , 1 h ), 3 . 70 - 3 . 94 ( m , 4 h ), 3 . 96 - 4 . 05 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 38 ( s , 2 h ), 6 . 23 - 6 . 34 ( m , 2 h ), 6 . 53 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 00 ( d , j = 8 . 2 hz , 2 h ), 7 . 11 - 7 . 19 ( m , 2 h ), 7 . 20 - 7 . 34 ( m , 4 h ), 7 . 43 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - isobutyramido - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 127 ). to a solution of 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 125 , 18 mg , 0 . 042 mmol ) in ch 2 cl 2 ( 1 ml ) was added i - prcocl ( 8 . 7 μl , 0 . 089 mmol ) and dmap ( 10 mg , 0 . 089 mmol ). the reaction was stirred at room temperature for 2 h , diluted with etoac , washed with aqueous na 2 co 3 and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 21 ( d , j = 6 . 7 hz , 6 h ), 1 . 34 ( d , j = 7 . 0 hz , 6 h ), 2 . 38 - 2 . 56 ( m , 1 h ), 3 . 48 - 3 . 65 ( m , 1 h ), 4 . 65 ( d , j = 6 . 2 hz , 2 h ), 5 . 39 ( s , 2 h ), 6 . 31 ( t , j = 6 . 0 hz , 1 h ), 6 . 88 - 6 . 95 ( m , 2 h ), 6 . 99 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 09 - 7 . 17 ( m , 2 h ), 7 . 19 - 7 . 29 ( m , 4 h ), 7 . 32 ( s , 1 h ), 7 . 51 ( d , j = 8 . 5 hz , 1 h ), 7 . 84 ( d , j = 1 . 5 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 2 - oxopyrrolidin - 1 - yl )- 1h - indole - 3 - carboxamide ( compound 128 ). a solution of 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 125 , 20 mg , 0 . 046 mmol ) and ethyl4 - bromobutanoate ( 13 μl , 0 . 092 mmol ) in nmp ( 1 ml ) was heated at 168 ° c . for 16 h , cooled to room temperature , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 2 . 06 - 2 . 20 ( m , 2 h ), 2 . 57 ( t , j = 8 . 1 hz , 2 h ), 3 . 59 - 3 . 74 ( m , 1 h ), 3 . 78 - 3 . 88 ( m , 2 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 44 ( s , 2 h ), 6 . 30 ( t , j = 6 . 4 hz , 1 h ), 6 . 94 ( dd , j = 7 . 9 , 1 . 8 hz , 2 h ), 7 . 10 - 7 . 18 ( m , j = 8 . 8 , 4 . 7 hz , 2 h ), 7 . 20 - 7 . 33 ( m , 5 h ), 7 . 56 - 7 . 63 ( m , 2 h ). dihydrofuran - 3 ( 2h )- one ( compound 129 ). to a suspension of pcc ( 4 . 2 g , 19 . 3 mmol ) and 4 å molecular sieves ( 2 . 0 g ) in ch 2 cl 2 ( 40 ml ) was added a solution of tetrahydrofuran - 3 - ol ( aldrich , 0 . 92 ml , 11 . 4 mmol ) in ch 2 cl 2 ( 20 ml ) and the mixture was heated to reflux for 16 h , cooled to room temperature , filtered through celite , diluted with et 2 o , filtered again through celite , washed successively with 2 m hcl , h 2 o , and brine , dried over na 2 so 4 , and concentrated in vacuo . the crude was used without further purification . 1 - benzyl - 6 -( cyclopentylamino )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 130 ). the title compound was prepared from 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 125 ) and cyclopentanone by general procedure t . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 31 - 1 . 47 ( m , 1 h ), 1 . 37 ( d , j = 7 . 3 hz , 6 h ), 1 . 50 - 1 . 76 ( m , 3 h ), 1 . 84 - 2 . 02 ( m , 3 h ), 2 . 12 - 2 . 23 ( m , 1 h ), 3 . 61 - 3 . 86 ( m , 2 h ), 4 . 66 ( d , j = 6 . 2 hz , 2 h ), 5 . 37 ( s , 2 h ), 6 . 25 - 6 . 37 ( m , 2 h ), 6 . 53 ( dd , j = 8 . 6 , 1 . 9 hz , 1 h ), 6 . 96 - 7 . 06 ( m , 2 h ), 7 . 10 - 7 . 18 ( m , 2 h ), 7 . 19 - 7 . 34 ( m , 4 h ), 7 . 40 ( d , j = 8 . 5 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 1 , 3 - oxazol - 2 - ylmethoxy )- 1h - indole - 3 - carboxamide ( compound 131 ). the title compound was prepared from 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 ) and 2 -( chloromethyl ) oxazole by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 38 ( d , j = 7 . 3 hz , 6 h ), 3 . 62 - 3 . 79 ( m , 1 h ), 4 . 67 ( d , j = 5 . 9 hz , 2 h ), 5 . 09 ( s , 2 h ), 5 . 40 ( s , 2 h ), 6 . 30 ( t , j = 6 . 0 hz , 1h ), 6 . 79 ( d , j = 2 . 1 hz , 1 h ), 6 . 88 - 7 . 00 ( m , 3 h ), 7 . 07 ( s , 1 h ), 7 . 11 - 7 . 19 ( m , 2 h ), 7 . 19 - 7 . 34 ( m , 4 h ), 7 . 54 ( d , j = 8 . 5 hz , 1 h ), 7 . 61 ( s , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 1 , 3 - thiazol - 2 - yloxy )- 1h - indole - 3 - carboxamide ( compound 132 ). general procedure u . to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 12 mg , 0 . 028 mmol ) in dmf ( 1 ml ) was added k 2 co 3 ( 19 mg , 0 . 14 mmol ) and 2 - bromothiazole ( 23 mg , 0 . 14 mmol ). the mixture was stirred at room temperature overnight and a small amount of naoh was added . the reaction was kept stirring for 72 h , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 39 ( d , j = 7 . 0 hz , 6 h ), 3 . 61 - 3 . 76 ( m , 1 h ), 4 . 67 ( d , j = 5 . 6 hz , 2 h ), 5 . 42 ( s , 2 h ), 6 . 24 - 6 . 32 ( m , 1 h ), 6 . 74 ( d , j = 3 . 8 hz , 1 h ), 6 . 94 ( dd , j = 8 . 1 , 1 . 3 hz , 3 h ), 7 . 06 - 7 . 32 ( m , 8 h ), 7 . 65 ( d , j = 9 . 1 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( tetrahydro - 2h - pyran - 4 - yloxy )- 1h - indole - 3 - carboxamide ( compound 133 ). the title compound was prepared from 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 ) and 4 - iodotetrahydro - 2h - pyran ( maybridge ) by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 38 ( d , j = 7 . 0 hz , 6 h ), 1 . 62 - 1 . 78 ( m , 2 h ), 1 . 83 - 1 . 96 ( m , 2 h ), 3 . 42 - 3 . 56 ( m , 2 h ), 3 . 65 - 3 . 80 ( m , 1 h ), 3 . 87 - 3 . 99 ( m , 2 h ), 4 . 28 - 4 . 41 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 39 ( s , 2 h ), 6 . 28 ( t , j = 5 . 7 hz , 1 h ), 6 . 66 ( d , j = 2 . 1 hz , 1 h ), 6 . 83 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 6 . 93 - 7 . 01 ( m , 2 h ), 7 . 10 - 7 . 18 ( m , 2 h ), 7 . 18 - 7 . 34 ( m , 4 h ), 7 . 51 ( d , j = 8 . 8 hz , 1 h ). 4 - methoxy - 1 -( 3 - methylbut - 1 - ynyl )- 2 - nitrobenzene ( compound 134 ). to a solution of 1 - iodo - 4 - methoxy - 2 - nitrobenzene ( aldrich , 10 g , 35 . 8 mmol ) in et 3 n ( 60 ml ) and dmf ( 6 ml ) was added cui ( 34 mg , 0 . 18 mmol ), pd ( pph 3 ) 2 cl 2 ( 126 mg , 0 . 18 mmol ), and 3 - methyl - 1 - butyne ( 5 . 0 ml , 73 . 5 mmol ). the mixture was stirred at room temperature for 16 h and was concentrated . the resulting mixture was diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 15 % etoac - hexanes ) to yield the title compound as a brown oil . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 27 ( d , j = 6 . 4 hz , 6 h ), 2 . 70 - 2 . 92 ( m , 1 h ), 3 . 86 ( s , 3 h ), 7 . 06 ( dd , j = 8 . 9 , 2 . 8 hz , 1 h ), 7 . 40 - 7 . 50 ( m , 2 h ). 5 - methoxy - 2 -( 3 - methylbut - 1 - ynyl ) aniline ( compound 135 ). to a solution of 4 - methoxy - 1 -( 3 - methylbut - 1 - ynyl )- 2 - nitrobenzene ( compound 134 , 2 . 97 g , 13 . 6 mmol ) in thf ( 45 ml ) and etoh ( 15 ml ) at 0 ° c . was added sncl 2 ( 12 . 9 g , 68 mmol ), followed by nabh 4 ( 3 . 1 g , 81 . 6 mmol ) in three equal portions with one hour between each addition . the reaction was stirred at 0 ° c . for a total of 3 . 5 h and was quenched with aqueous ammonia , filtered through a pad of celite , extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 20 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 27 ( d , j = 7 . 0 hz , 6 h ), 2 . 73 - 2 . 90 ( m , 1 h ), 3 . 75 ( s , 3 h ), 4 . 16 ( s , 2 h ), 6 . 16 - 6 . 34 ( m , 2 h ), 7 . 15 ( d , j = 8 . 2 hz , 1 h ). 2 - isopropyl - 6 - methoxy - 1h - indole ( compound 136 ). to a solution of 5 - methoxy - 2 -( 3 - methylbut - 1 - ynyl ) aniline ( compound 135 , 1 . 8 g , 9 . 5 mmol ) in dmf ( 20 ml ) was added cui ( 101 mg , 0 . 53 mmol ). the reaction was stirred at 160 ° c . for 1 . 5 h . the solvent was removed in vacuo and the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound as a brownish red solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 34 ( d , j = 7 . 0 hz , 6 h ), 2 . 97 - 3 . 10 ( m , 1 h ), 3 . 83 ( s , 3 h ), 6 . 13 - 6 . 19 ( m , 1 h ), 6 . 74 ( dd , j = 8 . 5 , 2 . 3 hz , 1 h ), 6 . 83 ( d , j = 2 . 3 hz , 1 h ), 7 . 39 ( d , j = 8 . 8 hz , 1 h ), 7 . 76 ( s , 1 h ). 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole ( compound 136 ) by general procedure i . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 44 ( d , j = 7 . 0 hz , 6 h ), 3 . 70 - 3 . 82 ( m , 1 h ), 3 . 84 ( s , 3 h ), 6 . 86 ( d , j = 2 . 1 hz , 1 h ), 6 . 91 ( dd , j = 8 . 8 , 2 . 3 hz , 1 h ), 8 . 14 ( d , j = 8 . 8 hz , 1 h ), 8 . 36 ( s , 1 h ), 10 . 21 ( s , 1 h ). 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carbaldehyde ( compound 138 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 139 ) by general procedure j . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 45 ( d , j = 7 . 0 hz , 6 h ), 3 . 43 - 3 . 64 ( m , 1 h ), 3 . 79 ( s , 3 h ), 5 . 50 ( s , 2 h ), 6 . 59 - 6 . 77 ( m , 2 h ), 6 . 94 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 7 . 17 - 7 . 26 ( m , 1 h ), 7 . 50 - 7 . 67 ( m , 1 h ), 8 . 28 ( d , j = 8 . 8 hz , 1 h ), 8 . 62 ( d , j = 5 . 3 hz , 1 h ), 10 . 44 ( s , 1 h ). 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carbaldehyde ( compound 138 ) by general procedure k . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 39 ( d , j = 7 . 0 hz , 6 h ), 3 . 76 ( s , 3 h ), 4 . 06 - 4 . 29 ( m , 1 h ), 5 . 58 ( s , 2 h ), 6 . 56 ( d , j = 7 . 9 hz , 1 h ), 6 . 62 ( d , j = 2 . 3 hz , 1 h ), 6 . 92 ( dd , j = 8 . 8 , 2 . 3 hz , 1 h ), 7 . 16 - 7 . 24 ( m , 1 h ), 7 . 49 - 7 . 60 ( m , 1 h ), 8 . 15 ( d , j = 9 . 1 hz , 1 h ), 8 . 64 ( d , j = 5 . 3 hz , 1 h ). 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- n -(( 6 -( trifluoromethyl ) pyridin - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 140 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ) and ( 6 -( trifluoromethyl ) pyridin - 3 - yl ) methanamine by general procedure c . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 3 . 68 - 3 . 87 ( m , 4 h ), 4 . 81 ( d , j = 6 . 2 hz , 2 h ), 5 . 52 ( s , 2 h ), 6 . 41 ( t , j = 5 . 9 hz , 1 h ), 6 . 52 ( d , j = 7 . 9 hz , 1 h ), 6 . 64 ( d , j = 2 . 1 hz , 1 h ), 6 . 85 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 19 ( dd , j = 7 . 5 , 4 . 8 hz , 1 h ), 7 . 47 - 7 . 58 ( m , 2 h ), 7 . 69 ( d , j = 7 . 9 hz , 1 h ), 7 . 98 ( d , j = 8 . 5 hz , 1 h ), 8 . 62 ( d , j = 4 . 7 hz , 1 h ), 8 . 79 ( s , 1 h ). 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- n -(( 6 -( trifluoromethyl ) pyridin - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 141 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- n -(( 6 -( trifluoromethyl ) pyridin - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 140 ) by general procedure l . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 36 ( d , j = 7 . 3 hz , 6 h ), 3 . 71 - 3 . 86 ( m , 1 h ), 4 . 80 ( d , j = 6 . 2 hz , 2 h ), 5 . 49 ( s , 2 h ), 6 . 40 ( t , j = 6 . 2 hz , 1 h ), 6 . 52 - 6 . 60 ( m , 2 h ), 6 . 74 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 7 . 15 - 7 . 23 ( m , 1 h ), 7 . 45 - 7 . 59 ( m , 2 h ), 7 . 69 ( d , j = 8 . 2 hz , 1 h ), 7 . 98 ( dd , j = 7 . 3 , 2 . 3 hz , 1 h ), 8 . 56 ( d , j = 4 . 7 hz , 1 h ), 8 . 79 ( d , j = 2 . 3 hz , 1 h ). 6 -( cyclopentyloxy )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- n -(( 6 -( trifluoromethyl ) pyridin - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 142 ). the title compound was prepared from 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- n -(( 6 -( trifluoromethyl ) pyridin - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 141 ) and cyclopentyl iodide by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 36 ( d , j = 7 . 0 hz , 6 h ), 1 . 49 - 1 . 64 ( m , 2 h ), 1 . 67 - 1 . 88 ( m , 6 h ), 3 . 71 - 3 . 91 ( m , 1 h ), 4 . 67 ( s , 1 h ), 4 . 80 ( d , j = 5 . 9 hz , 2 h ), 5 . 51 ( s , 2 h ), 6 . 46 ( t , j = 5 . 9 hz , 1 h ), 6 . 53 ( d , j = 7 . 9 hz , 1 h ), 6 . 62 ( d , j = 2 . 1 hz , 1 h ), 6 . 81 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 18 ( dd , j = 7 . 3 , 5 . 0 hz , 1 h ), 7 . 46 - 7 . 57 ( m , 2 h ), 7 . 68 ( d , j = 8 . 2 hz , 1 h ), 7 . 97 ( d , j = 7 . 9 hz , 1 h ), 8 . 61 ( d , j = 4 . 1 hz , 1 h ), 8 . 78 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( tetrahydro - 2h - pyran - 4 - yloxy )- 1h - indole - 3 - carboxamide ( compound 143 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ) by , in order , general procedure c , general procedure l , and general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 38 ( d , j = 7 . 0 hz , 6 h ), 1 . 62 - 1 . 79 ( m , 2 h ), 1 . 84 - 1 . 98 ( m , 2 h ), 3 . 44 - 3 . 57 ( m , 2 h ), 3 . 71 - 3 . 87 ( m , 1 h ), 3 . 87 - 4 . 00 ( m , 2 h ), 4 . 31 - 4 . 44 ( m , 1 h ), 4 . 67 ( d , j = 6 . 2 hz , 2 h ), 5 . 50 ( s , 2 h ), 6 . 28 ( t , j = 5 . 4 hz , 1 h ), 6 . 54 ( d , j = 7 . 9 hz , 1 h ), 6 . 68 ( d , j = 2 . 1 hz , 1 h ), 6 . 85 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 09 - 7 . 31 ( m , 4 h ), 7 . 45 - 7 . 58 ( m , 2 h ), 8 . 62 ( d , j = 4 . 7 hz , 1 h ). ( 2 , 6 - dichloro - 5 - fluoropyridin - 3 - yl ) methanamine ( compound 144 ). to a parr reaction bottle was added pd — c ( 10 %, 560 mg , 0 . 52 mmol ), followed by 6 m hcl ( 50 ml ) and a solution of 2 , 6 - dichloro - 5 - fluoronicotinonitrile ( aldrich , 10 . 0 g , 52 . 4 mmol ) in meoh ( 100 ml ). the mixture was placed under 50 psi h 2 on a shaker type parr apparatus for 21 h , filtered and concentrated . the crude was dissolved in etoac , basified with aqueous naoh , and the layers were separated . the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo to yield the title compound as crude light yellow oil . used without further purification . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 4 . 31 ( s , 2 h ), 8 . 06 ( d , j = 8 . 2 hz , 1 h ). ( 5 - fluoropyridin - 3 - yl ) methanamine ( compound 145 ). to a parr reaction bottle was added pd — c ( 10 %, 560 mg , 0 . 52 mmol ), followed by 28 % nh 3 . h 2 o ( 50 ml ) and a solution of ( 2 , 6 - dichloro - 5 - fluoropyridin - 3 - yl ) methanamine ( compound 144 , 10 . 1 g , 52 mmol ) in meoh ( 100 ml ). the mixture was placed under 51 psi h 2 on a shaker type parr apparatus for 16 h , filtered and concentrated . the resulting aqueous solution was basified with naoh , extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the crude product was purified by distillation under vacuum to yield the title compound as colorless oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 3 . 87 ( s , 2 h ), 7 . 61 - 7 . 73 ( m , 1 h ), 8 . 25 - 8 . 44 ( m , 2 h ). n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 146 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ) and ( 5 - fluoropyridin - 3 - yl ) methanamine ( compound 145 ) by general procedure c . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 ( d , j = 7 . 0 hz , 6 h ), 3 . 38 - 3 . 57 ( m , 1 h ), 3 . 73 ( s , 3 h ), 4 . 67 ( s , 2 h ), 5 . 56 ( s , 2 h ), 6 . 63 ( d , j = 7 . 9 hz , 1 h ), 6 . 76 - 6 . 85 ( m , 2 h ), 7 . 29 ( dd , j = 6 . 9 , 5 . 1 hz , 1 h ), 7 . 52 ( d , j = 9 . 1 hz , 1 h ), 7 . 62 - 7 . 75 ( m , 2 h ), 8 . 38 ( d , j = 2 . 6 hz , 1 h ), 8 . 50 ( s , 1 h ), 8 . 54 ( d , j = 4 . 1 hz , 1 h ). n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 147 ). the title compound was prepared from n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 146 ) by general procedure l . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 ( d , j = 7 . 0 hz , 6 h ), 3 . 44 - 3 . 57 ( m , 1 h ), 4 . 67 ( s , 2 h ), 5 . 48 ( s , 2 h ), 6 . 57 - 6 . 65 ( m , 2 h ), 6 . 70 ( dd , j = 8 . 4 , 1 . 9 hz , 1 h ), 7 . 29 ( dd , j = 7 . 2 , 4 . 8 hz , 1 h ), 7 . 46 ( d , j = 8 . 8 hz , 1 h ), 7 . 61 - 7 . 74 ( m , 2 h ), 8 . 38 ( d , j = 2 . 6 hz , 1 h ), 8 . 50 ( s , 1 h ), 8 . 54 ( d , j = 5 . 0 hz , 1 h ). 6 -( cyclopentyloxy )- n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 148 ). the title compound was prepared from n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 147 ) by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 1 . 50 - 1 . 61 ( m , 2 h ), 1 . 67 - 1 . 84 ( m , 6 h ), 3 . 73 - 3 . 88 ( m , 1 h ), 4 . 62 - 4 . 71 ( m , 1 h ), 4 . 75 ( d , j = 5 . 9 hz , 2 h ), 5 . 50 ( s , 2 h ), 6 . 37 ( t , j = 6 . 0 hz , 1 h ), 6 . 53 ( d , j = 7 . 9 hz , 1 h ), 6 . 61 ( d , j = 2 . 1 hz , 1 h ), 6 . 76 - 6 . 85 ( m , 1 h ), 7 . 18 ( dd , j = 7 . 6 , 5 . 0 hz , 1 h ), 7 . 47 - 7 . 57 ( m , 3 h ), 8 . 40 ( d , j = 2 . 3 hz , 1 h ), 8 . 49 ( s , 1 h ), 8 . 61 ( d , j = 3 . 8 hz , 1 h ). n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 6 - isobutoxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 149 ). the title compound was prepared from n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 147 ) by general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 0 . 98 ( d , j = 6 . 4 hz , 6 h ), 1 . 30 ( d , j = 7 . 3 hz , 6 h ), 1 . 91 - 2 . 06 ( m , 1 h ), 3 . 42 - 3 . 58 ( m , 1 h ), 3 . 66 ( d , j = 6 . 4 hz , 2 h ), 4 . 67 ( s , 2 h ), 5 . 54 ( s , 2 h ), 6 . 63 ( d , j = 7 . 9 hz , 1 h ), 6 . 75 ( d , j = 2 . 1 hz , 1 h ), 6 . 81 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 29 ( dd , j = 7 . 3 , 5 . 0 hz , 1 h ), 7 . 52 ( d , j = 8 . 8 hz , 1 h ), 7 . 61 - 7 . 75 ( m , 2 h ), 8 . 38 ( d , j = 2 . 6 hz , 1 h ), 8 . 50 ( s , 1 h ), 8 . 54 ( d , j = 5 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( thiazol - 2 - yloxy )- 1h - indole - 3 - carboxamide ( compound 150 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ) by , in order , general procedure c , general procedure l , and general procedure u . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 3 hz , 6 h ), 3 . 65 - 3 . 79 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 50 ( s , 2 h ), 6 . 31 - 6 . 41 ( m , 1 h ), 6 . 56 ( d , j = 7 . 9 hz , 1 h ), 6 . 74 ( d , j = 3 . 8 hz , 1 h ), 7 . 05 - 7 . 31 ( m , 7 h ), 7 . 48 - 7 . 58 ( m , 1 h ), 7 . 65 ( d , j = 9 . 1 hz , 1 h ), 8 . 58 ( d , j = 5 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 151 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ) and 3 -( bromomethyl ) pyridine . hbr by , in order , general procedure j , general procedure k , general procedure c , and general procedure l . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 3 . 66 - 3 . 81 ( m , 1 h ), 4 . 66 ( d , j = 6 . 2 hz , 2 h ), 5 . 36 ( s , 2 h ), 6 . 28 - 6 . 36 ( m , 1 h ), 6 . 53 ( d , j = 1 . 2 hz , 1 h ), 6 . 73 ( d , j = 7 . 0 hz , 1 h ), 7 . 08 - 7 . 31 ( m , 6 h ), 7 . 46 ( d , j = 8 . 5 hz , 1 h ), 8 . 41 ( d , j = 36 . 9 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 6 -( thiazol - 2 - yloxy )- 1h - indole - 3 - carboxamide ( compound 152 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 151 ) by general procedure u . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 35 ( d , j = 7 . 3 hz , 6 h ), 3 . 40 - 3 . 54 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 61 ( s , 2 h ), 6 . 95 ( d , j = 3 . 8 hz , 1 h ), 7 . 08 ( dd , j = 8 . 4 , 2 . 2 hz , 1 h ), 7 . 18 ( d , j = 4 . 1 hz , 1 h ), 7 . 21 - 7 . 28 ( m , 2 h ), 7 . 29 - 7 . 41 ( m , 4 h ), 7 . 68 ( d , j = 8 . 5 hz , 1 h ), 8 . 20 ( d , j = 1 . 2 hz , 1 h ), 8 . 41 ( dd , j = 4 . 4 , 1 . 8 hz , 1 h ). 6 -( cyclopentyloxy )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 153 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 151 ) by general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( d , j = 7 . 3 hz , 6 h ), 1 . 52 - 1 . 63 ( m , 2 h ), 1 . 64 - 1 . 87 ( m , 6 h ), 3 . 43 - 3 . 57 ( m , 1 h ), 4 . 57 ( s , 2 h ), 4 . 67 - 4 . 77 ( m , 1 h ), 5 . 55 ( s , 2 h ), 6 . 70 ( d , j = 2 . 1 hz , 1 h ), 6 . 76 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 19 - 7 . 27 ( m , 2 h ), 7 . 28 - 7 . 40 ( m , 3 h ), 7 . 49 ( d , j = 8 . 5 hz , 1 h ), 8 . 22 ( s , 1 h ), 8 . 41 ( dd , j = 4 . 4 , 2 . 1 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 154 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 151 ) by general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 21 ( d , j = 6 . 2 hz , 6 h ), 1 . 33 ( d , j = 7 . 3 hz , 6 h ), 3 . 42 - 3 . 57 ( m , 1 h ), 4 . 43 - 4 . 54 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 55 ( s , 2 h ), 6 . 74 - 6 . 83 ( m , 2 h ), 7 . 19 - 7 . 27 ( m , 2 h ), 7 . 28 - 7 . 39 ( m , 3 h ), 7 . 50 ( d , j = 9 . 1 hz , 1 h ), 8 . 21 ( s , 1 h ), 8 . 41 ( dd , j = 4 . 3 , 2 . 2 hz , 1 h ). 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxylic acid ( compound 155 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ) by general procedure k . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 30 ( d , j = 6 . 7 hz , 6 h ), 2 . 51 - 2 . 74 ( m , 1 h ), 3 . 89 ( s , 3 h ), 6 . 63 ( dd , j = 8 . 9 , 2 . 5 hz , 1 h ), 8 . 03 ( d , j = 9 . 1 hz , 1 h ), 8 . 48 ( d , j = 2 . 3 hz , 1 h ), 11 . 15 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxamide ( compound 156 ). to a solution of 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxylic acid ( compound 155 , 10 mg , 0 . 046 mmol ) in ch 2 cl 2 ( 1 ml ) was added i - pr 2 net ( 17 μl , 0 . 098 mmol ) and 3 , 4 - difluorobenzylamine ( 11 μl , 0 . 092 mmol ), followed by bop . after completion , the reaction was diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 27 ( d , j = 6 . 7 hz , 6 h ), 2 . 53 - 2 . 68 ( m , 1 h ), 3 . 86 ( s , 3 h ), 4 . 56 ( d , j = 5 . 9 hz , 2 h ), 6 . 47 ( dd , 1 h ), 6 . 57 ( dd , j = 8 . 8 , 2 . 6 hz , 1 h ), 7 . 01 - 7 . 22 ( m , 3 h ), 7 . 39 ( d , j = 8 . 8 hz , 1 h ), 8 . 41 ( d , j = 2 . 6 hz , 1 h ), 11 . 57 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 1 - isobutyl - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxamide ( compound 157 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ) and 1 - iodo - 2 - methylpropane by , in order , general procedure j , general procedure k , and general procedure c . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 0 . 96 ( d , j = 6 . 7 hz , 6 h ), 1 . 50 ( d , j = 7 . 0 hz , 6 h ), 2 . 13 - 2 . 26 ( m , 1 h ), 3 . 28 - 3 . 41 ( m , 1 h ), 3 . 86 ( s , 3 h ), 3 . 89 ( d , j = 7 . 6 hz , 2 h ), 4 . 65 ( d , j = 6 . 2 hz , 2 h ), 6 . 20 - 6 . 28 ( m , 1 h ), 6 . 76 - 6 . 83 ( m , 2 h ), 7 . 10 - 7 . 17 ( m , 2 h ), 7 . 19 - 7 . 30 ( m , 1 h ), 7 . 47 ( d , j = 8 . 5 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 1 - isobutyl - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 158 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 1 - isobutyl - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxamide ( compound 157 ) by general procedure l . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 0 . 95 ( d , j = 6 . 7 hz , 6 h ), 1 . 49 ( d , j = 7 . 0 hz , 6 h ), 2 . 11 - 2 . 27 ( m , 1 h ), 3 . 26 - 3 . 40 ( m , 1 h ), 3 . 86 ( d , j = 7 . 6 hz , 2 h ), 4 . 65 ( d , j = 6 . 2 hz , 2 h ), 4 . 79 ( s , 1 h ), 6 . 23 ( t , j = 6 . 2 hz , 1 h ), 6 . 68 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 6 . 77 ( d , j = 2 . 3 hz , 1 h ), 7 . 09 - 7 . 16 ( m , 2 h ), 7 . 18 - 7 . 28 ( m , 1 h ), 7 . 42 ( d , j = 8 . 5 hz , 1 h ). 6 -( cyclopentyloxy )- n -( 3 , 4 - difluorobenzyl )- 1 - isobutyl - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 159 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 1 - isobutyl - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 158 ) by general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 0 . 96 ( d , j = 6 . 7 hz , 6 h ), 1 . 49 ( d , j = 7 . 0 hz , 6 h ), 1 . 59 - 1 . 70 ( m , 2 h ), 1 . 73 - 1 . 97 ( m , 6 h ), 2 . 12 - 2 . 26 ( m , 1 h ), 3 . 27 - 3 . 40 ( m , 1 h ), 3 . 88 ( d , j = 7 . 6 hz , 2 h ), 4 . 65 ( d , j = 5 . 9 hz , 2 h ), 4 . 76 - 4 . 84 ( m , 1 h ), 6 . 24 ( t , j = 6 . 6 hz , 1 h ), 6 . 74 - 6 . 81 ( m , 2 h ), 7 . 09 - 7 . 16 ( m , 2 h ), 7 . 18 - 7 . 28 ( m , 1 h ), 7 . 42 - 7 . 48 ( m , 1 h ). 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 160 ). general procedure v . to a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 8 , 48 mg , 0 . 11 mmol ) in ch 2 cl 2 ( 2 ml ) was added 2 -[ n , n - bis ( trifluoromethylsulphonyl ) amino ]- 5 - chloropyridine ( 48 mg , 0 . 12 mmol ) and dmap ( 15 mg , 0 . 12 mmol ). the reaction was stirred at room temperature for 16 h , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 39 ( d , j = 7 . 3 hz , 6 h ), 3 . 57 - 3 . 72 ( m , 1 h ), 4 . 65 ( d , j = 5 . 9 hz , 2 h ), 5 . 43 ( s , 2 h ), 6 . 30 ( t , j = 5 . 7 hz , 1 h ), 6 . 89 - 6 . 98 ( m , 2 h ), 7 . 02 - 7 . 09 ( m , 2 h ), 7 . 11 - 7 . 18 ( m , 2 h ), 7 . 18 - 7 . 36 ( m , 4 h ), 7 . 66 ( d , j = 9 . 4 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( pyridin - 4 - yl )- 1h - indole - 3 - carboxamide ( compound 161 ). general procedure w . a mixture of 1 - benzyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 160 , 50 mg , 0 . 088 mmol ), pyridin - 4 - ylboronic acid ( 22 mg , 0 . 18 mmol ), pd ( pph 3 ) 4 ( 5 . 0 mg , 0 . 0043 mmol ), k 2 co 3 ( 61 mg , 0 . 44 mmol ), and licl ( 19 mg , 0 . 44 mmol ) in toluene ( 3 ml ), meoh ( 1 ml ), and h 2 o ( 0 . 5 ml ) was heated at 90 ° c . for 16 h . the reaction was then cooled to room temperature , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 35 ( d , j = 7 . 0 hz , 6 h ), 3 . 41 - 3 . 58 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 63 ( s , 2 h ), 6 . 94 - 7 . 06 ( m , 2 h ), 7 . 16 - 7 . 44 ( m , 5 h ), 7 . 49 - 7 . 81 ( m , 6 h ), 8 . 47 ( dd , j = 4 . 7 , 1 . 8 hz , 2 h ). n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 162 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ), 3 -( bromomethyl ) pyridine . hbr , and ( 5 - fluoropyridin - 3 - yl ) methanamine ( compound 145 ) by , in order , general procedure j , general procedure k , general procedure c , and general procedure l . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 0 hz , 6 h ), 3 . 41 - 3 . 58 ( m , 1 h ), 4 . 67 ( d , j = 6 . 2 hz , 2 h ), 5 . 50 ( s , 2 h ), 6 . 61 ( d , j = 2 . 1 hz , 1 h ), 6 . 71 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 7 . 29 - 7 . 39 ( m , 2 h ), 7 . 46 ( d , j = 8 . 5 hz , 1 h ), 7 . 69 ( d , j = 9 . 1 hz , 1 h ), 7 . 90 ( s , 1 h ), 8 . 21 ( s , 1 h ), 8 . 35 - 8 . 44 ( m , 2 h ), 8 . 50 ( s , 1 h ), 8 . 60 ( t , j = 5 . 7 hz , 1 h ). 6 -( cyclopentyloxy )- n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 163 ). the title compound was prepared from n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 162 ) and cyclopentyl iodide by general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 33 ( d , j = 7 . 3 hz , 6 h ), 1 . 50 - 1 . 64 ( m , 2 h ), 1 . 64 - 1 . 90 ( m , 6 h ), 3 . 44 - 3 . 58 ( m , 1 h ), 4 . 67 ( s , 2 h ), 4 . 70 - 4 . 77 ( m , 1 h ), 5 . 56 ( s , 2 h ), 6 . 72 ( d , j = 2 . 1 hz , 1 h ), 6 . 77 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 30 - 7 . 41 ( m , 2 h ), 7 . 51 ( d , j = 8 . 8 hz , 1 h ), 7 . 65 - 7 . 75 ( m , 1 h ), 8 . 22 ( s , 1 h ), 8 . 35 - 8 . 45 ( m , 2 h ), 8 . 50 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( pyridin - 4 - yl )- 1h - indole - 3 - carboxamide ( compound 164 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ), 3 , 4 - difluorobenzylamine , and pyridin - 4 - ylboronic acid by , in order , general procedure c , general procedure l , general procedure v , and general procedure w . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 35 ( d , j = 7 . 0 hz , 6 h ), 3 . 44 - 3 . 57 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 71 ( s , 2 h ), 6 . 74 ( d , j = 7 . 9 hz , 1 h ), 7 . 21 - 7 . 42 ( m , 4 h ), 7 . 56 ( dd , j = 8 . 2 , 1 . 8 hz , 1 h ), 7 . 62 - 7 . 79 ( m , 5 h ), 8 . 49 ( d , j = 6 . 2 hz , 2 h ), 8 . 54 ( d , j = 4 . 1 hz , 1 h ). 6 - cyclobutoxy - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 3 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 165 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ), 3 -( bromomethyl ) pyridine . hbr , 3 , 4 - difluorobenzylamine , and cyclobutyl bromide by , in order , general procedure j , general procedure k , general procedure c , general procedure l , and general procedure n . 1h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 39 ( d , j = 7 . 3 hz , 6 h ), 1 . 60 - 1 . 74 ( m , 2 h ), 2 . 04 - 2 . 15 ( m , 2 h ), 2 . 27 - 2 . 39 ( m , 2 h ), 3 . 70 - 3 . 81 ( m , 1 h ), 4 . 50 - 4 . 60 ( m , 1 h ), 4 . 66 ( d , j = 5 . 9 hz , 2 h ), 5 . 41 ( s , 2 h ), 6 . 29 ( t , j = 5 . 6 hz , 1 h ), 6 . 49 ( d , j = 2 . 2 hz , 1 h ), 6 . 75 ( dd , j = 8 . 7 , 2 . 1 hz , 1 h ), 7 . 11 - 7 . 18 ( m , 3 h ), 7 . 18 - 7 . 28 ( m , 2 h ), 7 . 50 ( d , j = 8 . 6 hz , 1 h ), 8 . 43 ( s , 1 h ), 8 . 52 ( s , 1 h ). ethyl 2 -( 5 - fluoro - 2 , 4 - dinitrophenyl )- 4 - methyl - 3 - oxopentanoate ( compound 166 ). general procedure x . to a solution of 1 , 5 - difluoro - 2 , 4 - dinitrobenzene ( aldrich , 10 . 6 g , 52 . 0 mmol ) in thf ( 100 ml ) was added ethyl isobutyryl acetate ( 8 . 4 ml , 52 . 0 mmol ) and k 2 co 3 ( 8 . 6 g , 62 . 3 mmol ). the mixture was stirred at room temperature for 2 h , diluted with etoac , washed with aqueous hcl and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 25 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 07 ( d , j = 6 . 7 hz , 3 h ), 1 . 13 ( t , j = 7 . 0 hz , 3 h ), 1 . 19 ( d , j = 6 . 7 hz , 3 h ), 2 . 22 - 2 . 48 ( m , 1 h ), 3 . 91 - 4 . 38 ( m , 2 h ), 7 . 24 ( d , j = 10 . 3 hz , 1 h ), 8 . 79 ( d , j = 7 . 0 hz , 1 h ), 13 . 21 ( d , j = 1 . 5 hz , 1 h ). ethyl 6 - amino - 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxylate ( compound 167 ). the title compound was prepared from ethyl2 -( 5 - fluoro - 2 , 4 - dinitrophenyl )- 4 - methyl - 3 - oxopentanoate ( compound 166 ) by general procedure r . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 34 ( d , j = 7 . 0 hz , 6 h ), 1 . 44 ( t , j = 7 . 0 hz , 3 h ), 3 . 70 ( s , 2 h ), 3 . 99 - 4 . 15 ( m , 1 h ), 4 . 37 ( q , j = 7 . 1 hz , 2 h ), 6 . 71 ( d , j = 7 . 6 hz , 1 h ), 7 . 69 ( d , j = 12 . 0 hz , 1 h ), 8 . 12 ( s , 1 h ). ethyl 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylate ( compound 92 ). general procedure y . to a solution of ethyl6 - amino - 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxylate ( compound 167 , 1 . 92 g , 7 . 3 mmol ) in acetone ( 20 ml ) and ch 2 cl 2 ( 20 ml ) was added saturated aqueous nahco 3 ( 10 ml ) and mcpba ( 6 . 3 g , 36 . 5 mmol ). the resulting reddish brown solution was stirred at room temperature for 2 h , extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 35 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 41 ( d , j = 7 . 0 hz , 6 h ), 1 . 46 ( t , j = 7 . 0 hz , 3 h ), 4 . 06 - 4 . 21 ( m , 1 h ), 4 . 42 ( q , j = 7 . 1 hz , 2 h ), 7 . 94 ( d , j = 12 . 3 hz , 1 h ), 8 . 16 ( d , j = 6 . 2 hz , 1 h ), 8 . 65 ( s , 1 h ). ethyl 1 - benzyl - 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylate ( compound 169 ). the title compound was prepared from ethyl5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylate ( compound 168 ) and benzyl bromide by general procedure j . 1h nmr ( 500 mhz , chloroform - d ) δ ppm 1 . 41 ( d , j = 7 . 3 hz , 6 h ), 1 . 50 ( t , j = 7 . 2 hz , 3 h ), 3 . 90 - 4 . 04 ( m , 1 h ), 4 . 45 ( q , j = 7 . 1 hz , 2 h ), 5 . 54 ( s , 2 h ), 6 . 93 ( d , j = 6 . 4 hz , 2 h ), 7 . 29 - 7 . 36 ( m , 3 h ), 7 . 96 ( d , j = 6 . 1 hz , 1 h ), 8 . 00 ( d , j = 12 . 7 hz , 1 h ). 1 - benzyl - 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylic acid ( compound 170 ). general procedure z . to a solution of ethyl1 - benzyl - 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylate ( compound 169 , 546 mg , 1 . 54 mmol ) in etoh ( 10 ml ) was added 5 m naoh ( 3 . 1 ml , 15 . 5 mmol ). the reaction was heated at 80 ° c . for 5 h , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 50 % etoac - hexanes ) to yield the title compound as a brown solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 46 ( d , j = 7 . 0 hz , 6 h ), 3 . 94 - 4 . 16 ( m , 1 h ), 5 . 57 ( s , 2 h ), 6 . 91 - 7 . 01 ( m , 2 h ), 7 . 32 ( t , j = 6 . 4 hz , 3 h ), 7 . 92 - 8 . 01 ( m , 1 h ), 8 . 16 ( d , j = 12 . 3 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxamide ( compound 171 ). the title compound was prepared from 1 - benzyl - 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxylic acid ( compound 170 ) and 3 , 4 - difluorobenzylamine by general procedure c . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 40 ( d , j = 7 . 0 hz , 6 h ), 3 . 48 - 3 . 63 ( m , 1 h ), 4 . 67 ( d , j = 5 . 9 hz , 2 h ), 5 . 48 ( s , 2 h ), 6 . 21 ( t , j = 6 . 0 hz , 1 h ), 6 . 92 ( dd , j = 7 . 5 , 2 . 2 hz , 2 h ), 7 . 12 - 7 . 36 ( m , 6 h ), 7 . 43 ( d , j = 12 . 0 hz , 1 h ), 7 . 98 ( d , j = 5 . 9 hz , 1 h ). 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 172 ). the title compound was prepared from 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 6 - nitro - 1h - indole - 3 - carboxamide ( compound 171 ) by general procedure s . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 ( d , j = 7 . 3 hz , 6 h ), 3 . 39 - 3 . 52 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 40 ( s , 2 h ), 6 . 70 ( d , j = 7 . 3 hz , 1 h ), 6 . 93 ( dd , j = 7 . 9 , 1 . 5 hz , 2 h ), 7 . 16 - 7 . 38 ( m , 7 h ). 1 - benzyl - 6 -( cyclopentylamino )- n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 173 ). the title compound was prepared from 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 172 ) and cyclopentanone by general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 33 ( d , j = 7 . 3 hz , 6 h ), 1 . 36 - 2 . 10 ( m , 8 h ), 3 . 46 - 3 . 59 ( m , 1 h ), 3 . 58 - 3 . 70 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 43 ( s , 2 h ), 6 . 46 ( d , j = 7 . 3 hz , 1 h ), 6 . 93 - 7 . 03 ( m , 2 h ), 7 . 13 - 7 . 41 ( m , 7 h ), 8 . 40 ( s , 1 h ). 1 - benzyl - n - cyclopentyl - 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 5 - fluoro - 2 - isopropyl - n , n - dimethyl - 1h - indol - 6 - aminium chloride ( compound 174 ). to a solution of 1 - benzyl - 6 -( cyclopentylamino )- n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 173 , 12 mg , 0 . 023 mmol ) in dmf ( 2 ml ) was added mei ( 15 μl , 0 . 23 mmol ) and k 2 co 3 ( 32 mg , 0 . 23 mmol ). the reaction was stirred at room temperature for 16 h , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by reverse phase chromatography on c18 bonded silica gel ( 90 % meoh — h 2 o ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 33 ( d , j = 7 . 0 hz , 6 h ), 1 . 57 - 1 . 89 ( m , 8 h ), 3 . 36 - 3 . 54 ( m , 1 h ), 3 . 65 ( s , 6 h ), 4 . 58 ( s , 2 h ), 4 . 74 - 4 . 83 ( m , 1 h ), 5 . 69 ( s , 2 h ), 6 . 92 - 7 . 01 ( m , 2 h ), 7 . 19 - 7 . 40 ( m , 7 h ), 7 . 60 ( d , j = 15 . 2 hz , 1 h ), 7 . 75 ( d , j = 6 . 7 hz , 1 h ), 8 . 77 ( t , j = 6 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 2 -( pyrrolidin - 1 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 175 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 2 - formyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 94 ) and pyrrolidine by , in order , general procedure p , general procedure m , and general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 30 ( d , j = 6 . 2 hz , 6 h ), 1 . 55 ( s , 4 h ), 2 . 34 ( s , 4 h ), 3 . 76 ( s , 2 h ), 4 . 45 - 4 . 62 ( m , 3 h ), 5 . 50 ( s , 2 h ), 6 . 51 ( d , j = 7 . 6 hz , 1 h ), 6 . 75 ( d , j = 1 . 8 hz , 1 h ), 6 . 92 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 05 - 7 . 30 ( m , 4 h ), 7 . 45 - 7 . 56 ( m , 1 h ), 8 . 29 ( d , j = 8 . 8 hz , 1 h ), 8 . 58 ( d , j = 4 . 7 hz , 1 h ), 10 . 15 ( t , j = 4 . 5 hz , 1 h ). 1 -(( 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 2 - yl ) methyl )- 1 - methylpyrrolidinium iodide ( compound 176 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 2 -( pyrrolidin - 1 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 175 , 17 mg , 0 . 033 mmol ) in acetone ( 1 ml ) was added mei ( 0 . 1 ml , 1 . 6 mmol ). the reaction was stirred at room temperature for 16 h and the solvent was removed in vacuo . the residue was purified by ptlc on silica gel ( 10 % meoh - etoac ) to yield the title compound . 1h nmr ( 300 mhz , acetone ) δ ppm 1 . 22 ( d , j = 5 . 9 hz , 6 h ), 2 . 25 ( s , 4 h ), 3 . 35 ( s , 3 h ), 3 . 72 - 3 . 97 ( m , 4 h ), 4 . 52 - 4 . 67 ( m , 1 h ), 4 . 70 ( t , j = 5 . 3 hz , 2 h ), 5 . 63 ( s , 2 h ), 6 . 84 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 01 ( d , j = 2 . 1 hz , 1 h ), 7 . 20 - 7 . 54 ( m , 5 h ), 7 . 70 - 7 . 79 ( m , 1 h ), 7 . 88 ( d , j = 9 . 1 hz , 1 h ), 8 . 19 ( t , j = 6 . 3 hz , 1 h ), 8 . 44 ( d , j = 4 . 1 hz , 1 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 3 , 4 - dihydro - 2h - pyrrol - 5 - ylamino )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 177 ). a mixture of 2 - pyrrolidinone ( 47 mg , 0 . 55 mmol ) and pocl 3 ( 0 . 10 ml , 1 . 1 mmol ) was stirred at 0 ° c . to room temperature for 2h . to the above mixture was then added a solution of 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 172 , 50 mg , 0 . 11 mmol ) in toluene ( 3 ml ). the reaction was heated to 110 ° c . for 16 h and was cooled to room temperature , diluted with etoac , washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by reverse phase chromatography on c18 bonded silica gel ( meoh ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 26 - 1 . 37 ( m , 8 h ), 2 . 53 ( t , j = 7 . 8 hz , 2 h ), 3 . 37 - 3 . 57 ( m , 3 h ), 4 . 57 ( s , 2 h ), 5 . 47 ( s , 2 h ), 6 . 90 - 7 . 02 ( m , 3 h ), 7 . 15 - 7 . 41 ( m , 7 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 5 - dihydrothiazol - 2 - ylamino )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 178 ). general procedure aa . to a solution of 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 172 , 39 mg , 0 . 086 mmol ) in ch 2 cl 2 ( 1 ml ) was added 2 - chloroethyl isothiocyanate ( 25 μl , 0 . 26 mmol ) and et 3 n ( 1 drop ). the reaction was stirred at room temperature for 16 h and was purified directly by chromatography on silica gel ( 0 → 60 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 36 ( d , j = 7 . 0 hz , 6 h ), 3 . 28 ( t , j = 7 . 0 hz , 2 h ), 3 . 58 - 3 . 70 ( m , 1 h ), 3 . 79 ( t , j = 6 . 9 hz , 2 h ), 4 . 65 ( d , j = 5 . 6 hz , 2 h ), 5 . 38 ( s , 2 h ), 6 . 17 - 6 . 25 ( m , 1 h ), 6 . 96 ( d , j = 6 . 4 hz , 2 h ), 7 . 10 - 7 . 18 ( m , 2 h ), 7 . 20 - 7 . 35 ( m , 6 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 6 - iodo - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 179 ). to a solution of 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 96 , 324 mg , 0 . 72 mmol ) in meoh ( 5 ml ) at − 10 ° c . was added 2 m h 2 so 4 ( 3 ml , 6 . 0 mmol ) followed by sodium nitrite ( 50 mg , 0 . 72 mmol ). the reaction was stirred at − 10 ° c . for 0 . 5 h and a solution of potassium iodide ( 477 mg , 2 . 9 mmol ) in h 2 o ( 3 ml ) was added . the mixture was stirred for another 0 . 5 h and was extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 3 . 37 - 3 . 52 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 47 - 5 . 53 ( m , 2 h ), 6 . 82 - 6 . 97 ( m , 2 h ), 7 . 17 - 7 . 39 ( m , 8 h ). 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carboxamide ( compound 180 ). to a mixture of sodium methoxide ( freshly prepared from 25 mg sodium and 1 ml meoh ) and cui ( 30 mg , 0 . 16 mmol ) was added a solution of 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 5 - fluoro - 6 - iodo - 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 179 , 30 mg , 0 . 053 mmol ) in dmf ( 0 . 5 ml ). the reaction was heated to 110 ° c . for 16 h , and was filtered and concentrated . the residue was purified by chromatography on silica gel ( 0 → 30 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 0 hz , 6 h ), 3 . 37 - 3 . 51 ( m , 1 h ), 3 . 76 ( s , 3 h ), 4 . 56 ( s , 2 h ), 5 . 50 ( s , 2 h ), 6 . 88 - 6 . 98 ( m , 3 h ), 7 . 17 - 7 . 38 ( m , 7 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - nitro - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 181 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , and general procedure c . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( d , j = 7 . 3 hz , 6 h ), 3 . 41 - 3 . 58 ( m , 1 h ), 4 . 59 ( s , 2 h ), 5 . 72 ( s , 2 h ), 6 . 90 ( d , j = 7 . 9 hz , 1 h ), 7 . 19 - 7 . 41 ( m , 4 h ), 7 . 67 - 7 . 78 ( m , 2 h ), 8 . 04 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 8 . 33 ( d , j = 2 . 1 hz , 1 h ), 8 . 51 ( d , j = 4 . 1 hz , 1 h ). 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 ( d , j = 7 . 0 hz , 6 h ), 3 . 41 - 3 . 58 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 48 ( s , 2 h ), 6 . 54 - 6 . 62 ( m , 2 h ), 6 . 66 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 17 - 7 . 37 ( m , 4 h ), 7 . 39 ( d , j = 8 . 5 hz , 1 h ), 7 . 58 - 7 . 70 ( m , 1 h ), 8 . 53 ( d , j = 4 . 1 hz , 1 h ). 6 -( cyclopentylamino )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 183 ). the title compound was prepared from 6 - amino - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 182 ) by general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 1 . 34 - 1 . 75 ( m , 6 h ), 1 . 80 - 1 . 95 ( m , 2 h ), 3 . 47 - 3 . 60 ( m , 1 h ), 3 . 61 - 3 . 73 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 49 ( s , 2 h ), 6 . 39 ( d , j = 1 . 8 hz , 1 h ), 6 . 58 - 6 . 67 ( m , 2 h ), 7 . 19 - 7 . 36 ( m , 4 h ), 7 . 38 ( d , j = 8 . 8 hz , 1 h ), 7 . 60 - 7 . 71 ( m , 1 h ), 8 . 54 ( d , j = 5 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 5 - dihydrothiazol - 2 - ylamino )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 184 ). the title compound was prepared from 6 - amino - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 106 ) by general procedure aa . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 3 . 24 ( t , j = 7 . 0 hz , 2 h ), 3 . 43 - 3 . 58 ( m , 1 h ), 3 . 79 ( t , j = 7 . 2 hz , 2 h ), 4 . 57 ( s , 2 h ), 5 . 54 ( s , 2 h ), 6 . 65 ( d , j = 7 . 9 hz , 1 h ), 6 . 93 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 14 - 7 . 39 ( m , 5 h ), 7 . 51 ( d , j = 8 . 5 hz , 1 h ), 7 . 61 - 7 . 69 ( m , 1 h ), 8 . 53 ( d , j = 4 . 1 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 5 - dihydrothiazol - 2 - ylamino )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide , hydrogen chloride salt ( compound 185 ). the title compound was also isolated in the synthesis of compound 184 . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 3 . 41 - 3 . 54 ( m , 1 h ), 3 . 58 ( t , j = 7 . 5 hz , 2 h ), 3 . 99 ( t , j = 7 . 6 hz , 2 h ), 4 . 59 ( d , j = 4 . 1 hz , 2 h ), 5 . 61 ( s , 2 h ), 6 . 81 ( d , j = 7 . 9 hz , 1 h ), 7 . 04 - 7 . 12 ( m , 1 h ), 7 . 19 - 7 . 41 ( m , 5 h ), 7 . 64 - 7 . 77 ( m , 2 h ), 8 . 51 ( d , j = 4 . 1 hz , 1 h ), 8 . 67 ( t , j = 6 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 -( 4 , 5 - dihydrooxazol - 2 - ylamino )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 186 ). to a solution of 6 - amino - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 182 , 48 mg , 0 . 11 mmol ) in ch 2 cl 2 ( 1 ml ) was added chloroethyl isocyanate ( 10 μl , 0 . 12 mmol ). the reaction was stirred at room temperature for 16 h , and the solvent was removed . to the residue was added h 2 o and the mixture was heated at 80 ° c . for 3 h , diluted with etoac , washed with aqueous k 2 co 3 and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 ( d , j = 7 . 3 hz , 6 h ), 3 . 40 - 3 . 53 ( m , 1 h ), 3 . 72 ( t , j = 8 . 4 hz , 2 h ), 4 . 34 ( t , j = 8 . 4 hz , 2 h ), 4 . 57 ( s , 2 h ), 5 . 55 ( s , 2 h ), 6 . 65 ( d , j = 7 . 9 hz , 1 h ), 7 . 01 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 19 - 7 . 38 ( m , 5 h ), 7 . 52 ( d , j = 8 . 8 hz , 1 h ), 7 . 60 - 7 . 68 ( m , 1 h ), 8 . 52 ( d , j = 4 . 1 hz , 1 h ). 6 -( 3 -( 2 - chloroethyl ) ureido )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 187 ). the title compound was also isolated in the synthesis of compound 186 . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 0 hz , 6 h ), 3 . 42 - 3 . 54 ( m , 3 h ), 3 . 55 - 3 . 67 ( m , 2 h ), 4 . 57 ( s , 2 h ), 5 . 54 ( s , 2 h ), 6 . 65 ( d , j = 7 . 9 hz , 1 h ), 6 . 99 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 7 . 17 - 7 . 38 ( m , 4 h ), 7 . 46 - 7 . 56 ( m , 2 h ), 7 . 61 - 7 . 72 ( m , 1 h ), 8 . 53 ( d , j = 4 . 7 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( pyrrolidin - 1 - yl )- 1h - indole - 3 - carboxamide ( compound 188 ). to a solution of 6 - amino - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 182 , 64 mg , 0 . 15 mmol ) in toluene ( 2 ml ) was added 1 , 4 - dibromobutane ( 19 μl , 0 . 16 mmol ) and i - pr 2 net ( 77 μl , 0 . 44 mmol ). the reaction was heated at 110 ° c . for 16 h , and was purified directly by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 0 hz , 6 h ), 1 . 92 - 2 . 00 ( m , 4 h ), 3 . 04 - 3 . 26 ( m , 4 h ), 3 . 40 - 3 . 65 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 50 ( s , 2 h ), 6 . 17 - 6 . 35 ( m , 1 h ), 6 . 50 - 6 . 67 ( m , j = 8 . 4 , 8 . 4 hz , 2 h ), 7 . 19 - 7 . 38 ( m , 4 h ), 7 . 45 ( d , j = 8 . 5 hz , 1 h ), 7 . 58 - 7 . 70 ( m , 1 h ), 8 . 54 ( d , j = 5 . 0 hz , 1 h ). 1 - benzyl - 6 -( cyclopentyl ( methyl ) amino )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 189 ). the title compound was prepared from 1 - benzyl - 6 -( cyclopentylamino )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 130 ) by general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( d , j = 7 . 0 hz , 6 h ), 1 . 41 - 1 . 57 ( m , 4 h ), 1 . 57 - 1 . 77 ( m , 4 h ), 2 . 68 ( s , 3 h ), 3 . 45 - 3 . 61 ( m , 1 h ), 3 . 69 - 3 . 81 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 47 ( s , 2 h ), 6 . 78 ( d , j = 1 . 8 hz , 1 h ), 6 . 88 - 7 . 01 ( m , 3 h ), 7 . 15 - 7 . 39 ( m , 6 h ), 7 . 50 ( d , j = 8 . 8 hz , 1 h ). 1 - benzyl - 6 -( cyclobutylamino )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 190 ). the title compound was prepared from 6 - amino - 1 - benzyl - n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 125 ) by general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 2 hz , 6 h ), 1 . 66 - 1 . 86 ( m , 4 h ), 2 . 18 - 2 . 32 ( m , 2 h ), 3 . 44 - 3 . 60 ( m , 1 h ), 3 . 73 - 3 . 88 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 41 ( s , 2 h ), 6 . 36 ( d , j = 1 . 9 hz , 1 h ), 6 . 57 ( dd , j = 8 . 6 , 2 . 0 hz , 1 h ), 6 . 94 - 7 . 01 ( m , 2 h ), 7 . 18 - 7 . 35 ( m , 6 h ), 7 . 38 ( d , j = 8 . 5 hz , 1 h ). 1 - benzyl - 6 -( cyclopentylamino )- n -( 3 , 5 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 191 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 0 hz , 6 h ), 1 . 35 - 1 . 47 ( m , 2 h ), 1 . 47 - 1 . 59 ( m , 2 h ), 1 . 60 - 1 . 73 ( m , 2 h ), 1 . 79 - 1 . 93 ( m , 2 h ), 3 . 46 - 3 . 59 ( m , 1 h ), 3 . 61 - 3 . 73 ( m , 1 h ), 4 . 55 - 4 . 64 ( m , 2 h ), 5 . 41 ( s , 2 h ), 6 . 45 ( d , j = 1 . 8 hz , 1 h ), 6 . 62 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 6 . 76 - 6 . 88 ( m , 1 h ), 6 . 93 - 7 . 08 ( m , 4 h ), 7 . 13 - 7 . 29 ( m , 3 h ), 7 . 41 ( d , j = 8 . 5 hz , 1 h ), 8 . 38 ( t , j = 6 . 2 hz , 1 h ). 1 - benzyl - 6 -( cyclopentylamino )- n -( 4 - fluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 192 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 1 . 35 - 1 . 45 ( m , 2 h ), 1 . 50 - 1 . 59 ( m , 2 h ), 1 . 62 - 1 . 75 ( m , 2 h ), 1 . 79 - 1 . 93 ( m , 2 h ), 3 . 44 - 3 . 58 ( m , 1 h ), 3 . 61 - 3 . 73 ( m , 1 h ), 4 . 58 ( d , j = 5 . 9 hz , 2 h ), 5 . 41 ( s , 2 h ), 6 . 44 ( d , j = 1 . 8 hz , 1 h ), 6 . 60 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 6 . 95 - 6 . 99 ( m , 2 h ), 7 . 03 - 7 . 12 ( m , 2 h ), 7 . 17 - 7 . 29 ( m , 3 h ), 7 . 36 ( d , j = 8 . 8 hz , 1 h ), 7 . 40 - 7 . 50 ( m , 2 h ), 8 . 30 ( t , j = 6 . 0 hz , 1 h ). 1 - benzyl - 6 -( cyclopentylamino )- n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 193 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 3 hz , 6 h ), 1 . 34 - 1 . 45 ( m , 2 h ), 1 . 47 - 1 . 60 ( m , 2 h ), 1 . 61 - 1 . 75 ( m , 2 h ), 1 . 80 - 1 . 94 ( m , 2 h ), 3 . 46 - 3 . 58 ( m , 1 h ), 3 . 60 - 3 . 72 ( m , 1 h ), 4 . 65 ( s , 2 h ), 5 . 40 ( s , 2 h ), 6 . 44 ( d , j = 1 . 8 hz , 1 h ), 6 . 62 ( dd , j = 8 . 6 , 1 . 9 hz , 1 h ), 6 . 94 - 7 . 00 ( m , 2 h ), 7 . 15 - 7 . 30 ( m , 3 h ), 7 . 40 ( d , j = 8 . 8 hz , 1 h ), 7 . 68 ( dd , j = 9 . 4 , 2 . 1 hz , 1 h ), 8 . 36 ( d , j = 2 . 6 hz , 1 h ), 8 . 49 ( s , 1 h ). 1 - benzyl - 6 -( cyclobutylamino )- n -( 3 , 5 - difluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 194 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( d , j = 7 . 3 hz , 6 h ), 1 . 67 - 1 . 82 ( m , 4 h ), 2 . 20 - 2 . 31 ( m , 2 h ), 3 . 46 - 3 . 61 ( m , 1 h ), 3 . 73 - 3 . 87 ( m , 1 h ), 4 . 56 - 4 . 62 ( m , 2 h ), 5 . 41 ( s , 2 h ), 6 . 36 ( d , j = 2 . 1 hz , 1 h ), 6 . 58 ( dd , j = 8 . 6 , 1 . 9 hz , 1 h ), 6 . 77 - 6 . 88 ( m , 1 h ), 6 . 93 - 7 . 07 ( m , 4 h ), 7 . 16 - 7 . 30 ( m , 3 h ), 7 . 41 ( d , j = 8 . 5 hz , 1 h ), 8 . 40 ( t , j = 6 . 0 hz , 1 h ). 1 - benzyl - 6 -( cyclobutylamino )- n -( 4 - fluorobenzyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 195 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 3 hz , 6 h ), 1 . 67 - 1 . 83 ( m , 4 h ), 2 . 18 - 2 . 33 ( m , 2 h ), 3 . 44 - 3 . 61 ( m , 1 h ), 3 . 72 - 3 . 86 ( m , 1 h ), 4 . 53 - 4 . 62 ( m , 2 h ), 5 . 40 ( s , 2 h ), 6 . 35 ( d , j = 2 . 1 hz , 1 h ), 6 . 55 ( dd , j = 8 . 5 , 2 . 1 hz , 1 h ), 6 . 92 - 7 . 00 ( m , 2 h ), 7 . 01 - 7 . 13 ( m , 2 h ), 7 . 15 - 7 . 30 ( m , 3 h ), 7 . 36 ( d , j = 8 . 5 hz , 1 h ), 7 . 40 - 7 . 49 ( m , 2 h ), 8 . 29 ( t , j = 6 . 3 hz , 1 h ). 1 - benzyl - 6 -( cyclobutylamino )- n -(( 5 - fluoropyridin - 3 - yl ) methyl )- 2 - isopropyl - 1h - indole - 3 - carboxamide ( compound 196 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 30 ( d , j = 7 . 3 hz , 6 h ), 1 . 64 - 1 . 86 ( m , 4 h ), 2 . 18 - 2 . 32 ( m , 2 h ), 3 . 44 - 3 . 60 ( m , 1 h ), 3 . 72 - 3 . 86 ( m , 1 h ), 4 . 64 ( s , 2 h ), 5 . 40 ( s , 2 h ), 6 . 36 ( d , j = 1 . 8 hz , 1 h ), 6 . 58 ( dd , j = 8 . 6 , 1 . 9 hz , 1 h ), 6 . 91 - 7 . 01 ( m , 2 h ), 7 . 15 - 7 . 31 ( m , 3 h ), 7 . 40 ( d , j = 8 . 8 hz , 1 h ), 7 . 63 - 7 . 73 ( m , 1 h ), 8 . 36 ( d , j = 2 . 6 hz , 1 h ), 8 . 48 ( s , 1 h ). 6 -( cyclobutylamino )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 197 ). the title compound was prepared from 1 - fluoro - 2 , 4 - dinitrobenzene and methyl isobutyryl acetate by , in order , general procedure x , general procedure r , general procedure y , general procedure j , general procedure z , general procedure c , general procedure s , and general procedure t . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 31 ( d , j = 7 . 3 hz , 6 h ), 1 . 67 - 1 . 83 ( m , 4 h ), 2 . 19 - 2 . 32 ( m , 2 h ), 3 . 46 - 3 . 61 ( m , 1 h ), 3 . 73 - 3 . 87 ( m , 1 h ), 4 . 56 ( s , 2 h ), 5 . 48 ( s , 2 h ), 6 . 31 ( d , j = 1 . 8 hz , 1 h ), 6 . 54 - 6 . 64 ( m , 2 h ), 7 . 17 - 7 . 43 ( m , 5 h ), 7 . 58 - 7 . 69 ( m , 1 h ), 8 . 54 ( d , j = 4 . 1 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide - d7 ( compound 198 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 ) by general procedure c , general procedure l , and general procedure n . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 37 ( d , j = 7 . 0 hz , 6 h ), 3 . 69 - 3 . 89 ( m , 1 h ), 4 . 67 ( d , j = 5 . 9 hz , 2 h ), 5 . 51 ( s , 2 h ), 6 . 30 ( t , j = 6 . 0 hz , 1 h ), 6 . 53 ( d , j = 7 . 9 hz , 1 h ), 6 . 65 ( d , j = 1 . 8 hz , 1 h ), 6 . 82 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 09 - 7 . 32 ( m , 4 h ), 7 . 45 - 7 . 57 ( m , 2 h ), 8 . 62 ( d , j = 4 . 7 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropenyl - 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide - d7 ( compound 199 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide - d7 ( compound 198 , 71 mg , 0 . 15 mmol ) in et 2 o ( 5 ml ) under air was added hcl ( 2 m in et 2 o , 0 . 15 ml , 0 . 30 mmol ). the solvent was removed and the residue was purified by ptlc ( 50 % etoac - hexanes ) to yield the title compound as a side product . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 2 . 00 ( t , j = 1 . 2 hz , 3 h ), 4 . 55 ( s , 2 h ), 5 . 18 - 5 . 25 ( m , 1 h ), 5 . 44 ( s , 2 h ), 5 . 57 ( t , j = 1 . 6 hz , 1 h ), 6 . 71 ( d , j = 1 . 8 hz , 1 h ), 6 . 76 ( d , j = 7 . 9 hz , 1 h ), 6 . 81 ( dd , j = 8 . 8 , 2 . 3 hz , 1 h ), 7 . 14 - 7 . 37 ( m , 4 h ), 7 . 62 - 7 . 73 ( m , 1 h ), 7 . 82 ( d , j = 8 . 8 hz , 1 h ), 8 . 50 ( d , j = 5 . 0 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 200 ). to a solution of 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 139 , 415 mg , 1 . 28 mmol ) in ch 2 cl 2 ( 20 ml ) at 0 ° c . was added ( cocl ) 2 ( 2 m in ch 2 cl 2 , 1 . 6 ml , 3 . 20 mmol ) and a catalytic amount of dmf . the mixture was stirred at room temperature for 1 h , and was concentrated in vacuo . the residue was dissolved in ch 2 cl 2 ( 20 ml ), cooled to 0 ° c ., and 3 , 4 - difluorobenzylamine ( 0 . 23 ml , 1 . 92 mmol ) was added , followed by et 3 n ( 0 . 53 ml , 3 . 84 mmol ). the reaction was stirred at room temperature for 4 h , diluted with etoac , washed with h 2 o , brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , chloroform - d ) δ ppm 1 . 36 ( d , j = 7 . 0 hz , 6 h ), 3 . 74 ( s , 3 h ), 3 . 74 - 3 . 83 ( m , 1 h ), 4 . 65 ( d , j = 6 . 2 hz , 2 h ), 5 . 51 ( s , 2 h ), 6 . 37 ( t , j = 5 . 9 hz , 1 h ), 6 . 52 ( d , j = 7 . 9 hz , 1 h ), 6 . 62 ( d , j = 2 . 3 hz , 1 h ), 6 . 82 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 08 - 7 . 30 ( m , 4 h ), 7 . 46 - 7 . 57 ( m , 2 h ), 8 . 61 ( d , j = 4 . 1 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 201 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 200 , 735 mg , 1 . 64 mmol ) in ch 2 cl 2 ( 25 ml ) at 0 ° c . was added bbr 3 ( 1 . 0 m in ch 2 cl 2 , 6 . 6 ml , 6 . 56 mmol ) dropwise . the reaction was stirred for 1 h at 0 ° c . and 1 h at room temperature , quenched with ice , extracted with etoac , the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 85 % etoac - hexanes ) to yield the title compound as a yellow oil . 1h nmr ( 500 mhz , methanol - d 4 ) δ ppm 1 . 30 ( s , 3 h ), 1 . 32 ( s , 3 h ), 3 . 43 - 3 . 57 ( m , 1 h ), 4 . 57 ( s , 2 h ), 5 . 48 ( s , 2 h ), 6 . 54 - 6 . 64 ( m , 2 h ), 6 . 68 ( dd , j = 8 . 56 , 2 . 20 hz , 1 h ), 7 . 19 - 7 . 37 ( m , 4 h ), 7 . 43 ( d , j = 8 . 56 hz , 1 h ), 7 . 66 ( td , j = 7 . 76 , 1 . 59 hz , 1 h ), 8 . 54 ( d , j = 4 . 89 hz , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 202 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 201 , 1 . 20 g , 2 . 76 mmol ) in ch 2 cl 2 ( 50 ml ) at 0 ° c . was added 2 -[ n , n - bis ( trifluoromethylsulfonyl ) amino ]- 5 - chloropyridine ( 1 . 20 g , 3 . 04 mmol ) and dmap ( 370 mg , 3 . 04 mmol ). the reaction was stirred at room temperature for 12 h , quenched with water , extracted with etoac , the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 40 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 500 mhz , methanol - d 4 ) δ ppm 1 . 33 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 42 - 3 . 54 ( m , 1 h ), 4 . 58 ( s , 2 h ), 5 . 62 ( s , 2 h ), 6 . 78 ( d , j = 7 . 83 hz , 1 h ), 7 . 11 ( dd , j = 8 . 68 , 1 . 83 hz , 1 h ), 7 . 21 - 7 . 39 ( m , 5 h ), 7 . 68 ( d , j = 8 . 80 hz , 2 h ), 8 . 52 ( d , j = 4 . 89 hz , 1 h ), 8 . 73 ( br . s ., 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( pyrimidin - 5 - yl )- 1h - indole - 3 - carboxamide ( compound 203 ). general procedure bb . to a solution of 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 202 , 33 mg , 0 . 06 mmol ) in toluene ( 8 ml ) and meoh ( 1 ml ) at 25 ° c ., bubbled with argon then added licl ( 8 mg , 0 . 18 mmol ), na 2 co 3 ( aqueous ) ( 2m , 0 . 1 ml ), pd ( pph 3 ) 4 ( 3 . 4 mg , 0 . 003 mmol ), and 5 - pyrimidine boronic acid ( 11 mg , 0 . 09 mmol ). the reaction was stirred for 12 h at 80 ° c ., diluted with etoac , the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( s , 3 h ), 1 . 36 ( s , 3 h ), 3 . 50 ( ddd , j = 14 . 54 , 7 . 14 , 6 . 89 hz , 1 h ), 4 . 61 ( s , 2 h ), 5 . 71 ( s , 2 h ), 6 . 76 ( d , j = 7 . 62 hz , 1 h ), 7 . 18 - 7 . 42 ( m , 4 h ), 7 . 46 - 7 . 63 ( m , 1 h ), 7 . 62 - 7 . 74 ( m , 2 h ), 7 . 78 ( d , j = 8 . 35 hz , 1 h ), 8 . 53 ( dd , j = 4 . 98 , 0 . 88 hz , 1 h ), 9 . 00 - 9 . 09 ( m , 3 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 1h - pyrazol - 5 - yl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 204 ). following general procedure bb , 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 202 , 29 mg , 0 . 05 mmol ), was reacted with 1h - pyrazole boronic acid ( 9 mg , 0 . 08 mmol ), licl ( 7 mg , 0 . 18 mmol ), na 2 co 3 ( aqueous ) ( 2m , 0 . 1 ml ), pd ( pph 3 ) 4 ( 3 mg , 0 . 003 mmol ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 49 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 61 ( d , j = 2 . 05 hz , 1 h ), 6 . 69 ( d , j = 8 . 06 hz , 1 h ), 7 . 19 - 7 . 42 ( m , 4 h ), 7 . 52 - 7 . 77 ( m , 5 h ), 8 . 54 ( d , j = 4 . 83 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 -( 1 - methyl - 1h - pyrazol - 5 - yl )- 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 205 ). following general procedure bb , 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 202 , 39 mg , 0 . 07 mmol ), was reacted with 1 - methyl - 1h - pyrazole - 5 - boronic acid pinocol ester ( 21 mg , 0 . 09 mmol ), licl ( 9 mg , 0 . 18 mmol ), na 2 co 3 ( aqueous ) ( 2m , 0 . 1 ml ), pd ( pph 3 ) 4 ( 4 mg , 0 . 003 mmol ) to yield the title compound as a white solid 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 32 ( s , 3 h ), 1 . 34 ( s , 3 h ), 3 . 49 ( m , 1 h ), 3 . 75 ( s , 3h ), 4 . 60 ( s , 2 h ), 5 . 65 ( s , 2 h ), 6 . 35 ( d , j = 2 . 05 hz , 1 h ), 6 . 69 ( d , j = 8 . 06 hz , 1 h ), 7 . 19 - 7 . 42 ( m , 4 h ), 7 . 52 - 7 . 77 ( m , 5 h ), 8 . 54 ( d , j = 4 . 83 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 -( 3 , 5 - dimethylisoxazol - 4 - yl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 206 ). following general procedure bb , 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 202 , 57 mg , 0 . 10 mmol ), was reacted with 3 , 5 - dimethylisoxazol - 4 - ylboronic acid ( 21 mg , 0 . 15 mmol ), licl ( 13 mg , 0 . 30 mmol ), na 2 co 3 ( aqueous ) ( 2m , 0 . 2 ml ), pd ( pph 3 ) 4 ( 6 mg , 0 . 006 mmol ) to yield the title compound as a yellow solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 36 ( s , 3 h ), 1 . 39 ( s , 3 h ), 2 . 12 ( s , 3 h ), 2 . 29 ( s , 3 h ), 3 . 50 - 3 . 65 ( m , 1 h ), 4 . 60 ( s , 2 h ), 5 . 64 ( s , 2 h ), 6 . 74 ( d , j = 7 . 91 hz , 1 h ), 7 . 09 ( dd , j = 8 . 28 , 1 . 39 hz , 1 h ), 7 . 17 ( d , j = 0 . 88 hz , 1 h ), 7 . 22 - 7 . 41 ( m , 5 h ), 7 . 70 ( dd , j = 8 . 20 , 0 . 59 hz , 2 h ), 8 . 53 ( ddd , j = 4 . 91 , 1 . 76 , 0 . 81 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - morpholino - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 207 ). to a solution of 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indol - 6 - yl trifluoromethanesulfonate ( compound 202 , 100 mg , 0 . 18 mmol ) in toluene ( 10 ml ) at 25 ° c ., bubbled with argon then added morpholine ( 22 mg , 0 . 25 mmol ), lin ( tms ) 2 ( 1m in thf , 0 . 37 ml , 0 . 40 mmol ), pd 2 ( dba ) 3 ( 3 . 2 mg , 0 . 0035 mmol ), and x - phos ( 4 mg , 0 . 011 mmol ). the reaction was stirred for 12 h at 110 ° c ., diluted with etoac , the organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a light brown solid . 1h nmr ( 300 mhz , & lt ; cd3od & gt ;) δ ppm 1 . 30 ( s , 3 h ), 1 . 32 ( s , 3 h ), 3 . 05 ( t , j = 4 . 98 , 4 h ), 3 . 49 ( m , 1 h ), 3 . 78 ( t , j = 4 . 98 , 4 h ), 4 . 57 ( s , 2 h ), 5 . 55 ( s , 2 h ), 6 . 62 ( d , j = 8 . 20 hz , 1 h ), 6 . 77 ( d , j = 1 . 76 hz , 1 h ), 6 . 93 ( dd , j = 8 . 79 , 2 . 05 hz , 1 h ), 7 . 20 - 7 . 38 ( m , 4 h ), 7 . 52 ( d , j = 8 . 79 hz , 1 h ), 7 . 65 ( td , j = 7 . 76 , 1 . 76 hz , 2 h ), 8 . 54 ( d , j = 4 . 40 hz , 2 h ). 2 - isopropyl - 6 - methoxy - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carbaldehyde ( compound 208 ). 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 , 0 . 54 g , 2 . 49 mmol ) and 2 -( chloromethyl ) oxazole ( 0 . 58 g , 4 . 4 mmol ) were reacted as described in general procedure j to give the title compound as an oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 52 ( d , j = 7 . 0 hz , 6 h ), 3 . 71 ( p , j = 7 . 0 hz , 1 h ), 3 . 82 ( s , 3 h ), 5 . 66 ( s , 2 h ), 6 . 87 ( dd , j = 8 . 8 , 2 . 2 hz , 1 h ), 7 . 04 ( d , j = 2 . 2 hz , 1 h ), 7 . 15 ( s , 1 h ), 7 . 88 ( s , 1 h ), 8 . 08 ( d , j = 8 . 8 hz , 1 h ), 10 . 32 ( s , 1 h ). 2 - isopropyl - 6 - methoxy - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 209 ). 2 - isopropyl - 6 - methoxy - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carbaldehyde ( compound 208 , 0 . 40 g , 1 . 34 mmol ) was oxidized to the title compound by general procedure k . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 42 ( d , j = 7 . 0 hz , 6 h ), 3 . 80 ( s , 3 h ), 4 . 04 ( p , j = 7 . 0 hz , 1 h ), 5 . 62 ( s , 2 h ), 6 . 81 ( dd , j = 8 . 5 , 2 . 0 hz , 1 h ), 6 . 95 ( d , j = 2 . 0 hz , 1 h ), 7 . 15 ( s , 1 h ), 7 . 83 ( s , 1 h ), 7 . 96 ( d , j = 8 . 5 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 210 ). 2 - isopropyl - 6 - methoxy - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxylic acid ( compound 209 , 0 . 83 g , 2 . 64 mmol ) was converted to the title compound by utilizing , in order , general procedure c and general procedure l . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 41 ( d , j = 7 . 0 hz , 6 h ), 3 . 59 ( p , j = 7 . 0 hz , 1 h ), 4 . 58 ( s , 2 h ), 5 . 52 ( s , 2 h ), 6 . 70 ( dd , j = 8 . 5 , 2 . 2 hz , 1 h ), 6 . 82 ( d , j = 2 . 2 hz , 1 h ), 7 . 15 ( s , 1 h ), 7 . 19 - 7 . 36 ( m , 3 h ), 7 . 40 ( d , j = 8 . 5 hz , 1 h ), 7 . 86 ( s , 1 h ). 6 -( cyclopentyloxy )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 211 ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 210 , 68 mg , 0 . 16 mmol ) was reacted according to general procedure n to give the title compound as an oil . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 41 ( d , j = 7 . 0 hz , 6 h ), 1 . 60 - 2 . 00 ( m , 8 h ), 3 . 50 ( p , j = 7 . 0 hz , 1 h ), 4 . 58 ( s , 2 h ), 5 . 54 ( s , 2 h ), 6 . 74 ( dd , j = 8 . 5 , 2 . 2 hz , 1 h ), 6 . 83 ( d , j = 2 . 2 hz , 1 h ), 7 . 13 ( s , 1 h ), 7 . 20 - 7 . 38 ( m , 3 h ), 7 . 42 ( d , j = 8 . 5 hz , 1 h ), 7 . 83 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 6 - propoxy - 1h - indole - 3 - carboxamide ( compound 212 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 210 ) and n - propyl iodide by general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 04 ( t , j = 7 . 5 hz , 3 h ), 1 . 39 ( d , j = 7 . 0 hz , 6 h ), 1 . 78 ( m , 2 h ), 3 . 57 ( p , j = 7 . 0 hz , 1 h ), 3 . 94 ( t , j = 6 . 5 hz , 2 h ), 4 . 55 ( s , 2 h ), 5 . 55 ( s , 2 h ), 6 . 78 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 6 . 95 ( d , j = 2 . 1 hz , 1 h ), 7 . 11 - 7 . 36 ( m , 4 h ), 7 . 43 ( d , j = 8 . 8 hz , 1 h ), 7 . 83 ( d , j = 0 . 88 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - isopropoxy - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 213 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 210 ) and isopropyl iodide by general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 29 ( d , j = 6 . 0 hz , 6 h ), 1 . 39 ( d , j = 7 . 0 hz , 6 h ), 3 . 59 ( p , j = 7 . 0 hz , 1 h ), 4 . 55 ( s , 2 h ), 4 . 57 ( p , j = 6 . 0 hz , 1 h ), 5 . 54 ( s , 2 h ), 6 . 74 ( dd , j = 8 . 5 , 2 . 4 hz , 1 h ), 6 . 78 ( d , j = 2 . 4 hz , 1 h ), 7 . 12 ( s , 1 h ), 7 . 20 - 7 . 38 ( m , 3 h ), 7 . 40 ( d , j = 8 . 5 hz , 1 h ), 7 . 83 ( s , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 6 -( thiazol - 2 - yloxy )- 1h - indole - 3 - carboxamide ( compound 214 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 210 ), 2 - bromothiazole and dmso with heating following general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 40 ( d , j = 7 . 0 hz , 6 h ), 3 . 57 ( p , j = 7 . 0 hz , 0 h ), 4 . 57 ( s , 2 h ), 5 . 61 ( s , 2 h ), 6 . 99 ( d , j = 3 . 81 hz , 1 h ), 7 . 07 ( dd , j = 8 . 5 , 1 . 8 hz , 1 h ), 7 . 11 ( d , j = 0 . 88 hz , 1 h ), 7 . 19 - 7 . 39 ( m , 4 h ), 7 . 48 ( d , j = 1 . 8 hz , 1 h ), 7 . 62 ( d , j = 8 . 5 hz , 1 h ), 7 . 83 ( d , j = 0 . 88 hz , 1 h ). 6 -( 5 - bromothiazol - 2 - yloxy )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( oxazol - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 215 ). the title compound was also isolated in the synthesis of compound 214 . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 40 ( d , j = 7 . 3 hz , 6 h ), 3 . 58 ( p , j = 7 . 3 hz , 0 h ), 4 . 56 ( s , 2 h ), 5 . 62 ( s , 2 h ), 7 . 08 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 7 . 11 ( d , j = 0 . 88 hz , 1 h ), 7 . 20 - 7 . 39 ( m , 4 h ), 7 . 50 ( d , j = 1 . 8 hz , 1 h ), 7 . 63 ( d , j = 8 . 8 hz , 1 h ), 7 . 83 ( d , j = 0 . 88 hz , 1 h ). 2 - isopropyl - 6 - methoxy - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carbaldehyde ( compound 216 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ) and 3 -( bromomethyl )- 5 - methylisoxazole by general procedure j . 1h nmr ( 300 mhz , methanol - d4 ) δ ppm 1 . 50 ( d , j = 7 . 3 hz , 6 h ), 2 . 35 ( s , 3 h ), 3 . 65 ( p , j = 7 . 3 hz ), 3 . 82 ( s , 3 h ), 5 . 53 ( s , 2 h ), 5 . 89 ( s , 1 h ), 6 . 88 ( dd , j = 2 . 3 , 8 . 7 hz , 1 h ), 7 . 00 ( d , j = 2 . 3 hz , 1 h ), 8 . 10 ( d , j = 8 . 7 hz , 1 h ), 10 . 23 ( s , 1 h ). 2 - isopropyl - 6 - methoxy - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carboxylic acid ( compound 217 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carbaldehyde ( compound 213 ) by general procedure k . 1h nmr ( 300 mhz , methanol - d4 ) δ ppm 1 . 42 ( d , j = 7 . 0 hz , 6 h ), 2 . 31 ( s , 3 h ), 3 . 55 ( p , j = 7 . 0 hz ), 3 . 80 ( s , 3 h ), 5 . 55 ( s , 2 h ), 5 . 78 ( s , 1 h ), 6 . 82 ( dd , j = 2 . 0 , 8 . 5 hz , 1 h ), 6 . 93 ( d , j = 2 . 0 hz , 1 h ), 7 . 90 ( d , j = 8 . 5 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 218 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carboxylic acid ( compound 217 ) by utilizing , in order , general procedure c and general procedure l . 1h nmr ( 300 mhz , methanol - d4 ) δ ppm 1 . 36 ( d , j = 7 . 0 hz , 6 h ), 2 . 32 ( s , 3 h ), 3 . 54 ( p , j = 7 . 0 hz ), 4 . 55 ( s , 2 h ), 5 . 38 ( s , 2 h ), 5 . 74 ( s , 1 h ), 6 . 67 ( dd , j = 2 . 2 , 8 . 5 hz , 1 h ), 6 . 74 ( d , j = 2 . 2 hz , 1 h ), 7 . 20 - 7 . 35 ( m , 3 h ), 7 . 38 ( d , j = 8 . 5 hz , 1 h ). 6 -( cyclopentyloxy )- n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 219 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -(( 5 - methylisoxazol - 3 - yl ) methyl )- 1h - indole - 3 - carboxamide ( compound 218 ) by general procedure n . 1h nmr ( 300 mhz , methanol - d4 ) δ ppm 1 . 38 ( d , j = 7 . 0 hz , 6 h ), 1 . 60 - 1 . 95 ( m , 8 h ), 2 . 31 ( s , 3 h ), 3 . 55 ( p , j = 7 . 0 hz ), 4 . 55 ( s , 2 h ), 5 . 43 ( s , 2 h ), 5 . 75 ( s , 1 h ), 6 . 74 ( dd , j = 2 . 0 , 8 . 8 hz , 1 h ), 6 . 85 ( d , j = 2 . 0 hz , 1 h ), 7 . 20 - 7 . 35 ( m , 3 h ), 7 . 43 ( d , j = 8 . 8 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 6 - hydroxy - 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 220 ). the title compound was prepared from n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 200 ) by general procedure l . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 23 ( t , j = 7 . 0 hz , 1 h ), 1 . 31 ( d , j = 7 . 0 hz , 7 h ), 3 . 46 ( p , j = 7 . 18 hz , 1 h ), 4 . 09 ( q , 1 h ), 4 . 57 ( s , 2 h ), 5 . 63 ( s , 2 h ), 6 . 58 ( d , j = 1 . 8 hz , 1 h ), 6 . 71 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 6 . 88 ( d , j = 8 . 2 hz , 1 h ), 7 . 19 - 7 . 38 ( m , 3 h ), 7 . 44 ( d , j = 8 . 5 hz , 1 h ), 7 . 60 ( d , j = 5 . 57 hz , 1 h ), 8 . 01 ( td , j = 7 . 8 , 1 . 6 hz , 1 h ), 8 . 68 ( d , j = 4 . 4 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( pyridin - 2 - yloxy )- 1h - indole - 3 - carboxamide ( compound 221 ). to a solution of n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 220 , 26 mg , 0 . 060 mmol ) in dimethylformamide ( 1 ml ) stirring at room temperature , was added cesium carbonate ( 83 mg , 0 . 25 mmol ) and the reaction stirred for 5 minutes . 2 - iodopyridine ( 0 . 05 ml , 0 . 09 g , 0 . 47 mmol ) and then copper powder ( 7 . 0 mg , 0 . 11 mmol ) was then directly added and the resulting mixture heated at 100 ° c . for 18 h . the reaction was cooled to room temperature , quenched with water , extracted with etoac , washed with brine , dried over na 2 so 4 , and concentrated under reduced pressure . the residue was purified by flash column chromatography on silica gel ( 50 % etoac - hexanes , 100 % etoac ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( d , j = 7 . 2 hz , 6 h ), 3 . 51 ( p , j = 7 . 2 hz , 1 h ), 4 . 60 ( d , j = 5 . 9 hz , 2 h ), 5 . 55 ( s , 2 h ), 6 . 73 ( d , j = 7 . 9 hz , 1 h ), 6 . 81 ( d , j = 8 . 2 hz , 1 h ), 6 . 91 ( dd , j = 8 . 5 , 2 . 2 hz , 1 h ), 7 . 01 - 7 . 10 ( m , 2 h ), 7 . 20 - 7 . 42 ( m , 4 h ), 7 . 65 ( d , j = 8 . 5 hz , 1 h ), 7 . 69 ( dd , j = 7 . 9 , 1 . 8 hz , 1 h ), 7 . 74 ( ddd , j = 8 . 2 , 7 . 2 , 2 . 0 hz , 1 h ), 8 . 07 ( dt , j = 5 . 7 , 1 . 9 hz , 1h ), 8 . 50 ( dt , j = 4 . 8 , 1 . 3 hz , 1 h ), 8 . 67 ( t , j = 5 . 9 hz , 1 h ). n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( pyridin - 3 - yloxy )- 1h - indole - 3 - carboxamide ( compound 222 ). general procedure g . to a solution of n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 3 - carboxamide ( compound 220 , 30 mg , 0 . 069 mmol ) in n , n - dimethylacetamide ( 1 . 50 ml ) stirring at room temperature , was added potassium hydroxide ( 80 mg , 1 . 43 mmol ) and the reaction stirred for 5 minutes . 3 - bromopyridine ( 0 . 05 ml , 0 . 08 g , 0 . 51 mmol ) and then copper powder ( 9 . 0 mg , 0 . 14 mmol ) was then directly added and the resulting mixture heated at 120 - 140 ° c . for 18 h . the reaction was cooled to room temperature , quenched with water , extracted with etoac , washed with brine , dried over na 2 so 4 , and concentrated under reduced pressure . the residue was purified by flash column chromatography on silica gel ( 50 % etoac - hexanes , 100 % etoac ) to yield n -( 3 , 4 - difluorobenzyl )- 2 - isopropyl - 1 -( pyridin - 2 - ylmethyl )- 6 -( pyridin - 3 - yloxy )- 1h - indole - 3 - carboxamide ( compound 222 ) as a yellow solid ( 2 . 3 mg ). 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 34 ( d , j = 7 . 0 hz , 6 h ), 4 . 59 ( s , 2 h ), 5 . 55 ( s , 2 h ), 6 . 72 ( d , j = 8 . 2 hz , 1 h ), 6 . 92 ( dd , j = 8 . 6 , 2 . 2 hz , 1 h ), 7 . 02 ( d , j = 2 . 0 hz , 1 h ), 7 . 19 - 7 . 42 ( m , 6 h ), 7 . 62 - 7 . 74 ( m , 2 h ), 8 . 14 - 8 . 24 ( m , 2 h ), 8 . 49 ( d , j = 5 . 0 hz , 1 h ). ethyl 2 -( 6 -( cyclopentyloxy )- 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 2 - isopropyl - 1h - indol - 1 - yl ) acetate ( compound 223 ). the title compound was prepared from 2 - isopropyl - 6 - methoxy - 1h - indole - 3 - carbaldehyde ( compound 137 ) and ethyl2 - bromoacetate by following , in order , general procedure j , general procedure k , general procedure c , general procedure l , and general procedure n . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 25 ( t , j = 7 . 0 hz , 3 h ), 1 . 39 ( d , j = 7 . 3 hz , 6 h ), 1 . 60 - 2 . 00 ( m , 8 h ), 3 . 48 ( p , j = 7 . 3 hz , 1 h ), 4 . 21 ( q , j = 7 . 0 hz , 2 h ), 4 . 56 ( s , 2 h ), 5 . 02 ( s , 2 h ), 6 . 76 ( dd , j = 9 . 0 , 2 . 1 hz , 1 h ), 6 . 77 ( d , j = 2 . 1 hz , 1 h ), 7 . 20 - 7 . 36 ( m , 3 h ), 7 . 45 ( d , j = 9 . 0 hz , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylic acid ( compound 224 ). general procedure l . to a solution of methyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 93 , 149 mg , 0 . 32 mmol ) in ch 2 cl 2 ( 10 ml ) was added bbr 3 ( 1m in ch 2 cl 2 , 1 . 6 ml , 1 . 6 mmol ) slowly at 0 ° c . the mixture was stirred at room temperature for 2 h , and was quenched with ice , extracted with etoac (× 3 ). the combined organic layer was washed with brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by ptlc on silica gel ( 10 % meoh — ch 2 cl 2 ) to yield the title compound . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 3 . 74 ( s , 3 h ), 4 . 57 ( s , 2 h ), 5 . 91 ( s , 2 h ), 6 . 77 ( d , j = 2 . 3 hz , 1 h ), 6 . 80 - 6 . 92 ( m , j = 8 . 9 , 2 . 2 hz , 2 h ), 7 . 12 - 7 . 37 ( m , 4 h ), 7 . 56 - 7 . 69 ( m , 1 h ), 8 . 18 ( d , j = 8 . 2 hz , 1 h ), 8 . 48 ( s , 1 h ). 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylic acid ( compound 225 ). general procedure m . to a solution of alcl 3 ( 1 . 8 g , 13 . 5 mmol ) in etsh ( 25 ml ) at room temperature was added a solution of methyl3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - methoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 93 , 1 . 26 g , 2 . 7 mmol ) in ch 2 cl 2 ( 75 ml ). the reaction was stirred for 2 h and was quenched with ice . the mixture was concentrated in vacuo , and the resulting white suspension in aqueous solution was acidified with 1m hcl and filtered . the cake was washed with h 2 o (× 3 ), taken in meoh , dried over mgso 4 , and concentrated in vacuo to yield the title compound as a crude yellowish white solid contaminated with unknown inorganic product . the crude was used without further purification . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 4 . 63 ( s , 2 h ), 5 . 92 ( s , 2 h ), 6 . 73 ( d , j = 1 . 5 hz , 1 h ), 6 . 82 ( dd , j = 8 . 8 , 2 . 1 hz , 1 h ), 6 . 94 ( d , j = 7 . 9 hz , 1 h ), 7 . 17 - 7 . 30 ( m , 2 h ), 7 . 30 - 7 . 44 ( m , 2 h ), 7 . 65 - 7 . 84 ( m , 2 h ), 8 . 47 - 8 . 57 ( m , 1 h ). methyl 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - isopropoxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylate ( compound 226 ). a solution of 3 -( 3 , 4 - difluorobenzylcarbamoyl )- 6 - hydroxy - 1 -( pyridin - 2 - ylmethyl )- 1h - indole - 2 - carboxylic acid ( compound 225 , crude 6 . 5 g ) and concentrated h 2 so 4 ( 0 . 1 ml , catalytic amount ) in meoh ( 100 ml ) was heated to 90 ° c . for 16 h . the mixture was cooled and the suspension was filtered . the filtrate was concentrated , diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo to give a pale brown solid as the crude product . general procedure n . to a solution of the crude product in dmf ( 10 ml ) was added 2 - iodopropane ( 2 . 2 ml , 22 mmol ) and k 2 co 3 ( 1 . 8 g , 13 . 2 mmol ). the reaction was stirred at room temperature for 16 h and was diluted with etoac , washed with h 2 o and brine , dried over na 2 so 4 , and concentrated in vacuo . the residue was purified by chromatography on silica gel ( 0 → 100 % etoac - hexanes ) to yield the title compound as a white solid . 1h nmr ( 300 mhz , methanol - d 4 ) δ ppm 1 . 26 ( d , j = 6 . 2 hz , 6 h ), 3 . 69 ( s , 3 h ), 4 . 50 - 4 . 66 ( m , 3 h ), 5 . 87 ( s , 2 h ), 6 . 79 - 6 . 93 ( m , 3 h ), 7 . 20 - 7 . 31 ( m , 3 h ), 7 . 33 - 7 . 44 ( m , 1 h ), 7 . 59 ( dd , j = 8 . 5 , 0 . 9 hz , 1 h ), 7 . 67 ( td , j = 7 . 8 , 1 . 8 hz , 1 h ), 8 . 48 ( ddd , j = 5 . 0 , 1 . 8 , 0 . 9 hz , 1 h ). the foregoing description details specific methods and compositions that can be employed to practice the present invention , and represents the best mode contemplated . thus , however detailed the foregoing may appear in text , it should not be construed as limiting the overall scope hereof , rather , the ambit of the present invention was to be governed only by the lawful construction of the appended claims . in particular , the present invention includes a 6 - substituted indole - 3 - carboxylic acid - n - arylmethyl amide having sphingosine - 1 - phosphate antagonist activity wherein the 6 - substituent is represented by the formula wherein x 1 is o ; r is 0 or 1 ; a 2 is absent or is ( ch 2 ) v , wherein v is 1 or 2 ; b is or 6 or nr 8 r 9 , wherein r 6 , r 8 and r 9 are methyl ; or b is cr 10 ═ no r 11 r 10 wherein r 10 is h and r 11 is methyl or i - butyl ; or b is conr 8 r 9 , wherein r 8 and r 9 are selected from the group consisting of h , methyl , ethyl and propyl or r 8 and r 9 , together with n , form a 5 - membered ring ; or b is or 6 , wherein r 6 is h ; or b is cor 10 , wherein r 10 is methyl . | 2 |
many aspects of the invention can be better understood with the references made to the drawings below . the components in the drawings are not necessarily drawn to scale . instead , emphasis is placed upon clearly illustrating the components of the present invention . moreover , like reference numerals designate corresponding parts through the several views in the drawings . selected embodiments of the current disclosure include a contact lens having an anterior surface away from the eye and a posterior surface facing the eye and a lens body bordered by the anterior and posterior surface . the contact lens is generally described as a low modulus lens ( soft ); even so the invention is applicable to a high modulus lens ( rigid ) or a lens having both rigid and soft materials ( hybrid ). the posterior surface is generally related in geometry to the ocular contour of the eye but may deviate in its shape from representing the ocular contour of the eye . the central geometry of the anterior surface of the lens is generally selected to produce the desired refractive correction for the eye but could be a secondary element in providing the refractive correction if lenslets or apertures within the lens or other means are used to produce the refractive correction . the body of the lens is defined as one or more lens substrate materials between or including the anterior surface and the posterior surface in the present invention . the lens body contains one or more components which have an oxygen permeability lower than the material posterior to them . the components can be on the anterior surface and / or within the body of the lens . portions of the components may be at different sagittal depths on or within the body of the lens . selected embodiments of the current invention provide for the use of a layer of the lens polymer of the lens body or a second lens polymer posterior to at least one element or component that has an oxygen permeability lower than the material , or medium , posterior to them . the material posterior to the respective components serves to deliver oxygen by way of the oxygen transmission through the exposed anterior surface and lens body above the posterior layer and the thickness of the material of the posterior layer . the thickness of the polymer posterior to the components which have an oxygen permeability lower than the material posterior to them is a function of the oxygen permeability of the polymer beneath the components ; the surface area of the components covering the cornea ; the oxygen transmissibility of the components covering the cornea ; and , the targeted equivalent oxygen percentage to be delivered to a predetermined location of the cornea . the thickness of the polymer layer is generally greater the lower the permeability of the material posterior to the components and the larger the area of the components which have an oxygen permeability lower than the material posterior to the components . conversely , the thickness of the polymer layer is generally lesser the greater the permeability of the material posterior to the components and the smaller the area of the components which have an oxygen permeability lower than the material posterior to the components . particular aspects of the current disclosure provide for increasing the lens thickness to increase the equivalent oxygen percentage delivered to the cornea covered by an element or component having low or no oxygen transmissibility . the traditional practice taught in prior art is to decrease thickness to increase oxygen transmissibility . materials having a sufficiently high oxygen permeability may be used with increased thickness to facilitate oxygen diffusion sufficient to maintain the physiological requirements of the cornea covered by at least one elements or component having limited or no oxygen permeability . since increasing the thickness decreases the oxygen transmissibility of the layer , the invention could not be practiced with materials having a permeability below a threshold determined by the area of the components which have an oxygen permeability lower than the material posterior to the components and the targeted equivalent oxygen percentage desired at the specified location on the corneal surface . for example , a material having a substantially low permeability and a component area covering a substantially large area of the cornea could not be made at any thickness to deliver the holden mertz minimum oxygen transmissibility for healthy daily wear contact lenses . particular embodiments of the current disclosure are directed to contact lenses having a posterior layer having a permeability substantially high to allow for increasing its thickness to provide a layer for oxygen delivery . the use of materials having a permeability of greater than dk = 100 × 10 − 11 ( cm 2 / sec ) ( ml o 2 )/( ml × mm hg ) is at least substantially high enough to allow for such an increase in thickness to provide a layer for oxygen delivery . the holden mertz criteria speak to an oxygen transmissibility that produces a minimum of corneal swelling from hypoxia ( low oxygen delivery ). a mathematical model may also use a percentage of oxygen in the gas arriving at the corneal surface as a metric for determining the appropriate thickness of the layer posterior to the component within a contact lens . hence , the third variable is the targeted equivalent oxygen percentage to a defined location on the anterior cornea . holden and mertz defined the equivalent oxygen percentage for daily wear as 9 . 9 % with a range of +/− 1 % as the standard error of the estimate . particular embodiments of the current disclosure use a target minimum equivalent oxygen percentage of 9 %. one embodiment of the present disclosure is a contact lens made of a single polymer polydimethylsiloxane and having a round polarizer filter that is 7 mm in diameter that has no gas permeability . the full surface area of the polarizer covers the cornea . the dk of the pdms is measured to be 340 × 10 − 11 ( cm 2 / sec ) ( ml o 2 )/( ml × mm hg ). the defined oxygen percentage to the cornea posterior to the center of the non - gas permeable filter is 9 %. one mathematical model for calculating the percentage of oxygen to reach the distance to the center as a function of the thickness and dk is : for this embodiment , the filter has an oxygen transmissibility of zero , or dk / t = 0 . 0 × 10 − 9 ( cm × ml o 2 )/( sec × ml × mmhg ). the filter diameter is 7 mm ( 38 . 48 mm 2 ); and the equivalent oxygen percentage target for the cornea under the center of the circular filter element is 9 %. in this case the thickness of the polymer layer having a dk = 340 × 10 − 11 ( cm 2 / sec ) ( ml o 2 )/( ml × mm hg ), and under the geometric center of the filter described above is calculated to be , 0 . 700 mm . it is to be understood by those skilled in the art that other mathematical models could be used to define the relationship between the oxygen permeability of at least one element , the area covered by the element , the oxygen reaching the layer beneath the element , the permeability of the layer beneath the element , and the equivalent oxygen percentage desired at a defined location . additional embodiments of the current disclosure include multiple elements or components that are non - gas permeable or having at least one element with gas permeability lower than the layer posterior to these components . other embodiments include components with spaces , fenestrations or channels for the purpose of increasing their oxygen transmission . further embodiments include multiple components with spaces between the components . in such embodiments , the average oxygen transmissibility is expected to exceed the transmissibility of the component with the lowest permeability . in the respective embodiments , the thickness of the layer posterior to the elements or components is modulated to produce the targeted oxygen percentage to the specified area of the corneal surface . selected embodiments of the current disclosure utilize one or more polymer layers posterior to at least one element or component having an oxygen permeability lower than the material of the body of the lens containing the element or component . the one or more layers can be configured in thickness and position for the purpose of delivering a predetermined equivalent oxygen percentage to one or more locations in the underlying cornea . referring now to the figures , fig1 depicts a component containing contact lens 100 in accordance with selected embodiments of the current disclosure . the component containing contact lens 100 has an anterior surface 101 , a lens body 102 , and a posterior surface 103 . the component containing contact lens 100 comprises a component 104 , generally peripheral lens areas 105 , which circumferentially surrounds the lens component 104 , and a layer 106 , which is posterior to the component 104 and contiguous with the peripheral areas 105 . with continued reference to fig1 , the component 104 is constructed at the anterior surface of the contact lens 100 and the lens body 103 includes a layer 106 posterior to the component 104 . as will be understood by those of skill in the art , the component 104 is not limited to a location at the anterior surface , to a symmetrical configuration , or to a uniform thickness profile , or to a centered position relative to the geometric center of the contact lens 100 . for example , additional elements or a deeper placement of the element may be employed , or a regional placement may be employed . in this manner , the lens can be customized for the inclusion of a number and variety of elements or components and the thickness of the posterior layer can be determined to provide a desired equivalent oxygen percentage to the surface of the cornea covered by the elements or components . fig2 depicts a component containing contact lens 200 in accordance with selected embodiments of the current disclosure . the component containing contact lens 200 has an anterior surface 201 , a lens body 202 , and a posterior surface 203 . the component containing contact lens 200 comprises a first component 204 which is a circular component with a central hole or space , a second component 205 at a different sagittal depth than the first component 204 , generally peripheral lens areas 206 which circumferentially surrounds the lens components 204 and 205 , and a layer 207 , which is posterior to the components 204 and 205 and contiguous with the peripheral areas 206 . with continued reference to fig2 , the component 204 is constructed at the anterior surface of the contact lens 200 and a second component 205 is deeper in the lens body 202 . the lens body 202 includes a layer 207 , which is posterior to the components 204 and 205 . as will be understood by those of skill in the art , the components 204 and 205 are not limited to locations at the anterior surface or the apparent relative depths in the lens body 202 , to a symmetrical configuration , or to a uniform thickness profile , or to a centered position relative to the geometric center of the contact lens 200 . for example , additional elements or a deeper placement of the element may be employed , or a regional placement may be employed . in this manner , the lens can be customized for the inclusion of a number and variety of elements or components and the thickness of the posterior layer can be determined to provide a desired equivalent oxygen percentage to the surface of the cornea covered by these elements or components . fig3 depicts a component containing contact lens 300 in accordance with selected embodiments of the current disclosure . the component containing contact lens 300 has an anterior surface 301 , a lens body 302 , and a posterior surface 303 . the component containing contact lens 300 includes a first component 304 , which is a first electronic component , a second component 305 , which is a second electronic component at a different sagittal depth than the first component 304 , a third component 306 , which is a wire , a fourth component 307 depicting a third electronic component at a different sagittal depth than the first component 304 , generally peripheral lens areas 308 , which circumferentially surrounds the lens components 304 , 305 , 306 and 307 , and a layer 309 , which is posterior to the components 304 , 305 , 306 and 307 and contiguous with the peripheral lens areas 308 . with continued reference to fig3 , the components 304 , 305 , 306 and 307 are depicted as having various relative dimensions and constructed in the lens body 302 at various depths the lens body 302 includes a layer 308 which is posterior to the components 304 , 305 , 306 and 307 . as will be understood by those of skill in the art , the components 304 , 305 , 306 and 307 are not limited to locations at the apparent relative depths in the lens body 302 , to a symmetrical configuration , or to a uniform thickness profile , or to a centered position relative to the geometric center of the contact lens 300 . for example , additional components or a deeper placement of the components may be employed , or a regional placement may be employed . in this manner , the lens can be customized for the inclusion of a number and variety of elements or components and the thickness of the posterior layer can be determined to provide a desired equivalent oxygen percentage to the surface of the cornea covered by these elements or components . fig4 is an iso - line drawing of the equivalent oxygen percentage values at the posterior surface of a contact lens having one component with a limited oxygen transmissibility and with a surface area defined by its dimensions and with a posterior polymer layer with an oxygen permeability and a thickness designed to deliver a minimum equivalent oxygen permeability in accordance with selected embodiments of the current disclosure . contact lens 400 is shown with iso - lines of equivalent oxygen percentage ( eop ) values 401 , at the posterior surface 402 of a lens having one component 403 with a limited oxygen transmissibility and of a surface area defined by its dimensions and with a posterior polymer layer with an oxygen permeability and a thickness ( t ) 404 to deliver a minimum equivalent oxygen permeability of 9 %. fig5 depicts a flow chart or process 500 for determining the thickness of a polymer layer posterior to at least one component in the lens body of a contact lens for the purpose of delivering a predetermined equivalent oxygen percentage to a predetermined location on the corneal surface . the process 500 starts by using the lens and component material properties 501 and the characterization of the component physical requirements 502 to estimate the thickness of the layer posterior to the at least one component of the present invention 503 . for example , the component material properties 501 include oxygen permeability , elastic modulus , refractive index , and spectral characteristics . continuing with the example , component physical requirements 502 include effective optical diameter , thickness , surface area , and sphericity . while the estimation of posterior thickness 503 could be a randomly guessed thickness , previous numerical simulations and final designs of lenses can be used as a guide for estimating posterior thickness . once the posterior thickness has been estimated , the component physical requirements 502 and the estimated posterior thickness 503 are applied in the process of the mechanical design 504 of the lens to produce a design of a lens that includes , for example , the optical zone diameter , outside diameter , edge thickness , center thickness , and other design criteria . in turn , the lens and component material properties 501 and the mechanical design of the lens 504 are integrated into the mathematical calculation or numerical simulation 505 to determine a resultant equivalent oxygen percentage across the posterior surface of the lens . the calculated equivalent oxygen percentage across the posterior surface of the lens is compared 506 to the targeted requirement . a successful passing , for example the resulting or calculated equivalent oxygen percentage across the posterior surface of the lens is greater than a targeted requirement or within a targeted range , advances the process to a final design 507 . failure 508 to meet the targeted equivalent oxygen percentage returns the process to lens mechanical design 504 and reintegration of component material properties 501 , including varying the posterior thickness to be larger or smaller to exceed the targeted requirement or fall within a target range . for example , should the resulting equivalent oxygen percentage fall below a targeted requirement of 9 %, the mechanical design of the lens is modified to increase the posterior thickness and a numerical simulation is performed again on the revised design to determine a resulting equivalent oxygen percentage across the posterior surface of the lens . while various embodiments of the present invention have been described above , it should be understood that they have been presented by way of example only , and not of limitation . likewise , the various diagrams may depict an example architectural or other configuration for the invention , which is provided to aid in understanding the features and functionality that can be included in the invention . the invention is not restricted to the illustrated example architectures or configurations , but the desired features can be implemented using a variety of alternative architectures and configurations . indeed , it will be apparent to one of skill in the art how alternative functional configurations can be implemented to implement the desired features of the present invention . additionally , with regard to flow diagrams , operational descriptions and method claims , the order in which the steps are presented herein shall not mandate that various embodiments be implemented to perform the recited functionality in the same order unless the context dictates otherwise . although the invention is described above in terms of various exemplary embodiments and implementations , it should be understood that the various features , aspects and functionality described in one or more of the individual embodiments are not limited in their applicability to the particular embodiment with which they are described , but instead can be applied , alone or in various combinations , to one or more of the other embodiments of the invention , whether or not such embodiments are described and whether or not such features are presented as being a part of a described embodiment . thus , the breadth and scope of the present invention should not be limited by any of the above - described exemplary embodiments . | 6 |
for the purposes of promoting an understanding of the principles of the invention , reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same . it will nevertheless be understood that no limitation of the scope is thereby intended . any alterations and further modifications in the described embodiments , and any further applications of the principles as described herein are contemplated as would normally occur to one skilled in the art . the system may be described in the general context as an application that improves the workflow process for resolving data elements , such as email addresses , but the system also serves other purposes in addition to these . in one implementation , one or more of the techniques described herein can be implemented as features within an email program such as microsoft ® office outlook ®, microsoft ® office outlook ® web access ( owa ), aol anywhere , or from any other type of program or service that allows creation of email messages . in another implementation , one or more of the techniques described herein are implemented as features with other applications that deal with data elements that need resolved , such as conference rooms , postal addresses , and / or patient data , to name a few non - limiting examples . in one implementation , a user enters a particular data element , such as a plain text name , and the system attempts to resolve that data element to an identifier associated with the particular element , such as an email address . in another implementation , the user enters a particular data element and the system attempts to resolve that data element to make sure it matches something that exists . as shown in fig1 , an exemplary computer system to use for implementing one or more parts of the system includes a computing device , such as computing device 100 . in its most basic configuration , computing device 100 typically includes at least one processing unit 102 and memory 104 . depending on the exact configuration and type of computing device , memory 104 may be volatile ( such as ram ), non - volatile ( such as rom , flash memory , etc .) or some combination of the two . this most basic configuration is illustrated in fig1 by dashed line 106 . additionally , device 100 may also have additional features / functionality . for example , device 100 may also include additional storage ( removable and / or non - removable ) including , but not limited to , magnetic or optical disks or tape . such additional storage is illustrated in fig1 by removable storage 108 and non - removable storage 110 . computer storage media includes volatile and nonvolatile , removable and non - removable media implemented in any method or technology for storage of information such as computer readable instructions , data structures , program modules or other data . memory 104 , removable storage 108 and non - removable storage 110 are all examples of computer storage media . computer storage media includes , but is not limited to , ram , rom , eeprom , flash memory or other memory technology , cd - rom , digital versatile disks ( dvd ) or other optical storage , magnetic cassettes , magnetic tape , magnetic disk storage or other magnetic storage devices , or any other medium which can be used to store the desired information and which can accessed by device 100 . any such computer storage media may be part of device 100 . computing device 100 includes one or more communication connections 114 that allow computing device 100 to communicate with one or more servers , such as server with email data store 115 . computing device 100 may also communicate with one or more computers and / or applications 117 . device 100 may also have input device ( s ) 112 such as keyboard , mouse , pen , voice input device , touch input device , etc . output device ( s ) 111 such as a display , speakers , printer , etc . may also be included . these devices are well known in the art and need not be discussed at length here . turning now to fig2 with continued reference to fig1 , an data element resolution application 200 operating on computing device 100 is illustrated . data element resolution application 200 is one of the application programs that reside on computing device 100 . alternatively or additionally , one or more parts of data element resolution application 200 can be part of system memory 104 , on other computers and / or servers 115 , or other such variations as would occur to one in the computer software art . data element resolution application 200 includes business logic 204 , which is responsible for carrying out some or all of the techniques described herein . business logic 204 includes logic for checking data elements entered by the user and determining whether they are unresolved 206 , logic for determining a list of potential data elements for unresolved item ( s ) 208 , logic for displaying a suggested list of potential data elements in the same context with rest of the application 210 , logic for allowing the user to continue working with the activity and resume the resolution process later 212 , logic for prompting the user with viable options for resolution 214 , and other logic for operating the application 220 . in one implementation , business logic 204 is operable to be called programmatically from another program , such as using a single call to a procedure in business logic 204 . in one implementation , business logic 204 resides on computing device 100 . however , it will be understood that business logic 204 can alternatively or additionally be embodied as computer - executable instructions on one or more computers and / or in different variations than shown on fig2 . alternatively or additionally , one or more parts of data element resolution application 200 can be part of system memory 104 , on other computers and / or applications 117 , or other such variations as would occur to one in the computer software art . the examples presented herein illustrate using these technologies and techniques with an email application in one implementation . however , as discussed previously , in other implementations these technologies and techniques are used with other systems for resolving other types of data elements , such as postal addresses , conference rooms , patient records , etc . turning now to fig3 - 4 with continued reference to fig1 - 2 , the stages for implementing one or more implementations of data element resolution application 200 are described in further detail . fig3 is a high level process flow diagram for data element resolution application 200 . in one form , the process of fig3 is at least partially implemented in the operating logic of computing device 100 . the procedure begins at start point 240 with analyzing information the user inputs into one or more data element fields ( stage 242 ), such as an email address entered into an address field in an email message . the system attempts to retrieve existing information from one or more data stores ( stage 244 ). data stores can include , but are not limited to , databases , files on a local and / or remote computer , and / or other data storage systems . as one non - limiting example , email addresses are retrieved from one or more central data stores of stored information known as “ contacts .” separate data stores can contain global and personal contact information . one example of a data store for global contacts is the email addresses for all employees in a company . another non - limiting example of contacts is email information that each employee can enter into a personal contacts repository . such original data sources can be used to obtain information , which can then be used by data element resolution application 200 . in another implementation , data elements are retrieved by data element resolution application 200 when accessed via a web server over the internet . the information is analyzed ( stage 246 ) and compared to user input . information regarding potential matches is grouped together appropriately and displayed as a context menu ( stage 248 ) within the application . other types of menus or dialogs that allow the user to remain in the same context in the application and select a particular operation could also be used . the context menu includes one or more options of appropriate action to take to resolve an ambiguous data element ( stage 260 ). when the user completes a valid action , resolution for that data element is complete ( stage 264 ). the process ends at point 266 . fig4 illustrates one implementation of a more detailed process for resolving data elements . in one form , the process of fig4 is at least partially implemented in the operating logic of computing device 100 . the procedure begins at start point 280 with the user entering part or all of an address into one or more data element fields ( stage 282 ). the user engages the resolution process ( stage 284 ), which cues the system to compare the user &# 39 ; s entries with data elements stored locally on the computing device 100 or remotely on a server 115 . in one implementation , the resolution process is engaged when the user selects a resolve option , such as upon selecting a check names option . in another implementation , the resolution process is engaged as the user types an address in the address field . other variations are also possible for controlling how the user engages the resolution process . the presence of one or more ambiguous data elements causes a context menu to appear within the user &# 39 ; s application ( stage 286 ). the user reconciles the discrepancy by selecting from a list of close matches or by otherwise resolving the discrepancy ( stage 288 ). the selected or keyed name replaces the ambiguous name in the address field ( stage 290 ). if more than one data element is ambiguous , the process is repeated ( stage 292 ) until all data elements are resolved . then the user is allowed to finalize the activity , such as send the email , when the resolution process is complete ( stage 294 ). the process ends at end point 296 . fig5 illustrates the stages involved in resolving data elements based on particular status identifiers in one implementation . in one form , the process of fig5 is at least partially implemented in the operating logic of computing device 100 . the user performs an action that activates the address resolution process ( stage 321 ). the system recognizes user input into one or more address fields ( stage 322 ). the system compares the input to available data stores of data elements ( e . g . contacts ) ( stage 324 ) and determines if the user entry is ambiguous or is an exact match to one address in the data stores ( decision point 326 ). if the address is not ambiguous because an exact match is found , the address is displayed in a resolved status ( stage 327 ) and the system checks to see if there are any other data elements to resolve ( decision point 350 ). if the address is ambiguous and no exact match is found ( decision point 326 ), the system uses business logic 208 to generate a list of potential matches and appropriate actions to take ( stage 328 ). the system displays a status message , a list of potential matches , and / or options for appropriate actions in a context menu in the same context as the rest of the application ( stage 336 ). if the status is unresolved because no match was found ( stage 338 ) the user resolves it by deleting the entry ( stage 340 ) or by selecting from a list of potential matches ( stage 346 ). if the status is ambiguous because more than one match was found , the user can select from a list of potential matches ( stage 346 ). the resolution process is repeated until all data elements are resolved ( decision point 350 ). when no more data elements remain to be resolved ( decision point 350 ), the process then ends at end point 352 . fig6 illustrates the process for resuming the resolution process in one implementation in more detail . in one form , the process of fig6 is at least partially implemented in the operating logic of computing device 100 . the process starts at start point 370 when the user selects a data element resolution option ( e . g . “ check names ”) ( stage 372 ) to check the validity of all data elements entered into data element fields ( decision point 374 ). in one implementation , a user enters a particular data element , such as a plain text name , and the system attempts to resolve that data element to an identifier associated with the particular element , such as an email address . in another implementation , the user enters a particular data element and the system attempts to resolve that data element to make sure it matches something that exists . if all data elements are recognized as valid ( decision point 374 ), the process ends at end point 376 . if one or more data elements are questionable , or ambiguous , the user will see a context menu ( stage 378 ) displaying a list of potential matches and actions to resolve the ambiguity without requiring the user to change context ( e . g . without having to go to another screen , etc .). if the user wishes to continue working with the activity ( e . g . email message ) ( decision point 380 ), they can work with it as desired ( stage 381 ). while returning to work with the activity ( e . g . email ), the user can close the context menu ( stage 380 ) by simply clicking elsewhere in the activity or message , by pressing a designated key or keys ( such as esc ), and / or by other methods that cause the context menu to lose focus . the user can return to the context menu any time before attempting to finalize the activity , such as send the email . the resolution process can be resumed later by selecting the unresolved address in a particular fashion ( e . g . right - click or other selection ) to resolve the potential list of matches ( stage 382 ). if the user does not wish to exit the resolution process to continue working with the activity ( decision point 380 ), or if the user stops and then resumes the resolution process ( stage 382 ), the user then selects a desired address from the list of potential matches and actions ( stage 384 ). in one implementation , ambiguous data elements are differentiated from valid data elements by appearing on - screen in a different color and / or by appearing with a dashed underline instead of a solid underline . when the data element is resolved , the user will either be allowed to finalize the activity ( e . g . send the email ) or resolve the next ambiguous data element ( if more than one is present ). a new context menu with potential matches and actions will appear in turn for each ambiguous data element . when all data elements are resolved ( decision point 386 ), the process ends at end point 388 . fig7 is a flow diagram for one implementation that illustrates what happens when a user attempts to finalize an activity , such as by attempting to send an email message . in one form , the process of fig7 is at least partially implemented in the operating logic of computing device 100 . fig7 begins at start point 400 with the user selecting an option that instructs the system that the user wishes to finalize the activity ( e . g . send an email ). the system checks all data elements for ambiguity and resolution status ( stage 412 ). the system then displays a context menu consisting of a status message and / or a list of actions that may be taken . options for actions vary according to whether the system encountered an error in the process , whether the system found no match , one or more partial matches , or more than one exact match . in one implementation , the system does not check elements until the user activates that feature , such as by selecting a “ check names ” option . in another implementation , the system checks elements automatically at a pre - determined point in time , such as when the user exits the data element field ( e . g . the address field ). when the system checks an element and it matches a unique address in the data store , then the address name is considered resolved ( stage 436 ). if a checked element cannot be matched to a data element in the data store ( stage 418 ), the user must delete that name from the address field or reenter the name ( stage 420 ). if one or more partial matches are found ( stage 422 ), or if more than one exact match is found ( stage 430 ), then the user can select the correct data element from a list that appears in the context menu ( 424 ). if a network or server error ( stage 432 ) occurs during the checking process , then the user is instructed to try again ( stage 434 ). the process may repeat itself ( stage 426 ) as needed . the process ends at end point 428 when all data elements have been resolved . it will be appreciated that some , all , or additional stages than as listed in the figures herein could be used in alternate embodiments , and / or in a different order than as described . turning now to fig8 - 11 , simulated screens are shown to illustrate a user interface that allows a user to view and interact with an email resolution context menu created using data element resolution application 200 . these screens can be displayed to users on output device ( s ) 111 . furthermore , these screens can receive input from users from input device ( s ) 112 . when the user selects the data element resolution option ( e . g . “ check names ”) ( stage 372 ), the system analyzes all entered data elements against existing data store ( s ) ( stage 324 ). the results of the analysis appear as a context menu . the information in the context menu can differ , as depicted in fig8 - 11 . fig8 shows a simulated screen 500 that appears in one implementation when the resolution process cannot find a match for an ambiguous data element 510 . the context menu 520 displays one option given for resolving such an address , that is , to remove it without sending the email 530 . clicking on this option deletes the ambiguous address from the address field indicated . then the user can re - enter an address or send the email . fig9 shows a simulated screen 600 of one implementation that appears when the resolution process finds no exact match , but finds partial or potential matches . the context menu 620 displays all potential matches that the user can select from 630 , plus the option of removing the data element 640 . if the user clicks on an address in the context menu , it replaces the ambiguous address 610 . fig1 shows a simulated screen 660 of one implementation that appears when the resolution process finds more than one exact match for an ambiguous data element 670 . the context menu 680 lists potential matches is seen in 690 . if the user clicks on an address in the context menu , it replaces the ambiguous address 670 . as in all other context menus , the option for removing the data element is listed 695 . fig1 shows a simulated screen 700 of one implementation that appears when a server error occurs . in the event that a system error prevents the analysis of a potential match , the user &# 39 ; s options are to close the context menu 720 and try again 730 when system integrity is restored , or to delete the address without sending the email ( 740 ). in these simulated screens illustrated in fig8 - 11 , the resolution context menu is shown within the same context as the rest of the email application , thereby allowing the user to fix the problem without having to go through one or more other screens and / or lose the ability to keep working with the email and resume the resolution process later . although the subject matter has been described in language specific to structural features and / or methodological acts , it is to be understood that the subject matter defined in the appended claims is not necessarily limited to the specific features or acts described above . rather , the specific features and acts described above are disclosed as example forms of implementing the claims . all equivalents , changes , and modifications that come within the spirit of the implementations as described herein and / or by the following claims are desired to be protected . for example , a person of ordinary skill in the computer software art will recognize that the client and / or server arrangements , user interface screen content , and / or data layouts as described in the examples discussed herein could be organized differently on one or more computers to include fewer or additional options or features than as portrayed in the examples . | 6 |
the above and other objects , features and advantages of the present disclosure will be described later in detail with reference to the accompanying drawings , and thus the technical spirit of the present disclosure can be easily implemented by those skilled in the art . in the following description of the present disclosure , if a detailed description of known configurations and functions is determined to obscure the interpretation of embodiments of the present disclosure , the detailed description thereof will be omitted . hereinafter , preferred embodiments according to the present disclosure will be described in detail with reference to the accompanying drawings . in the drawings , the same reference numerals refer to the same or similar elements throughout . fig3 and 4 are block diagrams of a hardware protocol stack to which a user - defined protocol is applied according to the present disclosure , respectively . as shown in fig3 and 4 , a hardware protocol stack to which a user - defined protocol is applied according to the present disclosure includes a comparison unit 110 for comparing a header of a received frame with a header stored in a register , a register unit 120 for storing a header , an interface logic unit 130 determining a process of a received frame , a logic process unit 140 for processing data of a received frame according to a logic , a frame receiving unit 150 for receiving and storing a frame , and a frame production unit 160 for generating a frame . the comparison unit 110 compares header information of a frame received from media , that is , frame header information with header information stored in the register unit 120 , that is , register header information . generally , the frame is configured with header information , that is , frame header information , data , and a frame check sequence ( fcs ). the comparison unit 110 compares the frame header information among the frame header information , the data , and the fcs with the register header information whether they are the same as each other . the register unit 120 stores header information of a protocol that is an analysis target . a user may store header information of a protocol , which is not used in a commercial stack product or is defined by the user so as to develop a product , in a register . such a register unit 120 may include a plurality of registers . the present disclosure exemplifies that the register unit 120 includes a first register 121 , a second register 122 , and an n th register 123 . here , the first register 121 includes in number of register header information ( m is a natural number ), and this exemplifies hdr_00 , hdr_01 , . . . , hdr_0m . the second register 122 also includes m number of register header information ( m is a natural number ), this exemplifies hdr_10 , hdr_11 , . . . , hdr_1m . also , the n th register 123 ( n is a natural number ) includes in number of register header information ( m is a natural number ), this exemplifies hdr_n0 , hdr_n1 , . . . , hdr_nm . when the m number of register header information ( m is a natural number ) included in a frame are exemplified as hdr_r0 , hdr_r1 , hdr_rm , the comparison unit 110 compares hdr_00 , hdr_01 , . . . , hdr_0m , which are the register header information included in the first register 121 , with hdr_r0 , hdr_r1 , . . . , , hdr_rm , which are the frame header information included in the frame . here , when the two header information ( that is , the frame header information and the register header information ) are not matched to each other , the comparison unit 110 compares hdr_10 , hdr_11 , . . . , hdr_1m , which are the register header information included in the second register 122 , with hdr_r0 , hdr_r1 , . . . , hdr_rm , which are the frame header information included in the frame . when the frame header information and the register header information included in the second register 122 are matched to each other , the header information comparison is terminated . on the other hand , when the frame header information and the register header information included in the second register 122 are not matched to each other , register header information included in a third register that is a next register is compared with the frame header information . also , the comparison unit 110 performs the comparison operation unit the frame header information and the register header information are matched to each other , and such a comparison operation may be performed up to the n th register 123 . however , the present disclosure is not limited thereto , and the frame header information and all the register header information may be simultaneously compared with each other as necessary . the interface logic unit 130 determines whether the frame header information of the received frame is compared with the register header information stored in the register unit 120 , a comparison range of the frame header information and the register header information , and whether the received frame is stored . that is , the interface logic unit 130 differently performs a frame process method on a frame according to a kind of a header included therein . here , the frame process method includes a processing or storing of the frame and a producing and transmitting of a response frame . when the frame header information of the frame and the register header information are matched to each other and the frame process method of the interface logic unit 130 with respect to corresponding frame header information is a processing of a frame , the logic process unit 140 processes data of the received frame according to a logic . here , the logic is a rule according to the frame header information , and , for example , it may include a unit designation of frame data according to the frame header information , and the like . in the unit designation of the frame data , a unit is not designated in the data included in the received frame . therefore , the logic process unit 140 designates a unit in data according to header information of a corresponding frame . for example , referring to table 1 , when a request for writing payload data in a size of 0 × 20 at a 0 × 10 region is received , a user may use the logic process unit 140 to have expandability capable of setting a basic offset to 0 × 1000 and a size unit to 4 bytes and storing payload at 0 × 1010 as much as 0 × 80 . when the frame header information and the register header information are matched to each other and a frame process method of the interface logic unit 130 with respect to a corresponding frame header information is a frame storing , the frame receiving unit 150 stores a corresponding frame at a preset position , that is , processes along a path { circle around ( 2 )} in fig3 . when the frame header information and the register header information are matched to each other and a frame process method of the interface logic unit 130 with respect to the corresponding frame header information is a response frame transmitting , the frame production unit 160 produces and transmits a response frame , that is , processes along a path { circle around ( 1 )} in fig3 . here , the frame production unit 160 may produce not only the response frame but also various frames designated according to the frame header information . next , a method for applying a user - defined protocol of a hardware protocol stack according to the present disclosure will be described with reference to the drawings . in the following description , contents , which are overlapped with the above described hardware protocol stack to which the user - defined protocol according to the present disclosure is applied , will be omitted or described in brief . fig5 is a flow chart of a method for applying a user - defined protocol of a hardware protocol stack according to the present disclosure . as shown in fig5 , the method for applying a user - defined protocol of a hardware protocol stack includes receiving an input of a register in operation s 1 , comparing header information in operation s 2 , determining a frame process in operation s 3 , processing a frame in operation s 4 , responding with the frame in operation s 5 , and storing the frame 56 . the register unit receives an input of a register from a user in operation s 1 . the register unit stores the received register input by the user so as to compare the received register with frame header information of a frame that will be received later , also , the received register input by the user includes header information , that is , register header information . when a frame is received in operation s 2 , the comparison unit compares the register header information of the received register input in operation s 1 with frame header information of the received frame . here , the register unit includes a first register to an n th register . also , the comparison unit compares the frame header information with register header information of each of the first register to the n th register until the two hear information are matched to each other . meanwhile , when the frame header information and the register header information are matched to each other in operation s 2 , the present disclosure may further include receiving additionally an input of a register from the user in operation s 2 - 1 . when the register header information matched to the frame header information exists in operation s 2 , the interface logic unit processes the frame with a frame process method according to the corresponding register header information in operation s 3 . here , the frame process method includes a processing or storing of the frame and a producing and transmitting of a response frame as described above . when the frame process method according to the header information is a processing of a frame in operation s 3 , the logic process unit processes the received frame in operation s 4 . on the other hand , when the frame process method according to the header information is a responding with a frame , that is , a transmitting a response frame in operation s 3 , the frame production unit produces and transmits a response frame in operation s 5 . further , when the frame process method according to the header information is a storing of a frame in operation s 3 , the frame receiving unit stored the received frame at a destination in operation s 6 . although the present disclosure has been described with reference to the embodiments , it should be understood that numerous other substitutions , modifications and alterations can be devised by those skilled in the art without departing the technical spirit of this disclosure , and thus it should be construed that the present disclosure is not limited by the embodiments described above and the accompanying drawings . | 7 |
referring to fig1 an installed jacket 10 is shown with its bottom portion being anchored to the sea bed 12 and its upper portion extending up above the water level to support a platform 16 which normally houses oil production equipmetn and facilities , not shown . the jacket comprises tubular legs 18 interconnected by suitable diagonal and horizontal braces 20 and 22 , respectively . each leg typically is comprised of sections of different diameer , with the upper section 24 being of lesser diameter than the intermediate section 26 and the lower leg section 28 being of greatest diameter . the manner of anchoring the jacket to the sea bed involves the use of a pile cluster 30 described in more detail below . it should be understood that while the jacket illustrated represents a suitable design which could be used in connection with the invention , other jacket designs could be used as well , provided , however , that the jacket is anchored by means of a pile cluster . referring now to fig2 , 4 and 5 , the pile cluster illustrated comprises five pile sleeves 32 spaced about a portion of the periphery of the support leg section 28 . it will be understood that the particular pile sleeve arrangement shown is only for the purpose of illustrating the invention , and that other pile sleeve cluster arrangements could also be employed as long as the basic manner of providing added buoyancy , as described in more detail hereinafter , is utilized . the leg 28 is shown as being disposed at an angle to the vertical , which is typical of offshore jacket design , while the pile sleeves are substantially vertically aligned . the sleeves are held in place at their top and bottom portions by upper and lower transversely extending plates 36 and 38 , respectively . as can be seen in fig3 the upper portions of the sleeves extend through openings 40 in the upper plate 36 and , as illustrated best in fig2 terminate in funnel - shaped guides 42 for facilitating the entry of a pile . although not shown , the guides 42 may be further supported if desired by vertical stiffener plates disposed between the guides and the upper plate 36 . also , an extension or pile catcher plate may be attached to the guides 42 , as is known in the art , to further facilitate entry of a pile into a pile sleeve . as shown by the dotted lines in fig3 and by solid lines in fig4 each pile sleeve 32 is connected to the jacket support leg 28 by a pair of spaced shear plate 44 as by welding or other means of attachment which provides an airtight connection . the shear plates 44 are shown in fig2 and 4 as being reinforced with vertically spaced stiffener plates 46 which extend between the sleeves 30 and 32 and the support leg section 28 . the rigidity and resistance to stresses contributed by the pairs of shear plates is such that their thickness and the thickness of the pile sleeves can be significantly less than the thickness of shear plates and pile sleeves in a design incorporating only one shear plate between the support leg and each pile sleeve . the tops of the shear plates 44 terminate at the upper plate 36 and the bottoms of the shear plates terminate at the lower plate 38 . by attaching the shear plates to the transverse plates 36 and 38 seal the space between each pair of shear plates and form with the sehar plates and the circumferences of the support leg and the associated pile sleeve an airtight compartment associated with each of the pile sleeves 32 . this arrangement is better illustrated in fig6 wherein the pile sleeves 32 are shown as extending through the openings 40 in the upper plate 36 and the bottoms of the sleeves 32 are shown as being connected to the bottom plate 38 . the tops of the plates 44 are attached to the upper plate 36 and the bottoms of the plates 44 are attached to the bottom plate 38 . the shear plates associated with adjacent pile sleeves 32 are connected by the horizontal stiffener plates 46 . the space defined by each pair of shear plates 44 , the upper plate 36 , the lower plate 38 and the circumferences of the leg 28 and sleeve 32 between the plates thus forms an airtight compartment between the pile sleeve and the support leg . with each pile sleeve being so constructed , the compartments add considerable buoyancy to the structure . after the structure is in place , piles are driven through the pile sleeves and into the sea bed to anchor the jacket . this is illustrated in fig7 which shows a pile 50 extending through the pile sleeve 32 down into the sea bed 12 . the pile is of course of a smaller diameter than the inside diameter of the pile sleeve to enable the pile to readily enter and move through the sleeve . the resultign annulus between the pile 50 and the inside surface of the sleeve 32 is filled with suitable grout 52 which is retained in place by packer 54 located adjacent the bottom portion of the sleeve . although the etails have not been shown since they are not important to the invention , it will be understood that any conventional form of packer and grout introduction valve means may be employed to introduce and maintain the grout in place until it has set . fig7 also shows the plates 36 and 38 as being welded to the pile sleeve 32 to seal off the chamber at these locations . similarly , welds between the shear plates and the top and bottom plates 36 and 38 and between the shear plates and the jacket leg make the chamber connections air tight . although the invention has been described in connection with a pile cluster associated with one of the support legs of the jacket , a similar arrangement obviously may be employed in connection with all of the support legs . further , the number of pile sleeves associated with the support leg may vary . it can now be appreciated that the invention provides a means for permitting the pile sleeves of a jacket anchoring cluster to be shortened , thereby reducing the weight of the assembly , by providing spaced shear plates which form side walls of airtight compartments . this arrangement not only provides added strength but also provides added buoyancy in an economical , efficient manner , thus facilitating and shortening the jacket installation time and eliminating the need to add separate buoyancy tanks . it will be understood that although not shown , diaphragms may be employed to seal the pile sleeves 32 at their ends to provide additional buoyancy . it should now be apparent that the invention is not necessarily limited to all the specific details described in connection with the preferred embodiment , but that changes to certain features of the preferred embodiment which do not alter the overall basic function and concept of the invention may be made without departing from the spirit and scope of the invention , as defined in the appended claims . | 4 |
the present invention now will be described more fully hereinafter with reference to the accompanying drawings , in which an embodiment of the invention is shown . this invention may be embodied in many different forms and should not be construed as limited to the embodiment set forth herein . many methods of manufacturing semiconductor devices are well known in the art . the following discussion focuses on modifying a conductive layer block mask used during the manufacture of semiconductor devices in order to confuse the reverse engineer . the discussion is not intended to provide all of the semiconductor manufacturing details , which are well known in the art . in order to confuse the reverse engineer , the placement of an artifact edge of a silicide layer that would be seen when a reverse engineer examines devices manufactured with other reverse - engineering - detection - prevention techniques is changed . in reverse - engineering - detection - prevention techniques , false , or non - operational , transistors are used along with true , or operational , transistors . some false transistors are manufactured without sidewall spacers , see fig1 b , while corresponding true transistors may well have sidewall spacers 19 , as shown in fig2 b . from a top - down view , and through most reverse engineering techniques , these false transistors look the same as operational transistors . however , under some reverse engineering techniques , such as chemical mechanical polishing ( cmp ) or other etching processes , the artifact edges of the silicide layer may give away the reverse - engineering - detection - prevention technique . as shown in fig1 a , for some non - operational transistors , the artifact edges 18 of a silicide layer 15 coincide with the edges 11 , 13 of the gate layer 14 . however , with operational transistors as shown in fig2 a , the artifact edges 18 ′ of a silicide layer 15 are offset from the edges 11 , 13 of the gate layer 14 by the width of sidewall spacers 19 . fig3 a is a top - down view and fig3 b is a cross - sectional view of a false transistor in accordance with the present invention . fig3 a depicts artifact edges 18 ″ of a conductive layer 15 that do not coincide with the edges 11 , 13 of gate layer 14 . a conductive layer block mask 21 , see fig4 , is preferably modified to prevent the silicide layer 15 from covering the entire active areas 12 , 16 . the conductive layer 15 is partially formed over a first active area 12 and a second active area 16 . the result is that the conductive layer 15 has a cross - sectional width 151 that is smaller than the cross - sectional width 121 , 161 of the active areas 12 , 16 . thus , when a reverse engineering process , such as cmp or other etching process , is used , the artifact edges 18 ″ of the conductive layer 15 do not give away the fact that the transistor is a false transistor . instead , the artifact edges 18 ″ are offset by a distance 17 , see fig3 a , from the gate layer 14 , with distance 17 having a width that is preferably approximately equivalent to the width of one typical sidewall spacer , as if sidewall spacers were present . therefore , the reverse engineer can no longer rely on the placement of the artifact edges 18 of conductive layer 15 to determine if a transistor is a true transistor or a false transistor . one skilled in the art will appreciate that the conductive layer block mask 21 will require different modifications depending on the feature size of the device . the offset distance 17 between the artifact edge 18 ″ of the conductive layer 15 and the edge 11 , 13 of the gate layer 14 is preferably approximately equal to the width of the sidewall spacers , which varies depending on the feature size of the device . one skilled in the art will appreciate that the difference between the width of the sidewall spacer 19 and the width of the offset 17 should be within the manufacturing tolerances for the process used , and thus the offset 17 and the width of the sidewall spacer 19 are approximately equal . for 0 . 35 μm technology , for example , the sidewall spacer width is approximately 0 . 09 μm . for typical cmos processes , the conductive layer 15 will be silicide while the gate layer 14 will be polysilicon . one skilled in the art will appreciate that regardless of the feature size of the device , the person laying out the masks should place the artifact edges 18 ″ of the conductive layer 15 for a false transistor in substantially the same relative locations as the artifact edges 18 ′ of the conductive layer 15 for a true transistor . thus , the reverse engineer will be unable to use the artifact edges 18 of the conductive layer 15 to determine if the transistor is a true transistor or a false transistor . additionally , false transistors manufactured in accordance with the invention are preferably used not to completely disable a multiple transistor circuit , but rather to cause the circuit to function in an unexpected or non - intuitive manner . for example , what appears to be an or gate to the reverse engineer might really function as an and gate . alternatively , what appears as an inverting input might really be non - inverting . the possibilities are endless and are almost sure to cause the reverse engineer so much grief that he or she would give up as opposed to pressing forward to discover how to reverse engineer the integrated circuit device on which this technique is utilized . having described the invention in connection with certain preferred embodiments thereof , modification will now certainly suggest itself to those skilled in the art . as such , the invention is not to be limited to the disclosed embodiments , except as is specifically required by the appended claims . | 7 |
one preferred embodiment of the present invention will be described with reference to the accompanying drawings . referring to fig3 ( a ), 3 ( b ) and 3 ( c ), the staple cartridge a has a staple sheet accommodating section 1 in which a number of staple sheets s are stacked . the staple sheet accommodating section 1 has a staple sheet let - off opening 3 in the lower portion of the front wall 2 thereof , so that the staple sheets s are conveyed out of the accommodating section 1 through the let - off opening 3 one after another beginning with the lowermost staple sheet sa . a depressing member 6 is connected to the cover 5 of the cartridge pushing down on the stack of staple sheets s . the lowermost staple sheet sa is confronted with the staple let - off opening 3 and moved by a conveyor belt 7 through the staple sheet let - off opening 3 . when the staple sheet is conveyed in this manner , the second staple sheet sb is moved to the lowermost position by depressing member 6 . in this manner , the staple sheets are successively moved downward and conveyed out of the accommodating section 1 through the let - off opening 3 into the forming and driving section of the stapler . the cartridge a has side wall 10 and opening 11 in the bottom , and a pair of supporting members 12 are extended from both edges of the opening 11 so as to support both sides of the lowermost staple sheet sa in such a manner that the front end of the lowermost staple sheet sa confronts the staple sheet let - off opening 3 . the upper portion of the let - off opening 3 is formed into a sloped surface 3a so as to facilitate movement of the lowermost staple sheet sa into the let - off opening 3 . a guide member 13 is extended from the lower end of the front wall 2 towards the forming and driving section of the stapler and a pair of elongated guide projections 13a are formed along both edges of the lower surface of the guide member 13 . a retaining protrusion 14 is formed at the center of the lower surface of the guide member 13 to retain the upper surface of the staple sheet s . the retaining protrusion 14 has a sloped guide surface 14a at the end facing the let - off opening 3 . the cartridge a is set on the magazine in such a manner that it is placed over the stapler sheet conveyor belt 7 in the stapler . in this position the retaining protrusion 14 of the guide member 13 is located above the conveyor belt 7 . the gap w1 between the lower surface 13b of the guide member 13 and the upper surface 7a of the conveyor belt 7 is slightly larger than the thickness w2 of the staple sheet s . the gap w3 between the lower surface 14b of the retaining protrusion 14 and the upper surface 7a of the conveyor belt 7 is slightly smaller than the thickness w2 of the staple sheet s . preferably , the width of the retaining protrusion 14 is equal to the width of the conveyor belt 7 and the front of the retaining protrusion 14 is located near the outer end of the conveyor belt 7 . in operation , with the cartridge a containing a stack of staple sheets s loaded on the stapler , the staple sheet conveyor belt 7 is driven . as a result , the lowermost staple sheet sa is moved out of the accommodating section 1 through the let - off opening 3 and delivered to the forming and driving section while being supported by the staple guide rails 16 and being guided by the elongated guide protrusions 13a of the guide member 13 and the upper surface 7a of the conveyor belt 7 . the lower surface of the lowermost staple sheet sa is pushed against the upper surface 7a of the conveyor belt 7 by the forces of the stack weight and the depressing member 6 . therefore the staple sheet sa is conveyed through the let - off opening 3 by the frictional force f at the conveyor and staple sheet interface . the staple sheet conveying is distributed evenly over the upper surface 7a of the conveyor belt 7 from the rear end p of the cartridge a to the front end r of the retaining protrusion 14 . since the gap w3 between the lower surface 14b of the retaining protrusion 14 and the upper surface 7a of the conveyor 7 is smaller than the thickness w2 of the staple sheet additional perpendicular force is applied , to the staple sheet s when it is below the retaining protrusion 14 . the retaining protrusion 14 also serves to insure that the staple sheet s is held flat on the conveyor , thereby maximizing the area of contact between the staple sheet s and the conveyor belt 7 . this additional perpendicular force and maximized area of contact serve to maximize the frictional force f , at the interface of the conveyor 7 and staple sheet s thereby providing a smooth positive delivery of the staple sheets s into the forming and driving section of the stapler without reliance on auxillary magnetic means . now with reference to fig4 the staple sheet accommodating section has relief recesses 8 at the corners of the walls which extend vertically so as to prevent the corners of the staple sheets from coming into contact with the corners of the staple sheet accommodating section . therefore burrs commonly found on the corners of the staple sheets will not prevent a smooth descent of the staple sheets to the bottom of the staple sheet accommodating section 1 . since the cartridge is usually inclined slightly to the rear in order to keep the staple sheets s in contact with the rear wall of the accommodating section 1 , it is not necessary to place recesses at all four corners but only in the rear corners of the accommodating section 1 . a flexible feeding film 17 , is suspended on the rear wall 9 of the cartridge a . the upper portion 18 of the feeding film 17 is folded over , thus providing a folded portion 19 u - shaped in cross section . an opening 20a is formed in the middle portion 20 of the feeding film 17 . the lower portion of the feeding film 17 is bent at a right angle , thus providing a bent portion 21 . the feeding film 17 is fitted in the cartridge a with the opening 19a engaging with a salient portion 22 on the outside of the rear wall of the cartridge a . the method of fitting the feeding film is not limited to the above , many other methods may be employed without departing from the spirit of the present invention . the feeding film 17 is positioned in the cartridge a in such a manner such that the middle portion 20 of the feeding film 17 is placed between the stack of the staple sheets s and the rear wall 9 of the cartridge a , and the bent portion 21 is under the rear part of the lowermost staple sheet sa . as described above the distance between the front and rear walls of the cartridge a is greater than the length of the staple sheets . therefore vibration of the stapler maintains a clearance c between the front wall 2 of the cartridge a and the staple sheets s in the cartridge a . as the frictional force exerted on the lowermost staple sheet sa by the conveyor belt 7 conveys the lowermost staple sheet sa into the let - off opening 3 it also tends to pull the bent portion 21 of the feeding film 17 forward bringing the staple sheets above the lowermost staple sheet sa into contact with the sloped surface 3a above the let - off opening . because subsequent staple sheets s are pulled forward with the second lowermost staple sheet sb there is no resultant shearing force tending to bend the second lowermost staple sheet sb as found in the prior art and illustrated in fig2 ( b ). this eliminates clogging of staple sheets s in the let - off opening 3 and permits the staple sheets s to be forwarded positively and smoothly , one after another , into the forming and driving section of the stapler . while a preferred embodiment of the present invention is described above , it will be obvious to those skilled in the art that various modifications may be made therein without departing from the scope and spirit of the present invention . | 1 |
[ 0019 ] fig1 illustrates a general schematic view of a vehicle 100 including an expendable miniature gas turbine engine 10 according to the present invention . the vehicle 100 includes a body 102 and one or more aerodynamic surfaces 104 . the engine 10 is coupled to , or within , the body 102 . an intake 106 provides air to the engine 10 , and an exhaust pipe 108 exhausts the thrust therefrom . the engine 10 of the invention may also be used in other single usage and reusable applications such as reconnaissance drones , cruise missiles , decoys and other weapon and non - weapon applications . referring to fig2 the miniature gas turbine engine 10 generally includes a housing 14 , a rotor shaft 16 rotationally mounted to a forward bearing 18 , a combustion system 20 and an exhaust pipe ( nozzle ) 22 . the rotor shaft 16 rotates about a longitudinal axis x although other forms of rotors , such as a monorotor configuration , would also benefit from the present invention . in the illustrated rotor configuration , a rotor 24 includes compressor blades 26 facing forward toward an inlet 28 and turbine blades 30 facing rearward toward the exhaust 22 to define a turbine wheel . the forwardly extending shaft 16 is received in the bearings 18 and is preferably coupled to a fuel pump ( illustrated schematically at 32 ) to provide fuel to an annular combustor liner 34 through a fuel manifold 36 . referring to fig3 a cross - section of the combustion system 20 is illustrated . the combustion system 20 generally includes the annular combustor liner 34 , the fuel manifold 36 and an igniter 38 . the combustor liner 34 is a reverse flow annular combustor , and thus has a leading end 40 generally disposed toward the rear of turbine engine 10 , and a trailing end 42 generally disposed toward the front of the turbine engine 10 . the combustor liner 34 includes an outer wall 44 in the form of a metal tube having an outer surface 46 and an opposing inner surface 48 . the combustor liner 34 further includes an inner wall 50 , and a dome 52 generally connected to , and joining , the inner and outer walls 44 , 50 at respective annular lines of intersection 54 and 56 . the exhaust pipe 22 extends rearwardly of the engine 10 from throat 60 , and interfaces with rear housing wall 62 , whereby the combustor liner 34 is enclosed on its outer and rear surfaces by housing 14 and on its inner surface by the exhaust pipe 58 . the combustor liner 34 interfaces with the exhaust pipe 22 through a combustor exit 64 such that exhaust gases from the combustor liner 34 are directed through the exhaust pipe 22 generating a high velocity thrust ( illustrated schematically by arrow t ). a compressor discharge plenum 66 is located between the outer wall 44 of the combustor liner 34 and the housing 14 . the discharge plenum 66 distributes air from the compressor ( fig2 ) into the combustor liner 34 through fuel - air tubes 68 which feed a fuel - rich mixture of fuel and air into the leading end 40 of the combustor liner 34 to form a primary burning region p . it should be understood that the term “ tubes ” is to be construed to broadly include openings , holes , apertures , bent metal deflectors and the like in addition to separate cylindrical member . moreover , any hole shape , including elliptical , rectangular , triangular and any hole condition including plain sharp - edged , plunged and the like will benefit from the present invention . fuel is introduced into the combustor liner 34 through a fuel passageway 70 which communicates fuel from the fuel manifold 36 into each of the fuel - air tubes 68 through a fuel orifice 71 . fuel orifices 71 are preferably drilled holes which direct fuel into the tubes 68 at a prescribed location . the fuel orifices 71 control fuel system pressure through proper predetermined sizing and quantity . the fuel orifices 71 preferably produce a predetermined allowable level of fuel pressure drop at the maximum required fuel flow rate such as 150 psid . the fuel orifices 71 essentially just pour fuel into tubes 68 . that is , fuel may just trickle from the fuel orifice 71 at low speed turbine engine 10 operation or a stream from the orifice 71 at high speed operation . at either extreme , a fine fuel spray is not necessary since a great deal of fuel - air mixing occurs within the fuel - air feed tubes 68 such that the fuel manifold 36 need not require precision machining . optimum fuel - air mixing is required to obtain optimum combustor performance . the fuel - air mixing tubes 68 are preferably designed with enough length and air momentum / velocity to break up and evaporate as much fuel as possible . it should be understood that as the present invention is directed toward expendable gas turbine engines longevity concerns relating to extending the fuel - air mixing tubes 68 relatively deep into the combustor 34 ( fig4 ) without complicated cooling systems is of minimal concern . since the fuel orifices 71 are relatively simple holes , and since the tubes 68 are directly attached to the combustor 34 , fueling is inexpensive and requires minimal hardware on the engine case . control of the fuel flow rate into the fuel manifold is performed by any variable system . the size of the fuel manifold jet holes is preferably set to maximize fuel jet velocity and maintain fuel flow uniformity from hole - to - hole . the fuel - air mixture within the injection tubes 68 is most preferably of a fuel - rich quality and the air velocities through these tubes 68 are of relatively high velocity , e . g ., mach 0 . 3 and greater . the fuel injection of the present invention makes the combustor relatively independent of the type of fuel burned . a wide range of fuels ranging from gasesous ( methane , propane , natural gas ) to pure , light hydrocarbons ( hexane , octane , butane ) to aviation fuels ( jet - a , jet - a1 , jp - 4 , jp - 5 , jp - 10 , jp - 8 ) to heavy diesel fuels ( df1 , df2 , marine diesel ) can be burned with fuel manifold system and combustor air apportionment readily available to one of ordinary skill in the art . since the primary zone stoichiometry is variable by design and since the reaction times in the primary zone are short by design , primary zone flame temperatures may be “ tuned ” such that they are low for certain chosen engine operating conditions . these predetermined designed low flame temperatures and short reaction times result in a combustion system that is capable of achieving extremely low levels of no x with a wide variety of liquid fuels . initial ignition of the combustion process is performed by a spark - gap or pyrotechnic flare - type igniter 38 preferably located through the dome 52 . the igniter 38 is placed in a position down - swirl of one of the fuel - air injection tubes 68 to ensure contact with fuel as it enters the combustor 34 . under extreme cold conditions and at low engine speeds fuel break - up is preferably assisted by a jet of high - velocity air , oxygen or air / oxygen mixture directed into the fuel - air tube 68 just upstream of the igniter 38 . this oxygen jet is used to improve ignition only and is not needed during normal combustor operation . once ignition is initiated , the igniter is no longer needed since the combustor 34 is a continuous ignition device . the air flow through fuel - air mixing tubes 68 breaks the fuel into small droplets and mixes the fuel with air before the fuel - air mixture enters the combustor liner 34 . fuel is further mixed with the combustion air by strong aerodynamic forces within the combustor . fuel break - up occurs through air - blast atomization , tube - wall impingement and vaporization . the discharge direction of the fuel - air mixture is generally circumferential and axial aft as the fuel - air tubes 68 preferably extend into the combustor liner 34 as a circumferential row which directs the mixture generally toward the dome 52 and igniter 38 ( fig5 ). the fuel air mixture is mixed with additional air injected through a row of secondary air - fed tubes 70 downstream of the fuel - air mixing tubes 68 . the secondary air - feed tubes 70 are located approximately midway between the combustor dome 52 and the exit 64 to form a secondary burning region s . it should be understood that the term “ tubes ” is to be construed to broadly include openings , holes , apertures , bent metal deflectors and the like in addition to separate cylindrical member . moreover , any hole shape , including elliptical , rectangular , triangular and any hole condition including plain sharp - edged , plunged and the like will benefit from the present invention . a row of dilution air - feed tubes 74 are located just upstream of the combustor exit 64 to form a final dilution mixing region d . the sets of tubes 68 , 70 and 72 produce a generally circumferential air velocity into the combustor liner 34 . it should be understood that the high degree of swirl produced via this air direction provides for high mixing and maximizes the path length experienced by the fuel entering the combustor . the combustor liner 34 is maintained at acceptable temperature levels by designing the combustor 34 for high air velocities . the high air velocity through the compressor discharge plenum 66 and over the external portion of the combustor 34 provides for convective cooling . it should be understood that other combustor cooling techniques , e . g ., splash cooling , film cooling , effusion cooling or the like which require air injection into the combustor may also be used , but is preferably designed to avoid interference with the primary and secondary burning . such additional cooling techniques will necessarily require slightly larger combustor volumes . the air flow into the combustor 34 is apportioned to provide the two burning regions p , s and the dilution - mixing region d . the two burning regions p , s allows the combustor 34 to operate at minimum overall burning time . in the primary burning region p , the fuel / air stoichiometry is preferably designed to be rich at full power engine operating conditions . combustion occurs in this region at temperatures that maintain high enough flame speeds for adequate stability , but all the fuel cannot react . the fuel that is unable to react in the primary region p is mixed with air in the secondary region s and then burned . the secondary region s results in near - stoichiometric fuel / air ratios and consequently , maximum flame temperatures . it should be understood that one of skill in the art utilizing the teaching of the present invention is readily able to design such a near - stoichiometric fuel / air ratio . the fuel / air ratios in the two burning regions p , s vary with engine operating condition , so the air apportionment within the combustor 34 is preferably designed to accommodate the full engine flight envelope . flame temperatures within the primary burning region p are critical and must be maintained at all times in order to maintain stable , efficient combustion . if the primary region is too lean or too rich , the flame temperature drops and burning rates fall to levels too low to maintain combustion . each combustion region approximates a “ well - stirred reactor ” and the combination of the two regions p , s results in a “ best possible ” use of combustion volume . downstream of the secondary burning region s , air is injected to mix out the hot flame gases at the dilution - mixing region d . the dilution - mixing region d is designed to preferably provides cool enough temperatures to avoid damage to the downstream turbine 30 . it should be understood that the mixing air may alternatively or additionally be introduced through tubes , drilled holes , or plunged holes and may be fed through the inner or outer combustor wall . referring to fig6 the igniter 38 is positioned between the two burning regions p , s and the fuel - air injection tubes 68 are located within the dome 52 of the combustor liner 34 . that is , the fuel - air injection tubes 68 are disposed toward the rear of turbine engine 10 through a leading end 40 of the combustor liner 34 generally between the inner and outer walls . the igniter 38 is placed in circumferential position about the outer wall of the combustor 34 . the fig6 arrangement provides advantages of the above - described design with different packaging constraints . the foregoing description is exemplary rather than defined by the limitations within . many modifications and variations of the present invention are possible in light of the above teachings . the preferred embodiments of this invention have been disclosed , however , one of ordinary skill in the art would recognize that certain modifications would come within the scope of this invention . it is , therefore , to be understood that within the scope of the appended claims , the invention may be practiced otherwise than as specifically described . for that reason the following claims should be studied to determine the true scope and content of this invention . | 8 |
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