adapt them to the digital signage model. the administrative staff who will be expected to update or import schedules to the digital signage system will have a much lower threshold of acceptance for a workflow that is completely unfamiliar or at odds with all their previous experience. an intuitive, easy - to - use system is more likely to be used in an emergency if it has become familiar in everyday practice. turnkey digital signage solutions provide end - to - end functionality without forcing users and integrators to work with multiple systems and interfaces. the key in selecting a vendor lies in ensuring that they share the same vision and are moving in the same direction as the end user. in addition to providing ease of use, digital signage solutions for the education market also must provide a high level of built - in security, preventing abuse or misuse by hackers, or by those without the knowledge, experience or authority to distribute content over the network. because the network is a conduit for emergency messaging, its integrity must be protected. so, the installer must not only identify the number of screens to be used and where, but also determine who gets access to the system and how that access remains secure. scalable systems that can grow in number of displays or accommodate infrastructure improvements and distribution of higher - bandwidth content will provide the long - term utility that makes the investment worthwhile. by going into the project with an understanding of existing infrastructure, such as cabling, firewalls, etc., and the client ’ s goals, the professional is equipped to advise the customer as to the necessity, options and costs for enhancing or improving on that infrastructure. as with any other significant deployment of av technology, the installation of a digital signage network also requires knowledge of the site, local building codes, the availability of power and so forth. ralph bachofen, senior director of product management and marketing, triveni digital, has more than 15 years of experience in voice and multimedia over internet protocol ( ip ), telecommunications and the semiconductor business. the infrastructure requirements of a school in deploying a digital signage network will vary, depending on the type of content being delivered through the system. hd and streaming content clearly are bandwidth hogs, whereas tickers and other text - based messages put a low demand on bandwidth. most facilities today are equipped with gigabit ethernet networks that can handle the demands of live video delivery and lighter content. however, even bandwidth - heavy video can be delivered by less robust networks, as larger clips can be “ trickled ” over time to the


how we found the missing memristor the memristor - - the functional equivalent of a synapse - - could revolutionize circuit design image : bryan christie design thinking machine this artist ' s conception of a memristor shows a stack of multiple crossbar arrays, the fundamental structure of r. stanley williams ' s device. because memristors behave functionally like synapses, replacing a few transistors in a circuit with memristors could lead to analog circuits that can think like a human brain. it ’ s time to stop shrinking. moore ’ s law, the semiconductor industry ’ s obsession with the shrinking of transistors and their commensurate steady doubling on a chip about every two years, has been the source of a 50 - year technical and economic revolution. whether this scaling paradigm lasts for five more years or 15, it will eventually come to an end. the emphasis in electronics design will have to shift to devices that are not just increasingly infinitesimal but increasingly capable. earlier this year, i and my colleagues at hewlett - packard labs, in palo alto, calif., surprised the electronics community with a fascinating candidate for such a device : the memristor. it had been theorized nearly 40 years ago, but because no one had managed to build one, it had long since become an esoteric curiosity. that all changed on 1 may, when my group published the details of the memristor in nature. combined with transistors in a hybrid chip, memristors could radically improve the performance of digital circuits without shrinking transistors. using transistors more efficiently could in turn give us another decade, at least, of moore ’ s law performance improvement, without requiring the costly and increasingly difficult doublings of transistor density on chips. in the end, memristors might even become the cornerstone of new analog circuits that compute using an architecture much like that of the brain. for nearly 150 years, the known fundamental passive circuit elements were limited to the capacitor ( discovered in 1745 ), the resistor ( 1827 ), and the inductor ( 1831 ). then, in a brilliant but underappreciated 1971 paper, leon chua, a professor of electrical engineering at the university of california, berkeley, predicted the existence of a fourth fundamental device, which he called a memristor. he proved that memristor behavior could not be duplicated by any circuit built using only the


professor of electrical engineering at the university of california, berkeley, predicted the existence of a fourth fundamental device, which he called a memristor. he proved that memristor behavior could not be duplicated by any circuit built using only the other three elements, which is why the memristor is truly fundamental. memristor is a contraction of ” memory resistor, ” because that is exactly its function : to remember its history. a memristor is a two - terminal device whose resistance depends on the magnitude and polarity of the voltage applied to it and the length of time that voltage has been applied. when you turn off the voltage, the memristor remembers its most recent resistance until the next time you turn it on, whether that happens a day later or a year later. think of a resistor as a pipe through which water flows. the water is electric charge. the resistor ’ s obstruction of the flow of charge is comparable to the diameter of the pipe : the narrower the pipe, the greater the resistance. for the history of circuit design, resistors have had a fixed pipe diameter. but a memristor is a pipe that changes diameter with the amount and direction of water that flows through it. if water flows through this pipe in one direction, it expands ( becoming less resistive ). but send the water in the opposite direction and the pipe shrinks ( becoming more resistive ). further, the memristor remembers its diameter when water last went through. turn off the flow and the diameter of the pipe ” freezes ” until the water is turned back on. that freezing property suits memristors brilliantly for computer memory. the ability to indefinitely store resistance values means that a memristor can be used as a nonvolatile memory. that might not sound like very much, but go ahead and pop the battery out of your laptop, right now — no saving, no quitting, nothing. you ’ d lose your work, of course. but if your laptop were built using a memory based on memristors, when you popped the battery back in, your screen would return to life with everything exactly as you left it : no lengthy reboot, no half - dozen auto - recovered files. but the memristor ’ s potential goes far beyond instant - on computers to embrace one of the grandest technology challenges : mimicking the functions of a brain. within a decade, memristors could let us emulate


recovered files. but the memristor ’ s potential goes far beyond instant - on computers to embrace one of the grandest technology challenges : mimicking the functions of a brain. within a decade, memristors could let us emulate, instead of merely simulate, networks of neurons and synapses. many research groups have been working toward a brain in silico : ibm ’ s blue brain project, howard hughes medical institute ’ s janelia farm, and harvard ’ s center for brain science are just three. however, even a mouse brain simulation in real time involves solving an astronomical number of coupled partial differential equations. a digital computer capable of coping with this staggering workload would need to be the size of a small city, and powering it would require several dedicated nuclear power plants. memristors can be made extremely small, and they function like synapses. using them, we will be able to build analog electronic circuits that could fit in a shoebox and function according to the same physical principles as a brain. a hybrid circuit — containing many connected memristors and transistors — could help us research actual brain function and disorders. such a circuit might even lead to machines that can recognize patterns the way humans can, in those critical ways computers can ’ t — for example, picking a particular face out of a crowd even if it has changed significantly since our last memory of it. the story of the memristor is truly one for the history books. when leon chua, now an ieee fellow, wrote his seminal paper predicting the memristor, he was a newly minted and rapidly rising professor at uc berkeley. chua had been fighting for years against what he considered the arbitrary restriction of electronic circuit theory to linear systems. he was convinced that nonlinear electronics had much more potential than the linear circuits that dominate electronics technology to this day. chua discovered a missing link in the pairwise mathematical equations that relate the four circuit quantities — charge, current, voltage, and magnetic flux — to one another. these can be related in six ways. two are connected through the basic physical laws of electricity and magnetism, and three are related by the known circuit elements : resistors connect voltage and current, inductors connect flux and current, and capacitors connect voltage and charge. but one equation is missing from this group : the relationship between charge moving through a circuit and the magnetic flux surrounded by that circuit — or more subtly, a mathematical doppelganger defined by faraday ’


and capacitors connect voltage and charge. but one equation is missing from this group : the relationship between charge moving through a circuit and the magnetic flux surrounded by that circuit — or more subtly, a mathematical doppelganger defined by faraday ’ s law as the time integral of the voltage across the circuit. this distinction is the crux of a raging internet debate about the legitimacy of our memristor [ see sidebar, ” resistance to memristance ” ]. chua ’ s memristor was a purely mathematical construct that had more than one physical realization. what does that mean? consider a battery and a transformer. both provide identical voltages — for example, 12 volts of direct current — but they do so by entirely different mechanisms : the battery by a chemical reaction going on inside the cell and the transformer by taking a 110a ¿ ¿ v ac input, stepping that down to 12 v ac, and then transforming that into 12 v dc. the end result is mathematically identical — both will run an electric shaver or a cellphone, but the physical source of that 12 v is completely different. conceptually, it was easy to grasp how electric charge could couple to magnetic flux, but there was no obvious physical interaction between charge and the integral over the voltage. chua demonstrated mathematically that his hypothetical device would provide a relationship between flux and charge similar to what a nonlinear resistor provides between voltage and current. in practice, that would mean the device ’ s resistance would vary according to the amount of charge that passed through it. and it would remember that resistance value even after the current was turned off. he also noticed something else — that this behavior reminded him of the way synapses function in a brain. even before chua had his eureka moment, however, many researchers were reporting what they called ” anomalous ” current - voltage behavior in the micrometer - scale devices they had built out of unconventional materials, like polymers and metal oxides. but the idiosyncrasies were usually ascribed to some mystery electrochemical reaction, electrical breakdown, or other spurious phenomenon attributed to the high voltages that researchers were applying to their devices. as it turns out, a great many of these reports were unrecognized examples of memristance. after chua theorized the memristor out of the mathematical ether, it took another 35 years for us to intentionally build the device at hp labs, and we only really understood the device about two years ago


examples of memristance. after chua theorized the memristor out of the mathematical ether, it took another 35 years for us to intentionally build the device at hp labs, and we only really understood the device about two years ago. so what took us so long? it ’ s all about scale. we now know that memristance is an intrinsic property of any electronic circuit. its existence could have been deduced by gustav kirchhoff or by james clerk maxwell, if either had considered nonlinear circuits in the 1800s. but the scales at which electronic devices have been built for most of the past two centuries have prevented experimental observation of the effect. it turns out that the influence of memristance obeys an inverse square law : memristance is a million times as important at the nanometer scale as it is at the micrometer scale, and it ’ s essentially unobservable at the millimeter scale and larger. as we build smaller and smaller devices, memristance is becoming more noticeable and in some cases dominant. that ’ s what accounts for all those strange results researchers have described. memristance has been hidden in plain sight all along. but in spite of all the clues, our finding the memristor was completely serendipitous. in 1995, i was recruited to hp labs to start up a fundamental research group that had been proposed by david packard. he decided that the company had become large enough to dedicate a research group to long - term projects that would be protected from the immediate needs of the business units. packard had an altruistic vision that hp should ” return knowledge to the well of fundamental science from which hp had been withdrawing for so long. ” at the same time, he understood that long - term research could be the strategic basis for technologies and inventions that would directly benefit hp in the future. hp gave me a budget and four researchers. but beyond the comment that ” molecular - scale electronics ” would be interesting and that we should try to have something useful in about 10 years, i was given carte blanche to pursue any topic we wanted. we decided to take on moore ’ s law. at the time, the dot - com bubble was still rapidly inflating its way toward a resounding pop, and the existing semiconductor road map didn ’ t extend past 2010. the critical feature size for the transistors on an integrated circuit was 350 nanometers ; we had a long way to go before atomic sizes would become a


resounding pop, and the existing semiconductor road map didn ’ t extend past 2010. the critical feature size for the transistors on an integrated circuit was 350 nanometers ; we had a long way to go before atomic sizes would become a limitation. and yet, the eventual end of moore ’ s law was obvious. someday semiconductor researchers would have to confront physics - based limits to their relentless descent into the infinitesimal, if for no other reason than that a transistor cannot be smaller than an atom. ( today the smallest components of transistors on integrated circuits are roughly 45 nm wide, or about 220 silicon atoms. ) that ’ s when we started to hang out with phil kuekes, the creative force behind the teramac ( tera - operation - per - second multiarchitecture computer ) — an experimental supercomputer built at hp labs primarily from defective parts, just to show it could be done. he gave us the idea to build an architecture that would work even if a substantial number of the individual devices in the circuit were dead on arrival. we didn ’ t know what those devices would be, but our goal was electronics that would keep improving even after the devices got so small that defective ones would become common. we ate a lot of pizza washed down with appropriate amounts of beer and speculated about what this mystery nanodevice would be. we were designing something that wouldn ’ t even be relevant for another 10 to 15 years. it was possible that by then devices would have shrunk down to the molecular scale envisioned by david packard or perhaps even be molecules. we could think of no better way to anticipate this than by mimicking the teramac at the nanoscale. we decided that the simplest abstraction of the teramac architecture was the crossbar, which has since become the de facto standard for nanoscale circuits because of its simplicity, adaptability, and redundancy. the crossbar is an array of perpendicular wires. anywhere two wires cross, they are connected by a switch. to connect a horizontal wire to a vertical wire at any point on the grid, you must close the switch between them. our idea was to open and close these switches by applying voltages to the ends of the wires. note that a crossbar array is basically a storage system, with an open switch representing a zero and a closed switch representing a one. you read the data by probing the switch with a small voltage. like everything else at the nanoscale, the switches


that a crossbar array is basically a storage system, with an open switch representing a zero and a closed switch representing a one. you read the data by probing the switch with a small voltage. like everything else at the nanoscale, the switches and wires of a crossbar are bound to be plagued by at least some nonfunctional components. these components will be only a few atoms wide, and the second law of thermodynamics ensures that we will not be able to completely specify the position of every atom. however, a crossbar architecture builds in redundancy by allowing you to route around any parts of the circuit that don ’ t work. because of their simplicity, crossbar arrays have a much higher density of switches than a comparable integrated circuit based on transistors. but implementing such a storage system was easier said than done. many research groups were working on such a cross - point memory — and had been since the 1950s. even after 40 years of research, they had no product on the market. still, that didn ’ t stop them from trying. that ’ s because the potential for a truly nanoscale crossbar memory is staggering ; picture carrying around the entire library of congress on a thumb drive. one of the major impediments for prior crossbar memory research was the small off - to - on resistance ratio of the switches ( 40 years of research had never produced anything surpassing a factor of 2 or 3 ). by comparison, modern transistors have an off - to - on resistance ratio of 10 000 to 1. we calculated that to get a high - performance memory, we had to make switches with a resistance ratio of at least 1000 to 1. in other words, in its off state, a switch had to be 1000 times as resistive to the flow of current as it was in its on state. what mechanism could possibly give a nanometer - scale device a three - orders - of - magnitude resistance ratio? we found the answer in scanning tunneling microscopy ( stm ), an area of research i had been pursuing for a decade. a tunneling microscope generates atomic - resolution images by scanning a very sharp needle across a surface and measuring the electric current that flows between the atoms at the tip of the needle and the surface the needle is probing. the general rule of thumb in stm is that moving that tip 0. 1 nm closer to a surface increases the tunneling current by one order of magnitude. we needed some similar mechanism by which we could change the effective spacing


needle is probing. the general rule of thumb in stm is that moving that tip 0. 1 nm closer to a surface increases the tunneling current by one order of magnitude. we needed some similar mechanism by which we could change the effective spacing between two wires in our crossbar by 0. 3 nm. if we could do that, we would have the 1000 : 1 electrical switching ratio we needed. our constraints were getting ridiculous. where would we find a material that could change its physical dimensions like that? that is how we found ourselves in the realm of molecular electronics. conceptually, our device was like a tiny sandwich. two platinum electrodes ( the intersecting wires of the crossbar junction ) functioned as the ” bread ” on either end of the device. we oxidized the surface of the bottom platinum wire to make an extremely thin layer of platinum dioxide, which is highly conducting. next, we assembled a dense film, only one molecule thick, of specially designed switching molecules. over this ” monolayer ” we deposited a 2 - to 3 - nm layer of titanium metal, which bonds strongly to the molecules and was intended to glue them together. the final layer was the top platinum electrode. the molecules were supposed to be the actual switches. we built an enormous number of these devices, experimenting with a wide variety of exotic molecules and configurations, including rotaxanes, special switching molecules designed by james heath and fraser stoddart at the university of california, los angeles. the rotaxane is like a bead on a string, and with the right voltage, the bead slides from one end of the string to the other, causing the electrical resistance of the molecule to rise or fall, depending on the direction it moves. heath and stoddart ’ s devices used silicon electrodes, and they worked, but not well enough for technological applications : the off - to - on resistance ratio was only a factor of 10, the switching was slow, and the devices tended to switch themselves off after 15 minutes. our platinum devices yielded results that were nothing less than frustrating. when a switch worked, it was spectacular : our off - to - on resistance ratios shot past the 1000 mark, the devices switched too fast for us to even measure, and having switched, the device ’ s resistance state remained stable for years ( we still have some early devices we test every now and then, and we have never seen a significant change in resistance ). but our fantastic results were inconsistent. worse yet, the success or failure of a


’ s resistance state remained stable for years ( we still have some early devices we test every now and then, and we have never seen a significant change in resistance ). but our fantastic results were inconsistent. worse yet, the success or failure of a device never seemed to depend on the same thing. we had no physical model for how these devices worked. instead of rational engineering, we were reduced to performing huge numbers of edisonian experiments, varying one parameter at a time and attempting to hold all the rest constant. even our switching molecules were betraying us ; it seemed like we could use anything at all. in our desperation, we even turned to long - chain fatty acids — essentially soap — as the molecules in our devices. there ’ s nothing in soap that should switch, and yet some of the soap devices switched phenomenally. we also made control devices with no molecule monolayers at all. none of them switched. we were frustrated and burned out. here we were, in late 2002, six years into our research. we had something that worked, but we couldn ’ t figure out why, we couldn ’ t model it, and we sure couldn ’ t engineer it. that ’ s when greg snider, who had worked with kuekes on the teramac, brought me the chua memristor paper from the september 1971 ieee transactions on circuits theory. ” i don ’ t know what you guys are building, ” he told me, ” but this is what i want. ” to this day, i have no idea how greg happened to come across that paper. few people had read it, fewer had understood it, and fewer still had cited it. at that point, the paper was 31 years old and apparently headed for the proverbial dustbin of history. i wish i could say i took one look and yelled, ” eureka! ” but in fact, the paper sat on my desk for months before i even tried to read it. when i did study it, i found the concepts and the equations unfamiliar and hard to follow. but i kept at it because something had caught my eye, as it had greg ’ s : chua had included a graph that looked suspiciously similar to the experimental data we were collecting. the graph described the current - voltage ( i - v ) characteristics that chua had plotted for his memristor. chua had called them ” pinched - hysteresis loops ” ; we called our i - v characteristics ” bow ties. ” a pinched hyst


voltage ( i - v ) characteristics that chua had plotted for his memristor. chua had called them ” pinched - hysteresis loops ” ; we called our i - v characteristics ” bow ties. ” a pinched hysteresis loop looks like a diagonal infinity symbol with the center at the zero axis, when plotted on a graph of current against voltage. the voltage is first increased from zero to a positive maximum value, then decreased to a minimum negative value and finally returned to zero. the bow ties on our graphs were nearly identical [ see graphic, ” bow ties ” ]. that ’ s not all. the total change in the resistance we had measured in our devices also depended on how long we applied the voltage : the longer we applied a positive voltage, the lower the resistance until it reached a minimum value. and the longer we applied a negative voltage, the higher the resistance became until it reached a maximum limiting value. when we stopped applying the voltage, whatever resistance characterized the device was frozen in place, until we reset it by once again applying a voltage. the loop in the i - v curve is called hysteresis, and this behavior is startlingly similar to how synapses operate : synaptic connections between neurons can be made stronger or weaker depending on the polarity, strength, and length of a chemical or electrical signal. that ’ s not the kind of behavior you find in today ’ s circuits. looking at chua ’ s graphs was maddening. we now had a big clue that memristance had something to do with our switches. but how? why should our molecular junctions have anything to do with the relationship between charge and magnetic flux? i couldn ’ t make the connection. two years went by. every once in a while i would idly pick up chua ’ s paper, read it, and each time i understood the concepts a little more. but our experiments were still pretty much trial and error. the best we could do was to make a lot of devices and find the ones that worked. but our frustration wasn ’ t for nothing : by 2004, we had figured out how to do a little surgery on our little sandwiches. we built a gadget that ripped the tiny devices open so that we could peer inside them and do some forensics. when we pried them apart, the little sandwiches separated at their weakest point : the molecule layer. for the first time, we could get a good look at what was going on inside. we were in for


them and do some forensics. when we pried them apart, the little sandwiches separated at their weakest point : the molecule layer. for the first time, we could get a good look at what was going on inside. we were in for a shock. what we had was not what we had built. recall that we had built a sandwich with two platinum electrodes as the bread and filled with three layers : the platinum dioxide, the monolayer film of switching molecules, and the film of titanium. but that ’ s not what we found. under the molecular layer, instead of platinum dioxide, there was only pure platinum. above the molecular layer, instead of titanium, we found an unexpected and unusual layer of titanium dioxide. the titanium had sucked the oxygen right out of the platinum dioxide! the oxygen atoms had somehow migrated through the molecules and been consumed by the titanium. this was especially surprising because the switching molecules had not been significantly perturbed by this event — they were intact and well ordered, which convinced us that they must be doing something important in the device. the chemical structure of our devices was not at all what we had thought it was. the titanium dioxide — a stable compound found in sunscreen and white paint — was not just regular titanium dioxide. it had split itself up into two chemically different layers. adjacent to the molecules, the oxide was stoichiometric tio 2, meaning the ratio of oxygen to titanium was perfect, exactly 2 to 1. but closer to the top platinum electrode, the titanium dioxide was missing a tiny amount of its oxygen, between 2 and 3 percent. we called this oxygen - deficient titanium dioxide tio 2 - x, where x is about 0. 05. because of this misunderstanding, we had been performing the experiment backward. every time i had tried to create a switching model, i had reversed the switching polarity. in other words, i had predicted that a positive voltage would switch the device off and a negative voltage would switch it on. in fact, exactly the opposite was true. it was time to get to know titanium dioxide a lot better. they say three weeks in the lab will save you a day in the library every time. in august of 2006 i did a literature search and found about 300 relevant papers on titanium dioxide. i saw that each of the many different communities researching titanium dioxide had its own way of describing the compound. by the end of the month, the pieces had fallen into place. i finally knew how our device worked. i knew why we had a


. i saw that each of the many different communities researching titanium dioxide had its own way of describing the compound. by the end of the month, the pieces had fallen into place. i finally knew how our device worked. i knew why we had a memristor. the exotic molecule monolayer in the middle of our sandwich had nothing to do with the actual switching. instead, what it did was control the flow of oxygen from the platinum dioxide into the titanium to produce the fairly uniform layers of tio 2 and tio 2 - x. the key to the switching was this bilayer of the two different titanium dioxide species [ see diagram, ” how memristance works ” ]. the tio 2 is electrically insulating ( actually a semiconductor ), but the tio 2 - x is conductive, because its oxygen vacancies are donors of electrons, which makes the vacancies themselves positively charged. the vacancies can be thought of like bubbles in a glass of beer, except that they don ’ t pop — they can be pushed up and down at will in the titanium dioxide material because they are electrically charged. now i was able to predict the switching polarity of the device. if a positive voltage is applied to the top electrode of the device, it will repel the ( also positive ) oxygen vacancies in the tio 2 - x layer down into the pure tio 2 layer. that turns the tio 2 layer into tio 2 - x and makes it conductive, thus turning the device on. a negative voltage has the opposite effect : the vacancies are attracted upward and back out of the tio 2, and thus the thickness of the tio 2 layer increases and the device turns off. this switching polarity is what we had been seeing for years but had been unable to explain. on 20 august 2006, i solved the two most important equations of my career — one equation detailing the relationship between current and voltage for this equivalent circuit, and another equation describing how the application of the voltage causes the vacancies to move — thereby writing down, for the first time, an equation for memristance in terms of the physical properties of a material. this provided a unique insight. memristance arises in a semiconductor when both electrons and charged dopants are forced to move simultaneously by applying a voltage to the system. the memristance did not actually involve magnetism in this case ; the integral over the voltage reflected how far the dopants had moved and thus how


both electrons and charged dopants are forced to move simultaneously by applying a voltage to the system. the memristance did not actually involve magnetism in this case ; the integral over the voltage reflected how far the dopants had moved and thus how much the resistance of the device had changed. we finally had a model we could use to engineer our switches, which we had by now positively identified as memristors. now we could use all the theoretical machinery chua had created to help us design new circuits with our devices. triumphantly, i showed the group my results and immediately declared that we had to take the molecule monolayers out of our devices. skeptical after years of false starts and failed hypotheses, my team reminded me that we had run control samples without molecule layers for every device we had ever made and that those devices had never switched. and getting the recipe right turned out to be tricky indeed. we needed to find the exact amounts of titanium and oxygen to get the two layers to do their respective jobs. by that point we were all getting impatient. in fact, it took so long to get the first working device that in my discouragement i nearly decided to put the molecule layers back in. a month later, it worked. we not only had working devices, but we were also able to improve and change their characteristics at will. but here is the real triumph. the resistance of these devices stayed constant whether we turned off the voltage or just read their states ( interrogating them with a voltage so small it left the resistance unchanged ). the oxygen vacancies didn ’ t roam around ; they remained absolutely immobile until we again applied a positive or negative voltage. that ’ s memristance : the devices remembered their current history. we had coaxed chua ’ s mythical memristor off the page and into being. emulating the behavior of a single memristor, chua showed, requires a circuit with at least 15 transistors and other passive elements. the implications are extraordinary : just imagine how many kinds of circuits could be supercharged by replacing a handful of transistors with one single memristor. the most obvious benefit is to memories. in its initial state, a crossbar memory has only open switches, and no information is stored. but once you start closing switches, you can store vast amounts of information compactly and efficiently. because memristors remember their state, they can store data indefinitely, using energy only when you toggle or read


, and no information is stored. but once you start closing switches, you can store vast amounts of information compactly and efficiently. because memristors remember their state, they can store data indefinitely, using energy only when you toggle or read the state of a switch, unlike the capacitors in conventional dram, which will lose their stored charge if the power to the chip is turned off. furthermore, the wires and switches can be made very small : we should eventually get down to a width of around 4 nm, and then multiple crossbars could be stacked on top of each other to create a ridiculously high density of stored bits. greg snider and i published a paper last year showing that memristors could vastly improve one type of processing circuit, called a field - programmable gate array, or fpga. by replacing several specific transistors with a crossbar of memristors, we showed that the circuit could be shrunk by nearly a factor of 10 in area and improved in terms of its speed relative to power - consumption performance. right now, we are testing a prototype of this circuit in our lab. and memristors are by no means hard to fabricate. the titanium dioxide structure can be made in any semiconductor fab currently in existence. ( in fact, our hybrid circuit was built in an hp fab used for making inkjet cartridges. ) the primary limitation to manufacturing hybrid chips with memristors is that today only a small number of people on earth have any idea of how to design circuits containing memristors. i must emphasize here that memristors will never eliminate the need for transistors : passive devices and circuits require active devices like transistors to supply energy. the potential of the memristor goes far beyond juicing a few fpgas. i have referred several times to the similarity of memristor behavior to that of synapses. right now, greg is designing new circuits that mimic aspects of the brain. the neurons are implemented with transistors, the axons are the nanowires in the crossbar, and the synapses are the memristors at the cross points. a circuit like this could perform real - time data analysis for multiple sensors. think about it : an intelligent physical infrastructure that could provide structural assessment monitoring for bridges. how much money — and how many lives — could be saved? i ’ m convinced that eventually the memristor will change circuit design


in 1962 president john f. kennedy ’ s administration narrowly averted possible nuclear war with the ussr, when cia operatives spotted soviet surface - to - surface missiles in cuba, after a six - week gap in intelligence - gathering flights. in their forthcoming book blind over cuba : the photo gap and the missile crisis, co - authors david barrett and max holland make the case that the affair was a close call stemming directly from a decision made in a climate of deep distrust between key administration officials and the intelligence community. using recently declassified documents, secondary materials, and interviews with several key participants, the authors weave a story of intra - agency conflict, suspicion, and discord that undermined intelligence - gathering, adversely affected internal postmortems conducted after the crisis peaked, and resulted in keeping congress and the public in the dark about what really happened. we asked barrett, a professor of political science at villanova university, to discuss the actual series of events and what might have happened had the cia not detected soviet missiles on cuba. the actual sequence of events... “ some months after the cuban missile crisis, an angry member of the armed services committee of the house of representatives criticized leaders of the kennedy administration for having let weeks go by in september and early october 1962, without detecting soviet construction of missile sites in cuba. it was an intelligence failure as serious as the u. s. ignorance that preceded the japanese attack on pearl harbor in 1941, he said. secretary of defense robert mcnamara aggressively denied that there had been an american intelligence failure or ineptitude with regard to cuba in late summer 1962. mcnamara and others persuaded most observers the administration ’ s performance in the lead - up to the crisis had been almost flawless, but the legislator was right : the cia had not sent a u - 2 spy aircraft over western cuba for about a six week period. there were varying reasons for this, but the most important was that the kennedy administration did not wish to have a u - 2 “ incident. ” sending that aircraft over cuba raised the possibility that soviet surface - to - air missiles might shoot one down. since it was arguably against international law for the u. s. to send spy aircrafts over another country, should one be shot down, there would probably be the same sort of uproar as happened in may 1960, when the soviet union shot down an american u - 2 flying over its territory. furthermore, most state department and cia authorities did not believe that the ussr would put nuclear - armed missiles into cuba that could strike the u. s


and the patient enduring loss, perceived loss, and / or trauma. time is well spent exploring the specific environmental stressors that precipitated the disorder. although ignoring circumstances surrounding onset might be prudent when employing strict behavioral treatment paradigms, it seems like a terrible waste of time to endure suffering without identifying some underlying meaning or purpose that would otherwise be missed if we overlook onset specifics. “ everything can be taken from a man but one thing : the last of human freedoms – to choose one ’ s attitude in any given set of circumstances, to choose one ’ s own way. ” ( frankl, 1997, p. 86 ) if we acknowledge that all behavior is purposeful, then we must know and understand the circumstances around onset if we will ever understand the purpose of said behavior. i liken this to a difference in professional opinion and personal preference because either position can be reasonably justified, but in the end the patient should make the ultimate decision about whether or not to explore onset contributions vis - a - vis “ imagery dialogue ” or a similar technique. ( young, klosko, & weishaar, 2003, p. 123 ) if such imagery techniques are unsuccessful or undesired by the client, a psychodynamic conversation between “ internal parts of oneself ” can add clarity to the persistent inability of the client to delay gratification. ( ingram, 2012, p. 292 ) such explorations are likely to be time consuming, comparatively speaking, and should not be explored with patients who are bound by strict eap requirements or managed care restrictions on the type and length of treatment. comorbid developmental disabilities and cognitive deficits may preclude this existential exploration. i employ the exploration of existential issues of origin in the interest of increasing treatment motivation, promoting adherence, enhancing the therapeutic milieu, and thwarting subsequent lapses by anchoring cognitive dissonance to a concrete event. tm represents a behavioral manifestation of a fixed action patterns ( faps ) that is rigid, consistent, and predicable. faps are generally thought to have evolved from our most primal instincts as animals – they are believed to contain fundamental behavioral ‘ switches ’ that enhance the survivability of the human species. ( lambert & kinsley, 2011, p. 232 ) the nature of faps that leads some researchers to draw parallels to tm is that faps appear to be qualitatively “ ballistic. ” it ’ s an “ all or nothing ” reaction that is comparable to an action potential


. 232 ) the nature of faps that leads some researchers to draw parallels to tm is that faps appear to be qualitatively “ ballistic. ” it ’ s an “ all or nothing ” reaction that is comparable to an action potential traveling down the axon of a neuron. once they are triggered they are very difficult to suppress and may have a tendency to “ kindle ” other effects. ( lambert & kinsley, 2011, p. 233 ) there are some unique considerations when it comes to assessing a new patient with tm. because chewing on or ingesting the hair is reported in nearly half of tm cases, the attending clinician should always inquire about oral manipulation and associated gastrointestinal pain associated with a connected hair mass in the stomach or bowel ( trichobezoar ). motivation for change should be assessed and measured because behavioral interventions inherently require a great deal of effort. family and social systems should not be ignored since family dynamics can exacerbate symptomatlogy vis - a - vis pressure to change ( negative reinforcement ), excessive attention ( positive reinforcement ), or both. ( kraemer, 1999, p. 299 ) what remains to be seen is the role of stress in the process of “ triggering ” a tm episode. some individuals experience an “ itch like ” sensation as a physical antecedent that remits once the hair is pulled. this “ itch like ” sensation is far from universal. some clinicians and researchers believe that the abnormal grooming behavior found in tm is “ elicited in response to stress ” with the necessary but not sufficient condition of “ limited options for motoric behavior and tension release. ” ( kraemer, 1999, p. 299 ) although this stress hypothesis may materialize as a tenable hypothesis in some cases, it ’ s by no means typical. most people diagnosed with tm report that the act of pulling typically occurs during affective states of relaxation and distraction. most individuals whom suffer from tm do not report clinically significant levels of anxiety as the “ trigger ” of bouts of hair pulling. we could attribute this to an absence of insight regarding anxiety related triggers or, perhaps anxiety simply does not play a significant role in the onset and maintenance of hair pulling episodes. regardless of the factors that trigger episodes, a comprehensive biopsychosocial assessment that includes environmental stressors ( past, present and anticipated ) should be explored. the options for treatment of tm are limited at best


pulling hair. ( ingram, 2012, p. 292 ) just like a compulsive gambling addict isn ’ t in any danger if spends all his money on rent, someone with tm is much less likely to pull hair if they are doing something else with their hands. antecedents, or triggers, are sometimes referred to as discriminative stimuli. ( ingram, 2012, p. 230 ) “ we sense objects in a certain way because of our application of priori intuitions … ” ( pirsig, 1999, p. 133 ) altering the underlying assumptions entrenched in maladaptive priori intuitions is the core purpose of awareness and mindfulness training. “ there is a lack of constructive self - talk mediating between the trigger event and the behavior. the therapist helps the client build intervening self - messages : slow down and think it over ; think about the consequences. ” ( ingram, 2012, p. 221 ) the connection to contingency management should be self evident. utilizing a customized self - monitoring record, the patient begins to acquire the necessary insight to “ spot ” maladaptive self talk. “ spotting ” is not a new or novel concept – it is central component of abraham low ’ s revolutionary self help system recovery international. ( abraham low self - help systems, n. d. ) the customized self - monitoring record should invariably include various data elements such as precursors, length of episode, number of hairs pulled, and a subjective unit of distress representing the level of “ urge ” or desire to pull hair. ( kraemer, 1999 ) the act of recording behavior ( even in the absence of other techniques ) is likely to produce significant reductions in tm symptomatlogy. ( persons, 2008, p. 182 - 201 ) perhaps more importantly, associated activities, thoughts, and emotions that may be contributing to the urge to pull should be codified. ( kraemer, 1999, p. 300 ) in session, this record can be reviewed and subsequently tied to “ high risk circumstances ” and “ priori intuitions ” involving constructs such as anger, frustration, depression, and boredom. relaxation training is a critical component if we subscribe to the “ kindling ” hypothesis explained previously. relaxation is intended to reduce the urges that inevitably trigger the habit. examples abound, but diaphragmatic breathing, progressive relaxation, and visualization are all techniques that can be employed in isolation or in conjunction with each other. contingency management is inexorably tied


urges that inevitably trigger the habit. examples abound, but diaphragmatic breathing, progressive relaxation, and visualization are all techniques that can be employed in isolation or in conjunction with each other. contingency management is inexorably tied to the existential anchor of cognitive dissonance described above. my emphasis on this element is where my approach might differ from some other clinicians. “ you are free to do whatever you want, but you are responsible for the consequences of everything that you do. ” ( ingram, 2012, p. 270 ) this might include the client writing down sources of embarrassment, advantages of controlling the symptomatlogy of tm, etc. ( kraemer, 1999 ) the moment someone with pyromania decides that no fire worth being imprisoned, they will stop starting fires. the same holds true with someone who acknowledges the consequences of pulling their hair. how do we define success? once habit reversal is successfully accomplished in one setting or situation, the client needs to be taught how to generalize that skill to other contexts. a hierarchical ranking of anxiety provoking situations can be helpful in this process since self - paced graduated exposure is likely to increase tolerability for the anxious client. ( ingram, 2012, p. 240 ) if skills are acquired, and generalization occurs, we can reasonably expect a significant reduction in tm symptomatlogy. the challenges are significant, cognitive behavioral therapy is much easier said than done. high levels of treatment motivation are required for the behavioral elements, and moderate to high levels of insight are exceptionally helpful for the cognitive elements. in addition, this is an impulse control disorder … impulsivity leads to treatment noncompliance and termination. the combination of all the above, in addition to the fact that tm is generally acknowledged as one of the more persistent and difficult to treat disorders, prevents me from providing any prognosis other than “ this treatment will work as well as the client allows it to work. ” abraham low self - help systems. ( n. d. ). recovery international terms and definitions. retrieved august 2, 2012, from http : / / www. lowselfhelpsystems. org / system / recovery - international - language. asp american psychiatric association. ( 2000 ). diagnostic and statistical manual of mental disorders ( 4th ed., text rev. ). washington, dc : author. frankl, v. e. ( 1997 ). man ’ s search for meaning ( rev. ed. ).


2000 ). diagnostic and statistical manual of mental disorders ( 4th ed., text rev. ). washington, dc : author. frankl, v. e. ( 1997 ). man ’ s search for meaning ( rev. ed. ). new york, ny : pocket books. ingram, b. l. ( 2012 ). clinical case formulations : matching the integrative treatment plan to the client ( 2nd ed. ). hoboken, nj : john wiley & sons. kraemer, p. a. ( 1999 ). the application of habit reversal in treating trichotillomania. psychotherapy : theory, research, practice, training, 36 ( 3 ), 298 - 304. doi : 10. 1037 / h0092314 lambert, k. g., & kinsley, c. h. ( 2011 ). clinical neuroscience : psychopathology and the brain ( 2nd ed. ). new york : oxford university press. ledley, d. r., marx, b. p., & heimberg, r. g. ( 2010 ). making cognitive - behavioral therapy work : clinical process for new practitioners ( 2nd ed. ). new york, ny : guilford press. persons, j. b. ( 2008 ). the case formulation approach to cognitive - behavior therapy. new york, ny : guilford press. pirsig, r. m. ( 1999 ). zen and the art of motorcycle maintenance : an inquiry into values ( 25th anniversary ed. ). new york : quill. shiel, w. c., jr., & stoppler, m. c. ( eds. ). ( 2008 ). webster ’ s new world medical dictionary ( 3rd ed. ). hoboken, nj : wiley publishing. young, j. e., klosko, j. s., & weishaar, m. e. ( 2003 ). schema therapy : a practitioner ’ s guide. new york : guilford press.


introduction to principles of chemistry and fundamentals of inorganic and biochemistry. structure and chemistry of carbohydrates, lipids, proteins, biochemistry of enzymes, metabolism, body fluids and radiation effects. on - line materials includes the course syllabus, copies of the lecture slides and animations, interactive periodic table, chapter summaries and practice exams. this course is targeted towards health science majors. introduction to principles of chemistry. this course is targeted towards chemistry majors. laboratory experiments to develop techniques in organic chemistry and illustrate principles. on - line materials include step - by - step prelabs for many of the experiments that students will be conducting. theoretical principles of quantitative and instrumental analysis. emphasis is placed on newer analytical tools and equipment. intermediate level course. includes a discussion of the structure, function and metabolism of proteins, carbohydrates and lipids. in addition, there is a review of enzymes, dna and rna. this course stresses theory and application of modern chromatographic methods. on - line materials include the course syllabus, copies of course lecture slides and animations. a ' short course ' covering the use of a mass spectrometer as a gc detector. basic instrumentation, data treatment and spectral interpretation methods will be discussed. on - line materials include copies of course lecture slides and tables to assist in the interpretation of mass spectra. coverage of statistical methods in analytical chemistry. course includes basic statistics, experimental design, modeling, exploratory data analysis and other multivariate techniques. on - line materials include the course syllabus, homework problems and copies of the lecture slides. a survey of the basic equipment, data and methodology of analytical methods that rely on radioisotopic materials. on - line materials include the course syllabus, homework problems. copies of the lecture slides and animations. why i missed the exam


now that we ’ ve said a lot about individual operators on vector spaces, i want to go back and consider some other sorts of structures we can put on the space itself. foremost among these is the idea of a bilinear form. this is really nothing but a bilinear function to the base field :. of course, this means that it ’ s equivalent to a linear function from the tensor square :. instead of writing this as a function, we will often use a slightly different notation. we write a bracket, or sometimes, if we need to specify which of multiple different inner products under consideration. another viewpoint comes from recognizing that we ’ ve got a duality for vector spaces. this lets us rewrite our bilinear form as a linear transformation. we can view this as saying that once we pick one of the vectors, the bilinear form reduces to a linear functional, which is a vector in the dual space. or we could focus on the other slot and define. we know that the dual space of a finite - dimensional vector space has the same dimension as the space itself, which raises the possibility that or is an isomorphism from to. if either one is, then both are, and we say that the bilinear form is nondegenerate. we can also note that there is a symmetry on the category of vector spaces. that is, we have a linear transformation defined by. this makes it natural to ask what effect this has on our form. two obvious possibilities are that and that. in the first case we ’ ll call the bilinear form “ symmetric ”, and in the second we ’ ll call it “ antisymmetric ”. in terms of the maps and, we see that composing with the symmetry swaps the roles of these two functions. for symmetric bilinear forms,, while for antisymmetric bilinear forms we have. this leads us to consider nondegenerate bilinear forms a little more. if is an isomorphism it has an inverse. then we can form the composite. if is symmetric then this composition is the identity transformation on. on the other hand, if is antisymmetric then this composition is the negative of the identity transformation. thus, the composite transformation measures how much the bilinear transformation diverges from symmetry. accordingly, we call it the asymmetry of the form. finally, if we ’ re working over a finite - dimensional vector space we can pick a basis for, and get a matrix for.


the gram - schmidt process now that we have a real or complex inner product, we have notions of length and angle. this lets us define what it means for a collection of vectors to be “ orthonormal ” : each pair of distinct vectors is perpendicular, and each vector has unit length. in formulas, we say that the collection is orthonormal if. these can be useful things to have, but how do we get our hands on them? it turns out that if we have a linearly independent collection of vectors then we can come up with an orthonormal collection spanning the same subspace of. even better, we can pick it so that the first vectors span the same subspace as. the method goes back to laplace and cauchy, but gets its name from jørgen gram and erhard schmidt. we proceed by induction on the number of vectors in the collection. if, then we simply set this “ normalizes ” the vector to have unit length, but doesn ’ t change its direction. it spans the same one - dimensional subspace, and since it ’ s alone it forms an orthonormal collection. now, lets assume the procedure works for collections of size and start out with a linearly independent collection of vectors. first, we can orthonormalize the first vectors using our inductive hypothesis. this gives a collection which spans the same subspace as ( and so on down, as noted above ). but isn ’ t in the subspace spanned by the first vectors ( or else the original collection wouldn ’ t have been linearly independent ). so it points at least somewhat in a new direction. to find this new direction, we define this vector will be orthogonal to all the vectors from to, since for any such we can check where we use the orthonormality of the collection to show that most of these inner products come out to be zero. so we ’ ve got a vector orthogonal to all the ones we collected so far, but it might not have unit length. so we normalize it : and we ’ re done.


sarin was developed in 1938 in germany as a pesticide. its name is derived from the names of the chemists involved in its creation : schrader, ambros, rudriger and van der linde. sarin is a colorless non - persistent liquid. the vapor is slightly heavier than air, so it hovers close to the ground. under wet and humid weather conditions, sarin degrades swiftly, but as the temperature rises up to a certain point, sarin ’ s lethal duration increases, despite the humidity. sarin is a lethal cholinesterase inhibitor. doses which are potentially life threatening may be only slightly larger than those producing least effects. signs and symptoms overexposure may occur within minutes or hours, depending upon the dose. they include : miosis ( constriction of pupils ) and visual effects, headaches and pressure sensation, runny nose and nasal congestion, salivation, tightness in the chest, nausea, vomiting, giddiness, anxiety, difficulty in thinking, difficulty sleeping, nightmares, muscle twitches, tremors, weakness, abdominal cramps, diarrhea, involuntary urination and defecation, with severe exposure symptoms progressing to convulsions and respiratory failure. breath until respiratory protective mask is donned. if severe signs of agent exposure appear ( chest tightens, pupil constriction, in coordination, etc. ), immediately administer, in rapid succession, all three nerve agent antidote kit ( s ), mark i injectors ( or atropine if directed by a physician ). injections using the mark i kit injectors may be repeated at 5 to 20 minute intervals if signs and symptoms are progressing until three series of injections have been administered. no more injections will be given unless directed by medical personnel. in addition, a record will be maintained of all injections given. if breathing has stopped, give artificial respiration. mouth - to - mouth resuscitation should be used when mask - bag or oxygen delivery systems are not available. do not use mouth - to - mouth resuscitation when facial contamination exists. if breathing is difficult, administer oxygen. seek medical attention immediately. contact : immediately flush eyes with water for 10 - 15 minutes, then don respiratory protective mask. although miosis ( pinpointing of the pupils ) may be an early sign of agent exposure, an injection will not be administered when miosis is the only sign present. instead, the individual will be taken immediately


the press release doesn ’ t contain any pictures, and really doesn ’ t do this new web tool justice, so i ’ ve added some screencaps. in a nutshell, the new iswa site lets you arrange graphical packages of solar images and plots oncsreen for simultaneous evaluation. stuff that had been scattered over several solar related websites is now in one interface. pretty cool. – anthony when nasa ’ s satellite operators need accurate, real - time space - weather information, they turn to the community coordinated modeling center ( ccmc ) of the space weather laboratory at nasa ’ s goddard space flight center in greenbelt, md. the ccmc ’ s newest and most advanced space - weather science tool is the integrated space weather analysis ( iswa ) system. the iswa is a robust, integrated system provides information about space weather conditions past, present, and future and, unlike many other programs currently in use, has an interface that the user can customize to suit a unique set of data requirements. “ the iswa space - weather data analysis system offers a unique level of customization and flexibility to maintain, modify, and add new tools and data products as they become available, ” says marlo maddox, iswa system chief developer at nasa goddard. iswa draws together information about conditions from the sun to the boundary of the sun ’ s influence, known as the heliosphere. the iswa systems digests information from spacecraft including the national oceanic and atmospheric administration ’ s ( noaa ) geostationary operational environmental satellites ( goes ), nasa ’ s solar terrestrial relations observatory ( stereo ), the joint european space agency and nasa mission solar and heliospheric observatory ( soho ), and nasa ’ s advanced composition explorer ( ace ). citizen scientists and science enthusiasts can also use the data, models, and tools of the iswa system. similar to the way in which armchair astronomers have used soho data to discover comets, enthusiasts will find the iswa system a wonderful resource for increasing their familiarity with the concept of space weather. “ we are continuously evolving the iswa system, and we hope that it will benefit not only nasa satellite operators, but also that it may also help space - weather forecasting at other agencies such as the air force weather agency and noaa, ” says michael hesse, chief of the space weather laboratory at nasa goddard. space - weather information tends to be scattered over various web sites. nasa goddard space physicist antti pulkkinen says the iswa system represents “ the most comprehensive single interface


” says michael hesse, chief of the space weather laboratory at nasa goddard. space - weather information tends to be scattered over various web sites. nasa goddard space physicist antti pulkkinen says the iswa system represents “ the most comprehensive single interface for general space - weather - related information, ” providing data on past and current space - weather events. the system allows the user to configure or design custom displays of the information. the system compiles data about conditions on the sun, in earth ’ s magnetosphere — the protective magnetic field that envelops our planet — and down to earth ’ s surface. it provides a user interface to provide nasa ’ s satellite operators and with a real - time view of space weather. in addition to nasa, the iswa system is used by the air force weather agency. access to space - weather information that combines data from state - of - the - art space - weather models with concurrent observations of the space environment provides a powerful tool for users to obtain a personalized “ quick look ” at space - weather information, detailed insight into space - weather conditions, as well as tools for historical analysis of the space - weather ’ s impact. development of the iswa system has been a joint activity between the office of the chief engineer at nasa headquarters and the applied engineering and technology directorate and the science and exploration directorate at nasa goddard. the iswa system is located at nasa goddard. the community coordinated modeling center is funded by the heliophysics division in the science mission directorate at nasa headquarters, and the national science foundation. layout selector tool :


- weak drug regulatory control and enforcement ; - scarcity and / or erratic supply of basic medicines ; - unregulated markets and distribution chains ; - high drug prices and / or - significant price differentials. at national level, governments, law enforcement agencies, heath professionals, the pharmaceutical industry, importers, distributors, and consumer organizations should adopt a shared responsibility in the fight against counterfeit drugs. cooperation between countries, especially trading partners is very useful for combating counterfeiting. cooperation should include the timely and appropriate exchange of information and the harmonization of measures to prevent the spread of counterfeit medicines. the world health organization has developed and published guidelines, guidelines for the development of measures to combat counterfeit medicines. these guidelines provide advice on measures that should be taken by the various stakeholders and interested parties to combat counterfeiting of medicines. governments and all stakeholders are encouraged to adapt or adopt these guidelines in their fight against counterfeiting of medicines. - guidelines for the development of measures to combat counterfeit medicines - rapid alert system for counterfeit medicines communication and advocacy - creating public awareness patients and consumers are the primary victims of counterfeit medicines. in order to protect them from the harmful effects of counterfeit medicines it is necessary to provide them with appropriate information and education on the consequences of counterfeit medicines. patients and consumers expect to get advice from national authorities, health - care providers, health professionals and others from where they should buy or get their medicines ; what measures they should take in case they come across such medicines or are affected by the use of such medicines. ministries of health, national medicines regulators, health professional associations, nongovernmental organizations and other stakeholders have the responsibility to participate in campaign activities targeting patients and consumers to promote awareness of the problem of counterfeit medicines. posters, brochures, radio and television programmes are useful means for disseminating messages and advice.


as part of work relevant to the war effort, he studied two - dimensional subsonic fluid flow. this was important at that time since aircraft wings were being designed for planes with jet engines capable of high speeds. between 1945 and 1949 bers worked at syracuse university, first at assistant professor, later as associate professor. gelbart wanted to build up the department at syracuse and attracting both bers and loewner was an excellent move. here bers began work on the problem of removability of singularities of non - linear elliptic equations. his major results in this area were announced by him at the international congress of mathematicians in 1950 and his paper isolated singularities of minimal surfaces was published in the annals of mathematics in 1951. courant writes : - the nonparametric differential equation of minimal surfaces may be considered the most accessible significant example revealing typical qualities of solutions of non - linear partial differential equations. with a view to such a general objective, [ bers ] has studied singularities, branch - points and behaviour in the large of minimal surfaces. abikoff writes in that this paper is : -... a magnificent synthesis of complex analytic techniques which relate the different parameterisations of minimal surfaces to the representations of the potential function for subsonic flow and thereby achieves the extension across the singularity. bers then became a member of the institute for advanced study at princeton where he began work on teichmuller theory, pseudoanalytic functions, quasiconformal mappings and kleinian groups. he was set in the right direction by an inequality he found in a paper of lavrentev who attributed the inequality to ahlfors. in a lecture he gave in 1986 bers explained what happened next : - i was in princeton at the time. ahlfors came to princeton and announced a talk on quasiconformal mappings. he spoke at the university so i went there and sure enough, he proved this theorem. so i came up to him after the talk and asked him " where did you publish it? ", and he said " i didn ' t ". " so why did lavrentev credit you with it? " ahlfors said " he probably thought i must know it and was too lazy to look it up in the literature ". when bers met lavrentev three years later he asked him the same questions and, indeed, ahlfors had been correct in guessing why lavrentev had credited him. bers continued in his 1986 lecture :


the literature ". when bers met lavrentev three years later he asked him the same questions and, indeed, ahlfors had been correct in guessing why lavrentev had credited him. bers continued in his 1986 lecture : - i immediately decided that, first of all, if quasiconformal mappings lead to such powerful and beautiful results and, secondly, if it is done in this gentlemanly spirit - where you don ' t fight over priority - this is something that i should spend the rest of my life studying. it is ironic, given bers strong political views on human rights, that he should find that teichmuller, a fervent nazi, had already made stunning contributions. in one of his papers on teichmuller theory, bers quotes plutarch : - it does not of necessity follow that, if the work delights you with its grace, the one who wrought it is worthy of your esteem. in 1951 bers went to the courant institute in new york, where he was a full professor, and remained there for 13 years. during this time he wrote a number of important books and surveys on his work. he published theory of pseudo - analytic functions in 1953 which protter, in a review, described as follows : - the theory of pseudo - analytic functions was first announced by [ bers ] in two notes. these lecture notes not only contain proofs and extensions of the results previously announced but give a self - contained and comprehensive treatment of the subject. the author sets as his goal the development of a function theory for solutions of linear, elliptic, second order partial differential equations in two independent variables ( or systems of two first - order equations ). one of the chief stumbling blocks in such a task is the fact that the notion of derivative is a hereditary property for analytic functions while this is clearly not the case for solutions of general second order elliptic equations. another classic text was mathematical aspects of subsonic and transonic gas dynamics published in 1958 : - it should be said, even though this is taken for granted by everybody in the case of professor bers, that the survey is masterly in its elegance and clarity. in 1958 bers address the international congress of mathematicians in edinburgh, scotland, where he lectured on spaces of riemann surfaces and announced a new proof of the measurable riemann mapping theorem. in his talk bers summarised recent work on the classical problem of moduli for compact riemann surfaces and sketched a proof of the te


on spaces of riemann surfaces and announced a new proof of the measurable riemann mapping theorem. in his talk bers summarised recent work on the classical problem of moduli for compact riemann surfaces and sketched a proof of the teichmuller theorem characterizing extremal quasiconformal mappings. he showed that the teichmuller space for surfaces of genus g is a ( 6g - 6 ) - cell, and showed how to construct the natural complex analytic structure for the teichmuller space. bers was a guggenheim fellow in 1959 - 60, and a fulbright fellow in the same academic year. from 1959 until he left the courant institute in 1964, bers was chairman of the graduate department of mathematics. in 1964 bers went to columbia university where he was to remain until he retired in 1984. he was chairman of the department from 1972 to 1975. he was appointed davies professor of mathematics in 1972, becoming emeritus davies professor of mathematics in 1982. during this period bers was visiting miller research professor at the university of california at berkeley in 1968. tilla weinstein describes in bers as a lecturer : - lipa ' s courses were irresistible. he laced his lectures with humorous asides and tasty tidbits of mathematical gossip. he presented intricate proofs with impeccable clarity, pausing dramatically at the few most critical steps, giving us a chance to think for ourselves and to worry that he might not know what to do next. then, just as the silence got uncomfortable, he would describe the single most elegant way to complete the argument. jane gilman describes bers ' character : - underneath the force of bers ' personality and vivacity was the force of his mathematics. his mathematics had a clarity and beauty that went beyond the actual results. he had a special gift for conceptualising things and placing them in the larger context. in bers life is summed up by abikoff as follows : - lipa possessed a joy of life and an optimism that is difficult to find at this time and that is sorely missed. those of us who experienced it directly have felt an obligation to pass it on. that, in addition to the beauty of his own work, is lipa ' s enduring gift to us. we have yet to say something about bers ' great passion for human rights. in fact this was anything but a sideline in his life and one could consider that he devoted himself full - time to both his mathematical work and to his work as


. we have yet to say something about bers ' great passion for human rights. in fact this was anything but a sideline in his life and one could consider that he devoted himself full - time to both his mathematical work and to his work as a social reformer. perhaps his views are most clearly expressed by quoting from an address he gave in 1984 when awarded an honorary degree by the state university of new york at stony brook : - by becoming a human rights activist... you do take upon yourself certain difficult obligations.... i believe that only a truly even - handed approach can lead to an honest, morally convincing, and effective human rights policy. a human rights activist who hates and fears communism must also care about the human rights of latin american leftists. a human rights activist who sympathises with the revolutionary movement in latin america must also be concerned about human rights abuses in cuba and nicaragua. a devout muslim must also care about human rights of the bahai in iran and of the small jewish community in syria, while a jew devoted to israel must also worry about the human rights of palestinian arabs. and we american citizens must be particularly sensitive to human rights violations for which our government is directly or indirectly responsible, as well as to the human rights violations that occur in our own country, as they do. bers received many honours for his contributions in addition to those we have mentioned above. he was elected to the american academy of arts and sciences, to the finnish academy of sciences, and to the american philosophical society. he served the american mathematical society in several capacities, particularly as vice - president ( 1963 - 65 ) and as president ( 1975 - 77 ). the american mathematical society awarded him their steele prize in 1975. he received the new york mayor ' s award in science and technology in 1985. he was an honorary life member of the new york academy of sciences, and of the london mathematical society. article by : j j o ' connor and e f robertson click on this link to see a list of the glossary entries for this page list of references ( 5 books / articles ) | | some quotations ( 3 ) | | mathematicians born in the same country | | honours awarded to lipman bers | ( click below for those honoured in this way ) | ams colloquium lecturer | | 1971 | | ams steele prize | | 1975 | | american maths society president | | 1975 - 1976 | | lms honorary member | | 1984 | other web sites | previous | | ( alphabetically


x2 / 3 + y2 / 3 = a2 / 3 x = a cos3 ( t ), y = a sin3 ( t ) click below to see one of the associated curves. | definitions of the associated curves | | evolute | | involute 1 | | involute 2 | | inverse curve wrt origin | | inverse wrt another circle | | pedal curve wrt origin | | pedal wrt another point | | negative pedal curve wrt origin | | negative pedal wrt another point | | caustic wrt horizontal rays | | caustic curve wrt another point | the astroid only acquired its present name in 1836 in a book published in vienna. it has been known by various names in the literature, even after 1836, including cubocycloid and paracycle. the length of the astroid is 6a and its area is 3πa2 / 8. the gradient of the tangent t from the point with parameter p is - tan ( p ). the equation of this tangent t is x sin ( p ) + y cos ( p ) = a sin ( 2p ) / 2 let t cut the x - axis and the y - axis at x and y respectively. then the length xy is a constant and is equal to a. it can be formed by rolling a circle of radius a / 4 on the inside of a circle of radius a. it can also be formed as the envelope produced when a line segment is moved with each end on one of a pair of perpendicular axes. it is therefore a glissette. other web site : | main index | | famous curves index | | previous curve | | next curve | | history topics index | | birthplace maps | | mathematicians of the day | | anniversaries for the year | | societies, honours, etc | | search form | the url of this page is :


arctic meltdown not caused by nature rapid loss of arctic sea ice - 80 per cent has disappeared since 1980 - is not caused by natural cycles such as changes in the earth ' s orbit around the sun, says dr karl. the situation is getting rather messy with regard to the ice melting in the arctic. now the volume of the ice varies throughout the year, rising to its peak after midwinter, and falling to its minimum after midsummer, usually in the month of september. over most of the last 1, 400 years, the volume of ice remaining each september has stayed pretty constant. but since 1980, we have lost 80 per cent of that ice. now one thing to appreciate is that over the last 4. 7 billion years, there have been many natural cycles in the climate — both heating and cooling. what ' s happening today in the arctic is not a cycle caused by nature, but something that we humans did by burning fossil fuels and dumping slightly over one trillion tonnes of carbon into the atmosphere over the last century. so what are these natural cycles? there are many many of them, but let ' s just look at the milankovitch cycles. these cycles relate to the earth and its orbit around the sun. there are three main milankovitch cycles. they each affect how much solar radiation lands on the earth, and whether it lands on ice, land or water, and when it lands. the first milankovitch cycle is that the orbit of the earth changes from mostly circular to slightly elliptical. it does this on a predominantly 100, 000 - year cycle. when the earth is close to the sun it receives more heat energy, and when it is further away it gets less. at the moment the orbit of the earth is about halfway between " nearly circular " and " slightly elliptical ". so the change in the distance to the sun in each calendar year is currently about 5. 1 million kilometres, which translates to about 6. 8 per cent difference in incoming solar radiation. but when the orbit of the earth is at its most elliptical, there will be a 23 per cent difference in how much solar radiation lands on the earth. the second milankovitch cycle affecting the solar radiation landing on our planet is the tilt of the north - south spin axis compared to the plane of the orbit of the earth around the sun. this tilt rocks gently between 22. 1 degrees and 24. 5 degrees from the vertical. this cycle has a period of about 41, 000 years. at the moment we are roughly halfway in the middle — we '


of the earth around the sun. this tilt rocks gently between 22. 1 degrees and 24. 5 degrees from the vertical. this cycle has a period of about 41, 000 years. at the moment we are roughly halfway in the middle — we ' re about 23. 44 degrees from the vertical and heading down to 22. 1 degrees. as we head to the minimum around the year 11, 800, the trend is that the summers in each hemisphere will get less solar radiation, while the winters will get more, and there will be a slight overall cooling. the third milankovitch cycle that affects how much solar radiation lands on our planet is a little more tricky to understand. it ' s called ' precession '. as our earth orbits the sun, the north - south spin axis does more than just rock gently between 22. 1 degrees and 24. 5 degrees. it also — very slowly, just like a giant spinning top — sweeps out a complete 360 degrees circle, and it takes about 26, 000 years to do this. so on january 4, when the earth is at its closest to the sun, it ' s the south pole ( yep, the antarctic ) that points towards the sun. so at the moment, everything else being equal, it ' s the southern hemisphere that has a warmer summer because it ' s getting more solar radiation, but six months later it will have a colder winter. and correspondingly, the northern hemisphere will have a warmer winter and a cooler summer. but of course, " everything else " is not equal. there ' s more land in the northern hemisphere but more ocean in a southern hemisphere. the arctic is ice that is floating on water and surrounded by land. the antarctic is the opposite — ice that is sitting on land and surrounded by water. you begin to see how complicated it all is. we have had, in this current cycle, repeated ice ages on earth over the last three - million years. during an ice age, the ice can be three kilometres thick and cover practically all of canada. it can spread through most of siberia and europe and reach almost to where london is today. of course, the water to make this ice comes out of the ocean, and so in the past, the ocean level has dropped by some 125 metres. from three million years ago to one million years ago, the ice advanced and retreated on a 41, 000 - year cycle. but from one million years ago until the present, the ice has advanced and retreated on a 100, 000 - year cycle. what


black holes growing faster than expected black hole find existing theories on the relationship between the size of a galaxy and its central black hole are wrong according to a new australian study. the discovery by dr nicholas scott and professor alister graham, from melbourne ' s swinburne university of technology, found smaller galaxies have far smaller black holes than previously estimated. central black holes, millions to billions of times more massive than the sun, reside in the core of most galaxies, and are thought to be integral to galactic formation and evolution. however astronomers are still trying to understand this relationship. scott and graham combined data from observatories in chile, hawaii and the hubble space telescope, to develop a data base listing the masses of 77 galaxies and their central supermassive black holes. the astronomers determined the mass of each central black hole by measuring how fast stars are orbiting it. existing theories suggest a direct ratio between the mass of a galaxy and that of its central black hole. " this ratio worked for larger galaxies, but with improved technology we ' re now able to examine far smaller galaxies and the current theories don ' t hold up, " says scott. in a paper to be published in the astrophysical journal, they found that for each ten - fold decrease in a galaxy ' s mass, there was a one hundred - fold decrease in its central black hole mass. " that was a surprising result which we hadn ' t been anticipating, " says scott. the study also found that smaller galaxies have far denser stellar populations near their centres than larger galaxies. according to scott, this also means the central black holes in smaller galaxies grow much faster than their larger counterparts. black holes grow by merging with other black holes when their galaxies collide. " when large galaxies merge they double in size and so do their central black holes, " says scott. " but when small galaxies merge their central black holes quadruple in size because of the greater densities of nearby stars to feed on. " somewhere in between the findings also solve the long standing problem of missing intermediate mass black holes. for decades, scientists have been searching for something in between stellar mass black holes formed when the largest stars die, and supermassive black holes at the centre of galaxies. " if the central black holes in smaller galaxies have lower mass than originally thought, they may represent the intermediate mass black hole population astronomers have been hunting for, " says graham. " intermediate sized black holes are between ten thousand and a few hundred thousand times the mass of the sun, and we think we '


science fair project encyclopedia the chloride ion is formed when the element chlorine picks up one electron to form the anion ( negatively charged ion ) cl−. the salts of hydrochloric acid hcl contain chloride ions and are also called chlorides. an example is table salt, which is sodium chloride with the chemical formula nacl. in water, it dissolves into na + and cl− ions. the word chloride can also refer to a chemical compound in which one or more chlorine atoms are covalently bonded in the molecule. this means that chlorides can be either inorganic or organic compounds. the simplest example of an inorganic covalently bonded chloride is hydrogen chloride, hcl. a simple example of an organic covalently bonded chloride is chloromethane ( ch3cl ), often called methyl chloride. other examples of inorganic covalently bonded chlorides which are used as reactants are : - phosphorus trichloride, phosphorus pentachloride, and thionyl chloride - all three are reactive chlorinating reagents which have been used in a laboratory. - disulfur dichloride ( scl2 ) - used for vulcanization of rubber. chloride ions have important physiological roles. for instance, in the central nervous system the inhibitory action of glycine and some of the action of gaba relies on the entry of cl− into specific neurons. the contents of this article is licensed from www. wikipedia. org under the gnu free documentation license. click here to see the transparent copy and copyright details


science fair project encyclopedia industrial design is an applied art whereby the aesthetics and usability of products may be improved. design aspects specified by the industrial designer may include the overall shape of the object, the location of details with respect to one another, colors, texture, sounds, and aspects concerning the use of the product ergonomics. additionally the industrial designer may specify aspects concerning the production process, choice of materials and the way the product is presented to the consumer at the point of sale. the use of industrial designers in a product development process may lead to added values by improved usability, lowered production costs and more appealing products. product design is focused on products only, while industrial design has a broader focus on concepts, products and processes. in addition to considering aesthetics, usability, and ergonomics, it can also encompass the engineering of objects, usefulness as well as usability, market placement, and other concerns. product design and industrial design can overlap into the fields of user interface design, information design and interaction design. various schools of industrial design and / or product design may specialize in one of these aspects, ranging from pure art colleges ( product styling ) to mixed programs of engineering and design, to related disciplines like exhibit design and interior design. in the us, the field of industrial design hit a high - water mark of popularity in the late 30 ' s and early 40 ' s, with several industrial designers becoming minor celebrities. raymond loewy, norman bel geddes, and henry dreyfuss remain the best known. in the uk, the term " industrial design " increasingly implies design with considerable engineering and technology awareness alongside human factors - a " total design " approach, promoted by the late stuart pugh ( university of strathclyde ) and others. famous industrial designers - egmont arens ( 1888 - 1966 ) - norman bel geddes ( 1893 - 1958 ) - henry dreyfuss ( 1904 - 1972 ) - charles and ray eames ( 1907 - 1978 ) and ( 1912 - 1988 ) - harley j. earl ( 1893 - 1969 ) - virgil exner ( 1909 - 1973 ) - buckminster fuller ( 1895 - 1983 ) - kenneth grange ( 1929 - ) - michael graves ( 1934 - ) - walter adolph gropius ( 1883 - 1969 ) - jonathan ive ( 1967 - ) - arne jacobsen ( 1902 - 1971 ) - raymond loewy ( 1893 - 1986 ) - ludwig mies van der rohe ( 1886 - 1969 ) - laszlo moholy -


- 1884 : publications : " ueber die erden des gadolinits von ytterby ", " ueber die seltenen erden ". 1885 : the first separation of the element " didymium " with help from a newly developed separation method from himself, based on the fractioned crystalisation of a didym - ammonium nitrat solution. after the characteristical colouring, auer gave the green components the name praseodymium, the pink components the name neodidymium. in time the latter element was more commonly known as neodymium. 1885 - 1892 : work on gas mantle for the incandescent lighting. development of a method to produce gas mantle ( " auerlicht ) based on the impregnation from cottontissue by means, measures, methods of liquids, that rare earth has been absolved in and the ash from the material in a following glow process. production of the first incandescent mantle out of lanthanum oxide, in which the gas flame is surrounded from a stocking ; definite improvement in light emmission, but lack of stability in humidity. continuous improvements in the chemical composition of the incandescent mantel " auerlicht ", experimentations of lanthanum oxide - magnesium oxide - variations. 18th of sept. 1885 : the patenting of a gas burner with a " actinophor " incandescent mantle made up of 60 % magnesium oxide, 20 % lanthanum oxide and 20 % yttrium oxide ; in the same year, the magnesium oxide part was replaced with zirconium oxide and the constitution of a second patent with reference to the additional use of the light body in a spirits flame. 9th of april 1886 : introduction the name " gasgluehlicht " through the journalist motiz szeps after the successful presentation from the actinophors in the lower austrian trade union ; regular production of the impregnation liquid, called " fluid ", at the chemical institute. 1887 : the acquisition of the factory wurth & co. for chemical - pharmaceutical products in atzgersdorf and the industrial production of the light bodies. 1889 : the beginning of sales problems because of the defaults with the earlier incandescent mantle, ie. it ` s fragility, the short length of use, as well as having an unpleasant, cold, green coloured light, and the relatively high price. the factory in atzgersdorf closes. the development of fraction


ethics of dementia research what are clinical trials and how are they controlled / governed? a clinical trial is a biomedical / health - related study into the effects on humans of a new medical treatment ( medicine / drug, medical device, vaccine or new therapy ), sometimes called an investigational medicinal product ( imp ). before a new drug is authorised and can be marketed, it must pass through several phases of development including trial phases in which its safety, efficacy, risks, optimal use and / or benefits are tested on human beings. existing drugs must also undergo clinical testing before they can be used to treat other conditions than that for which they were originally intended. organisations conducting clinical trials in the european union must, if they wish to obtain marketing authorisation, respect the requirements for the conduct of clinical trials. these can be found in the clinical trials directive ( “ directive 2001 / 20 / ec of the european parliament and of the council of 4 april 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use ” ). there are also guidelines to ensure that clinical trials are carried out in accordance with good clinical practice. these are contained in the “ commission directive 2005 / 28 / ec of 8 april 2005 laying down principles and detailed guidelines for good clinical practice as regards investigational medicinal products for human use, as well as the requirements for authorisation of the manufacturing or importation of such products ” ( also known as the good clinical practice or gcp for short ). this document provides more concrete guidelines and lends further support to the clinical trials directive. the london - based european medicines agency ( ema ) has published additional, more specific guidelines which must also be respected. these include guidelines on inspection procedures and requirements related to quality, safety and efficacy. copies of the above - mentioned documents in 22 languages can be found at : http : / / ec. europa. eu / enterprise / pharmaceuticals / clinicaltrials / clinicaltrials _ en. htm the protection of people participating in clinical trials ( and in most cases in other types of research ) is further promoted by provisions of : - the european convention on human rights and biomedicine ( oviedo convention, act 2619 / 1998 ), - the additional protocol to the oviedo convention concerning biomedical research - the nuremberg code of 1949, - the revised helsinki declaration of the world medical association regarding ethical principles for medical research involving human subjects, - the belmont report of 18 april 1979


), - the additional protocol to the oviedo convention concerning biomedical research - the nuremberg code of 1949, - the revised helsinki declaration of the world medical association regarding ethical principles for medical research involving human subjects, - the belmont report of 18 april 1979 on the ethical principles and guidelines for the protection of human subjects of research. what are the different phases of trials? testing an experimental drug or medical procedure is usually an extremely lengthy process, sometimes lasting several years. the overall procedure is divided into a series of stages ( known as phases ) which are described below. clinical testing on humans can only begin after a pre - clinical phase, involving laboratory studies ( in vitro ) and tests on animals, which has shown that the experimental drug is considered safe and effective. whilst a certain amount of testing can be carried out by means of computer modelling and by isolating cells and tissue, it becomes necessary at some point in time to test the drug on a living creature. animal testing is an obligatory stage in the process of obtaining regulatory approval for new drugs and medicines, and hence a legal requirement ( eu directive 2001 / 83 / ec relating to medicinal products for human use ). the necessity of carrying out prior testing on animals is also stated in the world medical association ’ s “ ethical principles for medical research involving human subjects. in order to protect the well - being of research animals, researchers are guided by three principles which are called the 3rs : reduce the number of animals used to a minimum refine the way that experiments are carried out so that the effect on the animal is minimised and animal welfare is improved replace animal experiments with alternative ( non - animal ) techniques wherever possible. in addition, most countries will have official regulatory bodies which control animal research. most animals involved in research are mice. however, no animal is sufficiently similar to humans ( even genetically modified ones ) to make human testing unnecessary. for this reason, the experimental drug must also be tested on humans. the main phases of clinical trials clinical trials on humans can be divided into three main phases ( literally, phase i, ii and iii ). each phase has specific objectives ( please see below ) and the number of people involved increases as the trial progresses from one phase to the next. phase i trials phase 1 trials are usually the first step in testing a new drug or treatment on humans after successful laboratory and animal testing. they are usually quite small scale and usually involve healthy subjects or sub - groups of patients who share a particular characteristic. the aims of these trials are : - to assess the safety of experimental


new drug or treatment on humans after successful laboratory and animal testing. they are usually quite small scale and usually involve healthy subjects or sub - groups of patients who share a particular characteristic. the aims of these trials are : - to assess the safety of experimental drugs, - to evaluate any possible side effects, - to determine a safe dose range, - to see how the body reacts to the drug ( how it is absorbed, distributed and eliminated from the body, the effects that it has on the body and the effects it has on biomarkers ). dose ranging, sometimes called dose escalation, studies may be used as a means to determine the most appropriate dosage, but the doses administered to the subjects should only be a fraction of those which were found to cause harm to animals in the pre - clinical studies. the process of determining an optimal dose in phase i involves quite a high degree of risk because this is the first time that the experimental treatment or drug has been administered to humans. moreover, healthy people ’ s reactions to drugs may be different to those of the target patient group. for this reason, drugs which are considered to have a potentially high toxicity are usually tested on people from the target patient group. there are a few sequential approaches to phase i trials e. g. single ascending dose studies, multiple ascending dose studies and food effect. in single ascending dose studies ( sad ), a small group of subjects receive a very low dose of the experimental drug and are then observed in order to see whether that dose results in side effects. for this reason, trials are usually conducted in hospital settings. if no adverse side effects are observed, a second group of subjects are given a slightly higher dose of the same drug and also monitored for side - effects. this process is repeated until a dose is reached which results in intolerable side effects. this is defined as the maximum tolerated dose ( mtd ). multiple ascending dose studies ( mad ) are designed to test the pharmacokinetics and pharmacodynamics of multiple doses of the experimental drug. a group of subjects receives multiple doses of the drug, starting at the lowest dose and working up to a pre - determined level. at various times during the period of administration of the drug, and particularly whenever the dose is increased, samples of blood and other bodily fluids are taken. these samples are analysed in order to determine how the drug is processed within the body and how well it is tolerated by the body. food effect studies are investigations into the effect of food intake