ucid;date;country;kind;lang;date_produced;status;family_id;main_code;further_codes;ipcr_codes;ecla_codes;title;abstract;description;claims;inventors;applicants;application_date;patent_number
EP-1030342-B1;20050914.0;EP;B1;EN;20100220.0;new;22961860.0;H01J29;;H01J29, H04N9;H01J  29/07B, T01J229:07C;Color picture tube having improved shadow mask frame assembly support;A color picture tube (8) includes an evacuated envelope (10) having a rectangular faceplate panel (12) with two approximately parallel long sides (22, 24), two approximately parallel short sides (26, 28) and four corners. The panel comprises a faceplate (18) and a peripheral sidewall (20), and includes a shadow mask-frame assembly (38) mounted therein by springs (42) located at the four corners of the panel. The springs have apertures engaging studs (34) that are located on the peripheral sidewall at the four corners. The panel includes additional studs (54, 56) on the peripheral sidewall located near the centers of at least one pair of approximately parallel sides (22, 24) of the panel. Brackets (50, 52) are located on opposite sides of the shadow mask-frame assembly at the locations of the additional studs. The brackets include slots (59) therein. The slots are open on sides thereof facing the faceplate. The additional studs are positioned within the slots.;"This invention relates to a color picture tube having a shadow mask attached to a peripheral frame which is suspended in relation to a cathodoluminescent screen and, particularly, to a support system for a mask-frame assembly in such a tube, which provides an improved shock handling capability. In most color picture tubes, a peripheral frame, supporting a shadow mask, is suspended in a faceplate panel by means of springs that are welded either directly to the frame or to plates which in turn are welded to the frame. In large size tubes, it is common to use four springs to support a mask-frame assembly within a rectangular faceplate panel of a tube. In many recent tubes, the springs are located at the four corners of the frame to minimize twisting and shifting of the assembly within the panel. An aperture in each spring engages a metal stud that is embedded in an interior corner of a glass panel. An embodiment for achieving such corner support is disclosed in U.S. Patent 4,723,088, issued to Sone et al. on February 2, 1988. That patent shows a mask frame having truncated corners with supports at each corner. In the examples designated ""prior art"", the mask-frame assembly supports are bent metal plates that are welded to the frame at one end and include an aperture at the other end. The aperture engages a metal stud that is embedded in the panel sidewall. The Sone et al. patent teaches forming each support from two members that are welded together. A first member, having a flat plate shape, is welded at several separated points to a mask frame. The second member is welded to the first member at one end and includes an aperture at the other end that engages a support stud in the panel sidewall. The use of a corner support system for the support of a color picture tube shadow mask offers many advantages over an on-axis support system. However, the corner support system has the undesirable characteristic of asymmetric resistance to shock loads. Tubes employing corner support systems typically are less capable of sustaining shock loads in the horizontal (X) direction and returning the shadow mask to within a tolerable distance of its original position, than it is for vertical (Y) direction shock loads. The measure of shock handling capability is a permanent deformation of the mask support system caused by subjecting tube assemblies to X-direction acceleration. Such deformation commonly leads to misalignment of the mask apertures with respect to their nominal positions, which, in turn, causes positional errors in the landings of the electron beams. Such mislandings are commonly referred to as misregistration, and, in operating tubes, the consequences of misregistration are white field nonuniformities and color purity errors. As is well known in the art, the continuous line screen tubes, by their basic operational principal, are very tolerant to Y-direction registration errors, but very intolerant to X-direction registration errors. As usually mounted on a shadow mask frame, the corner support system springs are typically flexible in the radial direction and very stiff in the tangential direction. These springs are typically mounted at the mask diagonal corners. Because the mask diagonal does not lie at 45 degrees to the X and Y axes, e.g., in a tube having a 4x3 or 16x9 (X to Y) aspect ratio, the resulting system stiffnesses in the X and Y directions are not equal. In 4x3 aspect ratio tubes, a line connecting the springs on opposite corners makes an angle of 36.87 degrees with respect to the horizontal (X) axis. One skilled in the art would anticipate that the horizontal (X) direction shock handling capability would be about 75% (tan 36.87 degrees) of that in the vertical (Y) direction. For 16x9 aspect ratio tubes, the difference between the shock load handling capabilities in the X and Y directions is anticipated to be even greater. The spring diagonal angle for a 16x9 aspect ratio tube is usually 29.00 degrees. This indicates that one should expect that the X direction shock handling capability would be about 55% (tan 29.00 degrees) of that in the Y direction. It has been found that the shock handling capability of such a 16x9 aspect ratio tube can be unacceptable in many applications. The present invention addresses the problem of inadequate shock load capability in a 16 x 9 aspect ratio tube. In accordance with the present invention, a color picture tube includes an evacuated envelope having a rectangular faceplate panel with two approximately parallel long sides, two approximately parallel short sides and four corners. The panel comprises a faceplate and a peripheral sidewall. The panel includes a shadow mask-frame assembly mounted therein by springs located at the four corners of the panel. The springs have apertures engaging studs that are located on the peripheral sidewall at the four corners. The panel includes additional studs on the peripheral sidewall located near the centers of at least one pair of approximately parallel sides of the panel. Brackets are located on opposite sides of the shadow mask-frame assembly at the locations of the additional studs. The brackets include slots therein. The slots are open on sides thereof facing the faceplate. The additional studs are positioned within the slots. In the drawings: FIGURE 1 is an axially sectioned side view of a color picture tube. FIGURE 2 is a plan view of a shadow mask-frame assembly embodying the present invention mounted within a faceplate panel of the tube of FIGURE 1. FIGURE 3 is a perspective view of a motion arresting bracket attached to a frame. FIGURE 4 is a perspective view of the motion arresting bracket of FIGURE 3 connected to a support stud. FIGURE 5 is the same perspective view of another motion arresting bracket attached to a frame. FIGURE 6 is a perspective view of a third motion arresting bracket attached to a frame. FIGURE 1 shows a rectangular color picture tube 8 having a glass envelope 10, comprising a rectangular faceplate panel 12 and a tubular neck 14 connected by a rectangular funnel 16. The panel 12 comprises a viewing faceplate 18 and a peripheral flange or sidewall 20 which is sealed to the funnel 16. The faceplate panel 12, also shown in FIGURE 2, includes two orthogonal axes: a major axis X, paralleling two approximately parallel long sides 22 and 24 (usually horizontal) of the panel 12, and a minor axis Y, paralleling two approximately parallel short sides 26 and 28 (usually vertical) of the panel 12. The major and minor axes are perpendicular to a central longitudinal axis Z of the tube which passes through the center of the neck 14 and the center of the panel 12. A mosaic three-color phosphor screen 30 is carried by the inner surface of the faceplate 18. The screen 30 preferably is a line screen with the phosphor lines extending substantially parallel to the minor axis Y. Alternatively, the screen may be a dot screen. A multiapertured color selection electrode or shadow mask 32 is removably mounted within the panel 12. The shadow mask 32 is part of a mask-frame assembly 38 that also includes a peripheral frame 40. The mask-frame assembly 38 also includes four springs 42 that engage four support studs 34, which are embedded in the four corners of the panel 12, in predetermined spaced relation to the screen 30. An electron gun 36 is centrally mounted within the neck 14, to generate and direct three electron beams along convergent paths through the mask 32 to the screen 30. A magnetic deflection yoke 41 is attached to the tube at the neck-to-funnel junction. The present invention improves the shock handling capability especially of a 16x9 tube by the addition of two brackets 50 and 52 to the mask-frame assembly 38, and two additional studs 54 and 56 to the panel 12, to provide means for stopping movement of a mask-frame assembly 38 along the major axis X of the tube 8, as caused by shock. Each bracket 50 or 52 is U-shaped and made from a single metal plate. As shown in FIGURES 3 and 4, one leg 57 of the U-shaped bracket is attached to the frame 40, while the other leg 58 includes a slot 59 that is open through the bottom 60 of the U-shape of the bracket. Because of the opening in the slot 59, the brackets 50 and 52 can slide onto their respective studs, 54 and 56, without the need for any additional device to depress the brackets. Therefore, the mask-frame assembly 38 can be inserted and removed from the panel 12 by depressing only the four corner springs 42. The additional X direction shock load resistance is achieved when the additional studs engage the sides of the bracket slots, as the shadow mask-frame assembly begins to deflect in the X direction. In order not to alter the position of the shadow mask 32 in the panel 12, as defined by the corner support springs 42, the brackets 50 and 52 are welded to the frame 40 after the shadow mask is installed in the panel. Preferably, for the brackets 50 and 52, there are small tolerances of about 0.127 mm (0.005 inch) between the studs 54 and 56 and the bracket slots 59. Use of an open slot in a bracket, as disclosed herein, prevents interference during insertion and removal of the shadow mask; also, the brackets do not interfere with any other processing equipment that is used in the tube manufacturing. The shape of the brackets used may vary to some extent from that described with respect to the first preferred embodiment. For example, a bracket 61, shown in FIGURE 5, is J-shaped, and another bracket 64, shown in FIGURE 6, has a somewhat twisted J-shape. Both of these brackets 61 and 64 have slots 62 and 66, respectively, therein that are open facing the faceplate 18, to permit insertion and removal of the mask-frame assembly without the need to depress the brackets. The slots are generally Y-shaped, with the upper tapered portion being used to capture and direct the bracket onto a stud, during mask insertion. The very bottom of the Y-shape is V-shaped to accurately center the slot on the stud, during installation of the bracket on the frame. Once the slot is centered, the bracket is backed-off slightly, so that the stud is centered between the two straight parallel sides of the slot, with slight tolerances therebetween. After the bracket has been so backed-off, it is welded to the frame. Tests were performed on two 97 cm (38 inch) diagonal tubes having 16 x 9 aspect ratios. A first tube had the four corner springs, but no brackets. The second tube was constructed with two brackets in addition to the four corner springs. Results indicate that the first tube did not have a shock handling capability to tolerate a 25gs X-direction shock, whereas the second tube, with the two brackets, demonstrated satisfactory X-direction shock handling capability at shock levels up to 35gs. Although the present invention has been described with respect to a tube having a line screen, which is more sensitive to horizontal misregister than to vertical misregister, it is to be understood that the invention may also be applied to a tube having a dot screen, which is sensitive to misregister in both the horizontal and vertical directions. In the latter case, however, two additional brackets could be installed at the centers of the short sides of the panel to also improve shock capability in the vertical direction.";A color picture tube (8) including an evacuated envelope (10) having a rectangular faceplate panel (12) with two approximately parallel long sides (22, 24), two approximately parallel short sides (26, 28) and four corners, said panel comprising a faceplate (18) and a peripheral sidewall (20), said panel further including a shadow mask-frame assembly (38) mounted therein by springs (42) located at the four corners of said panel, said springs having apertures engaging studs (34) located on said peripheral sidewall at said four corners, characterized by said panel (12) including additional studs (54, 56) on said peripheral sidewall (20) located near the centers of at least one pair of said approximately parallel sides (22, 24), and brackets (50, 52, 61, 64) located on the opposite sides of said shadow mask-frame assembly (38) at the locations of said additional studs, said brackets including slots (59, 62, 66) therein, said slots being open on sides thereof facing said faceplate (18), and said additional studs being positioned within said slots. The tube (8) as defined in Claim 1, characterized by said panel (12) including two additional studs (54, 56) on said peripheral sidewall (20) located near the centers of said long sides (22, 24), and two brackets (50, 52, 61, 64) located on the opposite long sides of said shadow mask-frame assembly (38) at the locations of said two additional studs. The tube (8) as defined in Claim 2, characterized in that there is a small tolerance between said two additional studs (54, 56) and said slots (59, 62, 66). The tube (8) as defined in Claim 2, characterized in that said panel (12) includes a line screen (30). The tube (8) as defined in Claim 2, characterized in that said panel (12) has an approximate 16 by 9 aspect ratio. The tube (8) as defined in Claim 2, characterized in that each of said slots (62, 66) is generally Y-shaped, with the Y-shape having a V-shape at the bottom thereof.;GOROG ISTVAN, HAMM KELLY EUGENE, POULOS ANTHONY SOCRATES, GOROG, ISTVAN, HAMM, KELLY EUGENE, POULOS, ANTHONY SOCRATES, Gorog, Istvan, c/o THOMSON multimedia, Hamm, Kelly Eugene, c/o THOMSON multimedia, Poulos, Anthony Socrates, c/o THOMSON multimedia;THOMSON LICENSING INC, THOMSON LICENSING, INC.;2005.0;1030342
EP-1493442-B1;20050928.0;EP;B1;EN;20100220.0;new;32831120.0;A61K31;A61P25;A61P29, A61K31, A61P21, A61P25, A61P13;A61K  31/5375;Reboxetine for treating peripheral neuropathy;The use of racemic reboxetine, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prophylaxis of peripheral neuropathy, is disclosed.;"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to the use of racemic reboxetine or a pharmaceutically acceptable salt thereof, the preparation of a non-transdermal medicament for the treatment or prophylaxis of peripheral neuropathy. Brief Description of Related Technology Many types of depression, mental, behavioral, and neurological disorders originate from disturbances in brain circuits that convey signals using certain monoamine neurotransmitters. Monoamine neurotransmitters include, for example, norepinephrine (noradrenaline), serotonin (5-HT), and dopamine. Lower-than-normal levels of norepinephrine are associated with a variety of symptoms including lack of energy, motivation, and interest in life. Thus, a normal level of norepinephrine is essential to maintaining drive and capacity for reward. These neurotransmitters travel from the terminal of a neuron across a small gap ( i.e., the synaptic cleft) and bind to receptor molecules on the surface of a second neuron. This binding elicits intracellular changes that initiate or activate a response or change in the postsynaptic neuron. Inactivation occurs primarily by transport (i.e., reuptake) of the neurotransmitter back into the presynaptic neuron. Abnormality in noradrenergic transmission results in various types of depression, mental, behavioral, and neurological disorders attributed to a variety of symptoms including a lack of energy, motivation, and interest in life. See generally , R.J. Baldessarini, ""Drugs and the Treatment of Psychiatric Disorders: Depression and Mania"" in Goodman and Gilman's The Pharmacological Basis of Therapeutics, McGraw-Hill, NY, NY, pp. 432-439 (1996). Reboxetine ( i . e ., 2-[(2-ethoxyphenoxy)(phenyl)methyl] morpholine) raises the concentration of physiologically active norepinephrine by preventing reuptake of norepinephrine, for example. Reboxetine is a norepinephrine reuptake inhibitor and has been shown to be effective in the short-term ( i . e ., less than eight weeks) and long-term treatment of depression. In fact, reboxetine has been shown to have effectiveness that is similar to fluoxetine, imipramine, and desipramine, commonly prescribed antidepressants, in both adults and elderly patients. See S.A. Montgomery, Reboxetine: Additional Benefits to the Depressed Patient, Psychopharmocol (Oxf) 11:4 Suppl., S9-15 (Abstract) (1997). Antidepressant drugs are sometimes divided into ""generations."" The first generation included the monoamine oxidase inhibitors (such as isocarboxazid and phenylhydrazine) and tricyclic agents (such as imipramine). The second generation of antidepressant drugs included compounds such as mianserin and trazodone. The third generation has included drugs called selective reuptake inhibitors (e.g., fluoxetine, sertraline, paroxetine, and reboxetine). Those drugs were characterized by relatively selective action on only one of the three main monoamine systems thought to be involved in depression (i.e., 5-HT (serotonin), noradrenaline (norepinephrine), and dopamine). APP Textbook of Psychopharmacology (A.F. Schatzberg and C.B. Nemeroff), American Psychiatric Press, 2d. ed., (1998); Lexicon of Psychiatry, Neurology and the Neurosciences (F.J. Ayd, Jr.) Williams and Wilkins (1995). The antidepressant efficacy of reboxetine is evidenced by its ability to prevent resperine-induced blepharospasm and hypothermia in mice, down regulation of β-adrenergic receptors and desensitization of noradrenaline-coupled adenylate cyclase. See M. Brunello and G. Racagni, ""Rationale for the Development of Noradrenaline Reuptake Inhibitors,"" Human Psychophramacology, vol. 13, S-13-519, Supp. 13-519 (1998). According to a survey by Brian E. Leonard, desipramine, maprotiline, and lofepramine are relatively selective norepinephrine reuptake inhibitors with proven efficacy. These materials increase brain noradrenaline and thereby function to relieve depression. Mianserin and mirtazepine also show antidepressant-like effects by increasing noradrenaline availability by means of blocking the pre-synaptic α 2 -adrenoceptors. Still further, oxaprotiline, fezolamine, and tomoxetine are potent and selective norepinephrine reuptake inhibitors that lack neurotransmitter receptor interactions and, thus, do not cause many of the side effects characteristic of classical tricyclic antidepressants. See Brian E. Leonard, ""The Role of Noradrenaline in Depression: A Review,"" Journal of Psychopharmacology, vol. 11, no. 4 (Suppl.), pp. S39-S47 (1997) Reboxetine also is a selective norepinephrine reuptake inhibitor, which also produces fewer of the side effects associated with the administration of classical tricyclic antidepressants. The antidepressant efficacy of reboxetine is evidenced by its ability to prevent resperine-induced blepharospasm and hypothermia in mice, down regulation of β-adrenergic receptors and desensitization of noradrenaline-coupled adenylate cyclase. See M. Brunello and G. Racagni, ""Rationale for the Development of Noradrenaline Reuptake Inhibitors,"" Human Psychopharmacology, vol. 13 (Supp.) 13-519 (1998). Reboxetine generally is described in Melloni et al . U.S. Patent Nos. 4,229,449, 5,068,433, and 5,391,735, and in GB-A-2,167,407. Chemically, reboxetine has two chiral centers and, therefore, exists as two enantiomeric pairs of diastereomers, shown below as isomers (I) through (IV): Many organic compounds exist in optically active forms, i . e ., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound the prefixes R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes D and L, or (+) or (-), designate the sign of rotation of plane-polarized light by the compound, with L or (-) meaning that the compound is levorotatory. In contrast, a compound prefixed with D or (+) is dextrorotatory. There is no correlation between nomenclature for the absolute stereochemistry and for the rotation of an enantiomer. Thus, D-lactic acid is the same as (-)-lactic acid, and L-lactic acid is the same as (+)-lactic acid. For a given chemical structure, each of a pair of enantiomers are identical except that they are non-superimposable mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric, or racemic, mixture. Stereochemical purity is important in the pharmaceutical field, where many of the most often prescribed drugs exhibit chirality. For example, the L-enantiomer of the beta-adrenergic blocking agent, propranolol, is known to be 100 times more potent than its D-enantiomer. Additionally, optical purity is important in the pharmaceutical drug field because certain isomers have been found to impart a deleterious effect, rather than an advantageous or inert effect. For example, it is believed that the D-enantiomer of thalidomide is a safe and effective sedative when prescribed for the control of morning sickness during pregnancy, whereas its corresponding L-enantiomer is believed to be a potent teratogen. When two chiral centers exist in one molecule, there are four possible stereoisomers: (R,R), (S,S), (R,S), and (S,R). Of these, (R,R) and (S,S) are an example of a pair of enantiomers (mirror images of each other), which typically share chemical properties and melting points just like any other enantiomeric pair. The mirror images of (R,R) and (S,S) are not, however, superimposable on (R,S) and (S,R). This relationship is called diastereoisomeric, and the (S,S) molecule is a diastereoisomer of the (R,S) molecule, whereas the (R,R) molecule is a diastereoisomer of the (S,R) molecule. Currently, reboxetine is commercially available only as a racemic mixture of enantiomers, (R,R) and (S,S) in a 1:1 ratio, and reference herein to the generic name ""reboxetine"" refers to this enantiomeric, or racemic, mixture. Reboxetine is commercially sold under the trade names of EDRONAX™, PROLIFT™, VESTRA™, and NOREBOX™. As previously noted, reboxetine has been shown to be useful in the treatment of human depression. Orally administered reboxetine is readily absorbed and requires once or twice a day administration. A preferred adult daily dose is in the range of about 8 to about 10 milligrams (mg). The effective daily dosage of reboxetine for a child is smaller, typically in a range of about 4 to about 5 mg. The optimum daily dosage for each patient, however, must be determined by a treating physician taking into account the patient's size, other medications which the patient may be taking, identity and severity of the particular disorder, and all of the other circumstances of the patient. It has been reported that other antidepressants have a high pharmacological selectivity for inhibiting reuptake of norepinephrine. For example, oxaprotiline has a pharmacological selectivity with respect to inhibiting norepinephrine reuptake compared to serotonin reuptake of about 4166, based on a ratio of K i values. The corresponding pharmacological selectivity for desipramine is about 377, and that for maprotiline is about 446. See Elliott Richelson and Michael Pfenning, ""Blockade by Antidepressants and Related Compounds of Biogenic Amine Uptake in Rat Brain Synaptosomes: Most Antidepressants Selectively Block Norepinephrine Uptake,"" European Journal of Pharmacology, vol. 14, pp. 277-286 (1984). Despite the relatively high selectivity of oxaprotiline, desipramine, and maprotiline, these and other known materials undesirably block receptor of other neurotransmitters to a sufficient degree that they also contribute to adverse side effects. WO 00/00120, which was published after the priority dates of the present application, but before the filing date, discloses a transdermal formulation suitable for the treatment of pain in a subject. The transdermal formulation includes an amine-containing compound, such as racemic reboxetine There is a need for medicaments for the treatment or prophylaxis of peripheral neuropathy containing racemic reboxetine, and the use of racemic reboxetine in the manufacture of such medicaments. SUMMARY OF THE INVENTION The present invention is directed to the use of racemic reboxetine or a pharmaceutically acceptable salt, thereof, in the manufacture of a non-transdermal medicament for the treatment or prophylaxis of peripheral neuropathy. Additional benefits and features of the present invention will become apparent to those skilled in the art from a review of the following detailed description, taken in conjunction with the example and the appended claims. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Reboxetine is a known compound that is active on the central nervous system, and has been used as an antidepressant. Heretofore, use of reboxetine has been limited to the treatment of depression, oppositional defiant disorder, attention-deficit/hyperactivity disorder, and conduct disorder. These proposed treatments are disclosed in International Publication Nos. WO 99/15163, WO 99/15176, and WO 99/15177. These treatment methods are limited to administration of a racemic mixture of the (S,S) and (R,R) reboxetine stereoisomers. Reboxetine does not act like most antidepressants. Unlike tricyclic antidepressants, and even selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is not a SSRI. Brian E. Leonard, ""Noradrenaline in basic models of depression."" European-Neuropsychopharmacol, 7 Suppl. 1 pp. S11-6 and S71-3 (April 1997). Reboxetine is a selective norepinephrine reuptake inhibitor, with only marginal serotonin and no dopamine reuptake inhibitory activity. Reboxetine displays no anticholinergic binding activity in different animal models, and is substantially devoid of monoamine oxidase (MAO) inhibitory activity. Racemic reboxetine exhibits a pharmacological selectivity of serotonin (K i )/norepinephrine (K i ) of about 80. The K i values are discussed in more detail hereafter. As used herein, the term ""reboxetine"" refers to the racemic mixture of the (R,R) and (S,S) enantiomers of reboxetine. In contrast, the term ""(S,S) reboxetine"" refers to only the (S,S) stereoisomer. Similarly, the term ""(R,R) reboxetine"" refers to only the (R,R) stereoisomer. The phrases ""pharmaceutically acceptable salts"" or ""a pharmaceutically acceptable salt thereof"" refer to salts prepared from pharmaceutically acceptable acids or bases, including organic and inorganic acids and bases. Because the active compound ( i . e ., racemic reboxetine) used in the present invention is basic, salts may be prepared from pharmaceutically acceptable acids. Suitable pharmaceutically acceptable acids include acetic, benzenesulfonic (besylate), benzoic, p-bromophenylsulfonic, camphorsulfonic, carbonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, hydroiodic, isethionic, lactic, maleic, malic, mandelic, methanesulfonic (mesylate), mucic, nitric, oxalic, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, and the like. Examples of such pharmaceutically acceptable salts of racemic reboxetine, thus, include, acetate, benzoate, β-hydroxybutyrate, bisulfate, bisulfite, bromide, butyne-1,4-dioate, carpoate, chloride, chlorobenzoate, citrate, dihydrogenphosphate, dinitrobenzoate, fumarate, glycollate, heptanoate, hexyne-1,6-dioate, hydroxybenzoate, iodide, lactate, maleate, malonate, mandelate, metaphosphate, methanesulfonate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, oxalate, phenylbutyrate, phenylproionate, phosphate, phthalate, phylacetate, propanesulfonate, propiolate, propionate, pyrophosphate, pyrosulfate, sebacate, suberate, succinate, sulfate, sulfite, sulfonate, tartrate, xylenesulfonate, and the like. A preferred pharmaceutical salt of racemic reboxetine is methanesulfonate ( i.e ., mesylate), which is prepared using methanesulfonic acid. As used herein, the terms ""treat,"" ""treatment,"" and ""treating,"" refer to: (a) preventing a disease, disorder, or condition from occurring in a human which may be predisposed to the disease, disorder and/or condition but has not yet been diagnosed as having it; (b) inhibiting the disease, disorder, or condition, i . e ., arresting its development; and (c) relieving the disease, disorder, or condition, i . e ., causing regression of the disease, disorder and/or condition. In other words, the terms ""treat,"" ""treatment,"" and ""treating,"" extend to prophylaxis, in other words ""prevent,"" ""prevention,"" and ""preventing,"" as well as treatment of established conditions. Accordingly, use of the terms ""prevent,"" ""prevention,"" and ""preventing,"" would be an administration of the pharmaceutical composition to a person who has in the past suffered from the aforementioned conditions, but is not suffering from the conditions at the moment of the composition's administration. For the sake of simplicity, the term ""conditions"" as used hereinafter encompasses conditions, diseases, and disorders. According to the present invention, racemic reboxetine is useful in treating peripheral neuropathy wherein inhibiting reuptake of norepinephrine provides a benefit. Racemic reboxetine may be administered, and preferably orally administered, in a sufficient amount to provide a total dose of 0.1 to 10 mg/day of the compound to an individual. The synthesis of a racemic mixture of reboxetine is disclosed in Melloni et al . U.S. Patent No. 4,229,449. While it is possible to administer racemic reboxetine or a pharmaceutically acceptable salt thereof directly without any formulation, a composition preferably is administered in the form of pharmaceutical medicaments comprising racemic reboxetine or a pharmaceutically acceptable salt thereof. The composition can be administered in oral unit dosage forms such as tablets, capsules, pills, powders, or granules. The inventive composition also can be introduced parenterally, (e.g., subcutaneously, intravenously, or intramuscularly), using forms known in the pharmaceutical art. The inventive composition further can be administered rectally or vaginally in such forms as suppositories or bougies. It may be desirable or necessary to introduce the composition or pharmaceutical compositions containing the selective norepinephrine reuptake inhibitor to the brain, either directly or indirectly. Direct techniques usually involve placement of a suitable drug delivery catheter into the ventricular system to bypass the blood-brain barrier. One such suitable delivery system used for the transport of biological factors to specific anatomical regions of the body is described in U.S. Patent No. 5,011,472. In general, the preferred route of administering the composition is oral, with a once or twice a day administration. The dosage regimen and amount for treating patients with the composition is selected in accordance with a variety of factors including, for example, the type, age, weight, sex, and medical condition of the patient, the severity of the condition, the route of administration and the particular compound employed, reboxetine racemate. An ordinarily skilled physician or psychiatrist can readily determine and prescribe an effective ( i . e ., therapeutic) amount of the compound to prevent or arrest the progress of the condition. In so proceeding, the physician or psychiatrist could employ relatively low dosages at first, subsequently increasing the dose until a maximum response is obtained. Pharmaceutical compositions suitable for oral administration can be of any convenient form, such as sachets, tablets, capsules, pills, or aerosol sprays, each containing a predetermined amount of the active compound either as a powder or granules, or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion. Such compositions can be prepared by any method that includes the step of bringing the active compound either into intimate association with a carrier, which constitutes one or more necessary or desirable ingredients. Generally, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into a desired form. For example, a tablet can be prepared by compression or molding techniques, optionally, using one or more accessory ingredients. Compressed tablets can be prepared by compressing the active ingredient in a suitable machine into a free-flowing form, such as a powder or granules. Thereafter, the compressed, free-flowing form optionally can be mixed with a binders, diluents, lubricants, disintegrating agents, effervescing agents, dyestuffs, sweeteners, wetting agents, and non-toxic and pharmacologically inactive substances typically present in pharmaceutical compositions. Molded tablets can be made by molding a mixture of the powdered compound moistened with an inert liquid diluent in a suitable machine. Suitable binders for use in the pharmaceutical preparation include, for example, starches, gelatine, methylcellulose, gum arabic, tragacanth, and polyvinylpyrrolidone. Suitable diluents for use in the pharmaceutical preparation include, for example, lactose, dextrose, sucrose, mannitol, sorbitol, and cellulose. Suitable lubricants for use in the pharmaceutical preparation include, for example, silica, talc, stearic acid, magnesium or calcium stearate, and or polyethylene glycols. Suitable disintegrating agents for use in the pharmaceutical preparation include, for example, starches, alginic acid, and alginates. Suitable wetting agents for use in the pharmaceutical preparation include, for example, lecithin, polysorbates, and laurylsulfates. Generally, any effervescing agents, dyestuffs, and/or sweeteners known by those of ordinary skill in the art can be used in the preparation of a pharmaceutical composition. According to the present invention racemic reboxetine is effective in the treatment of child, adolescent, and adult patients. For purposes of the present invention, a child is considered to be a person below the age of puberty, an adolescent is considered to be a person between the age of puberty and up to about 18 years of age, and an adult generally is a person of at least about 18 years of age. As previously noted, the optimum daily dosage for each patient must be determined by a treating physician taking into account each patient's size, other medications which the patient is taking, identity and severity of the disorder, and all of the other circumstances of the patient. As stated above, reboxetine acts as an antidepressant. Reboxetine, however, does not act like most antidepressants. Unlike trycyclic antidepressants, and even selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is not a selective serotonin reuptake inhibitor. Rather, reboxetine is selective for the noradrenergic system. Reboxetine is not an SSRI, but is a novel, selective, noradrenalinc reuptake inhibitor (NRI). B. Leonard, ""Noradrenaline in basic models of depression."" European-Neuropsychopharmacol, 7 Suppl. 1 pp. S11-6 and S71-3 (Apr., 1997). Unlike most prior generation drugs, reboxetine is a highly selective norepinephrine reuptake inhibitor, with only marginal serotonin and no dopamine reuptake inhibitory activity. Reboxetine displays no anticholinergic binding activity in different animal models, and is devoid of monoamine oxidase (MAO) inhibitory activity. Reboxetine also is a highly potent, pharmacologically specific, and fast acting agent. Investigations indicate that reboxetine has potent antireserpine activity, and combines the inhibitory properties of classical tricyclic antidepressants on the reuptake of noradrenaline with an ability to desensitize β-adrenergic receptor function, without showing any appreciable blocking action at muscarinic, cholinergic, histaminergic, and α-adrenergic receptors. Moreover, reboxetine shows less vagolytic activity than tricyclic antidepressants, and no evidence of cardiotoxicity. According, to the present invention, racemic reboxetine can be used to treat or prevent peripheral neuropathy. Specifically, reboxetine has been found particularly useful for treating or enhancing the treatment or prevention of peripheral neuropathy, with greater efficacy and with fewer side effects than with treatment by known drugs. The Mental and neurological disorder that may be treated or prevented by administration of a therapeutically effective amount of a racemic reboxetine (or a pharmaceutically acceptable salt thereof) according to the present invention is peripheral neuropathy. The racemate form of reboxetine is well tolerated and has a wide safety range. Racemic reboxetine can be administered to an individual in an amount in a range of 2 to 20 milligrams per patient per day (mg/day), and preferably 4 to 10 mg/day, and more preferably 6 to 10 mg/day. Depending upon the formulation and the individual's disorder, the total daily dosage can be administered in small amounts up to two times a day. Reboxetine typically is administered orally, for example, in the form of tablets, but can be adminstered parentally, rectally, or vaginally. A preferred method of administering racemic reboxetine is oral dosing once or twice a day. It can also be administered at dosages of 2, 4, 6, 8, 10, or 12 mg/day or fractions thereof. For example, suitable administrations could be 4 mg in the morning and 2 or 4 mg in the afternoon or evening. In some patients, the ideal dosing would be 3 to 5 mg in the morning and 3 to 5 mg in the afternoon. A skilled physician or psychiatrist can determine the precise level of dosing. The ideal dosing is routinely determined by an evaluation of clinical trials and the needs of specific patients. In accordance with the present invention, the racemic reboxetine also can be administered as the free base or a pharmaceutically acceptable salt thereof. The phrases ""pharmaceutically acceptable salts"" or ""a pharmaceutically acceptable salt thereof"" refer to salts prepared from pharmaceutically acceptable acids or bases, including organic and inorganic acids and bases as described above. A preferred pharmaceutical salt of reboxetine is methanesulfonate ( i.e. , mesylate), which is prepared using methanesulfonic acid. Treatment or prevention of above disorder involves the administration of reboxetine in a manner and form that result in a reduction in the symptoms of the disease or disorder. Typically, the symptoms exhibited by children, adolescents, and adults are similar to each other. Hence, as noted above, methods of the present invention are effective in the treatment of child, adolescent, and adult patients. EXAMPLE This example demonstrates the superior pharmacological selectivity and potency of a composition according to the present invention. Sprague-Dawley rats weighing about 250 to about 300 grams (g) were decapitated, and cerebral cortical tissue was removed immediately. Cerebral cortices were homogenized in nine volumes of medium each containing 0.32 molar (M) sucrose using a rotating pestle. The obtained homogenate was centrifuged at about 1000 x g for about 10 minutes at about 4°C. A supernatant was collected and further centrifuged at about 20,000 x g for about 20 minutes at a temperature of about 4°C. A protein pellet resulting from the centrifuge steps was re-suspended in a Kreb's-Hepes buffer to result in a protein concentration of about 2 mg/ml of buffer. The buffer was maintained at a pH of about 7.0 and contained: 20 mM Hepes; 4.16 mM NaHCO 3 ; 0.44 mM KH 2 PO 4 ; 0.63 mM NaH 2 PO 4 ; 127 mM NaCl; 5.36 mM KCI; 1.26 mM CaCl 2 ; and 0.98 mM MgCl 2 . Protein/buffer suspension was introduced into 166 assay tubes such that about 30 µg (10 -6 grams) to about 150 µg of the protein was added to each of 166 assay tubes ( i.e. , 80 assays per transporter assay). Binding to serotonin and norepinephrine reuptake sites was determined as follows. Synaptosomal uptake of 3 H-norpinephrine was determined as follows. About 1.4 nanomolar of [ 3 H]citalopram and about 1.9 nM of [ 3 H]nisoxetine were used to label serotonin and norepinephrine reuptake sites, respectively. Nonspecific binding was defined by 100 micromolar (µM) fluoxetine (for serotonin) and 10 µM desipramine (for norepinephrine). Incubation in total assay volume of about 500 microliters (µl) was carried out for about 60 minutes (for serotonin) and 120 minutes (for norepinephrine). Both incubations were carried out at about 25°C, and terminated by rapid filtration through a 48-well cell harvester though GFB filters (pre-soaked with about 0.5 PEI for about 4 hours) in a 3 x 5 ml of ice-cold 200 mM tris-HCl, pH 7.0. Punched-out filters were placed into 7 ml minivials and radioactive assayed by liquid scintillation counting. The ability of reboxetine ( i.e. , racemic mixture of (R,R) and (S,S) reboxetine), (R,R) reboxetine, and (S,S) reboxetine to bind to norepinephrine and serotonin reuptake sites was evaluated in binding assays using the two radioligands, [ 3 H]citalopram and [ 3 H]nisoxetine. The concentration of the test compound required to inhibit 50% of the specific binding at the two reuptake sites (IC 50 values) were determined by non-linear least square regression analysis. A conversion of IC 50 values to K i values was performed using the Cheng-Prassoff equation presented below: K i = IC 50 /(1 + ([L]/[K d of L])), wherein [L] is the radioligand concentration used in nM, and K d is the binding affinity of L in nM. See Y.C. Cheng and W.H. Prusoff, ""Relationship Between the Inhibitory Constant (K i ) and the Concentration of Inhibitor Which Causes 50% Inhibition (IC 50 ) of an Enzymatic Reaction,"" Biochemical Pharmacology, vol. 22, pp. 3099-3108 (1973). The K i values calculated according to the Cheng-Prassoff equation are provided in the table below: Compound Norepinephrine Reuptake (K i nM) Serotonin Reuptake (K i nM) Selectivity of K i of Serotonin/Norepinphrine (S,S) Reboxetine 0.23 ± 0.06 2937 ± 246 12,770 (R,R) Reboxetine 7.0 ± 1.7 104 ± 43 15 Reboxetine 1.6 ± 0.6 129 ± 13 81 The data shows that racemic reboxetine has an 81 fold selectivity favoring norepinephrine reuptake inhibition over serontonin reuptake inhibition.";The use of racemic reboxetine, or a pharmaceutically acceptable salt thereof, in the manufacture of a non-transdermal medicament for the treatment or prophylaxis of peripheral neuropathy. The use of claim 1, wherein the racemic reboxetine is to be administered in an amount of 2 to 20 mg/day. The use of claim 2, wherein the racemic reboxetine is to be administered in an amount of 4 to 10 mg/day. The use of claim 3, wherein the racemic reboxetine is to be administered in an amount of 6 to 10 mg/day. The use of any preceding claim, wherein the pharmaceutically acceptable salt of racemic reboxetine is the methanesulfonate.;AHMED SAEEDUDDIN, BIRGERSON LARS, CETERA PASQUALE, MARSHALL ROBERT CLYDE, MCARTHUR ROBERT, TAYLOR DUNCAN P, WONG ERIK H F, AHMED, SAEEDUDDIN, BIRGERSON, LARS, CETERA, PASQUALE, MARSHALL, ROBERT CLYDE, MCARTHUR, ROBERT, TAYLOR, DUNCAN P., WONG, ERIK H.F.;PHARMACIA & UPJOHN CO LLC, PHARMACIA & UPJOHN COMPANY LLC;2005.0;1493442
EP-1493913-B1;20051228.0;EP;B1;EN;20100220.0;new;33436032.0;F02M21;F02M41;F02M21;F02M  21/04;Fuel gas mixer;A fuel gas mixer and a method for controlling a fuel gas mixer comprising a throttle valve (4) provided for opening and closing an air intake passage (2) of an engine, and a fuel gas supply passage (6) connected to said air intake passage at a position upstream of said throttle valve (4). A fuel gas control valve (5) for opening and closing said air intake passage (6) is provided in said air intake passage at a position upstream of the position at which said fuel gas supply passage (6) is connected to said air intake passage. A fuel gas control valve controlling means (13,14) is provided for varying the degree of opening of said fuel gas control valve (5) according to the operating state of said engine. Said fuel gas control valve controlling means (13,14) comprises an electronic control unit (13) and a step motor (14) for opening and closing said fuel gas control valve (5).;"The present invention relates to a fuel gas mixer for use in an engine using a fuel gas such as LPG or natural gas as its fuel. The present invention also relates to a method for controlling a fuel gas mixer. One conventional fuel gas mixer is a fixed venturi type mixer generally having a structure shown in Fig. 13. A throttle valve 32 is provided in an air intake passage 31 connected to an engine for opening and closing the air intake passage 31. A main venturi (throttle part) 33 is formed upstream of the throttle valve 32. A main fuel gas passage 34 is connected to the main venturi 33 and a flow control valve 36 driven by a step motor 35 is provided in the main fuel gas passage 34. A gas injector 37 is provided closely downstream of the throttle valve 32. In a low-load operation range, the opening of the throttle valve 32 is small and a suction negative pressure is hardly created at the main venturi 33. Thus, high-pressure fuel gas is injected from the gas injector 37 and the air-fuel ratio is controlled by adjusting the injection time. In an intermediate- or high-load operation range, the opening of the throttle valve 32 is large and a suction negative pressure is created at the main venturi 33. Thus, the air-fuel ratio is controlled by adjusting the cross-sectional area of the main fuel gas passage 34 with the step motor 35. In the case of the fixed venturi type mixer, the venturi diameter (passage diameter) is limited by the flow rate characteristic of the gas injector 37 and thus has a low degree of freedom. Namely, in order to prevent a range where the air-fuel ratio is low from being generated between an operation range where the fuel is supplied from the gas injector 37 and an operation range where the fuel is supplied from the main venturi part, the fuel must start to be supplied from the main venturi part when the flow rate of the gas injector 37 gets close to the maximum. Thus, the venturi diameter is limited by the flow rate characteristic of the injector 37. As a result, in order to enlarge the main venturi diameter so as to be suitable for a large-displacement engine or a high-power engine, a plurality of injectors are needed, resulting in increase in costs. Additionally, it is necessary to control air-fuel ratios of the two systems: a main system for supplying fuel from the main venturi part and a slow system for supplying fuel from the gas injector. This makes the control system complicated and increases costs. The present invention has been made in view of the above problems of the prior arts and it is, therefore, an object of the present invention to provide a fuel gas mixer which does not need a main venturi and a gas injector, and thus is simple in structure and capable of reducing costs and which can be applicable from a small-displacement engine to a large-displacement engine. Said objective is solved by a fuel gas mixer having the features of independent claim 1. Preferred embodiments are laid down in the dependent claims. Moreover, said objective is also solved by a method for controlling a fuel gas mixer having the features of independent claim 5. Preferred embodiments are laid down in the dependent claims. The embodiments teach a fuel gas mixer comprising an air intake passage connected to an engine, a throttle valve provided in the air intake passage for opening and closing the air intake passage, and a fuel gas supply passage connected to the air intake passage at a position upstream of the throttle valve, characterized in that a fuel gas control valve for opening and closing the air intake passage is provided in the air intake passage at a position upstream of the position at which the fuel gas supply passage is connected to the air intake passage and in that fuel gas control valve controlling means is provided for varying the degree of opening of the fuel gas control valve according to the operating state of the engine. A specific embodiment teaches a fuel gas mixer wherein the fuel gas control valve controlling means comprises a link mechanism connecting the fuel gas control valve to the throttle valve, and the link mechanism is adapted to fully open the fuel gas control valve before the throttle valve is fully opened. A specific embodiment teaches a fuel gas mixer wherein an air passage is connected partway along the fuel gas supply passage, in which the amount of fuel gas to be supplied is controlled by controlling the cross-sectional area of the air passage. A specific embodiment teaches a fuel gas mixer wherein the fuel gas control valve controlling means comprises a step motor for opening and closing the fuel gas control valve. A specific embodiment teaches a fuel gas mixer wherein the amount of the fuel gas to be supplied is controlled by controlling the opening of the fuel gas control valve in at least a low-load operation range. Hereinafter the present invention is illustrated and explained by means of embodiments in conjunction with the accompany drawings. In the drawings wherein: Fig. 1 is a structural view of a system of a fuel gas mixer according to a first embodiment, which does not form part of the invention but represents background art and is useful for understanding the invention; Fig. 2 is a schematic structural view of the mixer; Fig. 3 is a graph showing opening characteristics of a fuel gas control valve of the mixer; Fig. 4 is a flowchart for explaining an operation of the mixer; Fig. 5 is a flowchart for explaining an operation of the mixer; Fig. 6 is a flowchart for explaining an operation of the mixer; Fig. 7 is maps for explaining operations of the mixer; Fig. 8 is a structural view of a system of a fuel gas mixer according to a second embodiment which shows the teaching of the independent claims; the mixer of Fig. 9 is a schematic structural view of the mixer of the second embodiment; Fig. 10 is a flowchart for explaining an operation of the mixer of the second embodiment; Fig. 11 is a flowchart for explaining an operation of the mixer of the second embodiment; Fig. 12 is a flowchart for explaining an operation of the mixer of the second embodiment; and Fig. 13 is a schematic structural view of a conventional fuel gas mixer. Fig. 1 to Fig. 7 are views for explaining a first embodiment which does not form part of the invention but represents background art and is useful for understanding the invention. Fig. 1 is a view illustrating a driving system of a fuel gas mixer of this embodiment, Fig. 2 is a schematic view of a link mechanism of the mixer, Fig. 3 is a view showing opening characteristics of a fuel gas control valve, Fig. 4 to Fig.6 are flowcharts for explaining operations of the mixer and Fig. 7 shows maps of various types. In Fig. 1 and Fig. 2, designated as 1 is a fuel gas mixer connected to an engine. In an air intake passage 2 of the mixer 1, a butterfly type throttle valve 4 and a fuel gas control valve 5 for opening and closing the air intake passage 2 are provided downstream and upstream, respectively, of a main venturi part 3 narrowing the air intake passage 2. The air intake passage 2 has an upstream end to which an air cleaner is connected. At the main venturi part 3, a discharge port 6a of a fuel gas passage 6 is opened. In fuel gas passage 6, an orifice (throttle) 6b is formed in the vicinity of the discharge port 6a. The fuel gas passage 6 is connected to a fuel gas source via a fuel cutoff valve 6c. An air passage 7 is connected to the fuel gas passage 6 upstream of the orifice 6b. The air passage 7 has an upstream end to which an air cleaner is connected. An orifice 7a is formed in the air passage 7 and there is provided an air bleed control valve 8 for varying the opening area of the orifice 7a. The air bleed control valve 8 is driven to move back and forth by a step motor 9 to control the flow rate of air passing therethrough. The throttle valve 4 has a valve shaft 4a having an outer end to which a driving pulley 10 is secured. The driving pulley 10 is connected via a throttle cable to a throttle pedal in the driver's compartment, although not shown. The throttle valve 4 is rotated in accordance with the amount by which the driver depresses the pedal. The fuel gas control valve 5 has a valve shaft 5a connected to the valve shaft 4a of the throttle valve 4 by a link mechanism 11. More specifically, the valve shaft 4a of the throttle valve 4 is connected to a throttle arm 11a such that they are incapable of rotating relative to each other, and the throttle arm 11a is in turn connected to a control arm 11c of the fuel gas control valve 5 by a connecting link 11b. The fuel gas control valve 5 abuts on a stopper when fully opened. The control arm 11c is connected to the valve shaft 5a of the fuel gas control valve 5 such that they are rotatable relative to each other and rotationally urged to its minimum open position by an urging spring. Thereby, the control arm 11c can be rotated following the movement of the throttle valve 4 and the connecting link 11b connected thereto even after the fuel gas control valve 5 is fully opened. When the throttle pedal is not stepped on, the throttle valve 4 and the fuel gas control valve 5 are maintained in their minimum open positions. The opening of the throttle valve 4 is increased in general proportion to the amount by which the throttle pedal is depressed. The fuel gas control valve 5 is fully opened when the opening of the throttle valve 4 becomes about 20-30 % and maintained in its full open position thereafter (see the characteristic curve A in Fig. 3). It is possible to omit the main venturi 3 from the air intake passage 2. In this case, the fuel gas control valve 5 is adapted to open not fully but by 40-50 % at the maximum as shown in the characteristic curve B in Fig. 3. Thereby, a suction negative pressure can be created at the connecting part of the fuel gas passage 6 without a main venturi. The opening of the throttle valve 4 is detected and inputted into the ECU 13 by a throttle position sensor 12. Also inputted into the ECU 13 are various signals such as a signal representing an oxygen concentration in exhaust gas from an O 2 sensor, a crank angle signal, a top signal representing the upper dead center, a suction pressure signal, a water temperature signal, and a catalyst temperature signal. From the ECU 13 are outputted various signals such as a driving signal to the step motor 9, an ignition timing signal, an OTP warning lamp signal for indicating that the catalyst is at an overheat temperature, and a radiator fan driving signal. Description will be next made of the operations and effects of this embodiment. A controlling operation by the ECU 13 will be first described by a flowchart in Fig. 4. When the ignition key is turned on, the temperature of the engine cooling water is read and the opening of the air bleed control valve 8 is set to a value in a start table (see Fig. 7(b)) depending upon the engine cooling water temperature at the moment (Steps S1 to S3). When cranking of the engine is started, a crank angle signal is read. When the crank angle signal is inputted, a fuel cutoff valve in a fuel gas supply system is opened and the rotational speed of the engine is read (Steps S4 to S8). When the thus read engine rotational speed is not lower than the start judging rotational speed and the idle switch is off, the engine rotational speed and the suction pressure are read. Then, based on the engine rotational speed and the suction pressure, the opening of the air bleed control valve 8 is set to a value in a basic A/F map (see Fig. 7(a)) as a normal operation mode. Then, when an A/F feedback flag is on, an A/F feedback control is started (Steps S9 to S14). The idle switch is not off in Step S10, the engine cooling water temperature is read again. Then, the opening of the air bleed control valve 8 is set to a value in an idle table shown in Fig. 7(c) and the engine rotational speed is read (Steps S15 to S17). Then, when an A/F feedback flag is not on, the process goes back to Step S15. When an A/F feedback flag is on, an A/F feedback control is started (Steps S18 and S19). Then, when the engine rotational speed is lower than a fuel cutoff rotational speed, the process goes back to Step S5. When the engine rotational speed is not lower than the fuel cutoff rotational speed (such as when the engine brake is in operation), a deceleration fuel cutoff is performed until the engine rotational speed becomes lower than the fuel cutoff rotational speed (Steps S20 and S21). When the ignition key is turned off (Step S22) or when a crank angle signal is not inputted in Step S6, the air bleed control valve 8 is fully opened and an initial setting thereof (correction of the initial value) is executed, whereby the air bleed control valve 8 is moved to a position of the designated step value (Steps S23 to S25). Hereupon, the fuel cutoff valve is closed and the power source of the ECU is turned off (Steps S26 and S27). Specifically, the A/F feedback control is performed as shown in Fig. 5. When the engine cooling water temperature is read and it is not lower than a temperature for starting an A/F feedback control, an O 2 sensor signal is read (Steps S31 to S33). When the O 2 sensor signal is a rich signal, the air bleed control valve 8 is opened at a specific rate selected from a map shown in Fig. 7 (e) based on the suction pressure and the engine rotational speed at the moment and by a specific degree selected in the same manner from a map shown in Fig. 7 (f) at a time until the rich signal is changed to a lean signal. Hereupon, the air bleed control valve 8 is closed at a specific rate selected in the same manner as above from a map shown in Fig. 7 (g) and by a specific degree selected in the same manner from a map shown in Fig. 7 (h) at a time until the O 2 sensor signal is changed to a rich signal (Steps S34 to S37). Then, when a rich signal is outputted from the O 2 sensor, the process goes to Step S35. When a rich signal is not outputted from the O 2 sensor, the process goes to Step S37 (Step S38). Specifically, the deceleration fuel cutoff control is performed as shown in Fig. 6. When the opening of the throttle is read and it is an idle opening, the engine rotational speed in read. When the thus read engine rotational speed is not lower than the deceleration fuel cutoff rotational speed (such as when the engine brake is in operation), the air bleed control valve 8 is opened to a value in a deceleration fuel cutoff table shown in Fig. 7(d) (Steps S41 to S45). Thereby, the amount of bleed air introduced is increased and the amount of fuel gas is decreased. Then, the process goes back to Step S41. The supply of the fuel gas may be cut off by closing the fuel cutoff valve 6c instead of opening the air bleed control valve 8. When the opening of the throttle is not the idle opening in Step S42, the opening of the air bleed control valve 8 is set to a value in a basic A/F map as a normal operation mode in Step S46. Then, the process goes back to Step S41. When the engine rotational speed is lower than the deceleration fuel cutoff rotational speed in Step S44, the opening of the air bleed control valve 8 is set to a value in the idle table map shown in Fig. 7(c) (Step S47). As described above, in the fuel gas mixer of this embodiment, since the fuel gas control valve 5, whose opening is adapted to vary depending upon the opening of the throttle valve 4 so that, in an operation range in which the opening of the throttle valve 4 is small, the opening of the fuel gas control valve 5 may be also small, is provided in the air intake passage 2 upstream of the connecting part of the fuel gas supply passage 6, it is possible to create a suction negative pressure, by which the flow rate of the fuel can be arbitrarily controlled, at the opening 6a of the fuel gas passage 6. The fuel gas mixer does not need a high-pressure gas injector as seen in a conventional device and thus receives no limitation caused by the characteristics of the injector. It is thus unnecessary to provide more than one mixer even in an engine with a large capacity per cylinder, so that an A/F feedback control can be performed with a simple control. Also, since a slow fuel system is unnecessary, it is only necessary to provide a main fuel system (the fuel gas passage 6). Thus, an A/F feedback control can be achieved over the entire operation range only by controlling the main fuel system. Additionally, in this embodiment, the fuel gas control valve 5 is connected to the throttle valve 4 by the link mechanism 11, thereby constituting the means for controlling the opening of the fuel gas control valve 5. Thus, it is possible to create a suction negative pressure by which the fuel flow rate can be controlled at the opening 6a of the fuel gas passage 6 by reducing the opening of the fuel gas control valve 5 when the opening of the throttle valve 4 is small with a simple structure. Moreover, since the link mechanism 11 is so constituted that the fuel gas control valve 5 is fully opened prior to the throttle valve 4 being fully opened, it is possible to prevent the fuel gas control valve 5 from being a resistance to the intake air flow because the fuel gas control valve 5 has fully been opened when the engine enters an intermediate- or high-load operation range in which the opening of the throttle valve 4 is large. Furthermore, since the air passage 7 is connected partway along the fuel gas supply passage 6 and the cross-sectional area of the air passage 7 is adapted to be controlled, the amount of the fuel gas to be supplied can be controlled more accurately and easily as compared with the case of being controlled only by the fuel gas control valve 5. The main venturi 3 can be omitted when the opening characteristic of the fuel gas control valve 5 is controlled to draw a characteristic curve like the curve B shown in Fig. 3. In this case, since a throttling loss of intake air caused by the main venturi 3 is not created, the amount of intake air at the time when the throttle valve 4 is fully opened can be increased, making it possible to obtain a high power. Fig. 8 to Fig. 12 are views for explaining a second embodiment, which shows the teaching of the independent claims, in which similar parts are designated by the same numerals as in Fig. 1 to Fig. 7. In the second embodiment, the fuel gas control valve 5 is rotatably driven directly by the step motor 14. The opening of the fuel gas control valve 5 is detected by an opening sensor 15 and a signal representing the opening of the fuel gas control valve 5 from the opening sensor 15 is inputted into the ECU 13. The operations of the second embodiment will be described by flowcharts shown in Fig. 10 and Fig. 11. The basic operations are the same as those of the first embodiment. In the first embodiment, the opening of the air bleed control valve 8 is controlled, whereas the opening of the fuel gas control valve 5 is controlled in the second embodiment. When an ignition key is turned on and the temperature of the engine cooling water is read (Steps S1 and S2), the opening of the fuel gas control valve 5 is set to a value in a start table (the table shown in Fig. 7(b) is utilized), in which the lower the temperature of the engine cooling water is, the smaller the opening of the fuel gas control valve 5 is, depending upon the engine cooling water temperature at the moment (Step S3'). When the engine is cranked and a crank angle signal is inputted, the fuel cutoff valve 6c is opened and the engine rotational speed is read. When the engine rotational speed is not lower than a start judging rotational speed and an idle switch is off (Steps S4 to S10), the engine rotational speed and the suction pressure are read. Then, based on the engine rotational speed and the suction pressure, the opening of the fuel gas control valve 5 is set to a value in a basic A/F map as a normal operation mode (the map shown in Fig. 7(a) is utilized) (Steps S11 and S12'). Then, when an A/F feedback flag is on, an A/F feedback control is started (Steps S13 and S14). When the idle switch is not off in Step S10, the engine cooling water temperature is read again (Step S15) and the opening of the fuel gas control valve 5 is set to a value in an idle table (the map shown in Fig. 7(c) is utilized) (Step S16'). Then, the engine rotational speed is read. When an A/F feedback flag is not on, the process returns to Step S15. When an A/F feedback flag is on, an A/F feedback control is started (Steps S17 to S19). Then, when the engine rotational speed is lower than the fuel cutoff rotational speed, the process returns to Step S5. When the engine rotational speed is not lower than the fuel cutoff rotational speed (such as when the engine brake is in operation), a deceleration fuel cutoff is performed until the engine rotational speed becomes lower than the fuel cutoff rotational speed (Steps S20 and S21). When the ignition key is turned off (Step S22) or when a crank angle signal is not inputted in Step S6, the fuel gas control valve 5 is fully opened (Step S23'). Then, the opening of the fuel gas control valve 5 detected by the opening sensor 15 is read (Step S24'), and the initial value of the opening sensor is corrected (Step S25'). Hereupon, the fuel cutoff valve is closed, and an ECU power source is turned off (Steps S26 and S27). Specifically, the A/F feedback control is performed as shown in Fig. 11. When the engine cooling water temperature is not lower than the A/F feedback control starting temperature and the O 2 sensor signal is a rich signal (Steps S31 to S34), the fuel gas control valve 5 is opened at a specific rate selected from a map obtained utilizing the map shown in Fig. 7 (e) based on the suction pressure and the engine rotational speed at the moment and by a specific degree selected in the same manner from a map obtained utilizing the map shown in Fig. 7 (f) at a time until the rich signal is changed to a lean signal (Step S35'). Then the fuel gas control valve 5 is closed at a specific rate selected in the same manner as above from the map obtained utilizing the map shown in Fig. 7 (g) and by a specific degree selected in the same manner from a map obtained utilizing the map shown in Fig. 7 (h) at a time until the O 2 sensor signal is changed to a lean signal (Steps S36 and S37'). Then, when a rich signal is outputted from the O 2 sensor, the process goes to Step S35'. When a rich signal is not outputted from the O 2 sensor, the process goes to Step S37' (Step S38). Specifically, the deceleration fuel cutoff control is performed as shown in Fig. 12. When the opening of the throttle is an idle opening, the engine rotational speed is read (Steps S41 to S43). When the thus read engine rotational speed is not lower than the deceleration fuel cutoff rotational speed (such as when the engine brake is in operation) (Step S44), the fuel gas control valve 5 is opened to a value in a deceleration fuel cutoff table (the table shown in Fig. 7(d) is utilized) (Step S45'). Thereby, the negative pressure exerted at the opening 6a is decreased and the amount of fuel gas sucked out therefrom is decreased. Then, the process goes back to Step S41. At this time, the supply of the fuel gas may be cut off by closing the fuel cutoff valve 6c instead of opening the fuel gas control valve 5. When the opening of the throttle is not the idle opening in Step S42, the opening of the fuel gas control valve 5 is set to a value in a basic A/F map (the map shown in Fig. 7 (a) is utilized) as a normal operation mode (Step S46'). Then, the process goes back to Step S41. When the engine rotational speed is lower than the deceleration fuel cutoff rotational speed in Step S44, the opening of the fuel gas control valve 5 is set to a value in an idle table map obtained utilizing the map shown in Fig. 7(c) (Step S47'). It is needless to say that since the values indicated in the maps shown in Fig. 7(a) to Fig. 7(h) are for setting the opening and so on of the air bleed control valve 8, the values must be changed to values for the openings and so on of the fuel gas control valve 5 when the maps are applied to the fuel gas control valve 5. According to the second embodiment, since the fuel gas control valve is opened and closed by the step motor 15, the opening of the fuel gas control valve 5 can arbitrarily be controlled to a desired degree with accuracy. Especially in an operation range in which the opening of the throttle valve is small (a low-load operation range), a suction negative pressure can arbitrarily be created by controlling the opening of the fuel gas control valve 5 and the amount of fuel to be supplied can be controlled with accuracy by the thus created suction negative pressure. As above, since the amount of fuel to be supplied can be controlled only by controlling the opening of the fuel gas control valve 5, the fuel supply system can be simplified in structure. INDUSTRIAL APPICABILITY According to the embodiments, since a fuel gas control valve, whose opening is adapted to vary depending upon the operating state of the engine, is provided in an air intake passage upstream of the connecting part of a fuel gas supply passage, a suction negative pressure, by which the flow rate of the fuel can arbitrarily be controlled, can be created at the connecting part of the fuel gas supply passage by reducing the opening of the fuel gas control valve in an operation range in which the opening of the throttle valve is small. This makes a main venturi unnecessary and thus can eliminate a throttling loss of intake air caused by the main venturi, making it possible to obtain a high power. Also, since there is no need to provide more than one mixer even in an engine having a large capacity per cylinder, an A/F feedback operation can be performed with a simple control. Additionally, since a slow fuel system is unnecessary, it is only necessary to provide a main fuel system. Thus, an A/F feedback control can be achieved over the entire operation range by controlling only the main fuel system. Moreover, since a high pressure gas injector is also unnecessary, a high pressure gas system including a regulator can be omitted, resulting in simplification of the structure and decrease in costs. According to an embodiment, since the fuel gas control valve is connected to the throttle valve by a link mechanism, it is possible to create a suction negative pressure by which the fuel flow rate can be controlled at the connecting part of the fuel gas passage by reducing the opening of the fuel gas control valve when the opening of the throttle valve is small with a simple structure. Also, since the link mechanism is so constituted that the fuel gas control valve is fully opened prior to the throttle valve being fully opened, it is possible to prevent the fuel gas control valve from being a resistance to intake air flow in an intermediate- or high-load operation range in which the opening of the throttle valve is large. According to an embodiment, since the air passage is connected partway along the fuel gas supply passage and the cross-sectional area of the air passage is adapted to be controlled, the amount of fuel gas to be supplied can be controlled with accuracy and ease. According to an embodiment, since the fuel gas control valve is opened and closed by a step motor, the opening of the gas control valve can be controlled to any degree with accuracy. Especially, as in the invention of Claim 5, the amount of fuel to be supplied can be controlled with accuracy by a suction negative pressure created depending upon the opening of the fuel gas control valve in at least a low-load operation range.";A fuel gas mixer comprising an air intake passage (2) connected to an engine, a throttle valve (4) provided in said air intake passage (2) for opening and closing said air intake passage (2), and a fuel gas supply passage (6) connected to said air intake passage (2) at a position upstream of said throttle valve (4), a fuel gas control valve (5) for opening and closing said air intake passage (2) is provided in said air intake passage (2) at a position upstream of the position at which said fuel gas supply passage (6) is connected to said air intake passage (2), and a fuel gas control valve controlling means (13,14) is provided for varying the degree of opening of said fuel gas control valve (5) according to the operating state of said engine, wherein said fuel gas control valve controlling means comprises an electronic control unit (13) and a step motor (14) for opening and closing said fuel gas control valve (5). A fuel gas mixer according to claim 1, wherein the amount of the fuel gas to be supplied is controlled by controlling the opening of said fuel gas control valve (5) in at least a low-load operation range. A fuel gas mixer according to claim 1 or 2, wherein a fuel cut-off valve (6c) is provided in said fuel gas supply passage (6) at a position between said air intake passage (2) and a fuel gas source A fuel gas mixer according to at least one of the claims 1 to 3, wherein a an opening sensor (15) is provided for detecting an opening of said fuel gas control valve (5). A method for controlling a fuel gas mixer comprising an air intake passage (2) connected to an engine, a throttle valve (4) provided in said air intake passage (2) for opening and closing said air intake passage (2), and a fuel gas supply passage (6) connected to said air intake passage (2) at a position upstream of said throttle valve (4), a fuel gas control valve (5) for opening and closing said air intake passage (2) is provided in said air intake passage (2) at a position upstream of the position at which said fuel gas supply passage (6) is connected to said air intake passage (2), a fuel gas control valve controlling means comprising an electronic control unit (13) and a step motor (14) for opening and closing said fuel gas control valve (5), said method comprises the steps of: varying the degree of opening of said fuel gas control valve (5) according to the operating state of said engine. A method for controlling a fuel gas mixer according to claim 5, further comprising: controlling the opening of said fuel gas control valve (5) in accordance with an engine cooling water temperature, when an ignition key is turned on. A method for controlling a fuel gas mixer according to claims 6, further comprising setting said fuel gas control valve (5) in a fully open position when the ignition key is turned off or a crank angle signal is not inputted. A method for controlling a fuel gas mixer according to claim 7, wherein a an opening sensor (15) is provided for detecting an opening of said fuel gas control valve (5) and reading a signal from said opening sensor (15) when the fuel gas control valve (5) is set in the fully open position and correcting said signal from said opening sensor (15) to the fully open position of the fuel gas control valve (5) A method for controlling a fuel gas mixer according to at least one of the claims 5 to 8, further comprising: controlling the opening of said fuel gas control valve (5) in accordance with an engine rotational speed and a suction pressure, when the rotational speed is not lower than a start judging rotational speed and the engine is not in idle condition. A method for controlling a fuel gas mixer according to claim 9, further comprising: controlling the opening of said fuel gas control valve (5) in accordance with an air/fuel ratio detected by an 02 sensor, wherein said fuel gas control valve (5) is opened at a specific rate based the engine rotational speed and the suction pressure, when a rich signal is detected by said O2 sensor until the signal of said O2 sensor changes from the rich signal to a lean signal, and said fuel gas control valve (5) is closed at a specific rate based the engine rotational speed and the suction pressure, when a lean signal is detected by said O2 sensor until the signal of said O2 sensor changes from the lean signal to a rich signal.;IIDA YOSHIKATSU, IIDA, YOSHIKATSU;YAMAHA MOTOR CO LTD, YAMAHA HATSUDOKI KABUSHIKI KAISHA;2005.0;1493913
EP-1494026-B1;20050831.0;EP;B1;EN;20100220.0;new;33436150.0;G01N27;;G01N27, C07K1;C07K   1/13, G01N  27/447B3A2;Difference gel electrophoresis using matched multiple dyes;A process and a kit are provided for detecting differences in two or more samples of protein. Protein extracts are prepared, for example, from each of a different group of cell samples (1, 2) to be compared. Each protein extract is labeled with a different one of a luminescent dye from a matched set of dyes. The matched dyes have generally the same ionic and pH characteristics but emit light at different wavelengths to exhibit a different color upon luminescence detection. The labeled protein extracts are mixed together and electrophoresed together. The gel (4) is observed to detect proteins unique to one sample or present in a greater ratio in one sample than in the other. Those unique or excess proteins will fluoresce the color of one of the dyes used. Proteins common to each sample migrate together and fluoresce the same.;"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a method for detecting differences in the protein composition of cells and cell extracts, and more particularly, to a method utilizing a matched pair of labeling reagents for detecting such differences. Background of the Invention Researchers studying various aspects of cell biology use a variety of tools to detect and monitor differences in cell structure, function and development. An essential part of studying cells is studying the differences and similarities in the protein composition between the different cell types, stages of development and condition. Determining differences in the protein content between normal and cancerous cells or wild type and mutant cells, for example, can be a valuable source of information and a valuable diagnostic tool. Mixtures of proteins can be separated into individual components according to differences in mass by electrophoresing in a polyacrylamide gel under denaturing conditions. One dimensional and two dimensional gel electrophoresis have become standard tools for studying proteins. One dimensional SDS (sodium dodecyl sulfate) electrophoresis through a cylindrical or slab gel reveals only the major proteins present in a sample tested. Two dimensional polyacrylamide gel electrophoresis (2D PAGE), which separates proteins by isoelectric focusing, i.e., by charge, in one dimension and by size in the second dimension, is the more sensitive method of separation and will provide resolution of most of the proteins in a sample. The proteins migrate in one- or two-dimensional gels as bands or spots, respectively. The separated proteins are visualized by a variety of methods; by staining with a protein specific dye, by protein mediated silver precipitation, autoradiographic detection of radioactively labeled protein, and by covalent attachment of fluorescent compounds. The latter method has been heretofore only able to be performed after the isoelectric focusing step of 2D PAGE. Immediately following the electrophoresis, the resulting gel patterns may be visualized by eye, photographically or by electronic image capture, for example, by using a cooled charge-coupled device (CCD). To compare samples of proteins from different cells or different stages of cell development by conventional methods, each different sample is presently run on separate lanes of a one dimensional gel or separate two dimensional gels. Comparison is by visual examination or electronic imaging, for example, by computer-aided image analysis of digitized one or two dimensional gels. Two dimensional electrophoresis is frequently used by researchers. O'Farrell, P.H., ""High resolution two-dimensional electrophoresis of proteins"", Journal of Biological Chemistry, 250:4007-4021 (1975), separated proteins according to their respective isoelectric points in the first dimension by the now well known technique of isoelectric focusing and by molecular weight in the second dimension by discontinuous SDS electrophoresis. Garrels, J.I., ""Two-dimensional Gel Electrophoresis and Computer Analysis of Proteins Synthesized By Clonal Cell Lines"", Journal of Biological Chemistry, Vol. 254, No. 16, 7961-7977 (1979), used a two dimensional gel electrophoresis system to study the pattern of protein synthesis in nerve cells and glial cells. Garrels conducted a comparative analysis of data from multiple samples to correlate the presence of particular proteins with specific functions. Computerized scanning equipment was used to scan a section of the gel fluorogram, detect the spots and integrate their densities. The information was stored and plotted according to intensity in each of several different scans. Urwin, V.E. and Jackson, P., ""A multiple High-resolution Mini Two-dimensional Polyacrylamide Gel Electrophoresis System: Imaging Two-dimensional Gels Using A Cooled Charge-Coupled Device After Staining With Silver Or Labeling With Fluorophore"", Analytical Biochemistry 195:30-37 (1991) describes a technique wherein several isoelectric focusing (IEF) gels were used to separate proteins by charge, then loaded onto a gradient slab gel such that the IEF gels were positioned end to end along the top of the slab gel. The gels were then electrophoresed. The resulting protein spots were visualized either by staining the second dimensional slab gel with silver or by fluorescent labeling following the isoelectric focusing step. Labeling must take place after the first electrophoresis, i.e., the isoelectric focusing because the presence of the fluorescein label on the protein changes the isoelectric point of the protein when subjected to electrophoresis. In addition, the label attaches to a sulfur on the protein forming an unstable bond which would tend to break during isoelectric focusing if the label is attached prior to the electrophoresis step. An article by Santaren, J. et al., ""Identification of Drosophila Wing Imaginal Disc Proteins by Two-Dimensional Gel Analysis and Microsequencing"", Experimental Cell Research 206: 220-226 (1993), describes the use of high resolution two dimensional gel electrophoresis to identify proteins in Drosophila melanogaster . The dry gel was exposed to X-ray film for five days. The developed X-ray film is analyzed by a computer to determine the differences in the samples. Two dimensional gel electrophoresis has been a powerful tool for resolving complex mixtures of proteins. The differences between the proteins, however, can be subtle. Imperfections in the gel can interfere with accurate observations. In order to minimize the imperfections, the gels provided in commercially available electrophoresis systems are prepared with exacting precision. Even with meticulous controls, no two gels are identical. The gels may differ one from the other in pH gradients or uniformity. In addition, the electrophoresis conditions from one run to the next may be different. Computer software has been developed for automated alignment of different gels. However, all of the software packages are based on linear expansion or contraction of one or both of the dimensions on two dimensional gels. The software cannot adjust for local distortions in the gels. US-A-5 242796 discloses sequencing of DNA fragments obtained by cleavage of a DNA sample. The DNA fragments or other molecules of biological interest are covalently labelled with respective ones of a family of closely-related but different fluorescent dyes for separation in an electrophoresis gel. The object of the present invention is to eliminate the problems associated with gel distortions and to provide a simple, relatively fast and reliable method of comparing and contrasting the protein content of different samples. BRIEF SUMMARY OF THE INVENTION The foregoing objects have been achieved by the method of the present invention wherein differences, if any, between multiple samples of proteins extracted for example, from different cells, are detected by labeling each sample of such proteins with a different one of a set of matched luminescent dyes. The matched dyes have generally the same ionic and pH characteristics but absorb and/or fluoresce light at different wavelengths, producing a different color fluorescence. In addition, the dyes should be similar in size. After an incubation period sufficient to permit the formation of covalent bonds between the dye and a plurality of attachment sites on the proteins in the cell extract, preferably reacting with up to about 2% of the total available attachment sites, the free reactive dye is then quenched to prevent further reaction with the proteins, the labeled samples are then mixed together and co-electrophoresed on a single gel. The proteins common to each sample comigrate to the same position. Proteins which are different will migrate alone to different locations on the gel and will fluoresce different colors, thereby identifying which initial sample has one or more proteins which differ from the other initial sample or samples. DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic diagram of the method of the present invention; FIGS. 2a and 2b are images of proteins labeled with a preferred matched pair of labels used in the present invention run on a single SDS polyacrylamide gel; FIG. 3 is an image of a portion of a two dimensional gel loaded with two different samples of bacterial extract, one IPTG-induced and the other uninduced, labeled with a different one of the dyes of the matched pair of dyes used in the method of the present invention; and, FIG. 4 is an image of a portion of a two dimensional gel loaded with two different samples of bacterial extract, one having exogenously added carbonic anhydrase and one without carbonic anhydrase, each labeled with a different one of the dyes of the matched pair of dyes used in the method of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The method of the present invention employs a matched set of dyes wherein each dye in the set is generally equal to the other dyes in ionic and pH characteristics, and chemical reactivity for covalent attachment to proteins, yet fluoresces at a different wavelength, thereby exhibiting a different color luminescence when viewed. The dyes are preferably roughly equal in molecular weight, but need not be. Each one of the dyes within the matched set of dyes is used to label proteins in a different one of a set of different samples of cell extract so that each cell extract sample is labeled with a different dye within the set of dyes. After labeling, the extracts are mixed and electrophoresed in the same gel, either by one or two dimensional electrophoresis. With reference to the schematic diagram of Figure 1, a first cell extract is prepared by known techniques from a first group of cells (1), then labeled with the first dye of a matched pair of dyes, such as propyl Cyanine (3)-NHS. A second cell extract is prepared by known techniques from a second group of cells (2) then labeled with the second dye of the matched pair of dyes, such as methyl - Cyanine (5)-NHS. The structures and methods of preparation of the cyanine (3) and (5) dyes are described below. To label the cell extract mixture, the reactive form of the dye and the protein extract are incubated in a suitable container, such as a test tube (3) for a period of time sufficient to allow for the formation of a covalent bond between the reactive form of the dye and potential attachment or binding sites on the proteins in the extract. The period of time is generally from 15 to 30 minutes, depending on the temperature. The temperature range is generally from about 0°C to 25°C. The reaction between the dye and the proteins may be quenched after a sufficient percentage of available binding sites on the protein molecule are covalently bound to the dye. Any suitable known quenching material may be used. The first and second group of cells (1,2) can be any two sets of cells the protein content of which one wishes to compare or contrast. For example, the first group of cells can be the wild-type, or normal, cells, and the second group of cells can be mutant cells from the same species. Alternatively, the first group of cells can be normal cells and the second group can be cancerous cells from the same individual. Cells from the same individual at different stages of development or different phases of the cell cycle can be used also. The cells from a developing embryo, from the ventral furrow of Drosophila melanogaster , for example, can be harvested as the first group of cells and cells that develop adjacent to the ventral furrow cells can be harvested as the second group of cells. The differences in protein composition between cells of the same type from different species can also be the subject of study by the method of the present invention. In addition, the method of the present invention can be used to monitor how cells respond to a variety of stimuli or drugs. All of the events that might alter cell behavior as expressed through protein changes can be detected without the need and expense of high precision 2D PAGE systems. Those skilled in the art will recognize that the proteins for comparison may also be derived from biological fluids, such as serum, urine, or spinal fluid. The labeled samples are mixed and, as illustrated in FIG. 1, applied in measured aliquots to one gel (4), then preferably subjected to 2D PAGE. One dimensional SDS electrophoresis can be used instead of 2D PAGE. The procedures for running one dimensional and two dimensional electrophoresis are well known to those skilled in the art. Proteins that the two cell groups have in common form coincident spots (6). The ratio of the fluorescent intensity between identical proteins from either group will be constant for the vast majority of proteins. Proteins that the two groups do not have in common (8, 9) will migrate independently. Thus, a protein that is unique or of different relative concentration to one group will have a different ratio of fluorescence intensity from the majority of protein spots, and will produce a color specific for one or the other of the protein extracts, depending on the label used. For example, the proteins that are in the first sample may be labeled red, while the second group is labeled blue. Under conditions where exactly equal amounts of protein from each group is mixed together and run on the same gel the ratio of fluorescence intensity will be one for the majority of proteins. Those proteins that are distinct to one or the other group will have a fluorescence intensity ratio less than or greater than one, depending on the order or ratioing. The gel can be analyzed by a two wavelength fluorescence scanner, by a fluorescent microscope or by any known means for detecting fluorescence. Gel analysis can be completely automated by means of computer aided identification of protein differences. Using an electronic detection system such as a laser scanning system with a photo multiplier tube or a charged-coupled device (CCD) camera and a white light source, two electronic images are made of the wet gel using different known filter sets to accommodate the different spectral characteristics of the labels. One image views fluorescence of the first dye using a first filter appropriate to filter out all light except that emitted at the wavelength of the first dye and the other image views fluorescence of the second dye using a second filter, appropriate to filter out all light except that emitted at the wavelength of the second dye. Exposure is about 5 to 500 seconds. The differences in the samples can be identified, either during electrophoresis or in less than 1/2 hour following electrophoresis. Several software packages are commercially available which will either subtract the first image from the second to identify spots that are different, or, alternatively, the images may be divided to leave only the spots not common to both images. In subtracting the images, like spots will cancel each other, leaving only those that are different. In ratio analysis, like spots will provide a value of one. Differences will result in values greater than one less than one. In conventional analysis, a control is run with known proteins for the cell type being studied. The known spots on the sample gel have to be identified and marked, compared to the control and the second gel to determine differences between the two gels. In the present invention, there is only one gel so no marking is necessary. In addition, the software used on conventional processes for alignment of different gels prior to comparing and contrasting protein differences does not correct for local distortions and inconsistencies between two or more gels. The method of the present invention eliminates the need for such correction because the extracts for all samples to be tested are mixed and run on the same gel. Any gel distortions are experienced equally by each sample. Selection and synthesis of the matched set of dyes is important. In the method of the present invention, the fluorescent dyes are covalently coupled to proteins, preferably via lysine residues of the proteins, but coupling may also be to sulfhydryl or carboxylic acid groups in the proteins. Regulation of the pH of proteins to force attachment of labels at one amino acid residue to the exclusion of other amino acids is a well known technique, as set forth in R. Baker, Organic Chemistry of Biological Components, (Prentice Hall, pub. 1971). For analysis of proteins, a plurality of attachment sites are labeled. The optimum percentage of attachment sites labeled will depend on the dyes chosen. When the preferred dyes specifically discussed hereinbelow are used, preferably no more than 2% of the attachment sites and more preferably, slightly less than 1%, are labeled, to avoid rendering the protein insoluble. Thus, where a typical protein is composed of about 7% lysines, there will be less than one modified amino acid per one thousand. A typical protein is composed of about 450 amino acids. When lysine is the attachment site, the covalent linkage destroys the positive charge of the primary amine of the lysine. Because isoelectric focusing depends on charge, it is important to compensate for the charge loss. A basic residue should remain basic. Changing the pKa of one residue per protein by as much as 3 can be tolerated, provided the basicity or acidity of the modified residue, as the case may be, is not altered. Dyes like rhodamine and fluorescein are not suitable because of the difference in charge. The first group of dyes evaluated were the fluorescent cyanine dyes described in Mujumdar, R.B. et al., ""Cyanine dye labeling reagents containing isothiocyanate groups"", Cytometry 10:11-19 (1989) and Waggoner et al., U.S. Patent No. 5,268,486 entitled ""Method for labeling and detecting materials employing arylsulfonate cyanine dyes"" issued in 1993. The cyanine dyes have the following general structure, where X and Y can be O, S or (CH 3 ) 2 -C, m is an integer from 1 to 3 and at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 or R 7 is a reactive group which reacts with amino, hydroxy or sulfhydryl nucleophiles. The dotted lines represent the carbon atoms necessary for the formation of the cyanine dye, preferably for the carbon atoms forming three fused rings having 5 to 6 atoms in each ring. R 3 , R 4 , R 6 and R 7 are attached to the rings. The reactive moiety can be any known reactive group. Reactive groups that may be attached directly or indirectly to the chromophore to form R 1 , R 2 , R 3 , R 4 , R 5 , R 6 or R 7 groups may include reactive moieties such as groups containing isothiocyanate, isocyanate, monochlorotriazine, dichlorotriazine, mono- or di-halogen substituted pyridine, mono- or di-halogen substituted diazine, maleimide, aziridine, sulfonyl halide, acid halide, hydroxysuccinimide ester, hydroxysulfosuccinimide ester, imido ester, hydrazine, azidonitrophenyl, azide, 3-(2-pyridyl dithio)- proprionamide, glyoxal and aldehyde. The cyanine dyes described in the Waggoner et al. patent were the fluorophors of choice because of their intrinsic positive charge. The cyanines attach to the protein via the activated ester of hexanoic acid. While the coupling destroys the charge of the lysine side chain, the intrinsic charge in the dye compensates. It in effect moves the charge away from the protein molecule but maintains the same overall charge within the sample to be electrophoresed. In the cyanine dye molecule, two functionalized indole rings are connected via a polyene linker. The spectral characteristics of cyanine dyes can be easily modulated by simply changing the length of the linker between the indole rings of the dye. A longer or shorter linker length will result in fluorescence at different wavelengths and thus, different colors. However, changing the length of the linker changes the molecular mass of the dye. Since electrophoresis depends also on the mass of the proteins, the effect of the dye on a protein's mass can also be of concern. Because the proteins are labeled before electrophoresing, the mass of the dye attached to the protein must not significantly alter the relative differences in the molecular weights of the various proteins in the extracts. Molecular weight is not critical, however, because only a relatively small number of sites on the protein are labeled. As indicated above, preferably less than 1%, up to about 2% of the possible attachment sites on the proteins are labeled. If more are labeled, maintaining generally equal molecular weights for the dyes within the set of matched dyes becomes a greater concern. The difference in molecular weight caused by changing the linker length in the fluorescent cyanine dyes can be compensated for by modulating the size of an aliphatic chain R 1 or R 2 , attached to one of the dye's indole rings. One of R 1 or R 2 must be a reactive group. These design constraints led to the modification of the cyanines and the development of a dye of the general formula wherein X and Y equal S, O, or CH 3 -C-CH 3 , m is an integer from 1 to 3 and either R 1 or R 2 is a reactive group capable of covalently binding to the protein in the cell extract, such as the reactive groups described above for the unmodified cyanine dyes. The dotted lines represent 1, 2 or 3 fused rings having 5 or 6 carbon atoms in each ring. Each side should balance the other side. An example of a matched pair of dyes developed according to the general formula follows: (Propyl Cyanine-NHS) which fluoresces red and, (Methyl Cyanine 5-NHS) which fluoresces far red in the spectrum wherein R is a reactive group. As stated above, O or S or a combination thereof can be placed in the X and Y positions in place of (CH 3 ) 2 C-. The cyanine dyes are one choice for the matched set of dyes used in the present invention. Other dye compounds may be used in place of the cyanines, such as dipyrromethene boron difluoride dyes, the derivatized 4,4-difluoro-4-bora-3a,4a,-diaza-S-indacene dyes, described in U.S. Patent No. 4,774,339 to Haugland et al., which are sold by Molecular Probes, Inc. under the trademark BODIPY®. The BODIPY® dyes, which have no net charge, are covalently linked to lysine side chains using an activated n-hydroxysuccinimidyl ester which forms an amide bond. The result is the loss of the lysine positive charge. Therefore, a positively charged linker group is used in the matched dyes used in the invention to replace the lost primary amine with the linker's tertiary amine. The procedures for making BODIPY® dyes are described in U.S. Patent No. 4,774,339. Addition of the positively charged linker is by techniques well known to those skilled in the art. A linker can be designed with three functional groups; (1) to react with the BODIPY®-NHS ester, (2) to carry the desired charge, and (3) to be activated so that the BODIPY®-linker construct will react with specific amino acid residues of the proteins in the extract. The major considerations for the matched set of dyes are the maintenance of charge and distinct and different spectral characteristics. Any neutral dyes with a positive linker or any positively charged dyes, preferably each having a +1 charge, that otherwise satisfy the requirements described herein can serve as the dyes in the matched set of dyes used in the present invention. Roughly equal molecular weight in the samples of labeled protein is desirable, but as explained above, not critical. The intrinsic positive charge of cyanine dyes is advantageously used in the preferred embodiment to replace the positive charge of lysine. The pK a of cyanines and lysine are rather different; however, conditions were selected for dye:protein ratio to be less than one. This low level of labeling ensures that there will be negligible changes in the protein's migration on two-dimensional electrophoresis gels. Dyes may be used which match the pK a of lysine more closely. Alternately, dyes that modify other amino acid residues may be used, provided the amino acid's ionic characteristics are preserved by the modification. Instead of a lysine, the attachment site on the protein may be a sulfhydryl or carboxylic group. When a sulfhydryl group is the attachment site on the protein, the corresponding attachment site on the dye is an iodoalkyl group. When a carboxylic acid group is the attachment site on the protein, the corresponding attachment site on the dye is a chloroketone or a carbodiimide. It is anticipated that the method of the present invention also can be used to detect the presence of different nucleic acids in different samples. The charge of nucleic acids is very negative. The addition of the dye does not therefore alter the overall charge in nucleic acids so the choice of the matched set of dyes does not have to compensate for charge loss when nucleic acid analysis is contemplated. To facilitate attachment of the dye, nucleic acids can be modified to have a free amino acid coming from the nucleic acid nucleus by techniques known to those skilled in the art. A lysine would be suitable in this instance also. EXAMPLE 1 Synthesis of the dyes (Methyl Cyanine 5 and Propyl Cyanine 3): 1. Synthesis of indole derivatives (common to both dyes) : 4.8 g (30 mmoles) of 2,3,3-trimethyl-(3H)-indole and 35 mmoles of the desired bromoalkyl reagent (6-bromohexanoic acid or 1-bromopropane) in 40 ml of 1,2-dichlorobenzene were heated to 110°C under nitrogen gas and stirred overnight with refluxing. The product (acid indole, methyl indole, or propyl indole) precipitated as an orangish gum. The supernatant was decanted and the gum was washed several times with ethyl ether. This intermediate was used as is. 2. Cyanine (3) (Cy-3) intermediate: 1.5 g (7.5 mmoles) of propyl indole was added to 1.6 g (7.6 mmoles) of N-N' diphenyl formamidine in 20 ml glacial acetic acid and was refluxed for 4 hrs. The solvent was removed under vacuum leaving a deep orange syrup. This intermediate was used as is. 2a. Cyanine (5) (Cy5) intermediate: The synthesis of the Cy-5 intermediate is the same as the synthesis of the Cy-3 intermediate in step 2 of the dye synthesis except that 2-methylene-1,3,3-trimethylindoline was used instead of propyl indole and the linker was malonaldehyde dianil. The gummy, bluish intermediate was washed twice with ethyl ether. 3. Cy-3: 2.5 ml of triethylamine and 1.8 ml of anhydrous Ac 2 O were added to the intermediate from step 2., and the mixture was boiled for 5 minutes. 1.70 g (5.0 mmoles) of acid indole was added and the mixture was refluxed for two hours. The solvent was removed under vacuum and the products were dissolved in 10 ml of EtOH. 3a. Cy-5: The preparation of Cy-5 is the same as that of Cy-3 except that the intermediate from step 2a. was used instead of the intermediate from step 2. 4. Purification of the products from steps 3. and 3a.: Methyl Cy-5 and propyl Cy-3 were separated from contaminating side products by running flash chromatography with a silica gel solid phase and 40% MeOH in dichloromethane as the mobile phase. 5. Activation of carboxyl groups: The carboxylic acid moiety of each dye was converted into an N-hydroxysuccinimidyl ester by dissolving a quantity of purified material in 5 ml of dry dimethylformamidine (DMF). 1.5 equivalents of N-N' disuccinimidyl carbonate (DSC) was added with 0.1 ml dry pyridine/100mg dye. The reaction was refluxed at 60°C for 90 minutes under nitrogen. EXAMPLE 2 Protein Labeling: 1. Bacterial culture: Initial experiments were performed on E. coli that expressed the chimeric GAL4VP16 protein under the control of the lac promoter as described in Chasman, D.I. et al., ""Activation of yeast polymerase II transcription by Herpesvirus VP16 and GAL4 derivatives in vitro"", Molecular Cell Biology 9:4746-4749 (1989). Two cultures of bacteria were grown to an OD 600 of 0.7 at 37°C. in 125 ml of standard LB medium containing 50 µg/ml ampicillin. Isophenylthiogalactopyranoside (IPTG), a non-hydrolyzable analog of lactose, was added to one culture at a final concentration of 1 mM. Both cultures were incubated for an additional 2.5 hours. 2. Protein isolation for two-dimensional gel electrophoresis: Isolation of protein was as follows. The bacteria was isolated by centrifugation. Each bacterial pellet was washed with sonication buffer containing 5 mM Hepes KOH pH 8.4, 5 mM Mg(OAc)2. The pellet was resuspended in sonication buffer containing 50 µg/ml RNase to a final volume of 100 µl. This was then sonicated in ice until the solution was clear, usually several minutes. DNase was added to 50 µg/ml and the sample was incubated for 30 min at 0°C. Solid urea and CHAPS were added to a final concentration of 8 M and 5% respectively. The sample was taken off the ice and 1 volume of lysis buffer added. The sample was either labeled immediately or stored at -80°C. 3. Protein labeling: Propyl Cy-3-NHS was added to the first sample and Methyl Cy-5-NHS was added to the second sample of cell extract at a concentration of 2 nmole of dye/50 µg of protein. The dye stock solution was typically 2 mM in dimethyl formamide. The reaction was incubated at 0°C for 30 minutes. Incubation times may vary from about 15 to about 30 minutes, depending on the temperature and the type of cells being studied. Incubation can be for 15 minutes when the temperature is about 25°C. The temperature should not be above that which will cause the proteins to be degraded. The labeled sample was immediately subjected to isoelectric focusing or stored at -80°C. 4. Protein isolation and labeling for SDS-gel electrophoresis: Bacteria were grown and isolated by sonication as in step 2. of the protein labeling procedure, except RNase or DNase was not added. The cell extract was directly labeled as in step 3 of the protein labeling procedure. SDS, glycerol, Tris HCl pH 6.8, and bromophenol blue were added to bring the final concentrations to 1%, 10%, 64 mM, and 5 µg/ml, respectively. The sample was then placed in a boiling water bath for 2 minutes and then subjected to electrophoresis. 5. Determination of dye to protein ratio: In order to prevent solubility problems with labeled proteins, conditions were chosen to only label 1-2% of the lysines in the cell extract. This is based on the assumption that 7% of an average protein's amino acids are lysine. The first step in determining the dye to protein ratio was the removal of free dye by adsorption to SM-2 beads (Bio-Rad). The protein concentration was determined by OD260/280. The dye content was determined by OD 548 and OD 650 for Propyl Cy-3 and Methyl Cy-5, respectively (∈=100,000 for both dyes). EXAMPLE 3 Gel Electrophoresis : 1. Two-dimensional electrophoresis: High resolution two-dimensional gel electrophoresis was carried out by well known techniques. 2. SDS polyacrylamide gel electrophoresis: SDS polyacrylamide gel electrophoresis was carried out by known techniques. EXAMPLE 4 Fluorescence Gel Imaging : At the end of electrophoresis, the gels were soaked in a solution of 25% methanol and 7% acetic acid. The fluorescently labeled proteins in the gel were imaged in the following manner. Gels were placed on a surface of anodized aluminum and irradiated at an incident angle of 60° with a 300 W halogen lamp housed in a slide projector. The light exiting the projector was passed through 1' diameter bandpass filters (Chroma Technologies, Brattleboro VT), 545 ± 10 nm and 635 ± 15 nm for Cy-3 and Cy-5, respectively. The images were collected on a cooled, CCD camera (Photometrics Inc., Tucson AZ) fitted with a 50 mm lens (Nikon) and a double bandpass emission filter (Chroma Technologies, Brattleboro VT), 587.5 ± 17.5 nm and 695 ± 30 nm for Cy-3 and Cy-5, respectively. The CCD camera was controlled by a Macintosh II si computer running Photometrics camera controller software. Image integration time ranged from tenths of seconds to several minutes. The excitation filters were housed in a filter wheel attached to the projector. Two successive images were recorded with irradiation from the two filters without moving the gel. EXAMPLE 5 Image processing: The image files were transferred to a Personal Iris 4D/35 (Silicon Graphics Inc., Mountain View CA). The image files were then processed using the DeltaVision™ software (Applied Precision, Mercer Island WA). The two schemes were used to determine the differences between the differently labeled samples on the gel: 1. Subtraction: Each image can be considered as a grid-like array of pixel intensities. These arrays of values can be manipulated by a number of arithmetic operations. Here one image was subtracted from the other. Because the two samples loaded onto the gel were not perfectly balanced for overall fluorescence, one image was multiplied by a balancing constant. This factor was determined arbitrarily so that the number of differences between the samples were kept small. 2. Ratio Imaging: Here one image was divided by the other. Before this operation was performed the images were first normalized to a common intensity range. This was done by setting the minimum and maximum pixel values of each image to zero and an arbitrarily large value, 4095, the maximum possible output value of the CCD camera employed. Intermediate pixel values were scaled linearly between these values. One image was then divided by the other. A balancing factor was also used here to keep the mean quotient at one. Regions of difference were those with a quotient greater than one. EXAMPLE 6 1. Difference SDS gel electrophoresis of induced GAL4VP16 expression in bacteria: Figure 2 shows images of Propyl Cy-3 and Methyl Cy-5 labeled proteins run on a single SDS polyacrylamide gel. Lanes 1-3 show Cy-3 labeled protein. The samples loaded in there lanes were: Lane 1. Propyl Cy-3 labeled IPTG-induced bacterial extract. Lane 2. Propyl Cy-3 labeled IPTG-induced bacterial extract plus Methyl Cy-5 labeled uninduced extract. Lane 3. Propyl Cy-3 labeled purified GAL4VP16 protein. Lanes 4-6 show Cy-5 labeled protein. The samples loaded in there lanes were: Lane 4. Propyl Cy-3 labeled IPTG-induced bacterial extract. Lane 5. Propyl Cy-3 labeled IPTG-induced bacterial extract plus Methyl Cy-5 labeled uninduced extract. Lane 6 Propyl Cy-3 labeled purified GAL4VP16 protein. Only Lane 5 showed Cy-5 fluorescence. Lanes 7 and 8 show the subtracted product of Lane 2 - Lane 5 and Lane 3 - Lane 6, respectively. The arrows point to the position of GAL4VP16 as confirmed by the position of the purified GAL4VP16 band in lane 8. The identity of the upper bands is not known. However, there are several proteins that are known to be induced by IPTG, including β-galactosidase. Lanes 9-11 show Cy-5 labeled protein. The samples loaded in these lanes were: Lane 9. Methyl Cy-5 labeled IPTG-induced bacterial extract. Lane 10. Methyl Cy-5 labeled IPTG-induced bacterial extract plus Propyl Cy-3 labeled uninduced extract. Lane 11. Methyl Cy-5 labeled purified GAL4VP16 protein. Lanes 12-15 show Cy-5 labeled protein. The samples loaded in there lanes were: Lane 12. Methyl Cy-5 labeled IPTG-induced bacterial extract. Lane 13. Methyl Cy-5 labeled IPTG-induced bacterial extract plus Propyl Cy-3 labeled uninduced extract. Lane 14. Methyl Cy-5 labeled purified GAL4VP16 protein. Only Lanes 12-15 all showed some Cy-3 fluorescence. This is due to slight crossover between the bandpass filters. This causes Cy-5 labeled material to appear when excited by Cy-3 light. The converse is not seen. Cy-3 material is not visualized by Cy-5 excitation light. There are two ways to eliminate the crossover effects: design better bandpass filters or computationally remove the Cy-5 contribution to the Cy-3 image by knowing the crossover constant. Lanes 15 and 16 show the subtracted product of Lane 2 - Lane 5 and Lane 3 - Lane 6, respectively. The arrows point to the position of GAL4VP16 as confirmed by the position of the purified GAL4VP16 band in Lane 8. The identity of the upper bands is not known. However, there are several proteins that are known to be induced by IPTG, including β-galactosidase. 2. Difference two-dimensional gel electrophoresis of induced GAL4VP16 expression in bacteria: Figure 3 shows images of a portion of a two-dimension gel loaded with Propyl Cy-3 labeled IPTG-induced bacterial extract plus Methyl Cy-5 labeled uninduced extract. Panel A. Images taken with Cy-3 excitation light showing the IPTG-induced proteins. Panel B. Images taken with Cy-5 excitation light showing the uninduced proteins. Panel C. Ratio of the Cy-3 image divided by the Cy-5 image. Panel D. Overlay of the image in Panel C, colored red, and placed on top of the image from Panel B, colored blue. 3. Difference two-dimensional gel electrophoresis of bacteria extract with exogenously added protein: Figure 4 shows images of a portion of a two-dimension gel loaded with Propyl Cy-3 labeled bacterial extract that had exogenously added carbonic anhydrase plus Methyl Cy-5 labeled extract without the added carbonic anhydrase. Panel A. Image taken with Cy-3 excitation light showing the bacterial proteins plus carbonic anhydrase. Panel B. Images taken with Cy-5 excitation light showing the bacterial proteins alone. Panel C. Ratio of the Cy-3 image divided by the Cy-5 image. Panel D. Overlay of the image in Panel C, colored red, and placed on top of the image from Panel B, colored blue. The method of the present invention provides a simple and inexpensive way to analyze the differences in protein content of different cells. The method eliminates problems which can occur using two separate gels which must be separately electrophoresed. The matched dyes used to label the different cell extracts allow simultaneous electrophoresis of two or more different samples of cell extract in a single gel. While the invention has been described with reference to two samples of cell extract and a matched pair of dyes, those skilled in the art will appreciate that more than two samples may be simultaneously tested using an equal number of matched dyes. As long as the spectral characteristics of the dyes can be manipulated to provide fluorescence at a number of different wavelengths resulting in visually distinct images and the pH and ionic characteristics of the dyes can be generally equalized to compensate for changes made to the protein by virtue of covalent bonding to the dye, multiple dyes can be used.";"A method of detecting differences in the protein components of at least two different samples, the components having covalent attachment sites thereon, the method comprising: a) preparing an extract of proteins from each of said at least two samples; b) adding a different luminescent dye chosen from a set of matched luminescent dyes to each separate sample of protein extract under conditions to covalently bind the dye to the protein extract, each luminescent dye within said set of dyes being capable of covalently binding to protein and wherein each dye within said matched set: i) has a net charge which will maintain the overall net charge of the protein upon such covalent binding and has ionic and pH characteristics whereby relative electrophoretic migration of a protein labeled with any one of said dyes is the same as relative electrophoretic migration of said protein labeled with another dye in said matched set, ii) emits luminescent light at a wavelength that is sufficiently different from the emitted luminescent light of the remaining dyes in said matched set to provide a detectably different light signal; c) mixing the extracts together to form a mixture; d) electrophoresing the mixture on a single gel to separate the components of the extracts by differences in charge and mass; and (e) detecting the difference in luminescent intensity between the different dye-labeled proteins of interest by: capturing images of the dye-labeled proteins at different wavelengths of emitted luminescence; and processing the images to determine the difference in luminescent intensity between the different dye-labeled proteins of interest. The method according to claim 1, wherein said samples are cell samples. The method according to claim 1 or claim 2, wherein said capturing and processing steps are performed on at least a first and a second image. The method according to claim 1 or claim 2, wherein detecting the difference in luminescent intensity between the different dye-labeled proteins of interest comprises: capturing first and second images of the dye-labeled proteins; and performing arithmetic operations on values representative of pixel intensities in the first and second images. The method according to claim 1 or claim 2, wherein detecting the difference in luminescent intensity between the different dye-labeled proteins of interest comprises: a) capturing a first image of the dye labeled proteins using a first filter or filters that only allows the passage of light having the wavelength of the luminescent light emitted by a first dye used to covalently bind to protein components of interest; b) capturing a second image of the dye labeled proteins using a second filter or filters that only allows the passage of light having the wavelength of the luminescent light emitted by a second dye used to covalently bind to protein components of interest; and c) processing the first and second images to determine the difference in luminescent intensity. The method of claim 5, wherein processing the first and second images includes subtracting the first image from the second image. The method of claim 6, wherein processing the first and second images further includes multiplying one of the first and second image by a fluorescence balancing factor prior to subtracting the first image from the second image. The method of claim 5, wherein processing the first and second images includes dividing the first image by the second image. The method of claim 8, wherein processing the first and second images further includes normalizing the first and second images to a common intensity range prior to dividing the first image by the second image. The method of claim 9, wherein processing the first and second images further includes multiplying one of the first and second images by a fluorescence balancing factor. The method according to any of the previous claims, wherein processing the images comprises processing the images with a computer.";MINDEN JONATHAN, WAGGONER ALAN, MINDEN, JONATHAN, WAGGONER, ALAN;UNIV CARNEGIE MELLON, CARNEGIE MELLON UNIVERSITY;2005.0;1494026
EP-1494511-B1;20051026.0;EP;B1;EN;20100220.0;new;33436028.0;H05G1;H05G1;H05G1;H05G   1/08, H05G   1/10;X-ray source;A compact X-ray source for improving insulation from unwanted high voltage effects, comprising an extension of a Faraday cage, whereby the secondary winding of a transformer used to supply power to components within the cage is shielded within a coaxial, tubular member connected to the cage and extending outwardly from it.;"This invention relates generally to the production of X-rays, and in particular, but not exclusively it relates to a compact X-ray source. A typical X-ray source comprises a thermionic source (typically a heated filament), a high-voltage supply to accelerate the electrons to a high energy, and a target made of a high atomic number metal. Figure 1 depicts a simple schematic diagram of a very basic and conventional X-ray source, although it will be realised that, in practice, much more complex arrangements are generally used, including the use of additional electrodes and magnetic fields to control and focus the electron beam. Electrons are emitted thermionically from a hot cathode filament 30 under the action of an isolated heater supply 10 and are attracted to a metal target 70 via an intervening anode 60. The electrons are accelerated in a beam 50 towards the target due to a high potential difference between the filament and the anode/target arrangement established by means of a high voltage supply 20. On striking the target 70 the electrons stimulate X-ray emission by various processes, resulting in the emission of an X-ray beam 80. Since it is desirable for the anode and target to be at, or substantially near, ground potential, the cathode filament must be at a very high negative potential with respect to ground. Moreover, the cathode filament requires several watts of power to reach operable temperatures. Figure 2 shows a typical X-ray source arrangement where a cathode filament 30 is heated by a voltage supplied from an isolating transformer 11. Typically the voltage is between 2V and 6V, whilst the electrons are accelerated by a high voltage supplied from a multiplier 90, known as a Cockcroft-Walton voltage multiplier. The high voltage may be in the range of hundreds of kilovolts, for example 160kV. It is often required to construct an X-ray source that is compact, and this requirement introduces or exacerbates various problems, for example those associated with providing accurate and effective control over the electron beam current, particularly where the source is desired to be capable of operating reliably with a low radiation output, and those associated with achieving sufficient insulation between various components. Control over the current of the electron beam 50 is usually desirable with X-ray sources in general and, in low performance X-ray sources, this is frequently achieved merely by varying the temperature of the filament; relying upon the principle that a hotter filament emits more current than does a cooler one. In higher performance systems, exemplified in very basic form in Figure 3, this is achieved by controlling the beam in the space charge limited regime by means of a field control electrode 40, often referred to as a focusing cup or Wehnelt. Such a focusing cup 40 is required to be at a negative potential with respect to the cathode filament in much the same way as the grid in a thermionic triode valve. The required potential can be supplied by either an electrically isolated bias supply, or self-biasing using a feedback resistor 120 between cathode filament 30 and focus cup 40. Current passing through the feedback resistor generates the required negative bias. However, such a negative feedback system has the drawback that it is difficult to adjust. When conventional X-ray sources are required to operate at low electron beam current levels, a problem occurs in that electron current leakage from the cathode and focus cup becomes significant compared to the total electron beam current. Often this problem arises from cold cathode discharge (field emission), 'surface tracking' or other such problematic phenomena. Conventional X-ray sources measure the electron beam current with a current sensing circuit located at the end of the high voltage supply that is at ground potential (shown schematically as 25 in Figure 4). A problem then arises in that any current measurement at this point in the system cannot differentiate between the actual thermionic electron beam current and the leakage current. This inability to separate the level of current leakage from the overall current measurement leads to variations in X-ray output since accurate control over the true electron beam current is not possible. Particularly where low radiation output levels are called for, variations in the measured electron beam current due to spurious factors such as those mentioned above can have a significant and adverse effect upon the radiation output levels and stability of operation. Another problem with conventional X-ray sources arises from the high voltages required to accelerate the electron beam. When employing such extreme potential differences, there is always a risk of an electrical discharge or breakdown. When such phenomena occur, rapidly changing electromagnetic fields arise. Such fields induce large currents to instantaneously flow within the electronic circuitry of the X-ray source, and these currents can damage or destroy circuit components leading to X-ray source failure. A common solution to this problem described e.g. in EP 0 497 517 is to enclose all susceptible components and circuitry within a Faraday shield to protect them from any rapidly changing fields. In known X-ray sources, the integrity of the Faraday shield is compromised by the need to leave a conduit through which power and signals can be introduced into the circuitry. The break in the shield to provide a signal path also provides a pathway for signal interference during a high voltage breakdown. The integrity of the shield is particularly compromised by the use of isolating transformers that are generally used to introduce power and signals into the Faraday shield. The present invention arose in an attempt to address some or all of the above problems. In accordance with the present invention, there is provided an X-ray source comprising a Faraday shield, in which electrical circuitry is housed, a high voltage power supply and an isolating transformer, wherein the isolating transformer is coaxially shielded; the shielding forming a continuation of the Faraday shield. The isolating transformer is preferably in electrical connection with both an electron accelerating means and a cathode filament transformer, or other cathode filament supply means. According to one aspect not being part of the claimed invention there is provided an X-ray source comprising: a high voltage power source; a cathode filament coupled to said high voltage power source; an active variable conductance device connected between the cathode filament and the high voltage power source; means for determining the amount of current flowing into said cathode filament through said variable conductance device and for providing a signal indicative thereof; and control means for utilising said signal to control said amount of current, thereby to control the current of an electron beam emitted from said cathode. This current control arrangement differs significantly, in concept and effect, from conventional circuit schemes, which typically employ a separate DC supply for the grid voltage, floating at cathode potential. The voltage levels of such supplies require accurate control and stabilisation. It has been proposed in United States Patent No. 5,528,657 to use such a series-regulating element to control the operative high voltage (anode/cathode) level, but this document does not teach series regulated control of the grid voltage level. The present X-ray source also differs substantially, in concept and effect, from circuit arrangements for pulsed grid X-ray tubes, such as those disclosed in Japanese patent application No. 59132599. This document teaches the use of a transistor as a switch in the grid circuit to effect fast beam-switching with minimal overshoot and distortion of the current pulse. Preferably, the active variable conductance device is a transistor, for example either a field effect transistor (FET) or a bipolar transistor. The active variable conductance device may alternatively comprise one or more light dependent resistors. The control means advantageously comprises fibre optics and electro-optical devices, or any other optical link. By using an active variable conductance device instead of a passive resistor as in the prior art, control over the electron beam current is greatly facilitated. Preferably, an optical link is used to control the variable conductance device, thereby reducing the risk of electromagnetic interference. Preferably, a current detector for detecting the current flow between the high voltage supply and the cathode filament is provided, either between the output of the high voltage power supply and the active variable conductance device or between the active variable conductance device and the cathode filament. By measuring the current at this point, rather than at the ground end of the high voltage power source, discrimination between the true thermionic emission from the filament and all other forms of leakage current becomes possible. Hence the true thermionic emission current can be measured and controlled. Embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying schematic drawings, in which: Figure 1 shows a conventional X-ray source circuit arrangement; Figure 2 shows conventional cathode filament heating in an X-ray source incorporating a high voltage multiplier circuit and isolating heater transformer; Figure 3 shows an X-ray source utilising negative feedback biasing; Figure 4 shows an embodiment of an X-ray source in accordance with one example not being part of the claimed invention; Figure 5 shows a further embodiment of an X-ray source in accordance with another example not being part of the claimed invention; Figure 6 shows an embodiment of an X-ray source in accordance with one example of the present invention; Figure 7 shows a further embodiment of an X-ray source in accordance with another example of the present invention; and Figure 8 shows a preferred embodiment of an X-ray source incorporating according to the invention. In all of Figures 1 to 7, identical reference numbers are used throughout to indicate similar components and features. In Figure 8, however, features and components directly comparable with those in Figures 1 to 7 are given reference numbers increased by 200 over those used in the earlier figures. In the conventional X-ray source shown in Figure 1, a cathode filament 30 is connected to an isolated power supply 10. Encircling the cathode filament 30, and connected to a high voltage supply 20, is a focusing cup 40. In operation, an electron beam 50 is accelerated through an annular anode 60 and focused onto a metal target 70 from which X-rays 80 radiate. The power supply 10 typically comprises an isolating step-down transformer (shown in Figure 2 as 11), supplying around 6V to heat the cathode filament 30. Figure 2 shows a conventional X-ray source including a high voltage multiplier circuit 90 connected to the focusing cup 40. Here, an isolating transformer 11 is shown connected to the cathode filament 30. The multiplier 90 is otherwise known as a Cockcroft-Walton voltage multiplier 90. Most modem X-ray sources use this type of multiplier, the functioning of which is well known to persons skilled in the art. Included in the conventional X-ray source shown in Figure 3 is a variable feedback resistor 120, which is connected between the cathode filament 30 and the focusing cup 40. This configuration provides negative biasing to the focusing cup 40, thus ensuring that it remains at a negative potential as compared to the potential of the cathode filament 30. Biasing is essential if the focusing cup is to provide space-charge control of the electron beam current and is often alternatively provided by an isolated negative bias supply. A problem arising from the X-ray source of Figure 3 stems from the difficulties associated with safely and precisely varying the value of the feedback resistor in order to maintain optimal control of the beam current. An embodiment of an X-ray source not part of the invention is shown in Figure 4. Here, instead of a feedback resistor, an active variable conductance device 130 is employed. This device may be a field effect transistor (FET) for example. Alternatively, a light dependent resistor (LDR) controlled by an optical link to vary the conductance can be used. Indeed, the reader will be aware that there are many other devices that may be suitable for the particular requirements of an application. In the X-ray source of Figure 4, the variable conductance device 130 is a bipolar transistor, controlled (by one of a variety of known methods) by a control circuit 140 in response to control signals 150. In the case where optical control is used, control signals 150 will be passed by one of a choice of known optical links such as a conventional fibre optic cable and transduced by suitable electro-optical devices such as light-emitting diodes (LEDs) and photodiodes. In this way it is possible to provide precise dynamic and inertialess control of the electron beam current. In another X-ray source, as shown in Figure 5, a current sensing circuit 160 is employed to provide a measurable indication of the electron beam current. This circuit can include an LED, the luminance of which is directly proportional to the amplified electron beam current. The circuit generates control signals 170 that are used in feedback control of the variable conductance device 130, through control signals 150 and associated control circuit 140. (This feedback loop is shown schematically by the broken line 155). In practice, other components may be included in the feedback loop, and these components may include ground circuitry 156, so that signal 170 returns to ground and signal 150 is transmitted from ground. The current sensing circuit 160 is shown between the high voltage supply and the active conductance device. This current sensing circuit could instead be at a position indicated byl 60A, between the active conductance device 130 and the filament 30. The advantage of the above X-ray source is that, in measuring the current flow at a point in the circuit shown in Figure 5 by circuit 160 (or alternatively 160A), it is possible to differentiate accurately between the thermionic current flow and the leakage current which, as described earlier, can be influenced by many extraneous factors. Measured current values can then be used in a feedback control loop via optic link 150 to facilitate optimal adjustment of the biasing level. The current sensitive circuit 160 may take many different forms, and may be optical or electronic or otherwise. Many such means will be apparent to the skilled reader. As discussed above, it is conventional to enclose all sensitive circuitry and components in a Faraday shield. However, it is not normally possible to completely electrically screen the components from potentially damaging electromagnetic fields, since a break in the Faraday shield is necessary to allow access to the circuit for power lines, control inputs etc. Referring to Figures 6 and 7, a transformer primary winding 180 is coupled to a transformer secondary winding 190 via a transformer core 200. The transformer secondary winding 190 feeds power into circuitry within a Faraday shield 210. In an embodiment of the second aspect of the invention, a toroidal metal sheath 193 surrounds the transformer secondary winding 190, and extends as a tube 194 from the secondary circuit 190 towards the main Faraday shield 210. For practical shielding purposes, the toroidal sheath 193 and tube 194 form an integral part of the Faraday shield 210. Tube 194 serves as a conduit, screening wires 195 connecting (or continuing) winding 190 to circuitry within the Faraday shield. The toroidal sheath has a discontinuity, or electrical break, 196, preventing it from acting as a shorted turn. The discontinuity is, however, such that total shielding is still obtained. Figure 7 shows a variant of Figure 6, in which the outer coaxial conductor forms part of the secondary winding; it connects to the secondary winding at point 197. Thus, the outer conductor forms part of the winding and its extension towards the Faraday shield. It is to be noted that, in Figures 6 and 7, only one turn is shown for the primary and secondary windings, for clarity. In practice, more than one turn may be present for either or both of these. Referring now to Figure 8, there is shown a preferred embodiment of the invention in which many features are incorporated into an integrated high voltage generator and x-ray source. The electron beam is produced by thermionic emission from a cathode 230, which is made from tungsten wire or other material typically formed into the shape of a hairpin. In order for it to emit electrons, the cathode must be heated to incandescence. The required cathode temperature is produced by resistive self-heating. Electrons are extracted from the cathode 230 by means of an electric field applied, in known manner, between the cathode 230 and an anode (not shown in Figure 8). As explained previously, the arrangement is such that the anode is at ground potential and the cathode is raised to a high negative potential. The magnitude of the beam current is controlled by a ""bias"" voltage imposed onto an annular grid electrode or Wehnelt 240 that surrounds the cathode. The bias voltage is always negative with respect to the cathode. The bias voltage also serves to produce a focussing electric field for the emitted electron beam, thereby controlling its diameter and ultimately the size of the x-ray source. The cathode 230 and the annular grid electrode 240 are, as is conventional, maintained in vacuum; the vacuum wall being shown in part as 235 in Figure 8. The grid bias voltage is obtained by a technique, known as self-bias, which is commonly used on triode devices including, in particular, electron microscopes. The electron beam current passes through a resistor connected between the grid and the cathode and develops, across the resistor, a voltage which constitutes the grid bias voltage. The system is thus self-stabilising and a separate power supply for the grid voltage is not required. The magnitude of the electron beam current depends on the size of the resistor and on physical characteristics of the gun which are geometry dependent. In accordance with this embodiment, the resistor is replaced by a device whose resistance can be altered electronically. A preferred device is a Field Effect Transistor (FET) 330, but the principle of operation could also be implemented using other devices, such as light dependent resistors. The beam current flows in series through a resistor 325, the FET 330 and a resistor 335. A Zener diode 336 protects the FET 330 from excessive voltage. As discussed above, this arrangement differs significantly, in both concept and effect, from conventional circuit schemes, which typically employ a separate DC supply for the grid voltage floating at cathode potential, and which may utilise a series-regulating element for voltage control and stabilisation. In conventional x-ray generators, the beam current sensing is typically achieved by measuring the current flowing at the bottom of the diode capacitor bank forming the high voltage multiplier (often called a Cockroft-Walton multiplier). In the present system, such a high voltage multiplier 290 is employed. A conventional sense resistor 300 is also shown. However, as described above, there is a serious disadvantage to using the voltage on sense resistor 300 as the means of measuring and controlling the electron beam current; namely that the current flowing at this point may include extraneous components in addition to the true electron beam current. These extraneous currents often include currents emitted from the vacuum facing surface of the housing surrounding the filament. The locations producing such emission are known as cold cathode or field emission sites, and are well known to those skilled in the art of the design of high voltage vacuum devices. Field emission sites are unstable and can be neither predicted nor eliminated. If the control signal for beam current stabilisation is derived from a sense resistor 300 then the control of the true electron beam, that is emitted thermionically from the cathode 230, will be corrupted by the unquantifiable inclusion of extraneous currents from field emission sites. This makes stable control at low operating beam currents and high cathode voltages very difficult and degrades x-ray image quality under such conditions. The present invention permits the true current flowing from the cathode to be measured This allows very precise control of the beam current even under usually difficult conditions, such as when operating at extreme high voltage with low beam currents, and even with field emission sites present. The true electron beam current is sensed as a voltage across resistor 325 and is fed into an integrated circuit 361 configured as a voltage to frequency converter. The frequency output of integrated circuit 361 drives an LED 362, which sends a frequency modulated light signal 371 down an optical fibre 355a. At the other end of the fibre 355a, the optical signal is incident upon a photodiode 363. This converts the optical signal back into an electrical signal which accurately represents the measured electron beam current and is applied, via a buffer amplifier 364, to circuitry (not shown) which interfaces in a known manner with a computer. Computer commands input by a user of the system are used to effect adjustment of the electron beam current. However, if a computer is not used, appropriate circuitry is presented at a location convenient for direct or remote manual adjustment by an operator, thus allowing the beam current to be controlled, which may be either in real time, or to predetermined values. It is necessary to provide a feedback signal for precise closed-loop control of the beam current against the predetermined demand level selected by the operator. Advantageously, since the resistance of the FET 330 may be varied by adjusting its gate voltage, this is accomplished by means of another photodiode 365 using optical signals 351 generated by a second LED 366; these optical signals 351 being amplitude modulated in a sense effective to indicate any desired change of the beam current. The signals are delivered into a second optical fibre 355b, the output of which illuminates the photodiode 365. Optical fibres are used to provide electrical isolation between electronic circuits at the high and low voltage ends of the high voltage multiplier 290. The current sensed on resistor 300 is not used for control or measurement, but may be used by circuits designed to protect the high voltage generator in the event of a fault causing excessively high current in the multiplier 290. Occasional electrical discharges can be expected to occur within the x-ray source. Such discharges lead to rapidly changing transient currents, and it is necessary to protect active electronic components from the potentially damaging effects of radiated and conducted electromagnetic interference generated by these transients. The electronic circuits associated with the cathode and grid are contained in a metal walled chamber 410. The whole of this container is connected to the grid and is therefore at a very high voltage with respect to ground. This container provides very substantial screening for the sensitive circuits within it, and acts as a ""Faraday shield"". Although it does not need to be hermetically sealed, the container is constructed in such a way that its openings are of minimal size. The integrity of such a Faraday shield may be compromised by the need to bring electrical signals in and out. In this embodiment, the power for all of the circuits within the shield is provided by a high voltage isolation transformer. The secondary winding 390 of the transformer is insulated so as to provide the required high voltage isolation, and is constructed as a co-axial system. The outer conducting member 393 of this co-axial arrangement forms a continuous extension of the main Faraday shield 410. Furthermore, only the outer conductor of the co-axial arrangement winds around the transformer core 400. The inner conductor 390 emerges from a hole in the side of the outer conductor and is then joined to the end of outer conductor 393. The length of inner conductor 390 and the size of the hole in the outer conductor 393 are kept very small. The co-axial self screening construction of the secondary winding ensures that conducted and radiated signals into the Faraday shield are so small that the reliability of the sensitive components housed within can be guaranteed. The core 400 of the isolating transformer lies outside the boundary of the Faraday shield 410; only the outer co-axial member 393 of the secondary winding 390 is integrated into the continuum of the Faraday shield wall. The Faraday shield may advantageously contain certain additional electronic circuits which might, for example, be used to monitor, control or stabilise the cathode filament voltage, current or power. Such circuitry, floating at high voltage, may also utilise fibre optics as the means of conveying signals to other electronic circuits operating near to ground potential.";"An X-ray source comprising a Faraday shield (210, 410), in which electrical circuitry is housed, a high voltage power supply and an isolating transformer, wherein an isolating transformer winding (190, 390) is coaxially shielded, the shielding (193, 194, 393) forming a continuation of the Faraday shield. An X-ray source as claimed in Claim 1, wherein said isolating transformer winding comprises a secondary winding (190, 390) to which a primary winding of said transformer is coupled via a transformer core (200, 400); the transformer secondary winding being arranged to feed power into circuitry within said Faraday shield. An X-ray source as claimed in Claim 2, wherein the shield is electrically connected to a winding. An X-ray source as claimed in Claim 2 or Claim 3, wherein said coaxial shield comprises a toroidal metal sheath (193) surrounding the transformer secondary winding (190) and extending as a tube (194) from the secondary winding towards the Faraday shield (210); the toroidal sheath being formed with a discontinuity (196) preventing it from acting as a shorted turn. An X-ray source as claimed in any of Claims 1 to 4, wherein the outer coaxial conductor (193, 393) is connected to the secondary winding at a point and thereby forms part of the secondary winding.";CRAWLEY ALAN COPELAND, HADLAND ROGER, HAIG IAN GEORGE, KEANLY PAUL JUSTIN, CRAWLEY, ALAN COPELAND, HADLAND, ROGER, HAIG, IAN GEORGE, KEANLY, PAUL JUSTIN, Keanly, Paul Justin X-Tek Systems Ltd.;X TEK SYSTEMS LTD, X-TEK SYSTEMS LIMITED;2005.0;1494511
EP-1495870-B1;20051228.0;EP;B1;EN;20100220.0;new;33458880.0;B41J2;;B41J2;B41J   2/165B1;Use of tube material excellent in gas barrier characteristic between cap and vacuum pump;A second tube (T3) constituting a tube pump is connected to a first tube (T1) connected to a suction hole (10e) in an above capping member (10) via a connecting member (21). The first tube (T1) connected to the suction hole (10e) formed in a capping member (10) is made of material excellent in the gas-barrier characteristic and preferably, butyl rubber is used. The second tube (T3) constituting the tube pump is made of elastic and restorable material to fulfill the function of a tube pump and preferably, silicon rubber is used. Hereby, the vaporization of an ink solvent from the tube (T1) which is inferior in the gas-barrier characteristic can be effectively inhibited and the moist state of an ink solvent in the capping member can be maintained for a long term.;"BACKGROUND OF THE INVENTION The present invention relates to a capping unit for an ink jet recording head incorporated in an ink jet recording apparatus, and a method of manufacturing the same. In particular, the ink jet recording apparatus comprises: an ink jet recording head installed on a carriage moved in the widthwise direction of recording paper, for jetting ink droplets from nozzle orifices by pressurizing ink from an ink tank supplied into associated pressure generating chamber by a pressure generating member such as piezoelectric vibrators, heating elements or the like; and a capping unit provided with a capping member for sealing a surface of the recording head on which the nozzle orifices are formed (hereinafter, the nozzle-formed surface), and receiving negative pressure generated by a negative pressure generating member, wherein vaporization of an ink solvent from the capping member is inhibited during the halt of recording operation in order to prevent from clogging of the nozzle orifices. As for an ink jet recording apparatus, noise in printing is relatively small and in addition, small dots can be formed in high density, such an ink jet recording apparatus is currently used for many types of printing including color printing. The ink jet recording apparatus described above provided with an ink jet recording head to which ink from an ink cartridge is supplied, and a paper feeding mechanism for relatively moving recording paper under the recording head. The recording is performed by jetting ink droplets onto the recording paper, moving the recording head on a carriage in the widthwise direction of the recording paper. Recording heads for jetting black ink and each color ink of yellow, cyan and magenta are mounted on the carriage, and full color printing is enabled by changing the ratio of the jetting of each ink in addition to text printing by black ink. The above ink jet recording head has a problem that printing failure is caused by the increase of ink viscosity caused by the vaporization of a solvent from nozzle orifices, the solidification of ink, the adhesion of dust, further the mixture of bubbles or the like, because the printing is performed by jetting ink pressurized in the pressure generating chambers onto recording paper from nozzle orifices as an ink droplet. Therefore, the above ink jet recording apparatus is provided with: a capping member normally composed of a plastic cap holder (cap case) and a cap made of elastic material such as rubber for sealing the nozzle orifices of the recording head while the printing is halted; and a cleaning member for cleaning a nozzle plate if necessary. The above capping member not only functions as a cap for preventing ink at nozzle orifices from drying while printing is halted but is provided with functions for sealing the nozzle plate by the cap in case the nozzle orifices are clogged, sucking ink from the nozzle orifices by negative pressure generated by a suction pump as a negative pressure generating member, and solving the clogging caused by the solidification of ink at the nozzle orifices and a failure in the jetting of ink caused by bubbles mixed in an ink passage. Fig. 23 schematically shows a state in which the nozzle-formed surface of the recording head is sealed by the capping member. As shown in Fig. 23, the capping member 10 is provided with a rectangular cap case 10a the upper face of which is opened and a cap 10b housed in the cap case 10a and made of flexible material such as rubber material, and the cap 10b is formed so that the upper edge thereof is slightly protruded from the top face of the cap case 10a. An ink absorber 10c made of porous material is housed at the inner bottom of the cap 10b and is held by a holder 10d integrally formed with the cap 10b. A suction hole 10e and an air hole 10f are formed at the bottom of the cap case 10a and penetrate the cap case 10a and the cap 10b. A suction pump 11 as a negative pressure generating member is connected to the suction hole 10e of the cap case 10a via a tube T1 and discharge side of the suction pump 11 is connected to a waste ink tank 13. Further, an air valve 14 is connected to the air hole 10f of the cap case 10a via a tube T2. In the meantime, a reference number 7 in Fig. 23 denotes a recording head. As the capping member 10 is moved upwards when the recording head 7 is moved toward above the capping member 10, the nozzle-formed surface, that is, a nozzle plate 7a is sealed (capped) by the above cap 10b. Plural nozzle orifices 7b are formed on the nozzle plate 7a, and black ink and each color ink such as yellow, cyan and magenta are jetted by the action of a piezoelectric vibrator 7c arranged corresponding to each nozzle orifices 7b. Owing to the above structure, ink is sucked from the recording head in a state in which the cap 10b is adhesively contacted to the nozzle plate 7a of the recording head 7 and the air valve 14 is closed as shown in Fig. 23. That is, negative pressure is applied to the internal space of the cap 10b by operating the suction pump 11 in this state and ink is discharged from the nozzle orifices 7b. When the above air valve 14 is opened while the suction pump is halted in a predetermined time and the negative pressure inside the cap decreases to some extent because ink is discharged, the air is introduced inside the cap and inside negative pressure is released. When the suction pump 11 is operated again in a state in which the air valve 14 is opened, operation for sending ink discharged inside the cap to a waste ink tank 13 via the tube T1 is executed. In the meantime, while the printing is halted, the nozzle-formed surface of the recording head, that is, the nozzle plate 7a is sealed by the cap 10b as shown in Fig. 23, the above air valve 14 is closed and the internal space of the cap 10b is kept moist by an ink solvent. Hereby, the nozzle orifices of the recording head is prevented from being clogged by drying, and the reliability of printing operation when printing is restarted can be secured. However, there is a problem that the ink solvent is vaporized in a passage communicating from the internal space of the cap to the suction hole or the air hole and further, in a path which leads to the suction pump connected to the suction hole and the air hole and the air valve. Fig. 24 shows an example which is a sectional view showing a passage making the internal space of a cap and a suction hole communicate in an example of a cap case in capping member currently used. The same reference number is allocated to a part shown in Fig. 24 equivalent to the part already described and shown in Fig. 23 and therefore, the description is omitted. As shown in Fig. 24, the passage 10g for making the internal space of the cap and the suction hole 10e communicate is formed so that the inner diameter is relatively large and the length is relatively short. A reference number 10n denotes a fitting member for fitting the cap. As described above, in a state in which the passage 10g is formed so that the inner diameter is large and the length is short, there is a problem that flow resistance on the side of a suction pump is small and therefore, the vaporization to the outside of an ink solvent is caused in a tube connected to the suction pump. Particularly, for the suction pump, a low-cost tube pump which is securely operated is used and for a tube composing the tube pump, elastic and restorable silicon rubber is used. However, silicon rubber has a problem that it is relatively inferior in gas-barrier characteristic, and thereby an ink solvent would be vaporized from the tube to the outside. Therefore, as an ink solvent is gradually vaporized from the internal space of the cap via the above passage and a moist state in the cap is deteriorated in case a recording apparatus is halted for a long term, clogging in the nozzle orifices of the recording head is caused. After the recording apparatus is halted for a long term, so-called timer cleaning that ink is automatically sucked from the nozzle orifices of the recording head when the recording apparatus is powered on is executed, however, when the solid material of ink is deposited in the minute nozzle orifices of the recording head, it is not easy to remove the solid material by the suction of ink and a problem that the reliability of printing operation is deteriorated is caused. The tube pump used for this type of recording apparatus is driven by utilizing the power of a paper feeding motor or the like which is not used while the printing is halted in order to suck ink from the nozzle orifices. The above tube pump is composed of an arcuate face for supporting a tube therealong and a roller which rolls while pressing the tube onto the supporting face. Therefore, for the material of the tube composing the tube pump, elastic and restorable silicon rubber is generally used. The sucking side of the tube made of silicon rubber is connected to the suction hole of the above capping member. If the above silicon rubber is used for the tube pump, the elastic and restorable characteristic can be utilized, however, silicon rubber has a problem that it is relatively inferior in the gas-barrier characteristic as described in the above, a rate in which an ink solvent is vaporized from the tube to the outside is considerably large. Further, recently, as a cap is also lengthened according to the large sizing of a recording head, there is a problem that deflection and deformation are easily caused when the cap is touched to the recording head, a gap is made between the recording head and the cap and airtightness is deteriorated. Such a problem can be solved by forming pleats at the top end of the cap in order to balance rigidity and elasticity, and suitably installing the cap in a cap holder. However, there is a problem that initial performance cannot be fulfilled by the aging change of the rigidity and elasticity of the cap, the reliability is deteriorated and others in addition to a problem that the process becomes complicated. To solve such problems, as disclosed in Japanese Patent Publication Nos. 61-213145A and 8-99331A for example, it is proposed that a member to function as a base is formed by first polymeric material by injection molding and an attachment is fixed by using the metallic mold as it is or reinstalling the base in a second metallic mold and injection-molding second polymeric material on the base. However, it is very difficult to acquire sufficient precision to form a packing member the volume of which is at most substantially 20cc and the thickness of which is a few mm as a cap for sealing nozzle orifices. SUMMARY OF THE INVENTION The present invention is made to solve the problems of the above related ink jet recording apparatus and the object is to provide an ink jet recording apparatus wherein a moist state in the internal space of a capping member can be maintained for a long term and the reliability of printing by a recording head can be enhanced. Another object of the present invention is to provide a capping unit by which the recording head can be securely sealed for a long term and a method of manufacturing the same simply. In order to achieve the above objects, there is provided an ink jet recording apparatus comprising: an ink jet recording head having a surface provided with nozzle orifices from which ink droplets are ejected; and a capping member for sealing the surface provided with the nozzle orifices to apply negative pressure generated by a negative pressure generating member. The capping member includes: a cap made of flexible material, which is to be abutted against the surface provided with the nozzle orifices; a cap case for holding the cap; a suction hole to which the negative pressure generating member is connected; and a first passage formed in either the cap or the cap case for communicating the internal space with the suction hole. In the apparatus, the capping member may further include: an air hole to which a valve introducing external air into an internal space defined by the cap; and a second passage formed in either the cap and the cap case for communicating the internal space with the air hole. Here, at least the first passage between the first and second passages is formed into a shape capable of inhibiting vaporization of an ink solvent in the internal space. In the apparatus, the cap may be bonded on an inner face of the cap case. In the apparatus, the cap may be integrally formed on an upper portion of the cap case. In the apparatus, a cylindrical body may be formed integrally with the cap case so as to protruded from a bottom face of the case. At least the first passage between the first and second passages may be formed in the cylindrical body. In the apparatus, a metal tube member may be inserted into at least the suction hole between the suction hole and the air hole. In the apparatus, at least the first passage between the first and second passages may be formed by a groove formed along an outer peripheral face of the cap case and a seal member for sealing the groove. The sealing member may be made of at least one material selected from the group consisting of an aluminum deposited film, a silicon oxide deposited film, polyethylene terephthalate, undrawn polypropylene, ethylene-vinylalcohol, ethylene-vinyl acetate copolymer, polyvinylidene chloride, and cyclic olefin copolymer. In the apparatus, at least the first passage between the first and second passages may be formed by a groove formed on the inner face of the cap case. In the apparatus, at least the first passage between the first and second passages may be formed by a groove formed on a bottom face of the cap. According to the ink jet recording apparatus configured as described above, the vaporization of the ink solvent from the internal space is inhibited. Hereby, a moist state of an ink solvent in the internal space of the capping member can be maintained for a long term. Therefore, the degree of the occurrence of the clogging of nozzle orifices in the recording head while the recording apparatus is halted for a long term can be reduced, a frequency in which so-called timer cleaning is executed can be reduced and if timer cleaning is executed, the reliability of printing in the recording head can be sufficiently recovered. The apparatus further comprises: a first tube made of a material having high gas-barrier characteristic and connected to the suction hole; and a second tube member made of an elastic and restorative material for connecting the negative pressure generating member with the first tube. In the apparatus, the negative pressure generating member is a tube pump including a supporting face for supporting the second tube in the shape of an arc and a roller rotating while pressing the second tube onto the supporting face. In the apparatus, a tube made of butyl rubber is used as the first tube, and a tube made of silicon rubber is used as the second tube. According to the ink jet recording apparatus configured as described above, the vaporization of an ink solvent from the tube while the recording apparatus is halted can be effectively inhibited. Therefore, the degree of the occurrence of the clogging of nozzle orifices in the recording head while the recording apparatus is halted for a long term can be reduced and the reliability of printing in the recording head can be sufficiently recovered by executing so-called timer cleaning. If the recording apparatus is halted for relatively a short term, the reliability of printing can be secured without executing the above timer cleaning. In the apparatus, the cup casing may be formed into a shape of cup having a brim portion on which an annular groove into which the cap is fitted is formed. In the apparatus, the cap case may be made of polymeric material, and the cap may be made by the injection molding of the flexible material. In the apparatus, the width of a bottom face of the cap may be equal or wider than the width of the brim portion of the cap casing. In the apparatus, the cap may be bonded onto the brim portion of the cap case. In the apparatus, the cap case may be made of either polypropylene or polyethylene, and the cap may be made of either styrene thermoplastic elastomer or styrene thermoplastic elastomer composite materials. In the apparatus, the groove may be provided with a portion communicating with the outside. In the apparatus, the injection molding is conducted by the steps of: sealing the groove on the brim portion by a mold defining a shape of the cap; and injecting the material which is to be the cap into the mold. In the apparatus, a first port from which the material which is to be the cap is injected and a second port from which air in the mold is discharged is formed in either the groove on the brim portion or the mold. According to the ink jet recording apparatus configured as described above, the cap case having high rigidity can be prevented from being deformed, and the whole periphery of the cap held by the cap case can be uniformly deformed owing to elasticity controlled depending upon the height thereof. Therefore, the airtightness of the cap for the recording head can be secured. BRIEF DESCRIPTION OF THE DRAWINGS In the accompanying drawings: Fig. 1 is a perspective view showing a main body of an ink jet recording apparatus to which the present invention is applied; Fig. 2 is a plan showing an example of a cap case of a capping member mounted in the recording apparatus shown in Fig. 1; Fig. 3 is a sectional view showing a capping member according to a first embodiment of the present invention; Fig. 4 is a sectional view showing a capping member according to a second embodiment of the present invention; Fig. 5 is a sectional view showing the capping member viewed from a direction perpendicular to Fig. 4; Fig. 6 is a sectional view showing a capping member according to a third embodiment of the present invention; Fig. 7 is a sectional view showing the capping member viewed from a direction perpendicular to Fig. 6; Fig. 8 is a sectional view showing a capping member according to a fourth embodiment of the present invention; Fig. 9 is a sectional view showing a capping member according to a fifth embodiment of the present invention; Fig. 10 is a sectional view showing a capping member according to a sixth embodiment of the present invention; Fig. 11 is a sectional view showing a capping member according to a seventh embodiment of the present invention; Fig. 12 is a sectional view showing a capping member according to an eighth embodiment of the present invention; Fig. 13 is a sectional view showing the capping member viewed from a direction perpendicular to Fig. 12; Fig. 14 is a sectional view showing a capping member according to a ninth embodiment of the present invention; Fig. 15 is a sectional view showing the capping member viewed from a direction perpendicular to Fig. 14; Fig. 16 is a perspective view showing a state in which a suction pump mounted in the recording apparatus of Fig. 1 and a tube are connected; Fig. 17 is a sectional view showing an example of a state in which a tube on the side of the capping member and a tube on the side of the suction pump are connected; Figs. 18A and 18B show an example of the internal constitution of the suction pump; Fig. 19 shows an embodiment of a capping unit; Figs. 20A to 20E are sectional views showing examples of a cap in the capping unit; Figs. 21A to 21C are views for explaining a manufacturing process of the cap; Fig. 22 shows a state after ink is sucked of a cap in a comparative example; Fig. 23 is a sectional view showing a related capping member and a peripheral configuration thereof; and Fig. 24 is a sectional view showing an example of a cap case in the related capping member. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An ink jet recording apparatus according to the present invention will be described below with reference to the accompanying drawings. Fig. 1 is a perspective view showing the whole configuration of a main body of an ink jet recording apparatus to which the present invention is applied. As shown in Fig. 1, a reference number 1 denotes a carriage and the carriage is constituted so that it is reciprocated in the axial direction of a platen 5, being guided by a guide member 4 via a timing belt 3 driven by a carriage motor 2. An ink jet recording head 7 is mounted on the side opposite to recording paper 6 of the carriage 1, and an ink cartridge 8 for black and an ink cartridge for color 9 respectively for supplying ink to the above recording head 7 are detachably mounted on the carriage. A reference number 10 denotes a capping member arranged in a non-printing area (in a home position) and the capping member is constituted so that the nozzle-formed surface of the recording head 7 can be sealed when the recording head 7 is moved on the capping member. A suction pump 11 as a negative pressure generating member for applying negative pressure to the inside space of the capping member 10 is arranged under the capping member 10. As has been already described with reference to Fig. 23, the above capping member 10 is composed of a cap 10b made of flexible material abutting against the nozzle-formed surface 7a of the recording head 7 and a cap case 10a for holding the outside surface of the cap 10b. The capping member 10 serves as a cover for preventing the nozzle orifices 7b of the recording head 7 from drying while the recording apparatus is halted, and as an ink receiver during a flushing operation in which a drive signal unrelated to printing is transmitted to the recording heads for the ejection of ink droplets, and is also provided with a cleaning function for applying negative pressure generated by the suction pump 11 to the recording head 7 so as to suck ink therefrom. As shown in Fig. 1, a wiping member 12 composed of an elastic plate such as rubber is arranged in the vicinity of the capping member 10 and wiping operation in which the nozzle-formed surface of the recording head 7 is wiped when the carriage 1 is reciprocated on the side of the capping member 10 is executed. Fig. 2 is a plan showing an example of the cap case in the above capping member 10, Fig. 3 is a section view taken along the line A-A in Fig. 2, which shows a first embodiment of the present invention. Fig. 3 is shown so that it can be compared with the above related structure shown in Fig. 24. Parts in Figs. 2 and 3 equivalent to the above parts in Figs. 23 and 24 are denoted by the same reference numbers and therefore, the description is omitted. In the structure shown in Fig. 3, only the cap case as described above is shown and the cap 10b formed by flexible material is fitted to fitting members 10n and housed inside the cap case 10a. A passage 10g for connecting the internal space of the cap and a suction hole 10e is formed in a cylindrical body integrated with the bottom of the cap case 10a. The inner diameter of the passage 10g formed in the above cylindrical body is formed so that it is thinner as it can be understood when the above inner diameter is compared with the inner diameter of the passage shown in Fig. 24, the above passage 10g is formed so that it is longer and the passage is constituted so that a tube T1 to the suction pump 11 is connected to the suction hole 10e formed at the lower end thereof. Owing to such structure, flow resistance on the side of the suction pump becomes larger and the vaporization of an ink solvent from a tube T1 which is inferior in the gas-barrier characteristic can be effectively inhibited. As a result, the nozzle orifices of the recording head while the recording apparatus is halted is prevented from drying and the reliability of printing operation when the operation of the recording apparatus is restarted can be secured. Next, Figs. 4 and 5 show a second embodiment of the present invention and the same reference number is allocated to a part equivalent to the part already described. Fig. 4 is a sectional view corresponding to a part equivalent to the cutting plane line A-A shown in Fig. 2 and shows that a tube member 10i made of stainless steel or the like is inserted into a passage 10g for making the internal space of a cap and s suction hole 10e communicate. A tube T1 which leads to a suction pump 11 is connected to the lower end of the tube member 10i. Fig. 5 is a sectional view corresponding to a part equivalent to the cutting plane line B-B shown in Fig. 2 and a tube member 10j made of stainless steel or the like is inserted into a passage 10h for making the internal space of the cap and an air hole 10f communicate. In this embodiment, the tube member 10j is inserted into a distal end portion of the L-shaped passage 10h so as to extend in substantially parallel with the bottom face of a cap case 10a. A tube T2 which leads to an air introduction valve 14 is connected to the tube member 10j. Owing to such structure, the vaporization of an ink solvent can be effectively inhibited because of the above tube members 10i and 10j respectively made of stainless steel, flow resistance on the side of the suction pump 11 and flow resistance on the side of the air valve 14 can be regulated by selecting the inside diameter and the length of the tube members 10i and 10j as in the example shown in Fig. 3 and the vaporization of an ink solvent from the tube which is inferior in the gas-barrier characteristic can be effectively inhibited. If no tube member made of stainless steel is inserted, the inside diameter of the passages 10g and 10h is limited because of a problem in forming the cap case, however, hereby, the problem is solved and a passage having a smaller diameter can be formed. Next, Figs. 6 and 7 show a third embodiment of the present invention and the same reference number is allocated to a part equivalent to the part already described. Fig. 6 is a sectional view corresponding to a part equivalent to the cutting plane line B-B shown in Fig. 2 and Fig. 7 is a sectional view corresponding to a part equivalent to the cutting plane line C-C shown in Fig. 2. In the example shown in Figs. 6 and 7, a passage for making the internal space of a cap and an air hole communicate is composed of a groove formed along the outer peripheral portion of a cap case and a sealing member covering the groove. That is, at the bottom a part of which is enlarged in a circle shown in Fig. 7 of the cap case 10a, the groove 10k the section of which is in the shape of an arc is formed in the longitudinal direction of the cap case 10a. The end of the groove 10k communicates with the internal space of the cap and the sealing member 10m formed in a strip to cover the groove 10k is stuck with the sealing member integrated with the cap case 10a. It is desirable that the above sealing member 10m is made of material excellent in the gas-barrier characteristic and it is suitable that material composed of a monolayer selected out of an aluminum (Al) deposited film, a silicon oxide (SiO x ) deposited film, polyethylene terephthalate (PET), undrawn polypropylene (CPP), ethylene-vinylalcohol (EVOH), ethylene-vinyl acetate copolymer (EVA), polyvinylidene chloride (PVDC), and cyclic olefin copolymer (COC) or a member acquired by laminating material composed of a monolayer is stuck by thermal welding. At the end of the groove 10k, an air hole 10f for connecting a tube T2 which leads to an air introduction valve 14 is protruded from the cap case 10a. The above air hole 10f may be previously made of the same synthetic resin material as the cap case 10a as another member which is to be welded onto the cap case 10a by an ultrasonic wave. A passage 10h for making the internal space of the cap and the air hole 10f communicate is composed of the above groove 10k and the sealing member 10m covering the groove 10k, and therefore, the passage which is smaller in a diameter and longer can be formed by regulating the cross section and the length of the groove 10k. Hereby, flow resistance on the side of the air introduction valve 14 can be regulated and the vaporization of an ink solvent from the tube and the air introduction valve 14 can be effectively inhibited. Next, Fig. 8 shows a fourth embodiment of the present invention and the same reference number is allocated to a part equivalent to the part already described. This embodiment is characterized in that a cap 10b is integrally formed with a cap case 10a by molding. A passage 10g for making internal space formed by the cap case 10a and the cap 10b and a suction hole 10e communicate is formed inside a cylindrical body integrated with the bottom of the cap case 10a. The inner diameter of the passage 10g formed inside the above cylindrical body is formed so that it is thinner than that shown in Fig. 24, the passage 10g is formed so that it is longer and a tube T1 which leads to a suction pump 11 is connected to the suction hole 10e formed at the lower end. Fig. 9 shows a fifth embodiment of the present invention and the same reference number is allocated to a part equivalent to the part already described. This embodiment is characterized in that a cap 10b is integrally formed with a cap case 10a by molding as well as the fourth embodiment. A passage for making internal space formed by the cap case 10a and the cap 10b and an air hole 10f communicate is composed of a groove 10k formed along the bottom face of the cap case 10a and a sealing member 10m covering the groove. The passage 10h is formed by the sealing member 10m formed in a strip for covering the groove 10k and the above sealing member 10m is made of material excellent in the gas-barrier characteristic described in relation to Fig. 6. Fig. 10 shows a sixth embodiment of the present invention and the same reference number is allocated to a part equivalent to the part already described. This embodiment is characterized in that a cap 10b is integrally formed with a cap case 10a by molding. The other structure is substantially similar to the second embodiment shown in Fig. 4. Next, Fig. 11 shows a seventh embodiment of the present invention and the same reference number is allocated to a part equivalent to the part already described. This embodiment is characterized in that a cap 10b is integrally formed with a cap case 10a by molding. The other structure is substantially similar to the second embodiment shown in Fig. 4. Further, Figs. 12 and 13 show an eighth embodiment of the present invention and show a sectional state in directions mutually perpendicular. The same reference number is allocated to a part equivalent to the part already described. In this embodiment, a groove 10k is formed on a top face of a cap case 10a, and the opened face of the groove 10k is sealed by a bottom face of a cap 10b to form a passage 10h for making the internal space of the cap 10b and an air hole 10f communicate. Figs. 14 and 15 show a ninth embodiment of the present invention and show a sectional state in directions mutually perpendicular. The same reference number is allocated to a part equivalent to the part already described. In this embodiment, a groove 10k is formed on a bottom face of a cap 10b, and the opened face of the groove 10k is sealed by a top face of a cap case 10a to form a passage 10h for making the internal space of the cap 10b and an air hole 10f communicate. Each passage described in the above embodiments can be applied to both of the passage which leads to the suction hole to which the suction pump is connected and the passage which leads to the air hole to which an air introduction valve is connected. As has been described heretofore, according to the present invention, since the passage for communicating the internal space of the capping member with the suction hole to which the negative pressure generating member is connected, or the passage for communicating the above internal space with the air hole to which the air introduction valve communicate is connected is formed in the cap case or between the cap case and the cap, the vaporization of an ink solvent in the cap case can be effectively inhibited owing to the passage. Hereby, the vaporization of an ink solvent from the tube which is inferior in the gas-barrier characteristic can be effectively inhibited and the moist state of an ink solvent in the capping member can be maintained for a long term. Therefore, the reliability of printing operation when printing is restarted after the long-term halt of a recording apparatus can be enhanced. Fig. 16 is a perspective view showing the suction pump 11, which constitutes a tube pump as described later. A tube (a second tube) T3 constituting the tube pump is connected to the first tube T1 connected to the suction hole 10e in the above capping member 10 via a connecting member 21 described later. In this case, the first tube T1 connected to the suction hole 10e formed in the capping member 10 is made of material excellent in the gas-barrier characteristic and preferably, butyl rubber is used. The second tube T3 constituting the tube pump is made of elastic and restorable material to fulfill the function of a tube pump and preferably, silicon rubber is used. The connecting member 21 is provided with a flange 21a, tube connections 21b and 21c respectively formed both sides thereof and a through hole 21d piercing therethrough. The above first tube T1 and the second tube T3 are respectively connected to the tube connections 21b and 21c in order to be communicated with each other. Figs. 18A and 18B show an example of the internal structure of the above suction pump 11. In the above suction pump 11, there is formed an supporting face 11a for supporting the tube T3 by substantially 180° in the shape of an arc. A wheel 11 c is provided with a driving shaft 11 b in the center thereof and a pair of curved grooves 11 d extended from the inner to outer diameter of the wheel 11c. A spindle 11 of a roller 11e is fitted into each groove 11d so that the spindle can be moved along the above groove 11d to rotate the roller. A press member 11 g made of an elastic material such as rubber is disposed on the rotation orbital of the roller 11e. Fig. 18A shows a state in which the driving shaft 11b of the wheel 11c is rotated in one direction, that is, in a direction shown by an arrow A and in this case, the roller 11e is moved by the press member 11g along the groove 11d toward the periphery of the wheel 11c. Therefore, the roller 11e is rolled while pressing the tube T3 onto the supporting face 11 a as the wheel 11c is rotated in the direction shown by the arrow A. As the above rollers 11e are arranged at an interval of 180° in the wheel 11c, the respective rollers 11e sequentially stroke the tube T3 and hereby, negative pressure is generated inside the tube. The above negative pressure is applied to the capping member through the first tube T1 via the connecting member 21 as described above. Fig. 18B shows a state in which the driving shaft 11b of the wheel 11c is rotated in the other direction, that is, in a direction shown by an arrow B and in this case, the roller 11e is moved by the press member 11g along the groove 11d toward the shaft 11b. Thus, a state in which the tube T3 is pressed by the roller 11e is released. As has been described heretofore, for the passage communicating the capping member with the negative pressure generating member, since the first tube made of the material excellent in the gas-barrier characteristic is used on the side of the capping member and the second tube made of the elastic and restorable material is used on the side of the negative pressure generating member, the vaporization of an ink solvent in the capping member can be effectively inhibited. Hereby, the moist state of an ink solvent in the capping member can be maintained for a long term and the reliability of printing operation when printing is restarted after the long-term halt of the recording apparatus can be enhanced. Fig. 19 shows an embodiment of a capping unit according to the present invention, a guide part composed of an upward tilted part 41 extended from the side of the leading end of a home position to the side of the trailing end (from the left to the right in Fig. 19) and a horizontal part 42 is provided on both sides of a cap frame 40 and the projection of a slider 43 is attached to the guide part so that the slider can be slid. On the side of the trailing end of the slider 43, a contact piece 44 which is to be abutted against the carriage 1 is formed, is held by a lever 45 rotationally urged by a spring (not shown) toward the leading end of the home position. Capping member 21 and 22 to which the present invention is applied is disposed on a top face of the slider 43 for sealing the nozzle orifices of the recording head 7. Fig. 20A shows an embodiment of the capping members 21 and 22, a main body 23 is formed by the injection molding of polymeric material such as polypropylene or polyethylene, or composites of the above polymeric material and polystyrene, so that the body is in the shape of a cup provided with the bottom. On an opened face 23a, an annular groove 24 is formed as shown in Fig. 21A. A packing part 25 made of a material having durability for ink such as styrene thermoplastic elastomer and styrene thermoplastic elastomer composite and easy to fit to a nozzle plate is integrally fitted into the groove 24. Particularly, for styrene thermoplastic elastomer as packing material, for example, a trade name ""Toughtec S2953"" manufactured by Asahi Chemical Industry Co., Ltd., a trade name ""Septon Compound CJ-103"" manufactured by Kuraray Co., Ltd., a trade name ""Actimer AJ-1020N"" manufactured by Riken Vinyl Co., Ltd. and a trade name ""Rubberon T320C"" manufactured by Mitsubishi Chemical Industries, Ltd. and for styrene thermoplastic elastomer composite materials, for example, a trade name ""MNCS SR"" manufactured by Bridgestone Tire Co., Ltd. are respectively high in the resistance to ink and in addition, are satisfactory in adhesiveness to the nozzle plate of the recording head and are extremely desirable material to prevent nozzle orifices from being clogged and to securely apply negative pressure when ink is sucked to the recording head. As shown in Figs. 20B to 20E, the packing part 25 may be formed so that the section thereof is in a shape suitable for sealing the recording head such as substantially rectangular, semicircular, triangular and trapezoidal. To take a shape shown in Fig. 20E as an example, it is desirable that the width w1 of the bottom of the packing part 25 is equal to or wider than the width w2 of the opened face (brim) 23a of the cup-shaped main body 23. Ink absorbing sheets 26 and 27 made of porous material are filled inside the main body 23 and an open part 28 communicating with a pump unit 11 is formed. A manufacturing method for the capping members 21 and 22 will be described. First, there is prepared the main body 23 on the opened face 23a of which an annular groove 24, an air inlet 36 and an air outlet 37 respectively communicating with the outside via the groove 24 are formed as shown in Fig. 21A. The opened face is sealed by a mold 31 provided with concave portions 30 each of which is equivalent to the sectional shape of the packing part 25 as shown in Fig. 21B. Then packing material 32 such as styrene thermoplastic low-hardness elastomer is injected from the inlet 26, the packing material 32 flows into the groove 24 and the concave portions 30, exhausting air in the groove 24 and the concave portions 30 from the outlet 27 as shown in Fig. 21C. When the mold 31 is removed after the packing material 32 is hardened and fixed on the main body 23, the capping members 21 and 22 the packing part 25 of each of which is integrated with the opened face 23a of the main body 23 are completed. In the above embodiment, the packing material 32 is injected from the main body 23, however, if an inlet and an air outlet are formed in a place except an area to be a sealed part of the mold 31, for example on the side and the packing material is injected, the similar action is also produced. In this embodiment, when the carriage 1 is moved in a capping position, the capping members 21 and 22 are moved on the side of the recording head and the packing part 25 is brought into contact onto the nozzle plate of the recording head. When a slider is moved to a predetermined position, the packing part 25 is elastically deformed to seal the nozzle plate. Originally, as the packing part 25 is held on the rigid main body 23, the useless deformation is inhibited and airtightness is secured by uniformly elastically deforming the whole periphery owing to elasticity controlled depending upon the height H of the packing part 25, sealing performance is maintained for a long term. If ink cartridges are replaced, the carriage 1 is moved in the capping position, the recording head 7 is sealed by the packing part 25 and negative pressure is supplied from the suction pump 11. Hereby, ink flows out of the recording head 7 and bubbles left in an ink passage in the recording head 7 and others are also exhausted from the capping member 21 (22) together with ink. At this time, a part of ink wets the packing part 25, however, as the width w1 of the bottom of the packing part 25 is formed so that it is wider than the width w2 of the opened face (brim) 23a of the cup-shaped main body 23, no thin gap G exists on the side of the face opposite to nozzles shown in Fig. 22 between a packing part 25' and the main body 23', therefore, no ink pool K is made at least in the vicinity of the nozzle plate and ink can be prevented from adhering to the nozzle plate again. As has been described heretofore, according to the present invention, since the annular groove is formed on the opened face of the cup-shaped body provided with the opening for covering the nozzle orifices of the recording head, and the packing part elastically deformable when it is brought into contact with the recording head is formed on the groove, not only the process can be simplified, compared with two-body structure but uniform airtightness between the whole periphery and the recording head can be secured for a long term by elasticity controlled depending upon the height of the packing part, holding the packing part on the rigid body to prevent useless deformation.";"An ink jet recording apparatus comprising: an ink jet recording head (7) having a surface provided with nozzle orifices from which ink droplets are ejected; and a capping member (10) for sealing the surface provided with the nozzle orifices to apply negative pressure generated by a negative pressure generating member (11); a first tube (T1) made of a material having high gas-barrier characteristic and connected to the capping member (10); and a second tube member (T3) made of an elastic and restorative material for connecting the negative pressure generating member (11) with the first tube (T1). The ink jet recording apparatus as set forth in claim 1, wherein the negative pressure generating member is a suction pump (11) including a supporting face (11a) for supporting the second tube (T3) in the shape of an arc and a roller (11e) rotating while pressing the second tube (T3) onto the supporting face (11a). The ink jet recording apparatus as set forth in claim 1, wherein a tube made of butyl rubber is used as the first tube (T1), and a tube made of silicon rubber is used as the second tube (T3).";FUKASAWA SHIGENORI, HARA KAZUHIKO, HAYAKAWA HITOSHI, KOMATSU KATSUHIRO, USUI MINORU, FUKASAWA, SHIGENORI, HARA, KAZUHIKO, HAYAKAWA, HITOSHI, KOMATSU, KATSUHIRO, USUI, MINORU;SEIKO EPSON CORP, SEIKO EPSON CORPORATION;2005.0;1495870
EP-1498327-B1;20051012.0;EP;B1;EN;20100220.0;new;33477686.0;B60R22;;B60R22;L60R22:46D7, L60R22:46D9, B60R  22/46D2, B60R  22/46D4;Pretensioner;A pretensioner for a vehicle safety restraint arrangement, the pretensioner comprising a piston mounted in a guide chamber for translational movement tangentially to a spool shaft, so that in travelling through the guide chamber, the piston engages the periphery of the spool shaft and causes it to rotate, and wherein the region of the chamber into which the piston moves after engaging the shaft has a wall which is weakened so as to be deformable to absorb force from the movement of the piston towards the end of a piston stroke.;"The present invention relates to a pretensioner for a vehicle occupant safety restraint and particularly to a buckle pretensioner. Pretensioners are used to rapidly pull in any slack in a safety restraint seat belt at the onset of a crash condition so as to more securely restrain the occupant against forward movement and potential injury by collision with internal features of the vehicle. In addition, the pretensioning operation aims to pull the occupant into, or at least towards, the correct seating position so as to maximise the effect of a second restraint such as an airbag. A pretensioner according to the preamble of claim 1 is known from EP 0 629 531 A. A modern seat belt is known as a 3-point restraint because it is secured to the vehicle at three points arranged about the occupant so as to provide a diagonal torso section and a horizontal lap portion to hold the occupant in the seat. The belt is attached to the vehicle by a spring loaded retractor tending to pull in the belt, and by a buckle for quick release of the belt. Pretensioners can be sited at the retractor or at the buckle end of the restraining seat belt. The present invention aims to provide an improved, and more compact pretensioner, than hitherto known. According to a the present invention there is provided a pretensioner for a vehicle safety restraint arrangement, the pretensioner comprising a piston mounted in a guide chamber for translational movement tangentially to a spool shaft, so that in travelling through the guide chamber, the piston engages the periphery of the spool shaft and causes it to rotate, and wherein the region of the chamber into which the piston moves after engaging the shaft has a wall which is weakened so as to be deformable to absorb force from the movement of the piston towards the end of a piston stroke. The pretensioner may be used directly with a vehicle safety restraint retractor in which case the spool is the spool of the retractor itself and provides for a compact and efficient retractor pretensioner. However, it can also be used with a safety restraint buckle if the spool is wound with a cable which is arranged to transfer force to the safety belt or the buckle mounting. The guide chamber for the piston may comprise a cylinder (which may have a rounded or rectangular cross section, depending upon the corresponding cross-section of the piston), optionally in combination with a load bearing cradle supporting the spool shaft. Either the wall of the cylinder or the wall of the cradle may be used for absorbing the kinetic energy of the piston. For example, the cylinder may be closed and its side walls at one end weakened so as to be deformable. Alternatively the cylinder may be mounted in a load bearing cradle which also supports the spool shaft. The walls of the end of the cradle are weakened, for example by means of cut-outs, and the kinetic energy of the piston absorbed in this way by the cradle as the cut-outs allow the wall effectively to stretch. For a better understanding of the present invention and to show the same may be carried into effect, reference will now be made by way of example to the accompanying drawings in which: Figure 1 is a perspective view of a pretensioner according to one embodiment of the invention, in an inactivated state; Figure 2 shows the pretensioner of figure 1 in an activated state; Figure 3 is a cross sectional view of the pretensioner of figure 1. A single piston 111 is arranged on one side of a rotatably mounted spool shaft 108. The piston 111 is mounted to be slidably movable along the inside of a cylinder 109 and so as to contact the spool shaft in the mid part of its stroke. It is driven by a gas generator (now shown) and teeth 117 on the piston 111 engage teeth 118 on the spool shaft 108 and cause the spool shaft to turn. The cylinder 109 is supported in a load bearing cradle 130, which may for example be made of steel, and which also supports the spool shaft 108 for rotation. The lower parts of the side walls of the cradle 130 are weakened with cutout portions 132. At its lower end the cylinder 111 is open and the moving piston therefore exits the cylinder after it has moved past and turned the spool shaft. It then impacts the end wall 131 of the cradle 130, as shown in Figure 5, and the force of impact stretches the sides of the cradle in the regions of cut-outs 132. Alternatively the end of the cylinder may be closed with a weak end wall which fractures relatively easily but which also absorbs some of the force of the piston 111. The cut-outs 132 may take a variety of shapes. Those illustrated are generally triangular and diamond shaped, so as to leave a diagonal lattice structure of metal in that region of the cradle. The force of the piston 111 pulls the diagonals into more vertical lines as the piston slows. Other shapes will be evident to a person skilled in the art: for example horizontal line cut-outs would also effect the requisite weakening of the walls of the cradle. It is however desirable to avoid the wall shearing or fracturing altogether since this would allow the piston to escape from the safety arrangement releasing a projectile into the vehicle occupant seating area!";A pretensioner for a vehicle safety restraint arrangement, the pretensioner comprising a piston mounted in a guide chamber for translational movement tangentially to a spool shaft, so that in travelling through the guide chamber, the piston engages the periphery of the spool shaft and causes it to rotate, and characterised in that the region of the chamber into which the piston moves after engaging the shaft has a wall which is weakened so as to be deformable to absorb force from the movement of the piston towards the end of a piston stroke. A pretensioner according to claim 1 wherein the spool is the spool of the retractor. A pretensioner according to claim 1 when used with a safety restraint buckle comprising a cable wound on the spool and arranged to transfer force to safety belt webbing or to the buckle mounting. A pretensioner according to any one of the preceding claims comprising a cradle supporting the spool shaft pinion, and being connected in load bearing manner to the frame of the retractor. A pretensioner according to claim 4 wherein the cradle is formed of steel. A pretensioner according to claim 4 or 5 wherein the cradle comprises means for absorbing forces. A pretensioner according to claim 6 comprising a weakened section in at least one wall of the cradle to absorb some of the energy of the moving piston. A pretensioner according to claim 7 wherein the weakened section comprises cut-outs. A pretensioner according to any one of the preceding claims wherein the cylinder is closed and at least one side wall at one end is weakened as to be deformable. A pretensioner according to any one of the preceding claims wherein the cylinder and piston have substantially circular cross-sections. A pretensioner according to any one of the preceding claims wherein the cylinder and piston have rectangular cross-sections.;AROLD JURGEN, JAIN TONY, JAMES FOSTER HOWARD, AROLD, JURGEN, JAIN, TONY, JAMES FOSTER, HOWARD;KEY SAFETY SYSTEMS INC, KEY SAFETY SYSTEMS, INC.;2005.0;1498327
EP-1500396-B1;20050928.0;EP;B1;EN;20100220.0;new;32831120.0;A61K31;A61P25;A61P25, A61P21, A61P13, A61K31, A61P29;A61K  31/5375;Reboxetine for treating migraine headaches;The use of racemic reboxetine, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment or prophylaxis of migraine headaches, is disclosed.;"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to the use of racemic reboxetine or a pharmaceutically acceptable salt thereof, in the preparation of a non-transdermal medicament for the treatment or prophylaxin of migraine headaches. Brief Description of Related Technology Many types of depression, mental, behavioral, and neurological disorders originate from disturbances in brain circuits that convey signals using certain monoamine neurotransmitters. Monoamine neurotransmitters include, for example, norepinephrine (noradrenaline), serotonin (5-HT), and dopamine. Lower-than-normal levels of norepinephrine are associated with a variety of symptoms including lack of energy, motivation, and interest in life. Thus, a normal level of norepinephrine is essential to maintaining drive and capacity for reward. These neurotransmitters travel from the terminal of a neuron across a small gap ( i.e ., the synaptic cleft) and bind to receptor molecules on the surface of a second neuron. This binding elicits intracellular changes that initiate or activate a response or change in the postsynaptic neuron. Inactivation occurs primarily by transport ( i . e ., reuptake) of the neurotransmitter back into the presynaptic neuron. Abnormality in noradrenergic transmission results in various types of depression, mental, behavioral, and neurological disorders attributed to a variety of symptoms including a lack of energy, motivation, and interest in life. See generally, R.J. Baldessarini, ""Drugs and the Treatment of Psychiatric Disorders: Depression and Mania"" in Goodman and Gilman's The Pharmacological Basis of Therapeutics , McGraw-Hill, NY, NY, pp. 432-439 (1996). Reboxetine ( i . e ., 2-[(2-ethoxyphenoxy)(phenyl)methyl] morpholine) raises the concentration of physiologically active norepinephrine by preventing reuptake of norepinephrine, for example. Reboxetine is a norepinephrine reuptake inhibitor and has been shown to be effective in the short-term ( i.e ., less than eight weeks) and long-term treatment of depression. In fact, reboxetine has been shown to have effectiveness that is similar to fluoxetine, imipramine, and desipramine, commonly prescribed antidepressants, in both adults and elderly patients. See S.A. Montgomery, Reboxetine: Additional Benefits to the Depressed Patient , Psychopharmocol (Oxf) 11:4 Suppl., S9-15 (Abstract) (1997). Antidepressant drugs are sometimes divided into ""generations."" The first generation included the monoamine oxidase inhibitors (such as isocarboxazid and phenylhydrazine) and tricyclic agents (such as imipramine). The second generation of antidepressant drugs included compounds such as mianserin and trazodone. The third generation has included drugs called selective reuptake inhibitors ( e.g. , fluoxetine, sertraline, paroxetine, and reboxetine). Those drugs were characterized by relatively selective action on only one of the three main monoamine systems thought to be involved in depression ( i.e ., 5-HT (serotonin), noradrenaline (norepinephrine), and dopamine). APP Textbook of Psychopharmacology (A.F. Schatzberg and C.B. Nemeroff), American Psychiatric Press, 2d. ed., (1998); Lexicon of Psychiatry, Neurology and the Neurosciences (F.J. Ayd, Jr.) Williams and Wilkins (1995). The antidepressant efficacy of reboxetine is evidenced by its ability to prevent resperine-induced blepharospasm and hypothermia in mice, down regulation of β-adrenergic receptors and desensitization of noradrenaline-coupled adenylate cyclase. See M. Brunello and G. Racagni, ""Rationale for the Development of Noradrenaline Reuptake Inhibitors,"" Human Psychophramacology, vol. 13, S-13-519, Supp. 13-519 (1998). According to a survey by Brian E. Leonard, desipramine, maprotiline, and lofepramine are relatively selective norepinephrine reuptake inhibitors with proven efficacy. These materials increase brain noradrenaline and thereby function to relieve depression. Mianserin and mirtazepine also show antidepressant-like effects by increasing noradrenaline availability by means of blocking the pre-synaptic α 2 -adrenoceptors. Still further, oxaprotiline, fezolamine, and tomoxetine are potent and selective norepinephrine reuptake inhibitors that lack neurotransmitter receptor interactions and, thus, do not cause many of the side effects characteristic of classical tricyclic antidepressants. See Brian E. Leonard, ""The Role of Noradrenaline in Depression: A Review,"" Joumal of Psychopharmacology. vol. 11, no. 4 (Suppl.), pp. S39-S47 (1997). Reboxetine also is a selective norepinephrine reuptake inhibitor, which also produces fewer of the side effects associated with the administration of classical tricyclic antidepressants. The antidepressant efficacy of reboxetine is evidenced by its ability to prevent resperine-induced blepharospasm and hypothermia in mice, down regulation of β-adrenergic receptors and desensitization of noradrenaline-coupled adenylate cyclase. See M. Brunello and G. Racagni, ""Rationale for the Development of Noradrenaline Reuptake Inhibitors,"" Human Psychopharmacology, vol. 13 (Supp.) 13-519 (1998). Reboxetine generally is described in Melloni et al . U.S. Patent Nos. 4,229,449, 5,068,433, and 5,391,735, and in GB-A-2,167,407. Chemically, reboxetine has two chiral centers and, therefore, exists as two enantiomeric pairs of diastereomers, shown below as isomers (I) through (IV): Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound the prefixes R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes D and L, or (+) or (-), designate the sign of rotation of plane-polarized light by the compound, with L or (-) meaning that the compound is levorotatory. In contrast, a compound prefixed with D or (+) is dextrorotatory. There is no correlation between nomenclature for the absolute stereochemistry and for the rotation of an enantiomer. Thus, D-lactic acid is the same as (-)-lactic acid, and L-lactic acid is the same as (+)-lactic acid. For a given chemical structure, each of a pair of enantiomers are identical except that they are non-superimposable mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric, or racemic, mixture. Stereochemical purity is important in the pharmaceutical field, where many of the most often prescribed drugs exhibit chirality. For example, the L-enantiomer of the beta-adrenergic blocking agent, propranolol, is known to be 100 times more potent than its D-enantiomer. Additionally, optical purity is important in the pharmaceutical drug field because certain isomers have been found to impart a deleterious effect, rather than an advantageous or inert effect. For example, it is believed that the D-enantiomer of thalidomide is a safe and effective sedative when prescribed for the control of morning sickness during pregnancy, whereas its corresponding L-enantiomer is believed to be a potent teratogen. When two chiral centers exist in one molecule, there are four possible stereoisomers: (R,R), (S,S), (R,S), and (S,R). Of these, (R,R) and (S,S) are an example of a pair of enantiomers (mirror images of each other), which typically share chemical properties and melting points just like any other enantiomeric pair. The mirror images of (R,R) and (S,S) are not, however, superimposable on (R,S) and (S,R). This relationship is called diastereoisomeric, and the (S,S) molecule is a diastereoisomer of the (R,S) molecule, whereas the (R,R) molecule is a diastereoisomer of the (S,R) molecule. Currently, reboxetine is commercially available only as a racemic mixture of enantiomers, (R,R) and (S,S) in a 1:1 ratio, and reference herein to the generic name ""reboxetine"" refers to this enantiomeric, or racemic, mixture. Reboxetine is commercially sold under the trade names of EDRONAX™, PROLIFT™, VESTRA™, and NOREBOX™. As previously noted, reboxetine has been shown to be useful in the treatment of human depression. Orally administered reboxetine is readily absorbed and requires once or twice a day administration. A preferred adult daily dose is in the range of about 8 to about 10 milligrams (mg). The effective daily dosage of reboxetine for a child is smaller, typically in a range of about 4 to about 5 mg. The optimum daily dosage for each patient, however, must be determined by a treating physician taking into account the patient's size, other medications which the patient may be taking, identity and severity of the particular disorder, and all of the other circumstances of the patient. It has been reported that other antidepressants have a high pharmacological selectivity for inhibiting reuptake of norepinephrine. For example, oxaprotiline has a pharmacological selectivity with respect to inhibiting norepinephrine reuptake compared to serotonin reuptake of about 4166, based on a ratio of K i values. The corresponding pharmacological selectivity for desipramine is about 377, and that for maprotiline is about 446. See Elliott Richelson and Michael Pfenning, ""Blockade by Antidepressants and Related Compounds of Biogenic Amine Uptake in Rat Brain Synaptosomes: Most Antidepressants Selectively Block Norepinephrine Uptake,"" European Journal of Pharmacology, vol. 14, pp. 277-286 (1984). Despite the relatively high selectivity of oxaprotiline, desipramine, and maprotiline, these and other known materials undesirably block receptor of other neurotransmitters to a sufficient degree that they also contribute to adverse side effects. WO 00/00120, which was published after the priority dates of the present application, but before the filling date, discloses a transdermal formulation suitable for the treatment of pain in a subject. The transdermal formulation includes an amine-containing compound, such as racemic neboxetine. There is a need for medicaments for the treatment or prophylaxis of migraine headaches containing racemic reboxetine and the use of racemic reboxetin in the manufacture of such medicaments. SUMMARY OF THE INVENTION The present invention is directed to the use of racemic reboxetine or a pharmaceutically acceptable salt thereof, in the manufacture of a non-transdermal medicament for the treatment or prophylaxis of migraine headaches. Additional benefits and features of the present invention will become apparent to those skilled in the art from a review of the following detailed description, taken in conjunction with the example and the appended claims. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Reboxetine is a known compound that is active on the central nervous system, and has been used as an antidepressant. Heretofore, use of reboxetine has been limited to the treatment of depression, oppositional defiant disorder, attention-deficit/hyperactivity disorder, and conduct disorder. These proposed treatments are disclosed in International Publication Nos. WO 99/15163, WO 99/15176, and WO 99/15177. These treatment methods are limited to administration of a racemic mixture of the (S,S) and (R,R) reboxetine stereoisomers. Reboxetine does not act like most antidepressants. Unlike tricyclic antidepressants, and even selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is not a SSRI. Brian E. Leonard, ""Noradrenaline in basic models of depression."" European-Neuropsychopharmacol , 7 Suppl. 1 pp. S11-6 and S71-3 (April 1997). Reboxetine is a selective norepinephrine reuptake inhibitor, with only marginal serotonin and no dopamine reuptake inhibitory activity. Reboxetine displays no anticholinergic binding activity in different animal models, and is substantially devoid of monoamine oxidase (MAO) inhibitory activity. Racemic reboxetine exhibits a pharmacological selectivity of serotonin (K i )/norepinephrine (K i ) of about 80. The K i values are discussed in more detail hereafter. As used herein, the term ""reboxetine"" refers to the racemic mixture of the (R,R) and (S,S) enantiomers of reboxetine. In contrast, the term ""(S,S) reboxetine"" refers to only the (S,S) stereoisomer. Similarly, the term ""(R,R) reboxetine"" refers to only the (R,R) stereoisomer. The phrases ""pharmaceutically acceptable salts"" or ""a pharmaceutically acceptable salt thereof"" refer to salts prepared from pharmaceutically acceptable acids or bases, including organic and inorganic acids and bases. Because the active compound ( i . e ., racemic reboxetine) used in the present invention is basic, salts may be prepared from pharmaceutically acceptable acids. Suitable pharmaceutically acceptable acids include acetic, benzenesulfonic (besylate), benzoic, p-bromophenylsulfonic, camphorsulfonic, carbonic, citric, ethanesulfonic, fumaric, gluconic, glutamic, hydrobromic, hydrochloric, hydroiodic, isethionic, lactic, maleic, malic, mandelic, methanesulfonic (mesylate), mucic, nitric, oxalic, pamoic, pantothenic, phosphoric, succinic, sulfuric, tartaric, p-toluenesulfonic, and the like. Examples of such pharmaceutically acceptable salts of racemic reboxetine, thus, include, acetate, benzoate, β-hydroxybutyrate, bisulfate, bisulfite, bromide, butyne-1,4-dioate, carpoate, chloride, chlorobenzoate, citrate, dihydrogenphosphate, dinitrobenzoate, fumarate, glycollate, heptanoate, hexyne-1,6-dioate, hydroxybenzoate, iodide, lactate, maleate, malonate, mandelate, metaphosphate, methanesulfonate, methoxybenzoate, methylbenzoate, monohydrogenphosphate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, oxalate, phenylbutyrate, phenylproionate, phosphate, phthalate, phylacetate, propanesulfonate, propiolate, propionate, pyrophosphate, pyrosulfate, sebacate, suberate, succinate, sulfate, sulfite, sulfonate, tartrate, xylenesulfonate, and the like. A preferred pharmaceutical salt of racemic reboxetine is methanesulfonate ( i.e., mesylate), which is prepared using methanesulfonic acid. As used herein, the terms ""treat,"" ""treatment,"" and ""treating,"" refer to: (a) preventing a disease, disorder, or condition from occurring in a human which may be predisposed to the disease, disorder and/or condition but has not yet been diagnosed as having it; (b) inhibiting the disease, disorder, or condition, i.e ., arresting its development; and (c) relieving the disease, disorder, or condition, i.e ., causing regression of the disease, disorder and/or condition. In other words, the terms ""treat,"" ""treatment,"" and ""treating,"" extend to prophylaxis, in other words ""prevent,"" ""prevention,"" and ""preventing,"" as well as treatment of established conditions. Accordingly, use of the terms ""prevent,"" ""prevention,"" and ""preventing,"" would be an administration of the pharmaceutical composition to a person who has in the past suffered from migraine headaches, but is not suffering from the conditions at the moment of the composition's administration. For the sake of simplicity, the term ""conditions"" as used hereinafter encompasses conditions, diseases, and disorders. According to the present invention, a racemic reboxetine is useful in treating migraine headaches wherein inhibiting reuptake of norepinephrine provides a benefit. Racemic reboxetine may be administered, and preferably orally administered in a sufficient amount to provide a total dose of 0.1 to 10 mg/day of the compound to an individual. Racemic reboxetine or a pharmaceutically acceptable salt thereof can be used to treat migraine headaches. Furthermore, racemic reboxetine or a pharmaceutically acceptable salt thereof can be used to treat headaches in migraineurs or people suffering from migraine headaches, including the treatment of symptoms of an existing headache, treatment to prevent the occurrence, intensity, and duration of a headache, prophylactic use to prevent or reduce the incidence or duration of migraines, as an adjuvant to facilitate the effectiveness of a medication or co-administered with other medications to reduce the required dosages (and side effects) of those medications. The synthesis of a racemic mixture of reboxetine is disclosed in Melloni et al. U.S. Patent No. 4,229,449. While it is possible to administer racemic reboxetine or a pharmaceuticathy acceptable salt thereof directly without any formulation, a composition preferably is administered in the form of pharmaceutical medicaments comprising racemic reboxetine or a pharmaceutically acceptable salt thereof. The inventive composition can be administered in oral unit dosage forms such as tablets, capsules, pills, powders, or granules. The inventive composition also can be introduced parenterally, ( e.g ., subcutaneously, intravenously, or intramuscularly), using forms known in the pharmaceutical art. The inventive composition further can be administered rectally or vaginally in such forms as suppositories or bougies. It may be desirable or necessary to introduce the composition or pharmaceutical compositions containing the selective norepinephrine reuptake inhibitor to the brain, either directly or indirectly. Direct techniques usually involve placement of a suitable drug delivery catheter into the ventricular system to bypass the blood-brain barrier. One such suitable delivery system used for the transport of biological factors to specific anatomical regions of the body is described in U.S. Patent No. 5,011,472. In general, the preferred route of administering the composition is oral, with a once or twice a day administration. The dosage regimen and amount for treating patients with the composition is selected in accordance with a variety of factors including, for example, the type, age, weight, sex, and medical condition of the patient, the severity of the condition, the route of administration and the particular compound employed, reboxetine recemate An ordinarily skilled physician or psychiatrist can readily determine and prescribe an effective ( i.e. , therapeutic) amount of the compound to prevent or arrest the progress of the condition. In so proceeding, the physician or psychiatrist could employ relatively low dosages at first, subsequently increasing the dose until a maximum response is obtained. Pharmaceutical compositions suitable for oral administration can be of any convenient form, such as sachets, tablets, capsules, pills, or aerosol sprays, each containing a predetermined amount of the active compound either as a powder or granules, or as a solution or a suspension in an aqueous liquid, a non-aqueous liquid, an oil-in-water emulsion, or a water-in-oil liquid emulsion. Such compositions can be prepared by any method that includes the step of bringing the active compound either into intimate association with a carrier, which constitutes one or more necessary or desirable ingredients. Generally, the compositions are prepared by uniformly and intimately admixing the active ingredient with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product into a desired form. For example, a tablet can be prepared by compression or molding techniques, optionally, using one or more accessory ingredients. Compressed tablets can be prepared by compressing the active ingredient in a suitable machine into a free-flowing form, such as a powder or granules. Thereafter, the compressed, free-flowing form optionally can be mixed with a binders, diluents, lubricants, disintegrating agents, effervescing agents, dyestuffs, sweeteners, wetting agents, and non-toxic and pharmacologically inactive substances typically present in pharmaceutical compositions. Molded tablets can be made by molding a mixture of the powdered compound moistened with an inert liquid diluent in a suitable machine. Suitable binders for use in the pharmaceutical preparation include, for example, starches, gelatine, methylcellulose, gum arabic, tragacanth, and polyvinylpyrrolidone. Suitable diluents for use in the pharmaceutical preparation include, for example, lactose, dextrose, sucrose, mannitol, sorbitol, and cellulose. Suitable lubricants for use in the pharmaceutical preparation include, for example, silica, talc, stearic acid, magnesium or calcium stearate, and or polyethylene glycols. Suitable disintegrating agents for use in the pharmaceutical preparation include, for example, starches, alginic acid, and alginates. Suitable wetting agents for use in the pharmaceutical preparation include, for example, lecithin, polysorbates, and laurylsulfates. Generally, any effervescing agents, dyestuffs, and/or sweeteners known by those of ordinary skill in the art can be used in the preparation of a pharmaceutical composition. According to the present invention racemic reboxetine is, effective in the treatment of child, adolescent, and adult patients. For purposes of the present invention, a child is considered to be a person below the age of puberty, an adolescent is considered to be a person between the age of puberty and up to about 18 years of age, and an adult generally is a person of at least about 18 years of age. As previously noted, the optimum daily dosage for each patient must be determined by a treating physician taking into account each patient's size, other medications which the patient is taking, identity and severity of the disorder, and all of the other circumstances of the patient. As stated above, reboxetine acts as an antidepressant. Reboxetine, however, does not act like most antidepressants. Unlike trycyclic antidepressants, and even selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is not a selective serotonin reuptake inhibitor. Rather, reboxetine is selective for the noradrenergic system. Reboxetine is not an SSRI, but is a novel, selective, noradrenaline reuptake inhibitor (NRI). B. Leonard, ""Noradrenaline in basic models of depression."" European-Neuropsychopharmacol, 7 Suppl. 1 pp. S11-6 and S71-3 (Apr., 1997). Unlike most prior generation drugs, reboxetine is a highly selective norepinephrine reuptake inhibitor, with only marginal serotonin and no dopamine reuptake inhibitory activity. Reboxetine displays no anticholinergic binding activity in different animal models, and is devoid of monoamine oxidase (MAO) inhibitory activity. Reboxetine also is a highly potent, pharmacologically specific, and fast acting agent. Investigations indicate that reboxetine has potent antireserpine activity, and combines the inhibitory properties of classical tricyclic antidepressants on the reuptake of noradrenaline with an ability to desensitize β-adrenergic receptor function, without showing any appreciable blocking action at muscarinic, cholinergic, histaminergic, and α-adrenergic receptors. Moreover, reboxetine shows less vagolytic activity than tricyclic antidepressants, and no evidence of cardiotoxicity. According to the present invention, racemic reboxetine can be used to treat or prevent migraine headaches. Specifically, reboxetine has been found particularly useful for treating or enhancing the treatment or prevention of migraine headaches, with greater efficacy and with fewer side effects than with treatment by known drugs. Mental and neurological disorders that may be treated or prevented by administration of a therapeutically effective amount of a racemic reboxetine (or a pharmaceutically acceptable salt thereof) according to the present invention comprise migraine headaches. Racemic reboxetine can be used to treat humans suffering from migraine headaches, paticularly to reduce the frequency, duration, intensity, and or complications resulting from migraine headaches. Furthermore, racemic reboxetine can be used to prevent migraine headaches. The racemate form of reboxetine is well tolerated and has a wide safety range. Racemic reboxetine can be administered to an individual in an amount in a range of 2 to 20 milligrams per patient per day (mg/day), and preferably 4 to 10 mg/day, and more preferably 6 to 10 mg/day. Depending upon the formulation and the individual's disorder, the total daily dosage can be administered in small amounts up to two times a day. Reboxetine typically is administered orally, for example, in the form of tablets, but can be adminstered parentally, rectally, or vaginally. A preferred method of administering racemic reboxetine is oral dosing once or twice a day. It can also be administered at dosages of about 2, 4, 6, 8, 10, or 12 mg/day or fractions thereof. For example, suitable administrations could be 4 mg in the morning and 2 or 4 mg in the afternoon or evening. In some patients, the ideal dosing would be about 3 to 5 mg in the morning and 3 to 5 mg in the afternoon. A skilled physician or psychiatrist can determine the precise level of dosing. The ideal dosing is routinely determined by an evaluation of clinical trials and the needs of specific patients. In accordance with the present invention, the racemic reboxetine also can be administered as the free base or a pharmaceutically acceptable salt thereof. The phrases ""pharmaceutically acceptable salts"" or ""a pharmaceutically acceptable salt thereof"" refer to salts prepared from pharmaceutically acceptable acids or bases, including organic and inorganic acids and bases as described above. A preferred pharmaceutical salt of reboxetine is methanesulfonate ( i.e ., mesylate), which is prepared using methanesulfonic acid. Treatment or prevention of above disorders involves the administration of reboxetine in a manner and form that result in a reduction in the symptoms of the disease or disorder. Typically, the symptoms exhibited by children, adolescents, and adults are similar to each other. Hence, as noted above, methods of the present invention are effective in the treatment of child, adolescent, and adult patients. EXAMPLE This example demonstrates the superior pharmacological selectivity and potency of a composition according to the present invention. Sprague-Dawley rats weighing about 250 to about 300 grams (g) were decapitated, and cerebral cortical tissue was removed immediately. Cerebral cortices were homogenized in nine volumes of medium each containing 0.32 molar (M) sucrose using a rotating pestle. The obtained homogenate was centrifuged at about 1000 x g for about 10 minutes at about 4°C. A supernatant was collected and further centrifuged at about 20,000 x g for about 20 minutes at a temperature of about 4°C. A protein pellet resulting from the centrifuge steps was re-suspended in a Kreb's-Hepes buffer to result in a protein concentration of about 2 mg/ml of buffer. The buffer was maintained at a pH of about 7.0 and contained: 20 mM Hepes; 4.16 mM NaHCO 3 ; 0.44 mM KH 2 PO 4 ; 0.63 mM NaH 2 PO 4 ; 127 mM NaCl; 5.36 mM KCI; 1.26 mM CaCl 2 ; and 0.98 mM MgCl 2 . Protein/buffer suspension was introduced into 166 assay tubes such that about 30 µg (10 -6 grams) to about 150 µg of the protein was added to each of 166 assay tubes ( i . e ., 80 assays per transporter assay). Binding to serotonin and norepinephrine reuptake sites was determined as follows. Synaptosomal uptake of 3 H-norpinephrine was determined as follows. About 1.4 nanomolar of [ 3 H]citalopram and about 1.9 nM of [ 3 H]nisoxetine were used to label serotonin and norepinephrine reuptake sites, respectively. Nonspecific binding was defined by 100 micromolar (µM) fluoxetine (for serotonin) and 10 µM desipramine (for norepinephrine). Incubation in total assay volume of about 500 microliters (µl) was carried out for about 60 minutes (for serotonin) and 120 minutes (for norepinephrine). Both incubations were carried out at about 25°C, and terminated by rapid filtration through a 48-well cell harvester though GFB filters (pre-soaked with about 0.5 PEI for about 4 hours) in a 3 x 5 ml of ice-cold 200 mM tris-HCl, pH 7.0. Punched-out filters were placed into 7 ml minivials and radioactive assayed by liquid scintillation counting. The ability of reboxetine ( i.e. , racemic mixture of (R,R) and (S,S) reboxetine), (R,R) reboxetine, and (S,S) reboxetine to bind to norepinephrine and serotonin reuptake sites was evaluated in binding assays using the two radioligands, [ 3 H]citalopram and [ 3 H]nisoxetine. The concentration of the test compound required to inhibit 50% of the specific binding at the two reuptake sites (IC 50 values) were determined by non-linear least square regression analysis. A conversion of IC 50 values to K i values was performed using the Cheng-Prassoff equation presented below: K i = IC 50 /(1 + ([L]/[K d of L])), wherein [L] is the radioligand concentration used in nM, and K d is the binding affinity of L in nM. See Y.C. Cheng and W.H. Prusoff, ""Relationship Between the Inhibitory Constant (K i ) and the Concentration of Inhibitor Which Causes 50% Inhibition (IC 50 ) of an Enzymatic Reaction,"" Biochemical Pharmacology, vol. 22, pp. 3099-3108 (1973). The K i values calculated according to the Cheng-Prassoff equation are provided in the table below: Compound Norepinephrine Reuptake (K i nM) Serotonin Reuptake (K i nM) Selectivity of K i of Serotonin/Norepinphrine (S,S) Reboxetine 0.23 ± 0.06 2937 ± 246 12,770 (R,R) Reboxetine 7.0 ± 1.7 104 ± 43 15 Reboxetine 1.6 ± 0.6 129 ± 13 81 The data show that racemic reboxetine has an 81 fold selectivity favoring norepinephrine reuptake inhibition over serontonin reuptake inhibition.";The use of racemic reboxetine, or a pharmaceutically acceptable salt thereof, in the manufacture of a non-transdermal medicament for the treatment or prophylaxis of migraine headaches. The use of claim 1, wherein the racemic reboxetine is to be administered in an amount of 2 to 20 mg/day. The use of claim 2, wherein the racemic reboxetine is to be administered in an amount of 4 to 10 mg/day. The use of claim 3, wherein the racemic reboxetine is to be administered in an amount of 6 to 10 mg/day. The use of any preceding claim, wherein the pharmaceutically acceptable salt of racemic reboxetine is the methanesulfonate.;AHMED SAEEDUDDIN, BIRGERSON LARS, CETERA PASQUALE, MARSHALL ROBERT CLYDE, MCARTHUR ROBERT, TAYLOR DUNCAN P, WONG ERIK H F, AHMED, SAEEDUDDIN, BIRGERSON, LARS, CETERA, PASQUALE, MARSHALL, ROBERT CLYDE, MCARTHUR, ROBERT, TAYLOR, DUNCAN P., WONG, ERIK H.F.;PHARMACIA & UPJOHN CO LLC, PHARMACIA & UPJOHN COMPANY LLC;2005.0;1500396
EP-1500823-B1;20051019.0;EP;B1;EN;20100220.0;new;28455856.0;F04D29;F04D29;B29C45, F04D29;B29C  45/27B3, L29C45:14J, L29C603:02, L29C45:27B3, F04D  29/66C2, F04D  29/32K8;Molded cooling fan;A cooling fan assembly (10) includes a hubless polymer fan body molded around the perimetrical flange (20) of a metallic mounting hub (12). The fan body includes a circumferential ring (18) interlocked with the flange (20) and a plurality of fan blades (16) projecting outwardly from the ring (18). The fan body (14) is formed in an injection mold with molten polymer material being introduced into the mold at hot runner locations (25) disposed between the circumferential ring (18) and the root diameter (17) of the fan blades (16). At one face of the hubless fan (14), the circumferential ring (18) includes a plurality of uniformly spaced raised bosses (30). Each boss (30) defines a bore (31) configured to receive a balancing weight therein, preferably in the form of a balancing screw (35) threaded into the bore. The bosses (30) are interconnected by a stiffening ring (33) having a height substantially equal to the height (h) of the bosses (30). The stiffening ring (33) is modified between a plurality of pairs of bosses (30) to define a recessed flat (38). On the opposite face of the hubless fan (14), the circumferential ring (18) includes a plurality of raised tabs (40), arranged and configured to mate within a corresponding recessed flat (38). The corresponding recessed flats (38) and raised tabs (40) nest between stacked fan assemblies (10) to enhance the stability and increase the number and height of stacked sets of assemblies.;"The present invention relates to cooling fans such as fans used in connection with an automotive or industrial cooling system. More specifically, the invention pertains to fans with integral blades formed in a molding process, such as an injection molding procedure. Most automotive and industrial power components require some form of auxiliary cooling system. In a typical automotive application, this cooling system includes a radiator and a cooling fan that directs air across the radiator. In these applications, the fan is mounted to a rotating flange of a fan drive that is separate from the power plant output. In the early design of such cooling fans, metal blades were mounted to a metal hub, which hub was then attached to the fan drive. In recent years, however, high-strength polymer materials have been used to form various components of the fan. The polymer fan design was found to be capable of withstanding the normal forces and stresses endured by a cooling fan in even the heaviest duty automotive or industrial application. Moreover, the use of polymer materials provided a significant reduction in weight of the cooling fan. Moreover, and perhaps most significantly, the use of polymers generated significant benefits in the manufacture of the fan, since materials of this type readily lend themselves to a variety of molding processes. The one-piece molded fan has eliminated the welds and rivets commonly associated with prior metal fans. In addition, the molding process facilitated the generation of smooth rounded contours, which ultimately reduced internal stresses within the fan structure. In one type of molded fan design, the entire fan and hub are formed in a single piece. An example of this form of a one-piece molded fan is shown in U.S. Patent No. 4,671,739 to Read et ai. Fans of this type were found to be better suited for smaller duty applications, such as for use in the cooling system of passenger automobiles. For larger, higher stress applications, a hubless molded fan design was found to be more appropriate. One such design is depicted in U.S. Patent No. 5,593,283 to Scott. In this design, a polymer hubless fan is integrally formed around a metallic mounting hub. This mounting hub can be supported within the molding apparatus, such as a typical injection molding machine. The polymer material is then injected into a mold surrounding the hub to form an interlocking ring around the metal hub. US4, 957, 414 discloses a fan assembly comprising a hub for connection to a drive means. A hubless fan is molded around the hub, and comprises a circumferential ring at the blade root diameter. The fan assembly can be nested in a corresponding assembly but the assemblies are relatively moveable which can allow the fans to be damaged during transit. In many automotive and industrial applications the molded fan includes a polymer, such as polypropylene, nylon or other resin compositions. In addition, many industrial fans include reinforcing material such as glass fibers or nylon strands. The reinforcing material can be oriented within the structure of the molded fan blade to provide additional strength and stiffness where needed based upon stress analysis of the working fan. The hubless fan design has evolved since its inception. While the metal mounting hub provides a certain degree of strength to the overall fan, the molded fan can include an enlarged polymer ring formed around the mounting hub. This ring helps provides strength and bending or flexure stiffness to the root of each of the fan blades. While the hubless polymer fan represents an improvement over prior metal and one-piece polymer fan constructions, improvements are still needed. For instance, cost and material considerations are implicated by current molded fan designs involving significant material waste. Cost considerations are also involved in the storing and shipping of an inventory of fans. There remains a need for a molded fan assembly that reduces the overall costs associated with manufacturing and shipping the final fan product. SUMMARY OF THE INVENTION The present invention provides a fan assembly comprising: a substantially rigid hub configured for mating with a fan drive and defining a perimetrical flange, a hubless fan having a first face and an opposite face and defining a circumferential ring molded about said perimetrical flange of said rigid hub and a plurality of outwardly projecting fan blades integrally formed with said ring; characterised in that the circumferential ring defines at least two recesses on said first face spaced around the circumference of said ring; and said circumferential ring further includes at least two raised tabs projecting therefrom on said opposite face, each of said tabs sized and arranged to reside within a corresponding one of said at least two recesses, whereby when two or more of said hubless fans are stacked, each of said raised tabs of one of said fans nests within corresponding recesses of an adjacent one of said hubless fans. The present invention enhances the stackability of the fan assemblies. The recesses can be situated between a corresponding adjacent pair of raised bosses. The recesses can comprise recessed flats. The stiffening ring can have a reduced height at each of the recesses which height is less than the height of the stiffening ring of bosses. When two or more of the hubless fans are stacked, the raised tabs of one of the fans nests within corresponding ones of the recessed flats of an adjacent one of the hubless fans. In a preferred embodiment, the number of raised tabs and recesses equals the number of fan blades. The tabs and recesses can be situated in radial alignment with the gap between adjacent fan blades. In one embodiment of the invention, the hubless fan can further include a plurality of hot runners for introduction of molten material into the hubless fan that are radially disposed between the circumferential ring and the root diameter of the fan blades. With this feature, molten polymer material is distributed more uniformly throughout the molded hubless fan. Moreover, less material is wasted in the form of a cold sprue that must be trimmed from the completed fan assembly. In a further aspect, each of the hot runners can be raised relative to the circumferential ring, which allows the hot runners to have a larger diameter to accept greater flow of molten material into the hubless fan mold. In a further embodiment of the invention, the circumferential ring of the hubless fan can define a plurality of bores dispersed about the circumference of the ring. Each of the bores is configured for receiving a balance weight therein. The balance weight can be in the form of a screw having a known weight and including self-tapping threads for screwing into a specific one of the bores. The ring can define a predetermined number of the bores radially aligned with a corresponding one of the fan blades, namely four such bores in the most preferred embodiment. Standard rotating body balancing techniques can be used to determine the magnitude of weight and the boss location for the addition of the balancing screw. The circumferential ring can include a plurality of raised bosses each of which includes a corresponding one of the plurality of bores. The bosses have a height from the circumferential ring, and the bores have a depth no greater than that height to avoid compromising the body of the circumferential ring supporting the fan blades. A stiffening ring can be formed between and interconnecting adjacent ones of the plurality of raised bosses that has a height substantially equal to the raised height of the bosses. It is one object of the present invention to provide a fan assembly utilizing a hubless fan that minimizes the amount of material required to form the fan in a molding process. Reducing the amount of material waste is also accomplished by features of the invention that eliminate the need to trim blade material for balancing the fan assembly. Another object of the invention is directed to improving the stackability of molded fan assemblies. An added object resides in features that enhance the stability of a stack of such fan assemblies. Other objects and particular benefits of the invention will become apparent to a person of skill in this art upon consideration of the following written description and accompanying figures. DESCRIPTION OF THE FIGURES FIG. 1 is a top elevational view of a fan assembly according to one embodiment of the present invention. FIG. 2 is a partial bottom elevational view of the opposite side of the fan assembly shown in FIG. 1. FIG. 3 is a side cross-sectional view of the fan assembly shown in FIG. 1 taken along line 3-3 as viewed in the direction of the arrows. FIG. 4 is a partial cross-sectional view of the fan assembly depicted in FIG. 2 , taken along line 4-4 as viewed in the direction of the arrows. FIG. 5 is a side, partial cross-sectional view of a pair of fan assemblies such as the assemblies of FIG. 1 and 2 , shown in a stacked configuration. DESCRIPTION OF THE PREFERRED EMBODIMENTS For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. The invention includes any alterations and further modifications in the illustrated devices and described methods and further applications of the principles of the invention which would normally occur to one skilled in the art to which the invention relates. Referring to FIG. 1, a fan assembly 10 is depicted which includes a mounting hub 12 and a separate hubless fan 14. In the preferred embodiment, the mounting hub 12 is formed of metal and is most preferably configured as a stamped circular plate. The configuration of the mounting hub 12 will vary depending upon the fan drive to which the fan assembly 10 is connected. In the illustrated embodiment, the mounting hub 12 includes a mounting hole array 23 that includes a number of openings for receiving mounting bolts of the fan drive. In some instances, the mounting hub 12 can simply constitute a flat annular disc. In other instances, such as that depicted in the side cross-sectional view of FIG. 3 , the mounting hub 12 is dish-shaped, it is understood, of course, that the configuration of the mounting hub 12 is not essential to the present invention, and instead can be dictated by the application of the particular fan assembly 10. The hubless fan 14 in the preferred embodiment is a molded polymer fan that includes integrally molded blades 16 . In the illustrated embodiment the hubless fan 14 includes nine (9) blades and has a diameter of 28 inches (71 cm.). The number of blades and their configuration (e.g., thickness, chord dimensions and curvature) can be dictated by the specific application for the fan assembly 10. The fan assembly 10 of this configuration can be used in a variety of applications, such as for a medium-duty truck cooling system fan. Each of the blades 16 is integrally formed with a uniformly molded polymer ring 18. The ring 18 presents a region of increased thickness relative to the thickness of each of the blades 16. In addition, the ring 18 is molded around the perimeter flange 20 (see FIG. 3 ) of the mounting hub 12 . The molded ring 18 and perimeter flange 20 are most preferably of an interlocking design. In other words, the flange 20 can include a plurality of openings 21 defined therethrough. When the hubless fan 14 is molded about the mounting hub 12 , the polymer material flows through each of the openings 21 and sets in place to form the molded ring 18 . This interlocking feature prevents the hubless fan 14 from rotating relative to the mounting hub 12 . Since the hubless fan 14 is a molded polymer material, the fan includes a number of locations at which the molten polymer material is introduced. More specifically, the fan 14 includes a plurality of hot runners 25 dispersed circumferentially around the molded ring 18 of the fan. Each of the hot runners 25 is arranged between adjacent blades 16 so that the weld line or knit line is located generally in the center of each blade, as is known in the art. The hot runners 25 are situated between the molded ring 18 and the root diameter 17 of each of the fan blades 16. In a further departure from prior fan molding processes, the hot runners 25 in accordance with the present invention are raised slightly from the surface of the molded ring 18 of the hubless fan 14 . Increasing the height of the hot runners allows these runners to be larger than in prior systems. This increased runner size, coupled with locating the runners outboard of the molded ring 18 , allow the present molded fan 14 to be formed more efficiently with less material waste. The hot runners 25 are radially aligned with the gap defined between adjacent fan blades 16. In prior molding processes, a cold sprue and runner system is utilized in which the sprue and runners are situated at the interior of the hubless fan body. A molding arrangement of this type is shown in U.S. Patent No. 4,957,414 to Willingham. In practice, the cold sprues or slugs must be removed after the fan has been assembled. With the present invention, the location of the hot runners does not require the same sprue removal step. This approach of the present invention reduces the amount of material that must be removed, and therefore reduces the amount of waste associated with the manufacture of each fan assembly 10 . Moreover, locating the hot runners outboard of the molded ring 18 allows the molten polymer material to flow more uniformly into the fan blade mold regions and into the ring mold sections. This increased flow uniformity results in a hubless fan blade with significantly fewer material voids that might compromise the integrity and strength of the fan assembly 10 . A further feature of the invention pertains to balancing the fan assembly. It is of course well known that any rotating component must be balanced to avoid excessive vibration and torque. In a typical prior art molded fan, this balancing is accomplished by removing material from the tips of one or more fan blades. This process is cumbersome and wasteful of material, and in some instances disruptive of the overall performance of the fan assembly. Moreover, removing blade material leaves little room for error - the excised material cannot be restored if the fan assembly is not balanced. In extreme cases, an entire fan assembly may be scrapped if the balancing process leads to the removal of too much blade material. In accordance with the present invention, the molded hubless fan 14 is provided with a ring of balance bosses 30 formed at one side of the molded ring 18 of the fan 14 , as seen best in FIG. 2 . These balance bosses 30 are preferably uniformly dispersed around the inner perimeter of the hubless fan 14 adjacent the root of each of the blades 16 , and most preferably are formed as part of the molded ring 18 . In the preferred embodiment, four (4) such balance bosses 30 are aligned with each blade 16. Each of the balanced bosses 30 defines an internal bore 31 that is configured to receive a balance weight, such as a rivet or screw therein. In a specific embodiment, as depicted in FIG. 4 , the balance weight is a balance screw 35 that is threaded into the bore 31 of a particular balance boss 30. Each balance screw 35 can have a known weight, and a selection of differently weighted balance screws 35 can be provided. The circumferential location and necessary weight for balancing the fan assembly 10 can be established using traditional rotating balancing techniques. In order to preserve the integrity of the molded ring 18 of the hubless fan 14 , the balance screws 35 are sized to be entirely disposed within the balance boss 30. In other words, each of the bosses 30 projects upward from the molded ring 18 by a predetermined height h ( FIG. 4 ). In one specific embodiment, that height h is about 0.375 inches (0.95 cm.). For this specific embodiment, the balance screws have a threaded length of less than the boss height. The balance screw 35 can have a variety of configurations. For instance, the enlarged head of screw 35 can be eliminated, the threads can be self-tapping or eliminated in favor of a press-fit configuration, etc. With the added height provided by each of the balance bosses, the hubless fan 14 further includes a stiffening ring 33 extending between each boss, as depicted best in FIGS. 2 and 4 . Nominally, the stiffening ring 33 has a height equal to the height h of each of the balance bosses 30 . In the illustrated embodiment, the balance bosses are uniformly spaced about the circumference of the molded ring. Alternatively, non-uniformly spaced bosses may be utilized, as well as varying numbers and sizes of such bosses, provided that a sufficient number of balance bosses are available to accurately balance the fan assembly 10 . For larger fan assemblies, two or more rows of balance bosses, such as bosses 30 can be provided, with bosses in adjacent rows offset relative to each other. In a further aspect of the invention, the stiffening ring 33 is modified between a few pairs of balance bosses 30 to define a recessed flat 38. More specifically, a pair of balance bosses 30 associated with each pair of fan blades 16 includes the recessed flat 38 defined therebetween. The recessed flat preferably has a thickness greater than the thickness of the stiffening ring. On the other hand, the flat 38 has a height that is less than the height h of the balance bosses 30 , as best seen in FIG. 4 . The position of each of the recessed flats 38 corresponds to the position of a plurality of raised tabs 40 formed on the opposite surface of the molded ring 18. The position of the tabs 40 is best seen in FIGS. 1 and 3. The raised tabs 40 are dimensioned to fit in contact with the recessed flats 38 between adjacent balance bosses 30. In a specific embodiment, the raised tabs 40 have a height equal to the depth of the recessed flats 38 below the top surface of the balance bosses 30. In a specific embodiment, that height is about 0.25 inches (0.6 cm.). As can be seen by a comparison of FIGS. 1 and 2 , the number and location of the raised tabs 40 corresponds to the number and location of recessed flats 38 . In the illustrated embodiment, nine such tabs 40 and flats 38 are provided, each being oriented in the gap between adjacent blades 16 . Of course, other orientations and numbers of flats and tabs can be provided, as long as the same number and positioning of one component relative to the other component is maintained. It is known that newly manufactured fan assemblies are stacked for storage or shipping. In the usual case, the fan blades rest upon each other to support adjacent fan assemblies in the stack. This stacking arrangement is unstable and often detrimental to the fan blades. In other fan designs, the inner ring of the fans are stacked on top of each other. In this instance, the fan blades are protected, but the resulting stack is again unstable. Moreover; the stackable height of the fan assemblies is limited when stacked in this manner. Referring to now to FIG. 5 , the purpose behind the recess flats 38 and raised tabs 40 can be discerned. In order to address these aforementioned problems with prior molded fan designs, the present invention contemplates that each of the raised tabs 40 reside or interlock within a corresponding flat 38 between adjacent balance bosses 30. This interlocking stacked relationship is depicted at FIG. 5 in which a first fan assembly 10 and second fan assembly 10' are stacked together. In this arrangement, it can be seen that the raised tab 40 of fan assembly 10 contacts the recessed flat 38' of fan assembly 10'. With this arrangement, the mounting hub 12' and the blades 16' can nest within the corresponding hub 12 and blades 16. This nesting capacity reduces the overall height of the stack of fan assemblies 10, 10', etc. In addition, the interlocking aspect of the tabs and flats greatly increases the stability of the stack of fan assemblies, increased stability means that a higher, more stable, stack of fan assemblies can be provided for transport or storage than with prior fan assembly designs.";"A fan assembly (10) comprising: a substantially rigid hub (12) configured for mating with a fan drive and defining a perimetrical flange (20), a hubless fan (14) having a first face and an opposite face and defining a circumferential ring (18) molded about said perimetrical flange (20) of said rigid hub (12) and a plurality of outwardly projecting fan blades (16) integrally formed with said ring (18); characterised in that the circumferential ring (18) defines at least two recesses (38) on said first face spaced around the circumference of said ring (18); and said circumferential ring (18) further includes at least two raised tabs (40) projecting therefrom on said opposite face, each of said tabs (40) sized and arranged to reside within a corresponding one of said at least two recesses (38), whereby when two or more of said hubless fans (14) are stacked, each of said raised tabs (40) of one of said fans nests within corresponding recesses (38) of an adjacent one of said hubless fans (14). A fan assembly (10) according to claim 1, wherein said circumferential ring (18) includes at least two pairs of raised bosses (30) projecting therefrom on said first face, each recess (38) being defined between a pair of raised bosses (30), and a stiffening ring (33) being provided between and integral with adjacent pairs of bosses (30). A fan assembly (10) according to claim 2, wherein the bosses (30) each include a bore (31) configured for receiving a balance weight therein and radially aligned with a corresponding one of said plurality of fan blades (16). A fan assembly (10) according to claim 2 or 3, wherein said circumferential ring (18) includes the stiffening ring (33) formed between and interconnecting adjacent ones of said plurality of raised bosses (30). A fan assembly (10) according to claim 4, wherein said stiffening ring (33) defines at least two of said recesses (38) in the form of recessed flats (38) between the raised bosses (30), said stiffening ring (33) having a reduced height at each of said recessed flats (38) which height is less than the height of said stiffening ring (33) A fan assembly (10) according to claim 5, wherein said stiffening ring (33) has a first thickness at each of said at least two recessed flats (38) and a second smaller thickness apart from said recessed flats (38). A fan assembly (10) according to any one of the preceeding claims, wherein the tabs (40) and recesses (38) are each situated in radial alignment with a fan blade (16).";STAGG JONATHAN B, WILLIAMS EUGENE E, STAGG, JONATHAN B., WILLIAMS, EUGENE E.;BORG WARNER INC, BORGWARNER INC.;2005.0;1500823
EP-1504834-B1;20051026.0;EP;B1;EN;20100220.0;new;10858545.0;B22D35;B22C9, C22B21, B22D41, B22D11, B22D7;B22D41, B22C9, B22D7, B22D11, B22D35, C22B21, B22D43, B22D21, B22D37;B22D  11/103, B22C   9/08A, B22D  41/50, B22D  35/04, C22B  21/00J, B22D  41/00P, B22D   7/12, B22D  11/119;Distributor device for use in metal casting;A distributor device for use in aluminium casting includes a rigid, substantially bowl-shaped receptacle (2) of a refractory material having a base member (4) and a peripheral wall (6) that extends upwards from the base. The receptacle has an inlet opening (8) towards the upper end thereof and a pair of outlet openings (14) towards the base thereof. The device is constructed and arranged such that, in use, molten aluminium poured into the distributor device through the inlet opening (8) is redirected by the distributor device and flows outwards into the mould through the outlet openings (14).;"The invention relates to a distributor device for use in an aluminium casting operation. In the process for manufacturing aluminium, after completion of the refining process, the molten aluminium is cast into ingots or billets that are subsequently used in processes for manufacturing aluminium products, for example aluminium foil. During the casting operation, the molten aluminium is transferred from a holding furnace into a water-cooled mould above a casting pit, where it solidifies to form an aluminium ingot. It is important that the flow of aluminium into the mould is smooth and non-turbulent, so that the solidification and temperature profile of the metal can be carefully controlled. If the flow is turbulent, impurities can be introduced into the aluminium, which can cause serious problems during subsequent manufacturing processes. To avoid turbulence and to optimise distribution, the molten aluminium is usually poured into the mould through a distributor device. Conventionally, this consists of a flexible bag of coated woven glass fibres, known as a ""combo bag"", having an outer shell of solid woven fabric with normally two large openings through which the molten aluminium flows, and an inner liner of open-weave fabric. In use, the molten aluminium flows through the small pores of the open-weave liner, then through the openings in the outer shell, which helps to prevent turbulence in the flow of aluminium. Conventional distributor devices can be used only once and are then discarded. However, because these devices are constructed largely by hand, they are relatively expensive and their use therefore adds significantly to the cost of the manufacturing process. Conventional distributor devices are normally quite flexible, or at best semi-rigid. This means that the positioning and shape of the device can be inconsistent, and the dimensional accuracy of the device is difficult to measure and control within normal engineering tolerances. Furthermore, the coatings on the woven glass fibre weaken at metal casting temperatures, leading to reduced rigidity of the distributor. These factors combine to limit the reliability of metal distribution, and this leads to inconsistencies in the casting operation. Further, fibres can occasionally come loose from the fabric of the distributor and become entrained in the molten aluminium, thereby introducing impurities into the aluminium ingot and potentially causing considerable difficulties in subsequent manufacturing processes. Further, conventional distributors do not drain well after use and are sometimes provided with additional drain apertures in the bottom wall of the outer shell to ensure complete drainage. However, aluminium can also flow through these apertures during casting, thereby disturbing the desired liquid metal flow pattern. Another distributor device described in US 5207974 has a ""bag-in-bag"" design, comprising an inner bag of impermeable fabric and an outer bag having outlet openings. The device is suspended above the mould and liquid metal is poured into the inner bag. When the metal reached the top of the inner bag, it overflows into the outer bag, then flows through the openings into the mould. The bag is flexible and is susceptible to the disadvantages mentioned above. US 5871660 describes two different distributor devices. One of these is a flexible bag type, which is susceptible to the disadvantages mentioned above. The other device comprises a rigid nozzle having four outlet openings that are angled to direct the molten metal towards the sides of the mould. The nozzle is geometrically complex and is difficult and expensive to produce. It is an object of the present invention to provide a distributor device that mitigates at least some of the problems of the aforementioned distributor devices. According to the present invention there is provided a distributor device for use in an aluminium casting operation to direct the flow of molten aluminium into a mould, the distributor device including a rigid, substantially bowl-shaped receptacle of a refractory material having a base member and a peripheral wall that extends upwards from the base, said receptacle having an inlet opening towards the upper end thereof and at least one outlet opening towards the base thereof, the device being constructed and arranged such that, in use, molten aluminium poured into the distributor device through the inlet opening is redirected by the distributor device and flows outwards into the mould through the at least one outlet opening, wherein at least one outlet opening may be provided in the lower part of the peripheral wall, adjacent the base member, and the base member is inclined towards the or each outlet opening. This provides good drainage. The distributor device serves to direct the metal flow during casting. One of the advantages of using a rigid material is that it allows far more complex geometries to be made than can be achieved with conventional non-rigid systems, and allows those geometries to be reproduced consistently. This allows greater control and optimisation of the flow patterns emerging from the distributor, as well as opening up new ways of predicting the flow patterns (since 3-D fluid flow computer models work better with rigid structures). Further, the device is not wetted by liquid aluminium and so is easy to clean. It may be slightly more expensive to manufacture than a disposable combo bag, but it can be re-used many times, thereby reducing wastage and providing a significant overall saving in costs. Also, the risk of loose fibres being trapped within the aluminium is avoided. Any refractory material that is suitable for prolonged contact with molten aluminium may be used. These include fused silica, alumina, mullite, silicon carbide, silicon nitride, silicon aluminium oxy-nitride, zircon, magnesia, zirconia, graphite, wollastonite, calcium silicate, boron nitride (solid BN), aluminium titanate, aluminium nitride (AIN) and titanium diboride (TiB2) etc., or any composite of these materials. Alternatively, a suitable metal may be used, for example grey cast iron or titanium. Advantageously, at least one outlet opening is provided in the peripheral wall, the device being constructed and arranged such that, in use, molten aluminium flows substantially horizontally outwards through said at least one outlet opening. This produces a good, non-turbulent flow pattern. Advantageously, the peripheral wall includes two side wall members and two end wall members. At least one outlet opening may be provided in each end wall member. Advantageously, the separation of the side wall members increases towards the ends thereof. Preferably, the side wall members are curved. These features also promote a good, non-turbulent flow pattern. The base member may include a raised flow deflector, to redirect the flow of aluminium as it is poured into the distributor device. Advantageously, the peripheral wall is inclined outwards. The distributor device may include a heating element for pre-heating the device, to prevent the metal freezing when pouring begins. The distributor device may include a support structure, which may be designed to allow the device to be removed and replaced easily. The distributor device may include a porous element constructed and arranged such that, in use, molten aluminium poured into the distributor device flows through said porous element. The porous element helps to reduce turbulence. It also acts as a filter device that traps inclusions and any large particles that may be washed into the distributor. Advantageously, the porous element includes a substantially bowl-shaped mesh of woven material that fits into and is supported by the receptacle, the arrangement being such that molten aluminium poured into the distributor device through the inlet opening flows through the mesh of woven material before exiting through the at least one outlet opening. Preferably, the porous element includes a mesh of coated glass fibres. Advantageously, the porous element includes a support frame that, in use, engages and is supported by the receptacle. According to another aspect of the invention there is provided a distributor device for use in aluminium casting, the distributor device including a rigid, substantially bowl-shaped receptacle of a refractory material having an inlet opening at the top and at least one outlet opening towards the base thereof, and an inner liner including a substantially bowl-shaped mesh of woven material that fits into and is supported by said rigid receptacle, the arrangement being such that molten aluminium poured into the distributor device through the inlet opening flows through the mesh of woven material before exiting through the at least one outlet opening. The rigid receptacle supports the inner liner during the casting process and directs the flow of molten aluminium, while the inner liner helps to prevent turbulence. The receptacle can be used several times. It is therefore only necessary to replace the relatively inexpensive inner lining for each casting process, thereby reducing the cost of the process. Advantageously, the rigid receptacle includes a ceramic shell. The ceramic shell can withstand the extremely high temperature of the molten aluminium and provide a rigid support for the inner liner. It is also relatively inexpensive. Further, because a fabric outer support is not required, the risk of loose fibres becoming entrained in the molten aluminium is significantly reduced. Advantageously, the device includes means for supporting the rigid receptacle, which preferably allows the receptacle to be replaced relatively quickly and easily, when necessary. Advantageously, the base of the rigid receptacle has an upper surface that is convex, to ensure good drainage of the device at the end of the casting process. Advantageously, the rigid receptacle includes at least one heating element. This allows the receptacle to be pre-heated in situ prior to pouring the molten aluminium. Advantageously, the inner liner includes a mesh of woven material, preferably of coated glass. This material can withstand the very high temperature of the molten aluminium. Advantageously, the inner liner includes a support frame that, in use, engages and is supported by the rigid receptacle. This retains the inner liner in position and prevents it floating on the molten aluminium. According to another aspect of the invention there is provided an aluminium casting installation including a mould, a delivery device for delivering molten aluminium into the mould and a distributor device according to any one of the accompanying claims, the distributor device being mounted below the delivery device and above the mould, the installation being constructed and arranged such that, in use, molten aluminium is poured from the delivery device into the mould through the distributor device. Advantageously, the distributor device is positioned so that, during pouring, it is partially immersed in the liquid metal in the mould with the at least one outlet opening below the surface of the liquid metal. Embodiments of the present invention will now be described, by way of example, with reference to the accompanying drawings, in which: Figure 1 is an isometric view of a first distributor device according to the invention; Figure 2 is an isometric view of the first distributor device, showing some hidden details in broken lines; Figure 3 is a top plan view of the first distributor device; Figure 4 is a side section on line A-A in Fig. 3; Figure 5 is an end section on line B-B in Fig. 3; Figure 6 is a side section showing the first distributor device mounted above a mould; Figures 7a and 7b are flow distribution diagrams, illustrating the flow of molten aluminium through the device, in plan view and side view; Figure 8 is a sectional isometric view of a second distributor device according to the invention, and Figure 9 is an isometric view of a fabric liner, forming an inner part of the second distributor device. A distributor device 2 according to a first embodiment of the invention is shown in Figs. 1 to 5 of the drawings. The device is intended for use in an aluminium casting operation to direct the flow of molten aluminium into a mould, the device being located in use just above the mould, so that during pouring it is partially submerged below the surface of the molten metal in the mould. The distributor device 2 includes a rigid, substantially bowl-shaped receptacle of a refractory material having a base member 4 and a peripheral wall 6 that extends ) upwards from the base and is inclined slightly outwards, forming an inlet opening 8 towards the upper end of the device. The peripheral wall 6 is four-sided and includes two side wall members 10 and two end wall members 12. The side wall members 10 are curved inwards lending the device a bi-concave shape, the separation of the side wall members increasing towards the ends of those walls. An outlet opening 14 is provided in the lower part of each end wall member 12, the lower edge of each opening being flush with the upper surface of the base member 4. Each opening 14 extends substantially horizontally through the walls and is constructed and arranged such that, in use, molten aluminium flows substantially horizontally outwards through it. The base member 4 is inclined towards the outlet openings 14 and includes a raised flow deflector element 16 that deflects the flow of molten aluminium poured into the device and directs it towards the outlet openings 14. The flow deflector element 16 is substantially hemi-spherical but has a flat top surface 18. The shape and dimensions of the distributor are very important to ensure a smooth and predictable flow pattern. A specific example and preferred ranges of these dimensions, which have been found to provide extremely good results, are given in the table below. Dimension Example Preferred range Base angle (A) 5° 0° - 10° Length (B) 380 mm 150 - 600 mm Max. width (C) 175 mm 75 - 300 mm Ratio B:C 2.17 1.25 - 4 Height (D) 125 mm 100 - 150 mm Height of upper part of wall (E) 75 mm 50 - 100 mm Height of opening (F) 35 mm 20 - 50 mm Radius of curvature of wall (G) 605 mm 300 - 1200 mm Radius of curvature of flow deflector (H) 40 mm 20 - 60 mm Diameter of central flat on flow detector (I) 30 mm 10 - 50 mm Wall Thickness (J) 12 mm 1 - 25 mm The distributor device 2 may be made from any refractory material that is suitable for prolonged contact with molten aluminium. These include fused silica, alumina, mullite, silicon carbide, silicon nitride, silicon aluminium oxy-nitride, zircon, magnesia, zirconia, graphite, wollastonite, calcium silicate, boron nitride (solid BN), aluminium titanate, aluminium nitride (AIN) and titanium diboride (TiB2) etc. Furthermore, the device may be made from a composite material formed from a combination of the materials listed above, or it may be formed by impregnating a combination of these materials into a fibrous mat substrate. Alternatively, the distributor device may be made of a suitable metal, for example grey cast iron or titanium. In use, the distributor device 2 is mounted within the upper part of a water-cooled mould 20, as shown in Fig. 6, with the outlet openings 14 just below the surface 22 of the molten aluminium in the mould. The distributor device is supported by two horizontal support rods 24 that pass through support loops 26 attached to the sides of the distributor device. Molten aluminium is poured from a holding furnace into a launder trough 28, from which it flows through a spout 30 into the open top of the distributor device 2. The liquid aluminium is deflected outwards by the deflector element 16 and is directed towards the end walls 12 by the curved side walls 10. The aluminium then flows outwards through the outlet openings 14 into the mould 20, where it solidifies to form an aluminium ingot. The flow of aluminium through the distributor device (which is illustrated by arrows 32) is determined by the shape of the device and the geometry of its outlets, which are designed to produce a smooth, controlled flow pattern of metal in the mould, with a predictable heat distribution. The flow pattern is illustrated in Figures 7a and 7b. As shown in plan view in Fig. 7a, the distributor device 2 directs the liquid metal towards the short sides 33 of the mould 20, and produces a diverging flow pattern with metal flowing towards the corners as well as the middle of those sides. The flow of metal from the distributor device is substantially horizontal initially, as shown in side section in Fig. 7b, and then turns downwards and inwards as it reaches the sides 33 of the mould, producing a heart-shaped pattern above the metal solidification front 34. This pattern is generally considered to be ideal, and results in a very high quality ingot or billet. The device provides numerous advantages when used in the aluminium casting process. It is not wetted by liquid aluminium and so is easy to clean. The device is re-useable, reducing wastage. It is inexpensive to manufacture, reducing costs. It has a sloped base so that metal runs out at the end of the cast and it drains easily. The flow deflector reduces or eliminates turbulence at the point of the direction change between spout and distributor. The rigid receptacle walls are curved to generate the desired metal flow pattern. With an appropriate mounting system, the device can be replaced quickly and easily when necessary, allowing consistent placement and thus reliable metal distribution. Various modifications of the device are possible, some of which will now be described. The device may include a mounting system for mounting it within the mould, for example by clamping or fixing a metal bracket to the top, sides, end or base of the device, or by integrating a suitable bracket into the device. The device may include a porous element for reducing turbulence further and trapping surface based oxide inclusions generated by turbulence in the metal or any large particles that may be washed into the distributor. This element may be formed from any suitable porous material. It can be made, for example, by sewing coated woven glass fibre cloth, thermally forming a resin coated woven glass fibre cloth, by incorporating a steel wire into the woven glass fibre cloth, by producing a ceramic replica of a reticulated polyurethane foam, etc. The device may include a heating element for heating the device in situ prior to use, to prevent the metal freezing when it first comes into contact with the device. For example, electrical heating elements can be incorporated into the walls and base of the device. A second form of the distributor device is shown in Figs. 8 and 9. This device 36 includes a rigid, bowl-shaped receptacle 2 and a woven fabric inner liner 38 that forms an inner part of the distributor device and fits inside the receptacle 2. The receptacle 2 is substantially identical to the first distributor device described above, and will not be further described. The same reference numbers have been used to refer to similar parts. The inner liner 38 is made from a coated open weave fabric of glass fibres. The coating can be either organic or inorganic. An organic coating may for example be a derivative of polyvinyl alcohol, whereas an inorganic coating can be a colloidal silica with a small quantity of starch to add stiffness. The liner 38 is substantially bowl-shaped and designed to fit into the rigid receptacle 2. As shown in Figure 9, it has a peripheral wall 40 with curved sides 41 and flat ends 42, and a substantially flat base 43. The upper part of the peripheral wall 40 is reinforced with a second layer 44 of woven glass fabric, which encapsulates a wire frame 45. The frame 45 is relatively springy, and provides additional stiffness to support the liner 38 in the outer receptacle 2. In use, the inner liner 38 is placed in the outer ceramic receptacle 2. The frame 45 supports the liner against the walls 10,12 of the receptacle 2, and the liner adopts the internal shape of the receptacle, moulding itself over the deflector element 16, as shown in Figure 8. The mesh extends over the outlet openings 14, so that liquid metal flowing through the distributor passes through the mesh. The distributor device is suspended above the casting pit, substantially as shown in Fig. 6. As molten aluminium is poured into the distributor, it flows through the pores in the fabric inner liner 38, and out through the openings 14 in the receptacle 2. The rigid receptacle 2 directs the flow of molten aluminium, controlling the distribution and temperature profile of the metal in the mould, while the inner liner 38 reduces turbulence and traps surface based oxide inclusions and any large particles that may be washed into the distributor. After use, the inner fabric liner 38 can be removed and discarded, leaving the ceramic receptacle 2 in place. The receptacle 2 may be used many times before it has to be replaced. It is not therefore necessary to replace the entire distributor after every casting operation, thereby simplifying the manufacturing process and reducing cost and waste. Optionally, the rigid receptacle 2 may include electric heating elements (not shown), allowing it to be pre-heated in situ to the temperature of the molten aluminium prior to the casting process. Various modifications of the distributor device are possible. For example, the distributor need not necessarily have exactly the shape shown in the drawings but may be any shape, according to the dimensions and shape of the casting mould and the desired flow pattern. Additional windows and drain holes may also be provided, if required. Further, the inner liner may be replaced by a woven fabric bag on the outside the rigid receptacle, so that it is the last component through which the molten aluminium passes before entering the mould. Alternatively, it may be replaced by a different porous element, for example a rigid reticulated ceramic foam block that fits inside the receptacle 2, or a woven sock that fits over the spout, to filter the metal as it is poured into the distributor device.";"A distributor device for use in an aluminium casting operation to direct the flow of molten aluminium into a mould, the distributor device including a rigid, substantially bowl-shaped receptacle (2) of a refractory material having a base member (4) and a peripheral wall (6) that extends upwards from the base member and includes two side wall members (10) and two end wall members (12), said receptacle having an inlet opening (8) towards the upper end thereof and at least one outlet opening (14) in each of said end wall members (12) towards the base thereof, the device being constructed and arranged such that in use, molten aluminium poured into the distributor device through the inlet opening (8) is redirected by the distributor device and flows substantially horizontally outwards into the mould through said at least one outlet opening (14); characterised in that the upper surface of the base member (4) is inclined downwards towards the or each outlet opening (14). A distributor device according to claim 1, wherein the separation of the side wall members (10) increases towards the ends thereof. A distributor device according to claim 2, wherein the side wall members (10) are curved. A distributor device according to any one of the preceding claims, wherein the base member (4) includes a raised flow deflector (16). A distributor device according to any one of the preceding claims, wherein the peripheral wall (6) is inclined outwards. A distributor device according to any one of the preceding claims, including a heating element for pre-heating the device. A distributor device according to any one of the preceding claims, including a support structure (24,26). A distributor device according to any one of the preceding claims, including a porous element (38) constructed and arranged such that, in use, molten aluminium poured into the distributor device flows through said porous element. A distributor device according to claim 8, in which the porous element (38) includes a substantially bowl-shaped mesh of woven material that fits into and is supported by said receptacle (2), the arrangement being such that molten aluminium poured into the distributor device through the inlet opening (8) flows through the mesh of woven material before exiting through said at least one outlet opening (14). A distributor device according to claim 9, in which the porous element (38) includes a mesh of coated glass fibres. A distributor device according to any one of claims 9 or 10, in which the porous element (38) includes a support frame (45) that, in use, engages and is supported by the receptacle (2). An aluminium casting installation including a mould (20), a delivery device (28,30) for delivering molten aluminium into the mould and a distributor device (2) according to any one of the preceding claims, the distributor device (2) being mounted below the delivery device (28,30) and above the mould (20), the installation being constructed and arranged such that, in use, molten aluminium is poured from the delivery device into the mould through the distributor device. An aluminium casting installation according to claim 12, wherein the distributor device (2) is positioned so that, during pouring, it is partially immersed in the liquid metal in the mould (20) with said at least one outlet opening (14) below the surface (22) of the liquid metal.";TREMBLAY SILVAIN, VINCENT MARK, TREMBLAY, SILVAIN, VINCENT, MARK;PYROTEK ENGINEERING MATERIALS, PYROTEK ENGINEERING MATERIALS LIMITED;2005.0;1504834
EP-1506787-B1;20051207.0;EP;B1;EN;20100220.0;new;33566338.0;A61K39;A61K38;C07K16, A61K38;M07K316:960, K61K39:505, C07K  16/22, A61K  38/17C, M07K319:30;Vascular endothelial cell growth factor antagonists;The present invention provides human vascular endothelial cell growth factor (hVEGF) antagonists, including monoclonal antibodies, hVEGF receptors, and hVEGF variants that are useful for the treatment of age-related macular degeneration, as well as other diseases and disorders characterized by undesirable or excessive neovascularization.;"Field of the Invention The present invention relates to methods of use of the (VEGF) antagonists for therapeutic purposes. Background of the Invention The two major cellular components of the vasculature are the endothelial and smooth muscle cells. The endothelial cells form the lining of the inner surface of all blood vessels, and constitute a nonthrombogenic interface between blood and tissue. In addition, endothelial cells are an important component for the development of new capillaries and blood vessels. Thus, endothelial cells proliferate during the angiogenesis, or neovascularization, associated with tumor growth and metastasis, and a variety of non-neoplastic diseases or disorders. Various naturally occurring polypeptides reportedly induce the proliferation of endothelial cells. Among those polypeptides are the basic and acidic fibroblast growth factors (FGF), Burgess and Maciag, Annual Rev. Biochem., 58 :575 (1989), platelet-derived endothelial cell growth factor (PD-ECGF), Ishikawa, et al ., Nature, 338 :557 (1989), and vascular endothelial growth factor (VEGF), Leung, et al ., Science 246 : 1306. (1989); Ferrara & Henzel, Biochem. Biophys. Res. Commun. 161 :851 (1989); Tischer, et al ., Biochem. Biophys. Res. Commun. 165 :1198 (1989); Ferrara, et al ., PCT Pat. Pub. No. WO 90/13649 (published November 15, 1990); VEGF was first identified in media conditioned by bovine pituitary follicular or folliculostellate cells. Biochemical analyses indicate that bovine VEGF is a dimeric protein with an apparent molecular mass of approximately 45,000 Daltons, and with an apparent mitogenic specificity for vascular endothelial cells. DNA encoding bovine VEGF was isolated by screening a cDNA library prepared from such cells, using oligonuclcotides based on the amino-terminal amino acid sequence of the protein as hybridization probes. Human VEGF was obtained by first screening a cDNA library prepared from human cells, using bovine VEGF cDNA as a hybridization probe. One cDNA identified thereby encodes a 165-amino acid protein having greater than 95% homology to bovine VEGF, which protein is referred to as human VEGF (hVEGF). The mitogenic activity of human VEGF was confirmed by expressing the human VEGF cDNA in mammalian host cells. Media conditioned by cells transfected with the human VEGF cDNA promoted the proliferation of capillary endothelial cells, whereas control cells did not. Leung, et al ., Science 246 : 1306 (1989). Several additional cDNAs were identified in human cDNA libraries that encode 121-, 189-, and 206-amino acid isoforms of hVECF (also collectively referred to as hVEGF-related protein). The 121-amino acid protein differs from hVEGF by virtue of the deletion of the 44 amino acids between residues 116 and 159 in hVEGF. The 189-amino acid protein differs from hVEGF by virtue of the insertion of 24 amino acids at residue 116 in hVEGF, and apparently is identical to human vascular permeability factor (hVPF). The 206-amino acid protein differs from hVEGF by virtue of an insertion of 41 amino acids at residue 116 in hVEGF. Houck. et al ., Mol. Endocrin. 5 :1806 (1991); Ferrara et al ., J. Cell. Biochem. 47 :211 (1991); Ferrara, et al ., Endocrine Reviews 13 :18 (1992); Keck, et al ., Science 246 :1309 (1989); Connolly, et al ., J. Biol. Chem. 264 :20017 (1989); Keck, et al ., EPO Pat. Pub. No. 0 370 989 (published May 30, 1990). VEGF not only stimulates vascular endothelial cell proliferation, but also induces vascular permeability and angiogenesis. Angiogenesis, which involves the formation of new blood vessels from preexisting endothelium, is an important component of a variety of diseases and disorders including age-related macular degeneration (AMD). A review by D'Amore in Investigative Ophthalmology & Visual Science 35(12), 3974-3979 (1994) discusses possible mechanisms of retinal and choroidal neovascularisation. An abstract by Smith et al ., in Investigative Ophthalmology & Visual Science 36(4), 5871 (15 March 1995) discloses that antisense VEGF reduces retinal neovascularisation. Summary of the Invention The present invention provides the use of an hVEGF antagonist comprising the extracellular domain of a hVEGF receptor in the preparation of a medicament for the treatment of AMD. The antagonist inhibits the mitogenic, angiogenic, or other biological activity of hVEGF, and thus is useful for the treatment of AMD, which is characterized by undesirable excessive neovascularization. The VEGF antagonist may be conjugated with a cytotoxic moiety. If desired, the VEGF antagonist is coadministered, either simultaneously or sequentially, with one or more VEGF antagonists or anti-angiogenic substances. Brief Description of the Drawings Figure 1 shows the effect of anti-hVEGF monoclonal antibodies (A4.6.1 or B2.6.2) or an irrelevant anti-hepatocyte growth factor antibody (anti-HGF) on the binding of the anti-hVEGF monoclonal antibodies to hVEGF. Figure 2 shows the effect of anti-hVEGF monoclonal antibodies (A4.6,1 or B2.6.2) or an irrelevant anti-HGF antibody on the biological activity ofhVEGF in cultures of bovine adrenal cortex capillary endothelial (ACE) cells. Figure 3 shows the effect of anti-hVEGF monoclonal antibodies (A4.6.1, B2.6.2, or A2.6.1) on the binding ofhVEGF to bovine ACE cells. Figure 4 shows the effect of A4.6.1 anti-hVEGF monoclonal antibody treatment on the rate of growth of growth ofNEG55 tumors in mice. Figure 5 shows the effect of A4.6.1 anti-hVEGF monoclonal antibody treatment on the size of NEG55 tumors in mice after five weeks of treatment. Figure 6 shows the effect of A4.6.1 anti-hVEGF monoclonal antibody (VEGF Ab) treatment on the growth of SK-LMS-1 tumors in mice. Figure 7 shows the effect of varying doses of A4.6.1 anti-hVEGF monoclonal antibody (VEGF Ab) treatment on the growth of A673 tumors in mice, is shown in Figure 8 shows the effect of A4.6.1 anti-hVEGF monoclonal antibody on the growth and survival of NEG55 (G55) glioblastoma cells in culture. Figure 9 shows the effect of A4.6.1 anti-hVEGF monoclonal antibody on the growth and survival of A673 rhabdomyosarcoma cells in culture. Figure 10 shows the effect of A4.6.1 anti-hVEGF monoclonal antibody on human synovial fluid-induced chemotaxis of human endothelial cells. Detailed Description of the Invention The term ""hVEGF"" as used herein refers to the 165-amino acid human vascular endothelial cell growth factor, and related 121-, 189-, and 206-amino acid vascular endothelial cell growth factors, as described by Leung, et al ., Science 246 : 1306 (1989), and Houck, et al ., Mol. Endocrin. 5 :1806 (1991) together with the naturally occurring allelic and processed forms of those growth factors. The present invention relates to antagonists of hVEGF which are capable of inhibiting one or more of the biological activities ofhVEGF, for example, its mitogenic or angiogenic activity. Antagonists of hVEGF act by interfering with the binding of hVEGF to a cellular receptor, by incapacitating or killing cells which have been activated by hVEGF, or by interfering with vascular endothelial cell activation after hVEGF binding to a cellular receptor. Thus, included within the scope of the invention are hVEGF receptor, and fragments and amino acid sequence variants thereof as defined in the claims, which are capable of binding hVEGF. The term ""hVEGF receptor"" or ""hVEGFr"" as used herein refers to a cellular receptor for hVEGF. ordinarily a cell-surface receptor found on vascular endothelial cells, as well as variants thereof which retain the ability to bind hVEGF. The hVEGF receptors and variants thereof that are hVEGF antagonists will be in isolated form, rather than being integrated into a cell membrane or fixed to a cell surface as may be the case in nature. One example of a hVEGF receptor is the fms -like tyrosine kinase ( flt ), a transmembrane receptor in the tyrosine kinase family. DeVries, et al ., Science 255: 989 (1992); Shibuya, et al ., Oncogene 5 :519 (1990). The flt receptor comprises an extracellular domain, a transmembrane domain, and an intracellular domain with tyrosine kinase activity. The extracellular domain is involved in the binding of hVEGF, whereas the intracellular domain is involved in signal transduction. Another example of an hVEGF receptor is the flk-1 receptor (also referred to as KDR). Matthews, et al ., Proc. Nat. Acad. Sci. 88 :9026 (1991); Terman, et al ., Oncogene 6 :1677 (1991); Terman, et al ., Biochem. Biophys. Res. Commun. 187 :1579 (1992). Binding of hVEGF to the flt receptor results in the formation of at least two high molecular weight complexes, having apparent molecular weight of 205,000 and 300,000 Daltons. The 300,000 Dalton complex is believed to be a dimer comprising two receptor molecules bound to a single molecule of hVEGF. Variants of hVEGFr containing the extracellular domain are included within the scope hereof. Representative examples include truncated forms of a receptor in which the transmembrane and cytoplasmic domains are deleted from the receptor, and fusions proteins in which non-hVEGFr polymers or polypeptides are conjugated to the hVEGFr or, preferably, truncated forms thereof. An example of such a non-hVEGF polypeptide is an immunoglobulin. In that case, for example, the extracellular domain of the hVEGFr is substituted for the Fv domain of an immunoglobulin light or (preferably) heavy chain, with the C-terminus of the receptor extracellular domain covalently joined to the amino terminus of the CH1, hinge, CH2 or other fragment of the heavy chain. Such variants are made in the same fashion as known immunoadhesons. See e.g ., Gascoigne, et al ., Proc. Nat. Acad. Sci. 84 :2936 (1987); Capon, et al ., Nature 337 :525 (1989): Aruffb, et al ., Cell 61 :1303 (1990): Ashkenazi, et al ., Proc. Nat. Acad. Sci. 88 :10535 (1991); Bennett, et al ., J. Biol. Chem. 266 :23060 (1991). In other embodiments, the hVEGFr is conjugated to a non-proteinaceous polymer such as polyethylene glycol (PEG) ( see e.g ., Davis, et al ., U.S. Patent No. 4,179,337; Goodson, et al ., BioTechnology 8 ;343-346 (1990); Abuchowski, et al ., J. Biol. Chem. 252 :3578 (1977); Abuchowski, et al ., J. Biol. Chem. 252 :3582 (1977)) or carbohydrates ( see e.g ., Marshall, et al ., Arch. Biochem. Biophys., 167 :77 (1975)). This serves to extend the biological half-life of the hVEGFr and reduces the possibility that the receptor will be immunogenic in the mammal to which it is administered. The hVEGFr is used in substantially the same fashion as antibodies to hVEGF, taking into account the affinity of the antagonist and its valency for hVEGF. The extracellular domain of hVEGF receptor, either by itself or fused to an immunoglobulin polypeptide or other carrier polypeptide, is especially useful as an antagonist of hVEGF, by virtue of its ability to sequester hVEGF that is present in a host but that is not bound to hVEGFr on a cell surface. The term ""recombinant"" used in reference to hVEGF, hVEGF receptor, monoclonal antibodies, or other proteins, refers to proteins that are produced by recombinant DNA expression in a host cell. The host cell may be prokaryotic (for example, a bacterial cell such as E . coli ) or eukaryotic (for example, a yeast or a mammalian cell). Conjugates with Cytotoxic Moieties In some embodiments it is desireable to provide a cytotoxic moiety conjugated to hVEGFr. In these embodiments the cytotoxin serves to incapacitate or kill cells which are expressing or binding hVEGF. The conjugate is targeted to the cell by the domain which is capable of binding to hVEGF. Typically, the cytotoxin is a protein cytotoxin, e.g. diptheria, ricin or Pseudomonas toxin, although in the case of certain classes of immunoglobulins the Fc domain of the monoclonal antibody itself may serve to provide the cytotoxin (e.g., in the case of IgG2 antibodies, which are capable of fixing complement and participating in antibody-dependent cellular cytotoxicity (ADCC)). However, the cytotoxin does not need to be proteinaceous and may include chemotherapeutic agents heretofore employed, for example, for the treatment of tumors. Where the targeting function is supplied by hVEGFr, the cytotoxic moiety is substituted onto any domain of the receptor that does not participate in hVEGF binding; preferably, the moiety is substituted in place of or onto the transmembrane and or cytoplasmic domains of the receptor. The optimal site of substitution will be determined by routine experimentation and is well within the ordinary skill. Conjugates which are protein fusions are easily made in recombinant cell culture by expressing a gene encoding the conjugate. Alternatively, the conjugates are made by covalently crosslinking the cytotoxic moiety to an amino acid residue side chain or C-terminal carboxyl of the receptor, using methods known per se such as disulfide exchange or linkage through a thioester bond using for example iminothiolate and methyl-4-mercaptobutyrimadate. Conjugates with other Moieties The hVEGFr that are antagonists of hVEGF also are conjugated to substances that may not be readily classified as cytotoxins in their own right, but which augment the activity of the compositions herein. For example, hVEGFr capable of binding to hVEGF, are fused with heterologous polypeptides, such as viral sequences, with cellular receptors, with cytokines such as TNF, interferons, or intetleukins, with polypeptides having procoagulant activity, and with other biologically or immunologically active polypeptides. Such fusions are readily made by recombinant methods. Typically such non-immunoglobulin polypeptides are substituted for the transmembrane and/or intracellular domain of an hVEGFr. hVEGF binding domains in hVEGFr are determined by methods known in the art, including X-ray studies, mutational analyses, and antibody binding studies. The mutational approaches include the techniques of random saturation mutagenesis coupled with selection of escape mutants, and insertional mutagenesis. Another strategy suitable for identifying receptor-binding domains in ligands is known as alanine (Ala)-scanning mutagenesis. Cunningham, et al. , Science 244, 1081-1985 (1989). This method involves the identification of regions that contain charged amino acid side chains. The charged residues in each region identified (i.e. Arg, Asp, His, Lys, and Glu) are replaced (one region per mutant molecule) with Ala and the receptor binding of the obtained ligands is tested, to assess the importance of the particular region in receptor binding. A further powerful method for the localization of receptor binding domains is through the use of neutralizing anti-hVEGF antibodies. Kim, et al ., Growth Factors 7 :53 (1992). Usually a combination of these and similar methods is used for localizing the domains involved in receptor binding. Fragments and amino acid sequence variants of hVEGF are readily prepared by methods known in the art, such as by site directed mutagenesis of the DNA encoding the native factor. The mutated DNA is inserted into an appropriate expression vector, and host cells are then transfected with the recombinant vector. The recombinant host cells and grown in suitable culture medium, and the desired fragment or amino acid sequence variant expressed in the host cells then is recovered from the recombinant cell culture by chromatographic or other purification methods. Alternatively, fragments and amino acid variants of hVEGF are prepared in vitro , for example by proteolysis of native hVEGF, or by synthesis using standard solid-phase peptide synthesis procedures as described by Merrifield (J. Am. Chem. Soc. 85 :2149 [1963]), although other equivalent chemical syntheses known in the art may be used. Solid-phase synthesis is initiated from the C-terminus of the peptide by coupling a protected α-amino acid to a suitable resin. The amino acids are coupled to the peptide chain using techniques well known in the art for the formation of peptide bonds. Therapeutic Uses For therapeutic applications, the antagonists of the invention are administered to a mammal, preferably a human, in a pharmaceutically acceptable dosage form, including those that may be administered to a human intravenously as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intracerobrospinal, subcutaneous, intra-articular, intrasynovial, intrathecal, oral, topical, or inhalation routes. The antagonists also are suitably administered by intralesional, or perilesional routes, to exert local as well as systemic therapeutic effects. Such dosage forms encompass pharmaceutically acceptable carriers that are inherently nontoxic and nontherapeutic. Examples of such carriers include ion exchangers, alumina, aluminum stearate, lecithin, serum serum proteins, such as human serum albumin, buffer substances such as phosphates, glycine, sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids, water, salts, or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substances, and polyethylene glycol. Carriers for topical or gel-based forms of antagonist include polysaccharides such as sodium carboxymethylcellulose or methylcellulose, polyvinylpyrrolidone, polyacrylates, polyoxyethylene-polyoxypropylene-block polymers, polyethylene glycol, and wood wax alcohols. For all administrations, conventional depot forms are suitably used. Such forms include, for example, microcapsules, nano-capsules, liposomes, plasters, inhalation forms, nose sprays, sublingual tablets, and sustained-release preparations. The antagonist will typically be formulated in such vehicles at a concentration of about 0.1 mg/ml to 100 mg/ml. Suitable examples of sustained release preparations include semipermeable matrices of solid hydrophobic polymers containing the antagonist, which matrices are in the form of shaped articles, e.g. films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate) as described by Langer et al ., J. Biomed. Mater. Res. 15 :167 (1981) and Langer. Chem. Tech., 12 : 98-105 (1982), or poly(vinylalcohol), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and gamma ethyl-L-glutamate (Sidman et al ., Biopolymers, 22 :547 (1983), non-degradable ethylene-vinyl acetate (Langer et al ., supra ), degradable lactic acid-glycolic acid copolymers such as the Lupron Depot™ (injectable micropheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods. When encapsulated polypeptide antagonists remain in the body for a long time, they may denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thiodisulfide interchange, stabilization may be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions. Sustained-release hVEGF antagonist compositions also include liposomally entrapped antagonist hVEGFr. Liposomes containing the antagonists are prepared by methods known in the art, such as described in Epstein, et al ., Proc. Natl. Acad. Sci. USA, 82 :3688 (1985); Hwang, et al ., Proc. Natl. Acad. Sci. USA, 11 :4030.(1980); U.S. Patent No. 4,485,045; U.S. Patent No. 4,544,545. Ordinarily the liposomes are the small (about 200-800 Angstroms) unilamelar type in which the lipid content is greater than about 30 mol.% cholesterol, the selected proportion being adjusted for the optimal HRG therapy. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556. Another use comprises incorporating an hVEGF antagonist into formed articles. Such articles can be used in modulating endothelial cell growth and angiogenesis. For the prevention or treatment of disease, the appropriate dosage of antagonist will depend on the type of disease to be treated, as defined above, the severity and course of the disease, whether the antibodies are administered for preventive or therapeutic purposes, previous therapy, the patient's clinical history and response to the antagonist, and the discretion of the attending physician. The antagonist is suitably administered to the patient at one time or over a series of treatments. Age-related macular degeneration (AMD) is a leading cause of severe visual loss in the elderly population. The exudative form of AMD is characterized by choroidal neovascularization and retinal pigment epithelial cell detachment. Because choroidal neovascularization is associated with a dramatic worsening in prognosis, the VEGF antagonists of the present invention are expected to be especially useful in reducing the severity of AMD. Depending on the type and severity of the disease, about 1 µg/kg to 15 mg/kg of antagonist is an initial candidate dosage for administration to the patient, whether, for example, by one or more separate administrations, or by continuous infusion. A typical daily dosage might range from about 1 µg/kg to 100 mg/kg or more, depending on the factors mentioned above. For repeated administrations over several days or longer, depending on the condition, the treatment is repeated until a desired suppression of disease symptoms occurs. However, other dosage regimens may be useful. The progress of this therapy is easily monitored by conventional techniques and assays. According to another embodiment of the invention, the effectiveness of the antagonist in preventing or treating disease may be improved by administering the antagonist serially or in combination with another agent that is effective for those purposes, such as tumor necrosis factor (TNF), an antibody capable of inhibiting or neutralizing the angiogenic activity of acidic or basic fibroblast growth factor (FGF) or hepatocyte growth factor (HGF), an antibody capable of inhibiting or neutralizing the coagulant activities of tissue factor, protein C, or protein S ( see Esmon, et al ., PCT Patent Publication No. WO 91/01753, published 21 February 1991), an antibody capable of binding to HER2 receptor ( see Hudziak, et al ., PCT Patent Publication No. WO 89106692. published 27 July 1989), or one or more conventional therapeutic agents such as, for example, alkylating agents, folic acid antagonists, anti-metabolites of nucleic acid metabolism, antibiotics, pyrimidine analogs. 5-fluorouracil, cisplatin, purine nucleosides, amines, amino acids, triazol nucleosides, or corticosteroids. Such other agents may be present in the composition being administered or may be administered separately. The following examples are offered by way of illustration only and are not intended to limit the invention in any manner. EXAMPLE 1 (BACKGROUND) Preparation of Anti- hVEGF Monoclonal Antibodies To obtain hVEGF conjugated to keyhole limpet hemocyanin (KLH) for immunization, recombinant hVEGF (165 amino acids), Leung, et al. , Science 246 :1306 (1989), was mixed with KLH at a 4:1 ratio in the presence of 0.05% glutaraldehyde and the mixture was incubated at room temperature for 3 hours with gentle stirring. The mixture then was dialyzed against phosphate buffered saline (PBS) at 4° C. overnight. BALB/c mice were immunized four times every two weeks by intraperitoneal injections with 5 µg of hVEGF conjugated to 20 µg of KLH, and were boosted with the same dose of hVEGF conjugated to KLH four days prior to cell fusion. Spleen cells from the immunized mice were fused with P3X63Ag8U.1 myeloma cells, Yelton, et al ., Curr. Top. Microbiol. Immunol. 81 :1 (1978), using 35% polyethylene glycol (PEG) as described. Yarmush. et al ., Proc. Nat. Acad. Sci. 77 :2899 (1980). Hybridomas were selected in HAT medium. Supernatants from hybridoma cell cultures were screened for anti-hVEGF antibody production by an ELISA assay using hVEGF-coated microtiter plates. Antibody that was bound to hVEGF in each of the wells was determined using alkaline phosphatase-conjugated goat anti-mouse IgG immunoglobulin and the chromogenic substrate p-nitrophenyl phosphate. Harlow & Lane, Antibodies: A Laboratory Manual, p.597 (Cold Spring Harbor Laboratory, 1988). Hybridoma cells thus determined to produce anti-hVEGF antibodies were subcloned by limiting dilution, and two of those clones, designated A4.6.1 and B2.6.2, were chosen for further studies. EXAMPLE 2 (BACKGROUND) Characterization of Anti-hVEGF Monoclonal Antibodies A. Antigen Specificity The binding specificities of the anti-hVEGF monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas were determined by ELISA. The monoclonal antibodies were added to the wells of microtiter plates that previously had been coated with hVEGF, FGF, HGF, or epidermal growth factor (EGF). Bound antibody was detected with peroxidase conjugated goat anti-mouse IgG immunoglobulins. The results of those assays confirmed that the monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas bind to hVEGF. but not detectably to those other protein growth factors. B. Epitope Mapping A competitive binding ELISA was used to determine whether the monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas bind to the same or different epitopes (sites) within hVEGF. Kim, et al ., Infect. Immun. 57 :944 (1989). Individual unlabeled anti-hVEGF monoclonal antibodies (A4.6.1 or B2.6.2) or irrelevant anti-HGF antibody (IgG1 isotype) were added to the wells of microtiter plates that previously had been coated with hVEGF. Biotinylated anti-hVEGF monoclonal antibodies (BIO-A4.6.1 or BIO-B2.6.2) were then added. The ratio of biotinylated antibody to unlabeled antibody was 1:1000. Binding of the biotinylated antibodies was visualized by the addition of avidin-conjugated peroxidase, followed by o-phenylenediamine dihydrochloride and hydrogen peroxide. The color reaction, indicating the amount of biotinylated antibody bound, was determined by measuring the optical density (O.D) at 495 nm wavelength. As shown in Figure 1, in each case, the binding of the biotinylated anti-hVEGF antibody was inhibited by the corresponding unlabeled antibody, but not by the other unlabeled anti-hVEGF antibody or the anti-HGF antibody. These results indicate that the monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas bind to different epitopes within hVEGF. C. Isotyping The isotypes of the anti-hVEGF monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas were determined by ELISA. Samples of culture medium (supernatant) in which each of the hybridomas was growing were added to the wells of microtiter plates that had previously been coated with hVEGF. The captured anti-hVEGF monoclonal antibodies were incubated with different isotype-specific alkaline phosphatase-conjugated goat anti-mouse immunoglobulins, and the binding of the conjugated antibodies to the anti-hVEGF monoclonal antibodies was determined by the addition of p-nitrophenyl phosphate. The color reaction was measured at 405 nm with an ELISA plate reader. By that method, the isotype of the monoclonal antibodies produced by both the A4.6.1 and B2.6.2 hybridomas was determined to be IgG1. D. Binding affinity The affinities of the anti-hVEGF monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas for hVEGF were determined by a competitive binding assays. A predetermined sub-optimal concentration of monoclonal antibody was added to samples containing 20,000 - 40,000 cpm 125 I-hVEGF (1 - 2 ng) and various known amounts of unlabeled hVEGF (1 - 1000 ng). After 1 hour at room temperature, 100 µl of goat anti-mouse lg antisera (Pel-Freez, Rogers, AR USA) were added, and the mixtures were incubated another hour at room temperature. Complexes of antibody and bound protein (immune complexes) were precipitated by the addition of 500 µl of 6% polyethylene glycol (PEG, mol. wt. 8000) at 4° C., followed by centrifugation at 2000 x G. for 20 min. at 4° C. The amount of 125 I-hVEGF bound to the anti-hVEGF monoclonal antibody in each sample was determined by counting the pelleted material in a gamma counter. Affinity constants were calculated from the data by Scatchard analysis. The affinity of the anti-hVEGF monoclonal antibody produced by the A4.6.1 hybridoma was calculated to be 1.2 x 10 9 liters/mole. The affinity of the anti-hVEGF monoclonal antibody produced by the B2.6.2 hybridoma was calculated to be 2.5 x 10° liters/mole. E. Inhibition of hVEGF Mitogenic Activity Bovine adrenal cortex capillary endothelial (ACE) cells, Ferrara, et al ., Proc. Nat. Acad. Sci. 84 :5773 (1987), were seeded at a density of 10 4 cells/ml in 12 multiwell plates, and 2.5 ng/ml hVEGF was added to each well in the presence or absence of various concentrations of the anti-hVEGF monoclonal antibodies produced by the A4.6.1 or B2.6.2 hybridomas, or an irrelevant anti-HGF monoclonal antibody. After culturing 5 days, the cells in each well were counted in a Coulter counter. As a control, ACE cells were cultured in the absence of added hVEGF. As shown in Figure 2, both of the anti-hVEGF monoclonal antibodies inhibited the ability of the added hVEGF to support the growth or survival of the bovine ACE cells. The monoclonal antibody produced by the A4.6.1 hybridoma completely inhibited the mitogenic activity of hVEGF (greater than about 90% inhibition), whereas the monoclonal antibody produced by the B2.6.2 hybridoma only partially inhibited the mitogenic activity of hVEGF. F. Inhibition of hVEGF Binding Bovine ACE cells were seeded at a density of 2.5 x 10 4 cells/0.5 ml/well in 24 well microtiter plates in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% calf serum, 2 mM glutamine, and 1 ng/ml basic fibroblast growth factor. After culturing overnight, the cells were washed once in binding buffer (equal volumes of DMEM and F12 medium plus 25 mM HEPES and 1% bovine serum albumin) at 4° C. 12,000 cpm 125 I-hVEGF (approx. 5 x 10 4 cpm/ng/ml) was preincubated for 30 minutes with 5 µg of the anti-hVEGF monoclonal antibody produced by the A4.6.1, B2.6.2, or A2.6.1 hybridoma (250 µl total volume), and thereafter the mixtures were added to the bovine ACE cells in the microtiter plates. After incubating the cells for 3 hours at 4° C., the cells were washed 3 times with binding buffer at 4° C.. solubilized by the addition of 0.5 ml 0.2 N. NaOH, and counted in a gamma counter. As shown in Figure 3 (upper), the anti-hVEGF monoclonal antibodies produced by the A4.6.1 and B2.6.2 hybridomas inhibited the binding of hVEGF to the bovine ACE cells. In contrast, the anti-hVEGF monoclonal antibody produced by the A2.6.1 hybridoma had no apparent effect on the binding ot hVEGF to the bovine ACE cells. Consistent with the results obtained in the cell proliferation assay described above, the monoclonal antibody produced by the A4.6.1 hybridoma inhibited the binding of hVEGF to a greater extent than the monoclonal antibody produced by the B2.6.2 hybridoma. As shown in Figure 3 (lower), the monoclonal antibody produced by the A4.6.1 hybridoma completely inhibited the binding of hVEGF to the bovine ACE cells at a 1:250 molar ratio of hVEGF to antibody. G. Cross-reactivity with otherVEGF isoforms To determine whether the anti-hVEGF monoclonal antibody produced by the A4.6.1 hybridoma is reactive with the 121- and 189-amino acid forms of hVEGF, the antibody was assayed for its ability to immunoprecipate those polypeptides. Human 293 cells were transfected with vectors comprising the nucleotide coding sequence of the 121-and 189-amino acid hVEGF polypeptides, as described. Leung. et al ., Science 246 :1306 (1989). Two days after transfection, the cells were transferred to medium lacking cysteine and methionine. The cells were incubated 30 minutes in that medium, then 100 µCi/ml of each 35 S-methionine and 35 S-cysteine were added to the medium, and the cells were incubated another two hours. The labeling was chased by transferring the cells to serum free medium and incubating three hours. The cell culture media were collected, and the cells were lysed by incubating for 30 minutes in lysis buffer (150 mM NaCl, 1% NP40, 0.5% deoxycholate, 0.1% sodium dodecyl sulfate (SDS), 50 mM Tris, pH 8.0). Cell debris was removed from the lysates by centrifugation at 200 x G. for 30 minutes. 500 µl samples of cell culture media and cell lysates were incubated with 2 µl of A4.6.1 hybridoma antibody (2.4 mg/ml) for 1 hour at 4° C., and then were incubated with 5 µl of rabbit anti-mouse IgG immunoglobulin for 1 hour at 4° C. Immune complexes of 35 S-labeled hVEGF and anti-hVEGF monoclonal antibody were precipitated with protein-A Sepharose (Pharmacia), then subjected to SDS - 12% polyacrylamide gel electrophoresis under reducing conditions. The gel was exposed to x-ray film for analysis of the immunoprecipitated, radiolabeled proteins by autoradiography. The results of that analysis indicated that the anti-hVEGF monoclonal antibody produced by the A4.6.1 hybridoma was cross-reactive with both the 121- and 189-amino acid forms of hVEGF. EXAMPLE 3 Preparation of hVEGF Receptor-IgG Fusion Protein The nucleotide and amino acid coding sequences of the flt hVEGF receptor are disclosed in Shibuya, et al ., Oncogene 5 :519-524 (1990). The coding sequence of the extracellular domain of the flt hVEGF receptor was fused to the coding sequence of human IgG 1 heavy chain in a two-step process. Site-directed mutagenesis was used to introduce a BstBI restriction into DNA encoding flt at a site 5' to the codon for amino acid 759 of flt , and to convert the unique BstEII restriction site in plasmid pBSSK FC. Bennett, et al ., J. Biol. Chem. 266 :23060-23067 (1991), to a BstBl site. The modified plasmid was digested with EcoRI and BstBI and the resulting large fragment of plasmid DNA was ligated together with an EcoRI-BstBI fragment of the flt DNA encoding the extracellular domain (amino acids 1-758) of the flt hVEGF receptor. The resulting construct was digested with Clal and Notl to generate an approximately 3.3 kb fragment, which is then inserted into the multiple cloning site of the mammalian expression vector pHEBO2 (Leung, et al ., Neuron 8 :1045 (1992) by ligation. The ends of 3.3. kb fragment are modified, for example by the addition of linkers, to obtain insertion of the fragment into the vector in the correct orientation for expression. Mammalian host cells (for example, CEN4 cells (Leung, et al . supra ) are transfected with the pHEBO2 plasmid containing the flt insert by electroporation. Transfected cells are cultured in medium containing about 10% fetal bovine serum, 2 mM glutamine, and antibiotics, and at about 75% confluency are transferred to serum free medium. Medium is conditioned for 3-4 days prior to collection, and the flt -IgG fusion protein is purified from the conditioned medium by chromatography on a protein-A affinity matrix essentially as described in Bennett, et al ., J. Biol. Chem. 266 :23060-23067 (1991). EXAMPLE 4 (BACKGROUND) Inhibition of Tumor Growth with hVEGF Antagonists Various human tumor cell lines growing in culture were assayed for production of hVEGF by ELISA. Ovary, lung, colon, gastric, breast, and brain tumor cell lines were found to produce hVEGF. Three cell lines that produced hVEGF, NEG 55 (also referred to as G55) (human glioma cell line obtained from Dr. M. Westphal, Department of Neurosurgery, University Hospital Eppendor, Hamburg, Germany, also referred to as G55), A-673 (human rhabdomyosarcoma cell line obtained from the American Type Culture Collection (ATCC), Rockville, Maryland USA 20852 as cell line number CRL 1598), and SK-LMS-1 (leiomyosarcoma cell line obtained from the ATCC as cell line number HTB 88), were used for further studies. Six to ten week old female Beige/nude mice (Charles River Laboratory, Wilmington, Massachusetts USA) were injected subcutaneously with 1 - 5 x 10 6 tumor cells in 100-200 µl PBS. At various times after tumor growth was established, mice were injected intraperitoneally once or twice per week with various doses of A4.6.1 anti-hVEGF monoclonal antibody, an irrelevant anti-gp120 monoclonal antibody (5B6), or PBS. Tumor size was measured every week, and at the conclusion of the study the tumors were excised and weighed. The effect of various amounts of A4.6.1 anti-hVEGF monoclonal antibody on the growth of NEG 55 tumors in mice is shown in Figures 4 and 5. Figure 4 shows that mice treated with 25 µg or 100 µg of A4.6.1 anti-hVEGF monoclonal antibody beginning one week after inoculation of NEG 55 cells had a substantially reduced rate of tumor growth as compared to mice treated with either irrelevant antibody or PBS. Figure 5 shows that five weeks after inoculation of the NEG 55 cells, the size of the tumors in mice treated with A4.6.1 anti-hVEGF antibody was about 50% (in the case of mice treated with 25 µg dosages of the antibody) to 85% (in the case of mice treated with 100 µg dosages of the antibody) less than the size of tumors in mice treated with irrelevant antibody or PBS. The effect of A4.6.1 anti-hVEGF monoclonal antibody treatment on the growth of SK-LMS-1 tumors in mice is shown in Figure 6. Five weeks after innoculation of the SK-LMS-1 cells, the average size of tumors in mice treated with the A4.6.1 anti-hVEGF antibody was about 75% less than the size tumors in mice treated with irrelevant antibody or PBS. The effect of A4.6.1 anti-hVEGF monoclonal antibody treatment on the growth of A673 tumors in mice is shown in Figure 7. Four weeks after innoculation of the A673 cells, the average size of tumors in mice treated with A4.6.1 anti-hVEGF antibody was about 60% (in the case of mice treated with 10 µg dosages of the antibody) to greater than 90% (in the case of mice treated with 50-400 µg dosages of the antibody) less than the size of tumors in mice treated with irrelevant antibody or PBS. EXAMPLE 5 (BACKGROUND) Analysis of the Direct Effect of Anti-hVEGF Antibody on Tumor Cells Growing in Culture NEG55 human glioblastoma cells or A673 rhabdomyosarcoma cells were seeded at a density of 7 x 10 3 cells/well in multiwells plates (12 wells/plate) in F12/DMEM medium containing 10% fetal calf serum, 2mM glutamine, and antibiotics. A4.6.1 anti-hVEGF antibody then was added to the cell cultures to a final concentration of 0 - 20.0 µg antibody/ml. After five days, the cells growing in the wells were dissociated by exposure to trypsin and counted in a Coulter counter. Figures 8 and 9 show the results of those studies. As is apparent, the A4.6.1 anti-hVEGF antibody did not have any significant effect on the growth of the NEG55 or A673 cells in culture. These results indicate that the A4.6.1 anti-hVEGF antibody is not cytotoxic, and strongly suggest that the observed anti-tumor effects of the antibody are due to its inhibition of VEGF-mediated neovascularization. EXAMPLE 6 (BACKGROUND) Effect of Anti-hVEGF Antibody on Endothelial Cell Chemotaxis Chemotaxis of endothelial cells and others cells, including monocytes and lymphocytes, play an important role in the pathogenesis of rheumatoid arthritis. Endothelial cell migration and proliferation accompany the angiogenesis that occurs in the rheumatoid synovium. Vascularized tissue (pannus) invades and destroys the articular cartilage. To determine whether hVEGF antagonists interfere with this process, we assayed the effect of the A4.6.1 anti-hVEGF antibody on endothelial cell chemotaxis stimulated by synovial fluid from patients having rheumatoid arthritis. As a control, we also assayed the effect of the A4.6.1 anti-hVEGF antibody on endothelial cell chemotaxis stimulated by synovial fluid from patients having osteoarthritis (the angiogenesis that occurs in rheumatoid arthritis does not occur in osteoarthritis). Endothelial cell chemotaxis was assayed using modified Boyden chambers according to established procedures. Thompson, et al ., Cancer Res. 51 :2670 (1991); Phillips, et al ., Proc. Exp. Biol. Med. 197 :458 (1991). About 10 4 human umbilical vein endothelial cells were allowed to adhere to gelatin-coated filters (0.8 micron pore size) in 48-well multiwell microchambers in culture medium containing 0.1% fetal bovine serum. After about two hours, the chambers were inverted and test samples (rheumatoid arthritis synovial fluid, osteoarthritis synovial fluid, basic FGF (bFGF) (to a final concentration of 1 µg/ml), or PBS) and A4.6.1 anti-hVEGF antibody (to a final concentration of 10 µg/ml) were added to the wells. After two to four hours, cells that had migrated were stained and counted. Figure 10 shows the averaged results of those studies. The values shown in the column labeled ""Syn. Fluid"" and shown at the bottom of the page for the controls are the average number of endothelial cells that migrated in the presence of synovial fluid, bFGF, or PBS alone. The values in the column labeled ""Syn. Fluid + mAB VEGF"" are the average number of endothelial cells that migrated in the presence of synovial fluid plus added A4.6.1 anti-hVEGF antibody. The values in the column labeled ""% Suppression"" indicate the percentage reduction in synovial fluid-induced endothelial cell migration resulting from the addition of anti-hVEGF antibody. As indicated, the anti-hVEGF antibody significantly inhibited the ability of rheumatoid arthritis synovial fluid (53.40 average percentage inhibition), but not osteorthritis synovial fluid (13.64 average percentage inhibition), to induce endothelial cell migration.";Use of a hVEGF antagonist in the preparation of a medicament for the treatment of age-related macular degeneration in a human patient, wherein the hVEGF antagonist comprises the amino acid sequence of the extracellular domain of a hVEGFr. Use according to claim 1, wherein the hVEGFr is the fit receptor or the flk-1 (also referred to as KDR) receptor. Use according to claim 1 or claim 2, wherein the transmembrane and cytoplasmic domains of the hVEGFr are deleted. Use according to any preceding claim 1, wherein the hVEGF antagonist is a fusion protein further comprising a non-hVEGFr polymer or polypeptide. Use according to claim 4, wherein the non-hVEGFr polypeptide is an immunoglobulin. Use according to claim 5, wherein the extracellular domain of the hVEGFr is substituted for the Fv domain of an immunoglobulin light or heavy chain. Use according to claim 6, wherein the Fv domain is of an immunoglobulin heavy chain. Use according to claim 7, wherein the C-terminus of the receptor extracellular domain is covalently joined to the amino terminus of the C H 1, hinge or C H 2 of the heavy chain. Use according to claim 4, wherein the hVEGFr is conjugated to a non-proteinaceous polymer. Use according to claim 9, wherein the non-proteinaceous polymer is polyethylene glycol.;FERRARA NAPOLEONE, KIM KYUNG JIN, FERRARA, NAPOLEONE, KIM, KYUNG JIN;GENENTECH INC, GENENTECH, INC.;2005.0;1506787
EP-1507165-A1;20050216.0;EP;A1;EN;20090605.0;new;33569097.0;G02F1;;C09D11, G02B26, G02F1, G04G1, G06F3, G09F9, G09G3;C09D  11/00C, G02B  26/02P, G02F   1/167, G09F   9/302, G09F   9/37E, G09G   3/34E2, S02F1:1333B, S02F1:1334, S09G3:34E2;Novel addressing schemes for electrophoretic displays;Novel addressing schemes for controlling electronically addressable displays include a scheme for rear-addressing displays, which allows for in-plane switching of the display material. Other schemes include a rear-addressing scheme which uses a retroreflecting surface to enable greater viewing angle and contrast. Another scheme includes an electrode structure that facilitates manufacture and control of a color display. Another electrode structure facilitates addressing a display using an electrostatic stylus. Methods of using the disclosed electrode structures are also disclosed. Another scheme includes devices combining display materials with silicon transistor addressing structures.;"The present invention relates to addressing apparatus and methods for electronic displays, and in particular to addressing apparatus and methods for encapsulated electrophoretic displays. Background of the Invention Traditionally, electronic displays such as liquid crystal displays have been made by sandwiching an optoelectrically active material between two pieces of glass. In many cases each piece of glass has an etched, clear electrode structure formed using indium tin oxide. A first electrode structure controls all the segments of the display that may be addressed, that is, changed from one visual state to another. A second electrode, sometimes called a counter electrode, addresses all display segments as one large electrode, and is generally designed not to overlap any of the rear electrode wire connections that are not desired in the final image. Alternatively, the second electrode is also patterned to control specific segments of the displays. In these displays, unaddressed areas of the display have a defined appearance. Electrophoretic display media, generally characterized by the movement of particles through an applied electric field, are highly reflective, can be made bistable, and consume very little power. Encapsulated electrophoretic displays also enable the display to be printed. These properties allow encapsulated electrophoretic display media to be used in many applications for which traditional electronic displays are not suitable, such as flexible displays. The electro-optical properties of encapsulated displays allow, and in some cases require, novel schemes or configurations to be used to address the displays. Summary of the Invention An object of the invention is to provide a highly-flexible, reflective display which can be manufactured easily, consumes little (or no in the case of bistable displays) power, and can, therefore, be incorporated into a variety of applications. The invention features a printable display comprising an encapsulated electrophoretic display medium. The resulting display is flexible. Since the display media can be printed, the display itself can be made inexpensively. An encapsulated electrophoretic display can be constructed so that the optical state of the display is stable for some length of time. When the display has two states which are stable in this manner, the display is said to be bistable. If more than two states of the display are stable, then the display can be said to be multistable. For the purpose of this invention, the term bistable will be used to indicate a display in which any optical state remains fixed once the addressing voltage is removed. The definition of a bistable state depends on the application for the display. A slowly-decaying optical state can be effectively bistable if the optical state is substantially unchanged over the required viewing time. For example, in a display which is updated every few minutes, a display image which is stable for hours or days is effectively bistable for that application. In this invention, the term bistable also indicates a display with an optical state sufficiently long-lived as to be effectively bistable for the application in mind. Alternatively, it is possible to construct encapsulated electrophoretic displays in which the image decays quickly once the addressing voltage to the display is removed (i.e., the display is not bistable or multistable). As will be described, in some applications it is advantageous to use an encapsulated electrophoretic display which is not bistable. Whether or not an encapsulated electrophoretic display is bistable, and its degree of bistability, can be controlled through appropriate chemical modification of the electrophoretic particles, the suspending fluid, the capsule, and binder materials. An encapsulated electrophoretic display may take many forms. The display may comprise capsules dispersed in a binder. The capsules may be of any size or shape. The capsules may, for example, be spherical and may have diameters in the millimeter range or the micron range, but is preferably from ten to a few hundred microns. The capsules may be formed by an encapsulation technique, as described below. Particles may be encapsulated in the capsules. The particles may be two or more different types of particles. The particles may be colored, luminescent, light-absorbing or transparent, for example. The particles may include neat pigments, dyed (laked) pigments or pigment/polymer composites, for example. The display may further comprise a suspending fluid in which the particles are dispersed. The successful construction of an encapsulated electrophoretic display requires the proper interaction of several different types of materials and processes, such as a polymeric binder and, optionally, a capsule membrane. These materials must be chemically compatible with the electrophoretic particles and fluid, as well as with each other. The capsule materials may engage in useful surface interactions with the electrophoretic particles, or may act as a chemical or physical boundary between the fluid and the binder. In some cases, the encapsulation step of the process is not necessary, and the electrophoretic fluid may be directly dispersed or emulsified into the binder (or a precursor to the binder materials) and an effective ""polymer-dispersed electrophoretic display"" constructed. In such displays, voids created in the binder may be referred to as capsules or microcapsules even though no capsule membrane is present. The binder dispersed electrophoretic display may be of the emulsion or phase separation type. Throughout the specification, reference will be made to printing or printed. As used throughout the specification, printing is intended to include all forms of printing and coating, including: premetered coatings such as patch die coating, slot or extrusion coating, slide or cascade coating, and curtain coating; roll coating such as knife over roll coating, forward and reverse roll coating; gravure coating; dip coating; spray coating; meniscus coating; spin coating; brush coating; air knife coating; silk screen printing processes; electrostatic printing processes; thermal printing processes; and other similar techniques. A ""printed element"" refers to an element formed using any one of the above techniques. This invention provides novel methods and apparatus for controlling and addressing particle-based displays. Additionally, the invention discloses applications of these methods and materials on flexible substrates, which are useful in large-area, low cost, or high-durability applications. In one aspect, the present invention relates to an encapsulated electrophoretic display. The display includes a substrate and at least one capsule containing a highly-resistive fluid and a plurality of particles. The display also includes at least two electrodes disposed adjacent the capsule, a potential difference between the electrodes causing some of the particles to migrate toward at least one of the two electrodes. This causes the capsule to change optical properties. In another aspect, the present invention relates to a colored electrophoretic display. The electrophoretic display includes a substrate and at least one capsule containing a highly-resistive fluid and a plurality of particles. The display also includes colored electrodes. Potential differences are applied to the electrodes in order to control the particles and present a colored display to a viewer. In yet another aspect, the present invention relates to an electrostatically addressable display comprising a substrate, an encapsulated electrophoretic display adjacent the substrate, and an optional dielectric sheet adjacent the electrophoretic display. Application of an electrostatic charge to the dielectric sheet or display material modulates the appearance of the electrophoretic display. In still another aspect, the present invention relates to an electrostatically addressable encapsulated display comprising a film and a pair of electrodes. The film includes at least one capsule containing an electrophoretic suspension. The pair of electrodes is attached to either side of the film. Application of an electrostatic charge to the film modulates the optical properties. In still another aspect, the present invention relates to an electrophoretic display that comprises a conductive substrate, and at least one capsule printed on such substrate. Application of an electrostatic charge to the capsule modulates the optical properties of the display. In still another aspect the present invention relates to a method for matrix addressing an encapsulated display. The method includes the step of providing three or more electrodes for each display cell and applying a sequence of potentials to the electrodes to control movement of particles within each cell. In yet another aspect, the present invention relates to a matrix addressed electrophoretic display. The display includes a capsule containing charged particles and three or more electrodes disposed adjacent the capsule. A sequence of voltage potentials is applied to the three or more electrodes causing the charged particles to migrate within the capsule responsive to the sequence of voltage potentials. In still another aspect, the present invention relates to a rear electrode structure for electrically addressable displays. The structure includes a substrate, a first electrode disposed on a first side of the substrate, and a conductor disposed on a second side of the substrate. The substrate defines at least one conductive via in electrical communication with both the first electrode and the conductor. Brief Description of the Drawings The invention is pointed out with particularity in the appended claims. The advantages of the invention described above, together with further advantages, may be better understood by referring to the following description taken in conjunction with the accompanying drawings. In the drawings, like reference characters generally refer to the same parts throughout the different views. Also, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. FIG. 1A is a diagrammatic side view of an embodiment of a rear-addressing electrode structure for a particle-based display in which the smaller electrode has been placed at a voltage relative to the large electrode causing the particles to migrate to the smaller electrode. FIG. 1B is a diagrammatic side view of an embodiment of a rear-addressing electrode structure for a particle-based display in which the larger electrode has been placed at a voltage relative to the smaller electrode causing the particles to migrate to the larger electrode. FIG. 1C is a diagrammatic top-down view of one embodiment of a rear-addressing electrode structure. FIG. 2A is a diagrammatic side view of an embodiment of a rear-addressing electrode structure having a retroreflective layer associated with the larger electrode in which the smaller electrode has been placed at a voltage relative to the large electrode causing the particles to migrate to the smaller electrode. FIG. 2B is a diagrammatic side view of an embodiment of a rear-addressing electrode structure having a retroreflective layer associated with the larger electrode in which the larger electrode has been placed at a voltage relative to the smaller electrode causing the particles to migrate to the larger electrode. FIG. 2C is a diagrammatic side view of an embodiment of a rear-addressing electrode structure having a retroreflective layer disposed below the larger electrode in which the smaller electrode has been placed at a voltage relative to the large electrode causing the particles to migrate to the smaller electrode. FIG. 2D is a diagrammatic side view of an embodiment of a rear-addressing electrode structure having a retroreflective layer disposed below the larger electrode in which the larger electrode has been placed at a voltage relative to the smaller electrode causing the particles to migrate to the larger electrode. FIG. 3A is a diagrammatic side view of an embodiment of an addressing structure in which a direct-current electric field has been applied to the capsule causing the particles to migrate to the smaller electrode. FIG. 3B is a diagrammatic side view of an embodiment of an addressing structure in which an alternating-current electric field has been applied to the capsule causing the particles to disperse into the capsule. FIG. 3C is a diagrammatic side view of an embodiment of an addressing structure having transparent electrodes, in which a direct-current electric field has been applied to the capsule causing the particles to migrate to the smaller electrode. FIG. 3D is a diagrammatic side view of an embodiment of an addressing structure having transparent electrodes, in which an alternating-current electric field has been applied to the capsule causing the particles to disperse into the capsule. FIG. 4A is a diagrammatic side view of an embodiment of a rear-addressing electrode structure for a particle-based display in which multiple smaller electrodes have been placed at a voltage relative to multiple larger electrodes, causing the particles to migrate to the smaller electrodes. FIG. 4B is a diagrammatic side view of an embodiment of a rear-addressing electrode structure for a particle-based display in which multiple larger electrodes have been placed at a voltage relative to multiple smaller electrodes, causing the particles to migrate to the larger electrodes. FIG. 5A is a diagrammatic side view of an embodiment of a rear-addressing electrode structure for a particle-based display having colored electrodes and a white electrode, in which the colored electrodes have been placed at a voltage relative to the white electrode causing the particles to migrate to the colored electrodes. FIG. 5B is a diagrammatic side view of an embodiment of a rear-addressing electrode structure for a particle-based display having colored electrodes and a white electrode, in which the white electrode has been placed at a voltage relative to the colored electrodes causing the particles to migrate to the white electrode. FIG. 6 is a diagrammatic side view of an embodiment of a color display element having red, green, and blue particles of different electrophoretic mobilities. FIGs. 7A-7B depict the steps taken to address the display of FIG. 6 to display red. FIGs. 8A-8D depict the steps taken to address the display of FIG. 6 to display blue. FIGs. 9A-9C depict the steps taken to address the display of FIG. 6 to display green. FIG. 10 is a perspective embodiment of a rear electrode structure for addressing a seven segment display. FIG. 11 is a perspective embodiment of a rear electrode structure for addressing a three by three matrix display element. FIG. 12 is a cross-sectional view of a printed circuit board used as a rear electrode addressing structure. FIG. 13 is a cross-sectional view of a dielectric sheet used as a rear electrode addressing structure. FIG. 14 is a cross-sectional view of a rear electrode addressing structure that is formed by printing. FIG. 15 is a perspective view of an embodiment of a control grid addressing structure. FIG. 16 is an embodiment of an electrophoretic display that can be addressed using a stylus. Detailed Description of the Invention An electronic ink is an optoelectronically active material which comprises at least two phases: an electrophoretic contrast media phase and a coating/binding phase. The electrophoretic phase comprises, in some embodiments, a single species of electrophoretic particles dispersed in a clear or dyed medium, or more than one species of electrophoretic particles having distinct physical and electrical characteristics dispersed in a clear or dyed medium. In some embodiments the electrophoretic phase is encapsulated, that is, there is a capsule wall phase between the two phases. The coating/binding phase includes, in one embodiment, a polymer matrix that surrounds the electrophoretic phase. In this embodiment, the polymer in the polymeric binder is capable of being dried, crosslinked, or otherwise cured as in traditional inks, and therefore a printing process can be used to deposit the electronic ink onto a substrate. An electronic ink is capable of being printed by several different processes, depending on the mechanical properties of the specific ink employed. For example, the fragility or viscosity of a particular ink may result in a different process selection. A very viscous ink would not be well-suited to deposition by an inkjet printing process, while a fragile ink might not be used in a knife over roll coating process. The optical quality of an electronic ink is quite distinct from other electronic display materials. The most notable difference is that the electronic ink provides a high degree of both reflectance and contrast because it is pigment based (as are ordinary printing inks). The light scattered from the electronic ink comes from a very thin layer of pigment close to the top of the viewing surface. In this respect it resembles an ordinary, printed image. Also, electronic ink is easily viewed from a wide range of viewing angles in the same manner as a printed page, and such ink approximates a Lambertian contrast curve more closely than any other electronic display material. Since electronic ink can be printed, it can be included on the same surface with any other printed material, including traditional inks. Electronic ink can be made optically stable in all display configurations, that is, the ink can be set to a persistent optical state. Fabrication of a display by printing an electronic ink is particularly useful in low power applications because of this stability. Electronic ink displays are novel in that they can be addressed by DC voltages and draw very little current. As such, the conductive leads and electrodes used to deliver the voltage to electronic ink displays can be of relatively high resistivity. The ability to use resistive conductors substantially widens the number and type of materials that can be used as conductors in electronic ink displays. In particular, the use of costly vacuum-sputtered indium tin oxide (ITO) conductors, a standard material in liquid crystal devices, is not required. Aside from cost savings, the replacement of ITO with other materials can provide benefits in appearance, processing capabilities (printed conductors), flexibility, and durability. Additionally, the printed electrodes are in contact only with a solid binder, not with a fluid layer (like liquid crystals). This means that some conductive materials, which would otherwise dissolve or be degraded by contact with liquid crystals, can be used in an electronic ink application. These include opaque metallic inks for the rear electrode (e.g., silver and graphite inks), as well as conductive transparent inks for either substrate. These conductive coatings include semiconducting colloids, examples of which are indium tin oxide and antimony-doped tin oxide. Organic conductors (polymeric conductors and molecular organic conductors) also may be used. Polymers include, but are not limited to, polyaniline and derivatives, polythiophene and derivatives, poly3,4-ethylenedioxythiophene (PEDOT) and derivatives, polypyrrole and derivatives, and polyphenylenevinylene (PPV) and derivatives. Organic molecular conductors include, but are not limited to, derivatives of naphthalene, phthalocyanine, and pentacene. Polymer layers can be made thinner and more transparent than with traditional displays because conductivity requirements are not as stringent. As an example, there are a class of materials called electroconductive powders which are also useful as coatable transparent conductors in electronic ink displays. One example is Zelec ECP electroconductive powders from DuPont Chemical Co. of Wilmington, Delaware. Referring now to FIGs. 1A and 1B, an addressing scheme for controlling particle-based displays is shown in which electrodes are disposed on only one side of a display, allowing the display to be rear-addressed. Utilizing only one side of the display for electrodes simplifies fabrication of displays. For example, if the electrodes are disposed on only the rear side of a display, both of the electrodes can be fabricated using opaque materials, because the electrodes do not need to be transparent. FIG. 1A depicts a single capsule 20 of an encapsulated display media. In brief overview, the embodiment depicted in FIG. 1 A includes a capsule 20 containing at least one particle 50 dispersed in a suspending fluid 25. The capsule 20 is addressed by a first electrode 30 and a second electrode 40. The first electrode 30 is smaller than the second electrode 40. The first electrode 30 and the second electrode 40 may be set to voltage potentials which affect the position of the particles 50 in the capsule 20. The particles 50 represent 0.1% to 20% of the volume enclosed by the capsule 20. In some embodiments the particles 50 represent 2.5% to 17.5% of the volume enclosed by capsule 20. In preferred embodiments, the particles 50 represent 5% to 15% of the volume enclosed by the capsule 20. In more preferred embodiments the particles 50 represent 9% to 11% of the volume defined by the capsule 20. In general, the volume percentage of the capsule 20 that the particles 50 represent should be selected so that the particles 50 expose most of the second, larger electrode 40 when positioned over the first, smaller electrode 30. As described in detail below, the particles 50 may be colored any one of a number of colors. The particles 50 may be either positively charged or negatively charged. The particles 50 are dispersed in a dispersing fluid 25. The dispersing fluid 25 should have a low dielectric constant. The fluid 25 may be clear, or substantially clear, so that the fluid 25 does not inhibit viewing the particles 50 and the electrodes 30, 40 from position 10. In other embodiments, the fluid 25 is dyed. In some embodiments the dispersing fluid 25 has a specific gravity matched to the density of the particles 50. These embodiments can provide a bistable display media, because the particles 50 do not tend to move in certain compositions absent an electric field applied via the electrodes 30, 40. The electrodes 30, 40 should be sized and positioned appropriately so that together they address the entire capsule 20. There may be exactly one pair of electrodes 30, 40 per capsule 20, multiple pairs of electrodes 30, 40 per capsule 20, or a single pair of electrodes 30, 40 may span multiple capsules 20. In the embodiment shown in FIGs. 1A and 1B, the capsule 20 has a flattened, rectangular shape. In these embodiments, the electrodes 30, 40 should address most, or all, of the flattened surface area adjacent the electrodes 30, 40. The smaller electrode 30 is at most one-half the size of the larger electrode 40. In preferred embodiments the smaller electrode is one-quarter the size of the larger electrode 40; in more preferred embodiments the smaller electrode 30 is one-eighth the size of the larger electrode 40. In even more preferred embodiments, the smaller electrode 30 is one-sixteenth the size of the larger electrode 40. It should be noted that reference to ""smaller"" in connection with the electrode 30 means that the electrode 30 addresses a smaller amount of the surface area of the capsule 20, not necessarily that the electrode 30 is physically smaller than the larger electrode 40. For example, multiple capsules 20 may be positioned such that less of each capsule 20 is addressed by the ""smaller"" electrode 30, even though both electrodes 30, 40 are equal in size. It should also be noted that, as shown in FIG. 1C, electrode 30 may address only a small comer of a rectangular capsule 20 (shown in phantom view in FIG. 1C), requiring the larger electrode 40 to surround the smaller electrode 30 on two sides in order to properly address the capsule 20. Selection of the percentage volume of the particles 50 and the electrodes 30, 40 in this manner allow the encapsulated display media to be addressed as described below. Electrodes may be fabricated from any material capable of conducting electricity so that electrode 30, 40 may apply an electric field to the capsule 20. As noted above, the rear-addressed embodiments depicted in FIGs. 1A and 1B allow the electrodes 30, 40 to be fabricated from opaque materials such as solder paste, copper, copper-clad polyimide, graphite inks, silver inks and other metal-containing conductive inks. Alternatively, electrodes may be fabricated using transparent materials such as indium tin oxide and conductive polymers such as polyaniline or polythiopenes. Electrodes 30, 40 may be provided with contrasting optical properties. In some embodiments, one of the electrodes has an optical property complementary to optical properties of the particles 50. In one embodiment, the capsule 20 contains positively charged black particles 50, and a substantially clear suspending fluid 25. The first, smaller electrode 30 is colored black, and is smaller than the second electrode 40, which is colored white or is highly reflective. When the smaller, black electrode 30 is placed at a negative voltage potential relative to larger, white electrode 40, the positively-charged particles 50 migrate to the smaller, black electrode 30. The effect to a viewer of the capsule 20 located at position 10 is a mixture of the larger, white electrode 40 and the smaller, black electrode 30, creating an effect which is largely white. Referring to FIG. 1B, when the smaller, black electrode 30 is placed at a positive voltage potential relative to the larger, white electrode 40, particles 50 migrate to the larger, white electrode 40 and the viewer is presented a mixture of the black particles 50 covering the larger, white electrode 40 and the smaller, black electrode 30, creating an effect which is largely black. In this manner the capsule 20 may be addressed to display either a white visual state or a black visual state. Other two-color schemes are easily provided by varying the color of the smaller electrode 30 and the particles 50 or by varying the color of the larger electrode 40. For example, varying the color of the larger electrode 40 allows fabrication of a rear-addressed, two-color display having black as one of the colors. Alternatively, varying the color of the smaller electrode 30 and the particles 50 allow a rear-addressed two-color system to be fabricated having white as one of the colors. Further, it is contemplated that the particles 50 and the smaller electrode 30 can be different colors. In these embodiments, a two-color display may be fabricated having a second color that is different from the color of the smaller electrode 30 and the particles 50. For example, a rear-addressed, orange-white display may be fabricated by providing blue particles 50, a red, smaller electrode 30, and a white (or highly reflective) larger electrode 40. In general, the optical properties of the electrodes 30, 40 and the particles 50 can be independently selected to provide desired display characteristics. In some embodiments the optical properties of the dispersing fluid 25 may also be varied, e.g. the fluid 25 may be dyed. In other embodiments the larger electrode 40 may be reflective instead of white. In these embodiments, when the particles 50 are moved to the smaller electrode 30, light reflects off the reflective surface 60 associated with the larger electrode 40 and the capsule 20 appears light in color, e.g. white (see FIG. 2A). When the particles 50 are moved to the larger electrode 40, the reflecting surface 60 is obscured and the capsule 20 appears dark (see FIG. 2B) because light is absorbed by the particles 50 before reaching the reflecting surface 60. The reflecting surface 60 for the larger electrode 40 may possess retroflective properties, specular reflection properties, diffuse reflective properties or gain reflection properties. In certain embodiments, the reflective surface 60 reflects light with a Lambertian distribution The surface 60 may be provided as a plurality of glass spheres disposed on the electrode 40, a diffractive reflecting layer such as a holographically formed reflector, a surface patterned to totally internally reflect incident light, a brightness-enhancing film, a diffuse reflecting layer, an embossed plastic or metal film, or any other known reflecting surface. The reflecting surface 60 may be provided as a separate layer laminated onto the larger electrode 40 or the reflecting surface 60 may be provided as a unitary part of the larger electrode 40. In the embodiments depicted by FIGs. 2C and 2D, the reflecting surface may be disposed below the electrodes 30, 40 vis-à-vis the viewpoint 10. In these embodiments, electrode 30 should be transparent so that light may be reflected by surface 60. In other embodiments, proper switching of the particles may be accomplished with a combination of alternating-current (AC) and direct-current (DC) electric fields and described below in connection with FIGs. 3A-3D. In still other embodiments, the rear-addressed display previously discussed can be configured to transition between largely transmissive and largely opaque modes of operation (referred to hereafter as ""shutter mode""). Referring back to FIGs. 1A and 1B, in these embodiments the capsule 20 contains at least one positively-charged particle 50 dispersed in a substantially clear dispersing fluid 25. The larger electrode 40 is transparent and the smaller electrode 30 is opaque. When the smaller, opaque electrode 30 is placed at a negative voltage potential relative to the larger, transmissive electrode 40, the particles 50 migrate to the smaller, opaque electrode 30. The effect to a viewer of the capsule 20 located at position 10 is a mixture of the larger, transparent electrode 40 and the smaller, opaque electrode 30, creating an effect which is largely transparent. Referring to FIG. 1B, when the smaller, opaque electrode 30 is placed at a positive voltage potential relative to the larger, transparent electrode 40, particles 50 migrate to the second electrode 40 and the viewer is presented a mixture of the opaque particles 50 covering the larger, transparent electrode 40 and the smaller, opaque electrode 30, creating an effect which is largely opaque. In this manner, a display formed using the capsules depicted in FIGs. 1A and 1B may be switched between transmissive and opaque modes. Such a display can be used to construct a window that can be rendered opaque. Although FIGs. 1A-2D depict a pair of electrodes associated with each capsule 20, it should be understood that each pair of electrodes may be associated with more than one capsule 20. A similar technique may be used in connection with the embodiment of FIGs. 3A, 3B, 3C, and 3D. Referring to FIG. 3A, a capsule 20 contains at least one dark or black particle 50 dispersed in a substantially clear dispersing fluid 25. A smaller, opaque electrode 30 and a larger, transparent electrode 40 apply both direct-current (DC) electric fields and alternating-current (AC) fields to the capsule 20. A DC field can be applied to the capsule 20 to cause the particles 50 to migrate towards the smaller electrode 30. For example, if the particles 50 are positively charged, the smaller electrode is placed a voltage that is more negative than the larger electrode 40. Although FIGs. 3A-3D depict only one capsule per electrode pair, multiple capsules may be addressed using the same electrode pair. The smaller electrode 30 is at most one-half the size of the larger electrode 40. In preferred embodiments the smaller electrode is one-quarter the size of the larger electrode 40; in more preferred embodiments the smaller electrode 30 is one-eighth the size of the larger electrode 40. In even more preferred embodiments, the smaller electrode 30 is one-sixteenth the size of the larger electrode 40. Causing the particles 50 to migrate to the smaller electrode 30, as depicted in FIG. 3A, allows incident light to pass through the larger, transparent electrode 40 and be reflected by a reflecting surface 60. In shutter mode, the reflecting surface 60 is replaced by a translucent layer, a transparent layer, or a layer is not provided at all, and incident light is allowed to pass through the capsule 20, i.e. the capsule 20 is transmissive. Referring now to FIG. 3B, the particles 50 are dispersed into the capsule 20 by applying an AC field to the capsule 20 via the electrodes 30, 40. The particles 50, dispersed into the capsule 20 by the AC field, block incident light from passing through the capsule 20, causing it to appear dark at the viewpoint 10. The embodiment depicted in FIGs. 3A-3B may be used in shutter mode by not providing the reflecting surface 60 and instead providing a translucent layer, a transparent layer, or no layer at all. In shutter mode, application of an AC electric field causes the capsule 20 to appear opaque. The transparency of a shutter mode display formed by the apparatus depicted in FIGs. 3A-3D may be controlled by the number of capsules addressed using DC fields and AC fields. For example, a display in which every other capsule 20 is addressed using an AC field would appear fifty percent transmissive. FIGs. 3C and 3D depict an embodiment of the electrode structure described above in which electrodes 30, 40 are on ""top"" of the capsule 20, that is, the electrodes 30, 40 are between the viewpoint 10 and the capsule 20. In these embodiments, both electrodes 30, 40 should be transparent. Transparent polymers can be fabricated using conductive polymers, such as polyaniline, polythiophenes, or indium tin oxide. These materials may be made soluble so that electrodes can be fabricated using coating techniques such as spin coating, spray coating, meniscus coating, printing techniques, forward and reverse roll coating and the like. In these embodiments, light passes through the electrodes 30, 40 and is either absorbed by the particles 50, reflected by retroreflecting layer 60 (when provided), or transmitted throughout the capsule 20 (when retroreflecting layer 60 is not provided). The addressing structure depicted in FIGs. 3A-3D may be used with electrophoretic display media and encapsulated electrophoretic display media. FIGs. 3A-3D depict embodiments in which electrode 30, 40 are statically attached to the display media. In certain embodiments, the particles 50 exhibit bistability, that is, they are substantially motionless in the absence of a electric field. In these embodiments, the electrodes 30, 40 may be provided as part of a ""stylus"" or other device which is scanned over the material to address each capsule or cluster of capsules. This mode of addressing particle-based displays will be described in more detail below in connection with FIG. 16. Referring now to FIGs. 4A and 4B, a capsule 20 of a electronically addressable media is illustrated in which the technique illustrated above is used with multiple rear-addressing electrodes. The capsule 20 contains at least one particle 50 dispersed in a clear suspending fluid 25. The capsule 20 is addressed by multiple smaller electrodes 30 and multiple larger electrodes 40. In these embodiments, the smaller electrodes 30 should be selected to collectively be at most one-half the size of the larger electrodes 40. In further embodiments, the smaller electrodes 30 are collectively one-fourth the size of the larger electrodes 40. In further embodiments the smaller electrodes 30 are collectively one-eighth the size of the larger electrodes 40. In preferred embodiments, the smaller electrodes 30 are collectively one-sixteenth the size of the larger electrodes. Each electrode 30 may be provided as separate electrodes that are controlled in parallel to control the display. For example, each separate electrode may be substantially simultaneously set to the same voltage as all other electrodes of that size. Alternatively, the electrodes 30, 40 may be interdigitated to provide the embodiment shown in FIGs. 4A and 4B. Operation of the rear-addressing electrode structure depicted in FIGs. 4A and 4B is similar to that described above. For example, the capsule 20 may contain positively charged, black particles 50 dispersed in a substantially clear suspending fluid 25. The smaller electrodes 30 are colored black and the larger electrodes 40 are colored white or are highly reflective. Referring to FIG. 4A, the smaller electrodes 30 are placed at a negative potential relative to the larger electrodes 40, causing particles 50 migrate within the capsule to the smaller electrodes 30 and the capsule 20 appears to the viewpoint 10 as a mix of the larger, white electrodes 40 and the smaller, black electrodes 30, creating an effect which is largely white. Referring to Fig. 4B, when the smaller electrodes 30 are placed at a positive potential relative to the larger electrodes 40, particles 50 migrate to the larger electrodes 40 causing the capsule 20 to display a mix of the larger, white electrodes 40 occluded by the black particles 50 and the smaller, black electrodes 30, creating an effect which is largely black. The techniques described above with respect to the embodiments depicted in FIGs. 1A and 1B for producing two-color displays work with equal effectiveness in connection with these embodiments. FIGs. 5A and 5B depict an embodiment of a rear-addressing electrode structure that creates a reflective color display in a manner similar to halftoning or pointillism. The capsule 20 contains white particles 55 dispersed in a clear suspending fluid 25. Electrodes 42, 44, 46, 48 are colored cyan, magenta, yellow, and white respectively. Referring to FIG 5A, when the colored electrodes 42, 44, 46 are placed at a positive potential relative to the white electrode 48, negatively-charged particles 55 migrate to these three electrodes, causing the capsule 20 to present to the viewpoint 10 a mix of the white particles 55 and the white electrode 48, creating an effect which is largely white. Referring to FIG. 5B, when electrodes 42, 44, 46 are placed at a negative potential relative to electrode 48, particles 55 migrate to the white electrode 48, and the eye 10 sees a mix of the white particles 55, the cyan electrode 42, the magenta electrode 44, and the yellow electrode 46, creating an effect which is largely black or gray. By addressing the electrodes, any color can be produced that is possible with a subtractive color process. For example, to cause the capsule 20 to display an orange color to the viewpoint 10, the yellow electrode 46 and the magenta electrode 42 are set to a voltage potential that is more positive than the voltage potential applied by the cyan electrode 42 and the white electrode 48. Further, the relative intensities of these colors can be controlled by the actual voltage potentials applied to the electrodes. In another embodiment, depicted in FIG. 6, a color display is provided by a capsule 20 of size d containing multiple species of particles in a clear, dispersing fluid 25. Each species of particles has different optical properties and possess different electrophoretic mobilities (µ) from the other species. In the embodiment depicted in FIG. 6, the capsule 20 contains red particles 52, blue particles 54, and green particles 56, and |µ R | 〉 |µ B | 〉 |µ G | That is, the magnitude of the electrophoretic mobility of the red particles 52, on average, exceeds the electrophoretic mobility of the blue particles 54, on average, and the electrophoretic mobility of the blue particles 54, on average, exceeds the average electrophoretic mobility of the green particles 56. As an example, there may be a species of red particle with a zeta potential of 100 millivolts (mV), a blue particle with a zeta potential of 60 mV, and a green particle with a zeta potential of 20 mV. The capsule 20 is placed between two electrodes 32, 42 that apply an electric field to the capsule. FIGs. 7A-7B depict the steps to be taken to address the display shown in FIG. 6 to display a red color to a viewpoint 10. Referring to FIG. 7A, all the particles 52, 54, 56 are attracted to one side of the capsule 20 by applying an electric field in one direction. The electric field should be applied to the capsule 20 long enough to attract even the more slowly moving green particles 56 to the electrode 34. Referring to FIG. 7B, the electric field is reversed just long enough to allow the red particles 52 to migrate towards the electrode 32. The blue particles 54 and green particles 56 will also move in the reversed electric field, but they will not move as fast as the red particles 52 and thus will be obscured by the red particles 52. The amount of time for which the applied electric field must be reversed can be determined from the relative electrophoretic mobilities of the particles, the strength of the applied electric field, and the size of the capsule. FIGs. 8A-8D depict addressing the display element to a blue state. As shown in FIG. 8A, the particles 52, 54, 56 are initially randomly dispersed in the capsule 20. All the particles 52, 54, 56 are attracted to one side of the capsule 20 by applying an electric field in one direction (shown in FIG. 8B). Referring to FIG. 8C, the electric field is reversed just long enough to allow the red particles 52 and blue particles 54 to migrate towards the electrode 32. The amount of time for which the applied electric field must be reversed can be determined from the relative electrophoretic mobilities of the particles, the strength of the applied electric field, and the size of the capsule. Referring to FIG. 8D, the electric field is then reversed a second time and the red particles 52, moving faster than the blue particles 54, leave the blue particles 54 exposed to the viewpoint 10. The amount of time for which the applied electric field must be reversed can be determined from the relative electrophoretic mobilities of the particles, the strength of the applied electric field, and the size of the capsule. FIGs. 9A-9C depict the steps to be taken to present a green display to the viewpoint 10. As shown in FIG. 9A, the particles 52, 54, 56 are initially distributed randomly in the capsule 20. All the particles 52, 54, 56 are attracted to the side of the capsule 20 proximal the viewpoint 10 by applying an electric field in one direction. The electric field should be applied to the capsule 20 long enough to attract even the more slowly moving green particles 56 to the electrode 32. As shown in FIG. 9C, the electric field is reversed just long enough to allow the red particles 52 and the blue particles 54 to migrate towards the electrode 54, leaving the slowly-moving green particles 56 displayed to the viewpoint. The amount of time for which the applied electric field must be reversed can be determined from the relative electrophoretic mobilities of the particles, the strength of the applied electric field, and the size of the capsule. In other embodiments, the capsule contains multiple species of particles and a dyed dispersing fluid that acts as one of the colors. In still other embodiments, more than three species of particles may be provided having additional colors. Although FIGS. 6-9C depict two electrodes associated with a single capsule, the electrodes may address multiple capsules or less than a full capsule In FIG. 10, the rear substrate 100 for a seven segment display is shown that improves on normal rear electrode structures by providing a means for arbitrarily connecting to any electrode section on the rear of the display without the need for conductive trace lines on the surface of the patterned substrate or a patterned counter electrode on the front of the display. Small conductive vias through the substrate allow connections to the rear electrode structure. On the back of the substrate, these vias are connected to a network of conductors. This conductors can be run so as to provide a simple connection to the entire display. For example, segment 112 is connected by via 114 through the substrate 116 to conductor 118. A network of conductors may run multiple connections (not shown) to edge connector 122. This connector can be built into the structure of the conductor such as edge connector 122. Each segment of the rear electrode can be individually addressed easily through edge connector 122. A continuous top electrode can be used with the substrate 116. The rear electrode structure depicted in FIG. 10 is useful for any display media, but is particularly advantageous for particle-based displays because such displays do not have a defined appearance when not addressed. The rear electrode should be completely covered in an electrically conducting material with room only to provide necessary insulation of the various electrodes. This is so that the connections on the rear of the display can be routed with out concern for affecting the appearance of the display. Having a mostly continuous rear electrode pattern assures that the display material is shielded from the rear electrode wire routing. In FIG. 11, a 3x3 matrix is shown. Here, matrix segment 124 on a first side of substrate 116 is connected by via 114 to conductor 118 on a second side of substrate 116. The conductors 18 run to an edge and terminate in a edge connector 122. Although the display element of FIG. 11 shows square segments 124, the segments may be shaped or sized to form a predefined display pattern. In FIG. 12, a printed circuit board 138 is used as the rear electrode structure. The front of the printed circuit board 138 has copper pads 132 etched in the desired shape. There are plated vias 114 connecting these electrode pads to an etched wire structure 136 on the rear of the printed circuit board 138. The wires 136 can be run to one side or the rear of the printed circuit board 138 and a connection can be made using a standard connector such as a surface mount connector or using a flex connector and anisotropic glue (not shown). Vias may be filled with a conductive substance, such as solder or conductive epoxy, or an insulating substance, such as epoxy. Alternatively, a flex circuit such a copper-clad polyimide may be used for the rear electrode structure of FIG. 10. Printed circuit board 138 may be made of polyimide, which acts both as the flex connector and as the substrate for the electrode structure. Rather than copper pads 132, electrodes (not shown) may be etched into the copper covering the polyimide printed circuit board 138. The plated through vias 114 connect the electrodes etched onto the substrate the rear of the printed circuit board 138, which may have an etched conductor network thereon (the etched conductor network is similar to the etched wire structure 136). In FIG. 13, a thin dielectric sheet 150, such as polyester, polyimide, or glass can be used to make a rear electrode structure. Holes 152 are punched, drilled, abraded, or melted through the sheet where conductive paths are desired. The front electrode 154 is made of conductive ink printed using any technique described above. The holes should be sized and the ink should be selected to have a viscosity so that the ink fills the holes. When the back structure 156 is printed, again using conductive ink, the holes are again filled. By this method, the connection between the front and back of the substrate is made automatically. In FIG. 14, the rear electrode structure can be made entirely of printed layers. A conductive layer 166 can be printed onto the back of a display comprised of a clear, front electrode 168 and a printable display material 170. A clear electrode may be fabricated from indium tin oxide or conductive polymers such as polyanilines and polythiophenes. A dielectric coating 176 can be printed leaving areas for vias. Then, the back layer of conductive ink 178 can be printed. If necessary, an additional layer of conductive ink can be used before the final ink structure is printed to fill in the holes. This technique for printing displays can be used to build the rear electrode structure on a display or to construct two separate layers that are laminated together to form the display. For example an electronically active ink may be printed on an indium tin oxide electrode. Separately, a rear electrode structure as described above can be printed on a suitable substrate, such as plastic, polymer films, or glass. The electrode structure and the display element can be laminated to form a display. Referring now to FIG. 15, a threshold may be introduced into an electrophoretic display cell by the introduction of a third electrode. One side of the cell is a continuous, transparent electrode 200 (anode). On the other side of the cell, the transparent electrode is patterned into a set of isolated column electrode strips 210. An insulator 212 covers the column electrodes 210, and an electrode layer on top of the insulator is divided into a set of isolated row electrode strips 230, which are oriented orthogonal to the column electrodes 210. The row electrodes 230 are patterned into a dense array of holes, or a grid, beneath which the exposed insulator 212 has been removed, forming a multiplicity of physical and potential wells. A positively charged particle 50 is loaded into the potential wells by applying a positive potential (e.g. 30V) to all the column electrodes 210 while keeping the row electrodes 230 at a less positive potential (e.g. 15V) and the anode 200 at zero volts. The particle 50 may be a conformable capsule that situates itself into the physical wells of the control grid. The control grid itself may have a rectangular cross-section, or the grid structure may be triangular in profile. It can also be a different shape which encourages the microcapsules to situate in the grid, for example, hemispherical. The anode 200 is then reset to a positive potential (e.g. 50V). The particle will remain in the potential wells due to the potential difference in the potential wells: this is called the Hold condition. To address a display element the potential on the column electrode associated with that element is reduced, e.g. by a factor of two, and the potential on the row electrode associated with that element is made equal to or greater than the potential on the column electrode. The particles in this element will then be transported by the electric field due to the positive voltage on the anode 200. The potential difference between row and column electrodes for the remaining display elements is now less than half of that in the normal Hold condition. The geometry of the potential well structure and voltage levels are chosen such that this also constitutes a Hold condition, i.e., no particles will leave these other display elements and hence there will be no half-select problems. This addressing method can select and write any desired element in a matrix without affecting the pigment in any other display element. A control electrode device can be operated such that the anode electrode side of the cell is viewed. The control grid may be manufactured through any of the processes known in the art, or by several novel processes described herein. That is, according to traditional practices, the control grid may be constructed with one or more steps of photolithography and subsequent etching, or the control grid may be fabricated with a mask and a ""sandblasting"" technique. In another embodiment, the control grid is fabricated by an embossing technique on a plastic substrate. The grid electrodes may be deposited by vacuum deposition or sputtering, either before or after the embossing step. In another embodiment, the electrodes are printed onto the grid structure after it is formed, the electrodes consisting of some kind of printable conductive material which need not be clear (e.g. a metal or carbon-doped polymer, an intrinsically conducting polymer, etc.). In a preferred embodiment, the control grid is fabricated with a series of printing steps. The grid structure is built up in a series of one or more printed layers after the cathode has been deposited, and the grid electrode is printed onto the grid structure. There may be additional insulator on top of the grid electrode, and there may be multiple grid electrodes separated by insulator in the grid structure. The grid electrode may not occupy the entire width of the grid structure, and may only occupy a central region of the structure, in order to stay within reproducible tolerances. In another embodiment, the control grid is fabricated by photoetching away a glass, such as a photostructural glass. In an encapsulated electrophoretic image display, an electrophoretic suspension, such as the ones described previously, is placed inside discrete compartments that are dispersed in a polymer matrix. This resulting material is highly susceptible to an electric field across the thickness of the film. Such a field is normally applied using electrodes attached to either side of the material. However, as described above in connection with FIGs. 3A-3D, some display media may be addressed by writing electrostatic charge onto one side of the display material. The other side normally has a clear or opaque electrode. For example, a sheet of encapsulated electrophoretic display media can be addressed with a head providing DC voltages. In another implementation, the encapsulated electrophoretic suspension can be printed onto an area of a conductive material such as a printed silver or graphite ink, aluminized mylar, or any other conductive surface. This surface which constitutes one electrode of the display can be set at ground or high voltage. An electrostatic head consisting of many electrodes can be passed over the capsules to addressing them. Alternatively, a stylus can be used to address the encapsulated electrophoretic suspension. In another implementation, an electrostatic write head is passed over the surface of the material. This allows very high resolution addressing. Since encapsulated electrophoretic material can be placed on plastic, it is flexible. This allows the material to be passed through normal paper handling equipment. Such a system works much like a photocopier, but with no consumables. The sheet of display material passes through the machine and an electrostatic or electrophotographic head addresses the sheet of material. In another implementation, electrical charge is built up on the surface of the encapsulated display material or on a dielectric sheet through frictional or triboelectric charging. The charge can built up using an electrode that is later removed. In another implementation, charge is built up on the surface of the encapsulated display by using a sheet of piezoelectric material. FIG. 16 shows an electrostatically written display. Stylus 300 is connected to a positive or negative voltage. The head of the stylus 300 can be insulated to protect the user. Dielectric layer 302 can be, for example, a dielectric coating or a film of polymer. In other embodiments, dielectric layer 302 is not provided and the stylus 300 contacts the encapsulated electrophoretic display 304 directly. Substrate 306 is coated with a clear conductive coating such as ITO coated polyester. The conductive coating is connected to ground. The display 304 may be viewed from either side. Microencapsulated displays offer a useful means of creating electronic displays, many of which can be coated or printed. There are many versions of microencapsulated displays, including microencapsulated electrophoretic displays. These displays can be made to be highly reflective, bistable, and low power. To obtain high resolution displays, it is useful to use some external addressing means with the microencapsulated material. This invention describes useful combinations of addressing means with microencapsulated electrophoretic materials in order to obtain high resolution displays. One method of addressing liquid crystal displays is the use of silicon-based thin film transistors to form an addressing backplane for the liquid crystal. For liquid crystal displays, these thin film transistors are typically deposited on glass, and are typically made from amorphous silicon or polysilicon. Other electronic circuits (such as drive electronics or logic) are sometimes integrated into the periphery of the display. An emerging field is the deposition of amorphous or polysilicon devices onto flexible substrates such as metal foils or plastic films. The addressing electronic backplane could incorporate diodes as the nonlinear element, rather than transistors. Diode-based active matrix arrays have been demonstrated as being compatible with liquid crystal displays to form high resolution devices. There are also examples of crystalline silicon transistors being used on glass substrates. Crystalline silicon possesses very high mobilities, and thus can be used to make high performance devices. Presently, the most straightforward way of constructing crystalline silicon devices is on a silicon wafer. For use in many types of liquid crystal displays, the crystalline silicon circuit is constructed on a silicon wafer, and then transferred to a glass substrate by a ""liftoff"" process. Alternatively, the silicon transistors can be formed on a silicon wafer, removed via a liftoff process, and then deposited on a flexible substrate such as plastic, metal foil, or paper. As another implementation, the silicon could be formed on a different substrate that is able to tolerate high temperatures (such as glass or metal foils), lifted off, and transferred to a flexible substrate. As yet another implementation, the silicon transistors are formed on a silicon wafer, which is then used in whole or in part as one of the substrates for the display. The use of silicon-based circuits with liquid crystals is the basis of a large industry. Nevertheless, these display possess serious drawbacks. Liquid crystal displays are inefficient with light, so that most liquid crystal displays require some sort of backlighting. Reflective liquid crystal displays can be constructed, but are typically very dim, due to the presence of polarizers. Most liquid crystal devices require precise spacing of the cell gap, so that they are not very compatible with flexible substrates. Most liquid crystal displays require a ""rubbing"" process to align the liquid crystals, which is both difficult to control and has the potential for damaging the TFT array. The combination of these thin film transistors with microencapsulated electrophoretic displays should be even more advantageous than with liquid crystal displays. Thin film transistor arrays similar to those used with liquid crystals could also be used with the microencapsulated display medium. As noted above, liquid crystal arrays typically requires a ""rubbing"" process to align the liquid crystals, which can cause either mechanical or static electrical damage to the transistor array. No such rubbing is needed for microencapsulated displays, improving yields and simplifying the construction process. Microencapsulated electrophoretic displays can be highly reflective. This provides an advantage in high-resolution displays, as a backlight is not required for good visibility. Also, a high-resolution display can be built on opaque substrates, which opens up a range of new materials for the deposition of thin film transistor arrays. Moreover, the encapsulated electrophoretic display is highly compatible with flexible substrates. This enables high-resolution TFT displays in which the transistors are deposited on flexible substrates like flexible glass, plastics, or metal foils. The flexible substrate used with any type of thin film transistor or other nonlinear element need not be a single sheet of glass, plastic, metal foil, though. Instead, it could be constructed of paper. Alternatively, it could be constructed of a woven material. Alternatively, it could be a composite or layered combination of these materials. As in liquid crystal displays, external logic or drive circuitry can be built on the same substrate as the thin film transistor switches. In another implementation, the addressing electronic backplane could incorporate diodes as the nonlinear element, rather than transistors. In another implementation, it is possible to form transistors on a silicon wafer, dice the transistors, and place them in a large area array to form a large, TFT-addressed display medium. One example of this concept is to form mechanical impressions in the receiving substrate, and then cover the substrate with a slurry or other form of the transistors. With agitation, the transistors will fall into the impressions, where they can be bonded and incorporated into the device circuitry. The receiving substrate could be glass, plastic, or other nonconductive material. In this way, the economy of creating transistors using standard processing methods can be used to create large-area displays without the need for large area silicon processing equipment. While the examples described here are listed using encapsulated electrophoretic displays, there are other particle-based display media which should also work as well, including encapsulated suspended particles and rotating ball displays. While the invention has been particularly shown and described with reference to specific preferred embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.";"An encapsulated electrophoretic display comprising an encapsulated electrophoretic display medium, the display being characterized by at least one thin-film transistor array addressing the medium. A display according to claim 1 wherein the thin-film transistor array is disposed on a glass substrate. A display according to claim 2 wherein the thin-film transistor array comprises silicon deposited on the glass substrate. A display according to claim 3 wherein the silicon has been deposited on the glass substrate under low pressure conditions. A display according to claim 3 wherein the silicon has been deposited on the glass substrate using a liftoff procedure. A display according to claim 2 wherein the thin-film transistor array comprises polysilicon deposited on the glass substrate. A display according to claim 2 wherein the glass substrate comprises peripheral drive circuitry. A method for manufacturing an encapsulated electrophoretic display, characterized by: (a) providing a substrate having a thin-film transistor array disposed thereon; and (b) printing an encapsulated electrophoretic display medium on the substrate such that the medium is in electrical communication with the array. An electrophoretic display characterized by: at least one capsule (20) containing a suspending fluid (25) and at least a first particle (52) and a second particle (54), the first particle (52) having a first optical property and a first electrophoretic mobility and the second particle (54) having a second optical property and a second electrophoretic mobility; and at least two electrodes (32, 34) disposed adjacent the capsule (20); whereby application of an electric field to the capsule (20) by the electrodes (32, 34) causes the capsule (20) to change visual state responsive to the optical properties and electrophoretic mobilities of the particles (52, 54). An electrophoretic display comprising: a substrate; at least one capsule (20) containing a suspending fluid (25) and at least one particle (50; 55); at least two electrodes (30, 40; 42, 44, 46, 48) disposed adjacent the capsule (20), the display being characterized in that the at least two electrodes (30, 40; 42, 44, 46, 48) are disposed between the substrate and the capsule (20), whereby application of a voltage potential to one of the two electrodes (30, 40; 42, 44, 46, 48) causes the particle (50; 55) to migrate within the capsule (20) causing the capsule (20) to change its visual state. An electrophoretic display comprising: at least one capsule (20) containing a suspending fluid (25) and at least one particle (55); and electrodes (42, 44, 46, 48) disposed adjacent the capsule (20), the display being characterized in that the particles (55) are white and in that the electrodes comprise: a cyan-colored electrode (42) disposed adjacent the capsule (20); a magenta-colored electrode (44) disposed adjacent the capsule (20) but spaced from the cyan-colored electrode (42); a yellow-colored electrode (46) disposed adjacent the capsule (20) but spaced from the cyan-colored electrode (42) and the magenta-colored electrode (44); and a white electrode (48) disposed adjacent the capsule (20) but spaced from the cyan-colored electrode (42), the magenta-colored electrode (44) and the yellow-colored electrode (46); whereby application of a voltage potential to the cyan-colored electrode (42), magenta-colored electrode (44), and yellow-colored electrode (46) causes the white particles (55) to migrate within the capsule (20) to locations adjacent the cyan-colored electrode (42), magenta-colored electrode (44) and yellow-colored electrode (46) causing the capsule (20) to appear white, but application of a second voltage potential to the cyan-colored electrode (42), magenta-colored electrode (44) and yellow-colored electrode (46) causes the white particles (55) to migrate within the capsule (20) to a location adjacent the white electrode (48) causing the capsule to appear substantially black. A method for matrix addressing a encapsulated display having at least one display cell containing charged particles (50), the method comprising: (a) providing a first (200) and a second (210) electrode for each display cell, the method being characterized by: (b) providing a third electrode (230) for each display cell, the third electrode (230) being disposed between the first (200) and second (210) electrodes and comprising a structure having edges defining interstices within which the at least one display cell is disposed; and applying a sequence of potentials to the first (200), second (210) and third (230) electrodes to control the movement of the charged particles (50) inside each display cell. A matrix-addressed electrophoretic display comprising: a capsule containing charged particles (50); a first electrode (200) disposed adjacent the capsule; and a second electrode (212) disposed adjacent the first electrode (200), the display being characterized by: a third electrode (230) disposed adjacent the second electrode (212) and having edges defining interstices within which the capsule is diposed, whereby a sequence of voltage potentials applied to first (200), second (210) and third (230) electrodes causes the charged particles (50) to move within the capsule responsive to the sequence of voltage potentials. An electrophoretic display comprising: a substrate; at least one capsule (20) containing a suspending fluid (25) and at least one charged particle (50; 55), the charged particle (50; 55) having an optical property; and at least two electrodes (30, 40; 42, 44, 46, 48) disposed adjacent the capsule (20) and spaced apart from one another, the display being characterized in that the at least two electrodes (30, 40; 42, 44, 46, 48) are disposed between the substrate and the capsule (20), whereby application of a potential difference between the electrodes (30, 40; 42, 44, 46, 48) causes the particles (50; 55) to migrate toward at least one of the electrodes (30, 40; 42, 44, 46, 48), thereby effecting change in visual state. An electrophoretic display comprising: at least one capsule (20) containing a suspending fluid (25) and at least one particle (50) having a first optical property; at least two electrodes (40) disposed adjacent the capsule (20), the display being characterized in that each of the at least two electrodes (40) has a second optical property and in that at least one electrode (30) having the first optical property is disposed adjacent the capsule (20), whereby application of a voltage potential to the at least two electrodes (40) causes the capsule to change visual state. An electrostatically addressable display, comprising: (a) a substrate (306); and (b) an encapsulated electrophoretic display (304) disposed adjacent the substrate, the display being characterized by: (c) an electrode (300) capable of being scanned over a surface of the encapsulated electrophoretic display (304), whereby application of electrostatic charge by the electrode (300) to the encapsulated electrophoretic display (304) modulates the optical properties of the display (304). An electrostatically addressable encapsulated electrophoretic image display comprising: a film (170) including at least one capsule containing an electrophoretic suspension and dispersed in a binder; and at least one pair of electrodes (166, 168) disposed adjacent the film (170), the display being characterized in that the electrodes (166, 168) comprise printable conductive ink, whereby application of electrostatic charge to the film (170) modulates the optical qualities of the electrophoretic image display. An electrostatically addressable, encapsulated electrophoretic image display comprising: a film including at least one capsule containing an electrophoretic suspension and dispersed in a binder; and a clear electrode disposed adjacent a first side of the film, the display being characterized in that the electrode comprises a printable substance; wherein an electrostatic charge applied to a second side of said film modulates the optical qualities of said electrophoretic suspension. A method for manufacturing an encapsulated electrophoretic display, characterized by: (a) providing a first substrate having a thin-film transistor array disposed thereon; (b) providing a second substrate; (c) printing an encapsulated electrophoretic display medium on the second substrate; and (d) disposing the first substrate adjacent the second substrate such that the encapsulated electrophoretic display medium is in electrical communication with the thin-film transistor array. A method for manufacturing an encapsulated electrophoretic display, characterized by: (a) providing a first substrate; (b) printing on the first substrate a first electrode; (c) printing on the first electrode a dielectric layer; (d) printing on the dielectric layer a second electrode; (e) providing a second substrate; (f) printing an encapsulated electrophoretic display medium on the second substrate; and (g) disposing the first substrate adjacent the second substrate such that the encapsulated electrophoretic display medium is in electrical communication with the second electrode.";ALBERT JONATHAN D, COMISKEY BARRETT, DRZAIC PAUL, JACOBSON JOSEPH M, ALBERT, JONATHAN D., COMISKEY, BARRETT, DRZAIC, PAUL, JACOBSON, JOSEPH M.;E INK CORP, E INK CORPORATION, E Ink Corporation;2005.0;1507165
EP-1524121-A3;20061129.0;EP;A3;EN;20090516.0;new;34382199.0;B41J2;;B41J2;B41J   2/505B1;Printing with reduced outline bleeding;Outline bleeding of printed images can be reduced in a printer in which ink dots are formed on a print medium, because the amount of ink contained in the dots for forming boundary lines, which bleed easily, is reduced by skipping some dots or varying the dot size. As a result, texts and other printed images having sharply defined outlines can be printed with high legibility.;"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates to a technique for printing images on a print medium by ink ejection. Description of the Related Art Ink-jet printers for forming ink dots into images on print media by ejecting ink droplets are widely used as devices for outputting images created by computers and digital cameras. When non-picture image such as characters, illustrations, and line drawings are printed by an ink-jet printer, the ink sometimes bleeds along the outlines of the non-picture image. Such ink bleeding is attributed to the fact that the ink ejected into the line-drawing area accumulates without being absorbed by the print medium, and flows out toward the areas not intended to form dot therein. In particular, ink dots tend to elongate in the direction of main scanning when they are formed while the print head is moved in the direction of main scanning, so contour lines extending parallel to the direction of main scanning are prone to ink accumulation and bleeding. Contour lines extending parallel to the direction of higher resolution are also apt to accumulate ink when different resolutions are set for the directions of main and sub-scan. Not only does such bleeding affect the outline portions, but it sometimes occurs in cases in which differently colored high-concentration regions are brought close together to form an outline. Document US 5,596,352 describes a printing apparatus and method for printing color boundary regions having reduced color bleed. In a printer assembly which includes a print head for depositing ink onto a media, an image is formed by processing the data before the image is printed such that a border strip is formed between adjoining regions of different secondary colors. A boarder strip is printed in a color which is common to both of the secondary color regions. Document US 5,872,896 describes an ink-jet-printer driver which employs clustered-dot dither to generate binary image signals that represent an image that has been adjusted for the ink-duty limit that must be imposed to avoid bleeding on some print media. Some image values that would result in ink duties that exceed the limit without adjustment are reduced by more than needed to meet the ink-duty limit. The resultant adjusted value is an increasing function of unadjusted value even for unadjusted values that exceed the ink-duty limit. To impose the limit, a Bayer dither process receives an input that represents the ratio of ink-limit-adjusted ink duty to unadjusted ink duty. A gating operation permits an ink request only at those locations where both dither processes indicate that an ink is permitted. Document US 5,633,662 describes a process for controlling ink volume in liquid ink printing systems such as ink jet printers. The process examines the total ink volume per pixel as specified in source image data, i. e. before digital halftoning. For each pixel of data, the specified ink volume is compared to a selected maximum total ink volume per pixel. The maximum total ink volume is selected, depending upon the printing medium and environmental conditions, so as to provide good color coverage while avoiding curl, bleeding and other adverse effects of excessive ink volume. A threshold ink volume is also selected, below which no ink limiting is applied, thereby avoiding washed-out images at lower ink volumes. Above the threshold, the ink volume is scaled to a value below the maximum by linear scaling. Document EP 0628415 A2 describes an ink jet printing system, wherein improved gray scale and color resolution is achieved by reducing the ink droplet volume to a level below the unit droplet volume selected to cover a nominal printing grid location. Multiple passes of the print head are used to print an integer multiple number of the reduced-volume droplets. Multiple different droplet volumes are provided without a linear increase in the number of print passes. Furthermore, multiple different dye load concentrations are provided. SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to reduce ink bleeding in outline portions in a printing device for printing images by ejecting ink droplets. The object is solved with the features of the independent claims. The independent claims relate to preferred embodiments of the invention. According to one aspect of the invention, a printing control apparatus for generating print data to be supplied to a printing unit capable of printing images on print medium with multiple print resolution comprises a dot data generator configured to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation in each pixel; a contour line extractor configured to extract a transverse contour line parallel to a main scan direction of an image area composed of pixels at which a specific type dot to be formed by the dot data, the specific type dot being defined by the fact that a first value is greater than the predetermined first threshold, the first value being obtained by dividing the length of the specific type dot in a main scan direction by the pixel length in the main scan direction, assuming that the specific type dot is formed individually; and a dot data adjuster configured to adjust the dot data so as to regularly reduce an amount of ink for forming dots an the transverse contour line. According to one embodiment, a printing control apparatus for generating print data to be supplied to a printing unit to perform printing during main scans is provided, the printing unit comprising a print head having a plurality of nozzles and a plurality of ejection driving elements for causing ejection of ink droplets respectively from the plurality of nozzles, each nozzle being adaptable to form a selected one of N different dots having different sizes in one pixel area on the print medium, N being an integer of at least 2, the N different dots including a specific size dot that is one of comparatively large dots among the N different dots; and a dot data generator configured to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation in each pixel; a contour line extractor configured to extract a contour line of a specific type image area represented by the dot data, the specific type image area being composed of pixels at which specific size dots are to be formed; and a dot data adjuster configured to adjust the dot data so as to reduce the amount of ink by reducing dot size when the contour line is formed with the specific size dot. The present invention can be realized in various forms such as a method and apparatus for printing, a method and apparatus for producing print data for a printing unit, and a computer program product implementing the above scheme. These and other objects, features, aspects, and advantages of the present invention will become more apparent from the following detailed description of the preferred embodiments with the accompanying drawings. BRIEF DESCRIPTION OF THE DRAWINGS Figs. 1(a)-1(d) are diagrams illustrating the manner in which some of the pixels in a dot pattern are skipped by means of a procedure performed in accordance with a working example of the present invention; Fig. 2 is a block diagram depicting the structure of a print system configured according to a working example of the present invention; Fig. 3 is a diagram depicting the structure of a printer; Fig. 4 is a block diagram depicting the structure of the control circuit 40 in a color printer 20; Fig. 5 is a flowchart of a dot skipping procedure performed in accordance with the first working example of the present invention; Fig. 6(a)-6(c) depict the filters used to extract contour lines according to the first working example of the present invention; Fig. 7(a)·(f) are diagrams depicting the manner in which the amount of ink is reduced in accordance with the first working example of the present invention; Fig. 8 is a flowchart depicting the exact order in which the dots to be skipped are processed in a specific manner during step S102; Fig. 9 is a flowchart of a dot skipping procedure performed in accordance with a second working example of the present invention; Fig. 10(a)·10(f) are diagrams illustrating the manner in which a first ink rate reduction procedure is performed in accordance with the second working example of the present invention; Fig. 11 is a flowchart of a first dot skipping procedure performed in accordance with the second working example of the present invention; Fig. 12(a)-12(e) are diagrams depicting the manner in which first and second ink rate reduction procedures are performed in accordance with the ) second working example of the present invention; Fig. 13(a)-13(c) are diagrams showing the dot pattern obtained after the amount of ink has been reduced by another skipping method; Fig. 14(a) and 14(b)are diagrams depicting the dot pattern obtained after the amount of ink has been reduced by varying the dot size; Fig. 15 is a diagram depicting an example of skipping performed when print resolution is higher in the direction of main scanning than in the direction of sub-scan; Fig. 16(a) and 16(b) are diagrams depicting an example of skipping performed when printing is carried out using a high-density nozzle array configured to print resolution is higher in the direction of sub-scan than in the direction of main scanning; Fig. 17 is a diagram depicting the manner in which dots are formed using a regular nozzle array with a nozzle pitch of 1/180 th of an inch; Fig. 18 is a diagram depicting the manner in which dots are formed using a high-density nozzle array with a nozzle pitch of 1/360 th of an inch; Fig. 19 is a flowchart depicting the printing and processing sequence adopted for a third working example of the present invention; Fig. 20 is a block diagram depicting the structure of the print system adopted for the third working example of the present invention; Fig. 21 is a diagram depicting an example of the basic setup screen for print modes displayed on a CRT 21; Fig. 22 is a diagram depicting the specifics defined for the skipping procedure in accordance with the print mode in the third working example of the present invention; Fig. 23(a) and 23(b) are diagrams depicting the dot pattern obtained after the amount of ink has been reduced both for a transverse contour line and a longitudinal contour line; Fig. 24 is a diagram depicting the relation between print resolution and the skipping procedure; Fig. 25 is a diagram outlining the printer adopted for a fourth working example of the present invention; Fig. 26 is a block diagram outlining the printing device adopted for the fourth working example of the present invention; Fig. 27(a) and 27(b) are diagrams depicting the matrices used in the fourth working example of the present invention as filters for extracting contour lines; Fig. 28(a) and 28(b) are diagrams depicting the process for extracting the contour line of text A according to the fourth working example of the present invention; Fig. 29 is a diagram depicting the contour line data compiled according to the fourth working example of the present invention; Fig. 30(a)-30(g) are diagrams depicting the progress of the skipping and fill-in procedures performed in accordance with the fourth working example of the present invention; Fig. 31 is a diagram depicting the images printed after the skipping and fill-in procedures have been performed regarding text A in accordance with the fourth working example of the present invention; and Fig. 32(a)-32(c) are diagrams depicting a process in which text B is created with an outline font. DESCRIPTION OF THE PREFERRED EMBODIMENT The present invention is explained in the following sequence based on embodiments. A. Overview of Embodiments B. Device Structure C. First Working Example D. Second Working Example E. Third Working Example F. Fourth Working Example G. Modifications A. Overview of Embodiments Fig. 1 is a diagram illustrating the manner in which some of the pixels in a dot pattern are skipped by means of a procedure performed in accordance with a working example of the present invention. Figs. 1a and 1b are diagrams depicting in enlarged form some of the dots forming the letter ""B"" as a printed image. Fig. 1a depicts the dot pattern existing before the procedure pertaining to the example of the present invention has been performed, whereas Fig. 1b depicts the dot pattern obtained following the procedure. Although in practice all adjacent dot pairs overlap to form solid areas, slightly smaller dots are shown herein for the sake of clarity. As can be seen in the drawings, the dot pattern processed in accordance with an example of the present invention is configured to some of the dots in the contour lines extending in the direction of main scanning are skipped. Performing this procedure reduces ink bleeding along the contour lines of the letter ""B"" in the direction of main scanning and yields a sharply defined outline. In the present working example, some of the dots in the contour lines extending in the direction of main scanning are skipped because the contour lines tend to bleed in this direction in the above-described manner. The reason that contour lines are prone to bleeding in the direction of main scanning is that ink dots tend to be longer in the direction of main scanning than in the direction of sub-scan. This is because a print head ejects ink while moving relative to the print medium in the direction of main scanning, causing ink droplets to also move at a certain speed in this direction in relation to the print medium. Figs. 1c and 1d depict in enlarged form some of the dots forming the letter ""L"" as a printed image. Fig. 1c depicts the dot pattern existing before the procedure pertaining to another example of the present invention has been performed, whereas Fig. 1d depicts the dot pattern obtained following the procedure. This procedure is an example of two pixel skipping procedures being combined. According to the first pixel skipping procedure, all the dots formed by the pixels one row inward from the contour line are skipped. The second pixel skipping procedure is identical to the one shown in Fig. 1a. Such skipping is particularly effective when a special type of print medium is used, such as in cases in which, for example, text is printed on plain paper with low ink absorption. This method will be described in detail below with reference to a second working example. According to the present invention, bleeding along contour lines is controlled by establishing a specific rule for reducing the amount of ink for the dots in the contour lines disposed parallel to the direction of main scanning in a printing device for forming images by ejecting ink dots, with some components moving in the direction of main scanning. In the example shown in Fig. 1, the high-concentration regions constituting the characters correspond to image areas composed of pixel arrays for forming specific types of dots in accordance with the claims. The present invention is also applicable to cases in which contour lines are formed by disposing high-concentration regions of different colors adjacent to each other, such as when, for example, black characters are printed on a yellow background. B. Device Structure Fig. 2 is a block diagram depicting the structure of a print system configured according to a working example of the present invention. The print system comprises a computer 88 as a print control device, and a color printer 20 as a print unit. A combination of the color printer 20 and computer 88 can be broadly referred to as a printing device. The computer 88 executes an application program 95 with the aid of a special operating system. The operating system has a video driver 94 or printer driver 96, and the print data PD to be forwarded to the color printer 20 are output by the application program 95 via these drivers. The application program 95 processes images in the desired manner and displays these images on a CRT 21 via the video driver 94. When the application program 95 issues a print command, the printer driver 96 of the computer 88 receives video data from the application program 95, and the result is converted to the print data PD to be sent to the color printer 20. In the example shown in Fig. 2, the printer driver 96 comprises a resolution conversion module 97, a color conversion module 98, halftone module 99, a print data generator 100, a contour line extractor 101, an ink amount reducer 102, and a color conversion table LUT. In the present working example, the resolution conversion module 97, color conversion module 98, and halftone module 99 constitute the dot data generator referred to in the claims. The role of the resolution conversion module 97 is to convert the resolution (that is, the number of pixels per unit length) of the color video data handled by the application program 95 to a resolution that can be handled by the printer driver 96. The video data whose resolution has been converted in this manner constitute video information, which is composed of the three colors RGB. The color conversion module 98 converts the RGB video data to multi-tone data to obtain a plurality of ink colors suitable the color printer 20. The conversion is performed for each pixel while the color conversion table LUT is referenced. The color-converted multi-tone data may, for example, have 256 gray scale values. The halftone module 99 performs a halftone procedure designed to represent these gray scale values with the aid of the color printer 20 by forming dispersed ink dots. The halftone data generated as a result of the halftone procedure are queued in the order of the data to be forwarded to the color printer 20 by the print data generator 100, and are output as final print data PD. The print data PD comprise raster data for specifying the manner in which dots are recorded during each main scan, and data for specifying the amount of feed in the direction of sub-scan. The functions performed by the contour line extractor 101 and ink amount reducer 102 will be described below. The print data generator 100 and the ink amount reducer 102 corresponds to a dot data adjuster in the claims. The printer driver 96 is a program for executing the functions involved in generating print data PD. The programs for executing the functions of the printer driver 96 are supplied as products stored on computer-readable storage media. Examples of such storage media include floppy disks, CD-ROMs, magneto optical disks, IC cards, ROM cartridges, punch cards, printed matter containing bar codes and other symbols, computer internal storage devices (RAM, ROM, and other types of memory) and external storage devices, and various other types of computer readable media. Fig. 3 is a schematic block diagram of the color printer 20. The color printer 20 comprises a secondary scan/feed mechanism for transporting printing paper P in the direction of sub-scan by means of a paper feed motor 22, a main scan/feed mechanism for reciprocating a carriage 30 in the axial direction (direction of main scanning) of a platen 26 by means of a carriage motor 24, a head drive mechanism for ejecting the ink and forming dots by actuating the print head unit 60 (print head assembly) mounted on the carriage 30, and a control circuit 40 for exchanging signals among the paper feed motor 22, the carriage motor 24, the print head unit 60, and a control panel 32. The control circuit 40 is connected by a connector 56 to the computer 88. The secondary scan/feed mechanism for transporting the printing paper P comprises a gear train (not shown) for transmitting the rotation of the paper feed motor 22 to the platen 26 and a roller (not shown) for transporting the printing paper. The main scan/feed mechanism for reciprocating the carriage 30 comprises a sliding shaft 34 mounted parallel to the axis of the platen 26 and designed to slidably support the carriage 30, a pulley 38 for extending an endless drive belt 36 from the carriage motor 24, and a position sensor 39 for sensing the original position of the carriage 30. Fig. 4 is a block diagram depicting the structure of a color printer 20 based on the control circuit 40. The control circuit 40 is composed as an arithmetic Boolean circuit comprising a CPU 41, a programmable ROM (PROM) 43, a RAM 44, and a character generator (CG) 45 containing dot matrices for characters. The control circuit 40 further comprises a dedicated I/F circuit 50 for creating a dedicated interface with external motors and the like, a head drive circuit 52 connected to the dedicated I/F circuit 50 and designed to eject ink by actuating the print head unit 60, and a motor drive circuit 54 for actuating the paper feed motor 22 and carriage motor 24. The dedicated I/F circuit 50 contains a parallel interface circuit and is capable of receiving print data PD from the computer 88 via the connector 56. The color printer 20 prints images in accordance with the print data PD. RAM 44 functions as a buffer memory for the temporary storage of raster data. The print head unit 60 has a print head 28 and allows ink cartridges to be mounted. The print head unit 60 can be mounted on the color printer 20 and removed therefrom as a single component. In other words, the print head unit 60 is replaced when the print head 28 needs to be replaced. C. First Working Example Fig. 5 is a flowchart of a dot skipping procedure performed in accordance with the first working example of the present invention. According to the first working example, every second dot in the contour lines disposed parallel to the direction of main scanning is skipped, as shown in Fig. 1b. The amount of ink is thus reduced in a systematic manner in the direction of main scanning, and less ink is deposited along the contour lines. In step S101, the contour line extractor 101 extracts the contour lines that are parallel to the direction of main scanning. In the present working example, a first derivation filter such as the one shown in Fig. 6a may be used as the simplest contour line extraction filter for such extraction. This filter has directionality in the direction of sub-scan and can extract contour lines that are parallel to the direction of main scanning. As used herein, the term ""contour line"" refers to an area of single pixel width that defines the outermost boundary of an image area composed of a pixel array for forming specific types of dots. Such a line is disposed adjacent to a discontinuity whose unique attributes (dot size or color) define this image area. The discontinuity may be a border between dot-forming pixels and dot-free pixels, as shown, for example, in Fig. 1a. Contour lines disposed parallel to the direction of main scanning will be referred to hereinbelow as ""transverse contour lines,"" and those disposed parallel to the direction of sub-scan will be referred to as ""longitudinal contour lines."" The contour line extraction filter can be any filter capable of extracting transverse contour lines. It can be a directional filter such as the one shown in Fig. 6b, or a nondirectional filter such as the one shown in Fig. 6c. Fig. 7 is a diagram illustrating the ink rate reduction procedure. Fig. 7a depicts the dot pattern existing prior to the ink rate reduction procedure. In this example, a single type of dot size is involved, and the halftone data can assume only two values ""0"" (dot absent) and ""1"" (dot present). The empty columns in the drawings depict cases of zero data. Applying the above-described first derivation filter to this dot pattern yields results such as those shown in Fig. 7b. These filtering results indicate that although the contour lines on the upper side of an image are extracted unchanged, the contour lines on the lower side of the image appear as contour lines of opposite sign at pixel positions disposed one pixel lower. Contour lines such as the one shown in Fig. 7c can be obtained by reversing the sign of the contour lines on the lower side of the image and moving them one pixel higher. In step S102, the ink amount reducer 102 specifies the dots to be skipped. The number of skipped dots may, for example, be equal to about half the dots in a contour line, in which case even-numbered dots are skipped in the direction of main scanning. As a result, the amount of ink supplied to form a contour line can be reduced in half, and the dots extended in the direction of main scanning can be joined together, making it possible to minimize ink accumulation. Fig. 8 is a flowchart depicting the exact order in which the dots to be skipped are processed in a specific manner during step S102. In step S201, default setting are selected by the ink amount reducer 102. Selecting the default settings in this manner includes performing an operation in which the flags F0 for specifying the dots to be skipped are set to zero for each pixel. In step S202, the ink amount reducer 102 operates configured to the data processed in step S101 are scanned in the direction of main scanning for each scan line. In step S203, the ink amount reducer 102 determines whether a dot is on a contour line in the direction of main scanning. The processing result obtained in step S101 can be used to determine the outcome on the basis of the corresponding pixel value. In the example under consideration, it can be concluded that a dot is on the contour line if the pixel value is 1. The operation proceeds to step S204 if it is determined that the dot is on the contour line, and to step S207 if it is determined that the dot is outside the contour line. In step S204, the ink amount reducer 102 counts the dots on the contour line. In step S205, the ink amount reducer 102 selects a setting for the flag F0 on the basis of the count. Specifically, ""-1"" is selected for the flag F0 of a pixel, indicating that the dot is to be skipped, if an even count N is obtained (step S2606). Conversely, the default setting of 0 is retained for the flag F0 if an odd count N is obtained. In step S203, the count N is reset to zero if the ink amount reducer 102 has determined that the dot lies outside the contour line in the direction of main scanning. A flag F0 such as the one shown in Fig. 7d can be obtained as a result of such processing. Such flags F0 represent data for specifying the dots to be skipped. Obtaining this processing result concludes the procedure for specifying the dots to be skipped (step S102 in Fig. 5). In step S103, the ink amount reducer 102 skips some dots. The procedure is performed by a method in which the values of pixels specified by the flag F0 in Fig. 7d are changed from the unprocessed dot pattern shown in Fig. 7a. In this example, the dots are skipped by a method in which the values of pixels with a flag F0 of -1 are changed from ""1"" to ""0"" in the unprocessed dot pattern shown in Fig. 7a. A sparser dot pattern (Fig. 7e) is thus obtained. Such skipping can regularly reduce the amount of ink supplied to form the dots for the contour lines disposed parallel to the direction of main scanning, which is the direction in which the ink tends to accumulate. Bleeding from the contour line can be reduced as a result. Although the above example was described with reference to a case in which the amount of ink was regularly reduced by the skipping of even-numbered dots, the concept of ""systematic"" is not limited to this method alone. It is possible, for example, to adopt a method in which one out of every three dots is skipped. The amount of ink supplied to form a contour line is not necessarily reduced by skipping some dots. For example, the amount of ink can be reduced by reducing dot size. Alternatively, the method in which the amount of ink is reduced in a systematic manner can be limited to cases in which large dots are formed. In the above example, the amount of ink was reduced by deleting even-numbered dots from a continuous series of dots extending in the direction of main scanning in step S205. Even with even numbers, however, it is inadvisable to skip any dots in a contour line disposed in the direction of sub-scan. As shown, for example, in Fig. 7f, a contour line is formed in the direction of sub-scan by column I in the absence of dots in column J. It is inadvisable to skip dots in such cases. This type of procedure may, for example, be carried out in step S206 with regard to the pixel values disposed next to each other in the direction of main scanning. D. Second Working Example Fig. 9 is a flowchart of a dot skipping procedure performed in accordance with the second working example of the present invention. In the second working example, two skipping procedures are performed. In the first skipping procedure, the amount of ink is reduced for the dots designed to form pixels one row inward from a contour line, rather than on the contour line itself. It is thus possible, for example, to print high-concentration images with sharply defined outlines on plain paper with low ink absorption. The second skipping procedure involves deleting dots from a contour line and is the same procedure as the one described with reference to the first working example. The ink amount reducer 102 performs the first skipping procedure in step S301. Such skipping is carried out in order to regularly reduce the supply of ink to the dots for forming pixels one row inward from the contour line, as described above. Fig. 10 is a diagram illustrating the manner in which the amount of ink is reduced according to the second working example of the present invention. The drawing depicts the halftone data representing a single main scan line. The data existing prior to a skipping procedure are shown in Fig. 10a. According to these data, ""1"" indicates the presence of a dot; ""0,"" the absence of a dot. Fig. 10b depicts results obtained by extracting a longitudinal contour line by a method based on the technique described with reference to the first working example. Figs. 10c and 10d depict flags F1 and F2, which are used to determine the need for forming dots for particular pixels. The method for setting up the flags F1 and F2 will be described below. Fig. 10e shows a logical product of flags F1 and F2, which is used to obtain the data shown in Fig. 10f. The data shown in Fig. 10f represent the dot pattern resulting from the first skipping procedure. The above-described procedure is carried out in the following sequence. Fig. 11 is a flowchart of a first dot skipping procedure performed in accordance with the second working example of the present invention. In step S401, default settings are selected by the ink amount reducer 102. Selecting default settings in this manner includes selecting ""0"" as the initial state of the flags F1 and F2 for determining whether a target pixel is to be recorded. In step S402, the contour line extractor 101 extracts a contour line from halftone data. Unlike in the first working example, this contour line also contains a longitudinal contour line. An oblique contour line may also be extracted in this case. In step S403, the ink amount reducer 102 uses data generated by the aforementioned contour line extraction procedure (Fig. 10b) to determine the type of setting for the flag F1i of an i-th target pixel Gi on the basis of a pixel value Gi + 1, which is disposed one pixel to the right from the target pixel Gi. If the pixel value Gi + 1 is zero, the flag F1i is set to the same value as the flag F1i - 1 of the immediately preceding target pixel, and the operation proceeds to step S408 (step S404). Consequently, the same value (zero) is selected for the flag F11 of pixel 1 as for the flag F10 in the initial state (Fig. 10c). The following procedure is performed (step S405) if the pixel value Gi + 1 is equal to 1. The flag F1i is set to 1 if the flag F1i - 1 is equal to zero (step S406). The flag F1i is set to zero if the flag F1i - 1 is equal to 1 (steps S405 and S407). Consequently, the flag F12 of pixel 2 is equal to 1, and the flag F19 of pixel 9 is equal to zero (Fig. 10c). Once the flag F1 is set, the operation proceeds to step S408. Flag F1 is thus created. In step S408, the ink amount reducer 102 uses data generated by the contour line extraction procedure (Fig. 10b) to determine the type of setting for the flag F2i of a target pixel Gi on the basis of a pixel value Gi - 2, which is disposed two pixels to the left from the target pixel Gi. If the pixel value Gi - 2 is zero, the flag F2i is set to the same value as the flag F2i - 1 of immediately preceding target pixel, and the operation proceeds to step S413 (step S409). Consequently, the same value (zero) is selected for the flags F21-F24 of pixels 1-4 as for the flag F20 in the initial state (Fig. 10d). The following procedure is performed (step S410) if the pixel value Gi - 2 is equal to 1. The flag F2i is set to 1 if the flag F2i - 1 is equal to zero (step S411). The flag F2i is set to zero if the flag F2i - 1 is equal to 1 (step S412). Consequently, the flag F15 of pixel 5 is equal to 1, and the flag F112 of pixel 12 is equal to zero (Fig. 10d). Once the flag F2 is set, the operation proceeds to step S413. Flag F2 is thus created. In step S413, the ink amount reducer 102 performs specific calculations and generates a sparser pattern. These calculations are performed using extracted contour line data X (Fig. 10b) in conjunction with flags F1 and F2. The above-described procedure is shifted one target pixel at a time (step S414) to cover the entire data (step S415). Dots adjacent to the contour line can this be skipped, as shown in Fig. 10f. Specifically, pixels 3 and 10 constitute a longitudinal contour line in Fig. 10f while pixels 4 and 9, which are adjacent thereto and disposed inwardly therefrom, are skipped. This procedure is different from the skipping procedure of the first working example and involves both the direction of main scanning and the direction of sub-scan. This procedure may also be performed in an oblique direction. Fig. 12 is a diagram depicting the manner in which first and second ink rate reduction procedures are performed in accordance with the second working example of the present invention. Fig. 12a depicts a dot pattern existing prior to the skipping procedure. Fig. 12b depicts data obtained by extracting a contour line during step S402 in Fig. 11. These data correspond to the data shown in Fig. 10b. It can be seen in the drawings that contour lines are extracted both in the direction of main scanning and in the direction of sub-scan. Fig. 12c depicts the dot pattern obtained following the first skipping procedure, which is the procedure shown in Fig. 11. The resulting data correspond to the data shown in Fig. 10b. In this procedure, some of the pixel dots on the inside of transverse and longitudinal contour lines are skipped. Once the first skipping procedure is completed, the operation proceeds to step S 302 (Fig. 9). In steps S302 and S303, the ink amount reducer 102 performs the same procedure as in the first working example, generating flag data such as those shown in Fig. 12d. The flag data shown in Fig. 12d are the same as in Fig. 7d. The sparser dot pattern of the second working example can be obtained in the manner shown in Fig. 12d (5304) by adding together these flag data and the dot pattern obtained by the first skipping procedure in Fig. 12b. Fig. 13 is a diagram showing the dot pattern obtained after the amount of ink has been reduced by another skipping method. In Fig. 13a, only the dots adjacent to the inside of the transverse contour line are skipped, while no skipping is applied to the dots adjacent to the inside of the transverse contour line. In Fig. 13b, only half of the dots adjacent to the inside of the transverse contour line are skipped. In Fig. 13c, the dots on a transverse contour line and the dots inside the line are arranged in a staggered fashion by skipping only half of the dots adjacent to the inside of the transverse contour line. The present working example also allows dots that are larger than a specific size to be skipped alone in the case of a printer 20 capable of forming dots of different sizes. Dot skipping may also be replaced by varying the dot size. Fig. 14 is a diagram depicting the dot pattern obtained after the amount of ink has been reduced by varying the dot size. If Fig. 14a, small dots are formed at positions in which large dots have been skipped in accordance with the second working example. In Fig. 14b, small dots are formed at positions in which large dots have been deleted from the area inside a contour line, without the formation of small dots at positions in which large dots have been deleted from a transverse contour line. The amount of ink can thus be reduced by selectively skipping some dots or forming smaller dots in accordance with dot positions inside an image area (line-drawing area). Bleeding from contour lines should preferably be reduced in a more detailed manner by reducing the dot size or adopting a method whereby dots adjacent to the contour lines are skipped as described above. The methods described with reference to the second working example are particularly effective when an attempt is made to print high-concentration images with clearly defined outlines on plane paper with low ink absorption. E. Third Working Example The third working example differs from the above-described working examples in that the skipping procedure is varied in accordance with the print mode. The following print mode parameters are used to determine the specifics of the skipping procedure adopted in the present working example. (1) Print resolution (2) Ink color (selected from ""all-black"" and ""color"") (3) Type of print medium Fig. 15 is a diagram depicting an example of skipping performed when print resolution is higher in the direction of main scanning than in the direction of sub-scan. The drawing depicts, in enlarged form, some of the ink dots that form the letter ""B"" as a printed image. The drawing illustrates the manner in which some pixels are skipped when the print resolution is 720 dpi in the direction of main scanning, and 360 dpi in the direction of sub-scan. The left side of the drawing depicts the condition existing prior to the skipping procedure, and the right side of the drawing depicts the dot pattern obtained following the skipping procedure. It can be seen in the drawing that it is the dots constituting the contour lines (transverse contour lines) in the direction of main scanning that are skipped. The following is the reason for skipping some of the pixels in a contour line disposed parallel to the direction of main scanning. A solid image is formed by completely filling pixels with ink dots. When, however, the pixels are larger in the direction of main scanning than in the direction of sub-scan in the manner shown in the drawing, the ink ultimately extends far outside the pixels in the direction of main scanning. In the particular case of a printing process in which ink droplets are ejected while the print head moves in the direction of main scanning, the dots arranged in the direction of main scanning form a continuous arrangement, so the ink for forming transverse contour lines tends to accumulate and bleed. Another feature of the process in which ink droplets are ejected while the print head moves in the direction of main scanning is that because the ink droplets acquire a certain speed in the direction of main scanning in the above-described manner, the process tends to yield dots that are longer in the direction of main scanning than in the direction of sub-scan. These results indicate that it is commonly preferable to skip some of the ink dots that make up a transverse contour line when print resolution is higher in the direction of main scanning than in the direction of sub-scan. Fig. 16 is a diagram depicting an example of skipping performed when printing is carried out using a high-density nozzle array configured to print resolution is higher in the direction of sub-scan than in the direction of main scanning. As used herein, the term ""high-density nozzle array"" refers to a row of nozzles spaced at less than 1/300 th of an inch, as in the present working example. Fig. 16a is similar to Fig. 15 in that it is a diagram depicting in enlarged form some of the ink dots that make up a printed image in the form of a character. The drawing illustrates the manner in which some pixels are skipped when the print resolution is 360 dpi in the direction of main scanning, and 720 dpi in the direction of sub-scan. The left side of the drawing depicts the condition existing prior to the skipping procedure, and the right side of the drawing depicts the dot pattern obtained following the skipping procedure. It can be seen in the drawing that it is the dots constituting the contour lines in the direction of sub-scan that are skipped. The only difference between this example and the example shown in Fig. 15 is that the skipping procedure is performed only when printing is carried out using a high-density nozzle array. Fig. 16b is a diagram depicting a print head 28 containing a high-density nozzle array. The print head 28 comprises a black ink nozzle array K, a dark cyan ink nozzle array C, a light cyan ink nozzle array, a dark magenta ink nozzle array, a light magenta ink nozzle array, and a yellow ink nozzle array. The black ink nozzle array K is a high-density nozzle array because it has a nozzle pitch of 1/360 th of an inch. The other nozzle arrays are not high-density nozzle arrays because their nozzle pitch is 1/180 th of an inch The reason that the black ink nozzle array K is considered to be a high-density nozzle array is that the number of nozzles is increased by a factor of 2 to allow black text or line drawings to be printed at a high speed. The following is the reason that skipping is performed only when printing is carried out using a high-density nozzle array. Fig. 17 is a diagram depicting the manner in which dots are formed using a regular nozzle array with a nozzle pitch of 1/180 th of an inch. As shown in the drawing, the dots are formed at a pitch of 1/720 th of an inch (720 dpi) in the direction of sub-scan with the aid of a nozzle array whose nozzle pitch is 1/180 th of an inch. When a transverse contour line is considered herein, it can be seen that dots belonging to a first raster are formed in the course of a first pass (pass 1) in the direction of main scanning, dots belonging to a second raster are formed in the course of a second pass (pass 2), dots belonging to a third raster are formed in the course of a third pass (pass 3), and dots belonging to a fourth raster are formed in the course of a fourth pass (pass 4). It can thus be seen that adjacent dots are formed in a single longitudinal direction by successive main scans when these dots are formed using an ordinary nozzle array. It is apparent that when, for example, the dots belonging to the second raster are formed, the dots belonging to the first raster are formed during the immediately preceding pass, but the dots belonging to the third raster are not yet formed. When the dots belonging to the fourth raster are formed, the dots belonging to the fifth raster have already been formed. The ink is thus less likely to accumulate because the dots have been formed in the course of the three preceding passes. Fig. 18 is a diagram depicting the manner in which dots are formed using a high-density nozzle array with a nozzle pitch of 1/360 th of an inch. As shown in the drawing, the dots are formed at a pitch of 1/720 th of an inch (720 dpi) in the direction of sub-scan with the aid of a nozzle array whose nozzle pitch is 1/360 th of an inch. When a longitudinal contour line is considered herein, it can be seen that dots belonging to first, third, and fifth rasters are formed in the course of a first pass (pass 1), and dots belonging to second and third rasters, which are interposed between the aforementioned odd-numbered rasters, are subsequently formed in the course of a second pass (pass 2). It can thus be seen that dots adjacent to each other in the direction of sub-scan are formed by successive main scans when these dots are formed using a high-density nozzle array. It is apparent that the ink is more likely to accumulate than in the case shown in Fig. 17. This situation makes it more desirable to apply a skipping procedure to the dots for forming longitudinal contour lines when these dots are formed using a high-density nozzle array. The ease with which ink accumulates varies with the print medium. For example, ink is less likely to accumulate when images are printed on a print medium with a high ink absorption rate (such as specialty paper), whereas ink accumulation tends to be facilitated when images are printed on a print medium with a low ink absorption rate (such as plain paper). It can thus be seen that the specifics of a particular skipping procedure vary with print resolution, nozzle array density, and print medium type. Fig. 19 is a flowchart depicting the printing and processing sequence adopted for the third working example of the present invention. Fig. 20 is a block diagram depicting the structure of the print system adopted for the third working example of the present invention. Fig. 21 is a diagram depicting an example of the basic setup screen for print modes displayed on a CRT 21. The structure of the print system adopted for the third working example differs from the structure adopted for the first working example by the addition of a print mode selector 103. The printing procedure allows the specifics of the skipping procedure to be varied depending on print mode parameters. In step S501, the user instructs the computer 88 to print. When a property button (not shown) inside the print dialog box on the CRT 21 is clicked in step S502, the print mode selector 103 (Fig. 20) causes the property setup screen shown in Fig. 21 to be displayed on the CRT 21. The user can specify various parameters for selecting the print mode on the property setup screen. The basic setup screen for print modes in Fig. 21 contains the following elements for specifying these parameters. (1) Paper type menu PW: A pull-down menu for selecting plain paper or specialty paper (2) Ink color selection button CLR: A button for selecting the use of color inks or the use of a black ink (3) Print resolution setting switch SW: A pull-down menu for selecting combinations of resolutions in the direction of main scanning and sub-scan. The user can also select other parameters on a full setup screen for print modes, but these parameters will be omitted from the description that follows. Once the user selects the various parameters for the print modes in step S503 in Fig. 19 and the printing is started, the printer driver 96 defines the specifics of the skipping procedure in step S504. Fig. 22 is a diagram depicting the specifics of the skipping procedure defined in accordance with the print mode in step S504. In the present working example, the specifics of the skipping procedure are defined in accordance with print medium type, ink color, and print resolution, which are the parameters for specifying the print mode. In the present working example, the print medium can be plain paper or specialty paper. In addition, there are only two options for the ink color: color and all-black. There are three options for the print resolution: 720 dpi x 360 dpi (direction of main scanning x direction of sub-scan), 360 dpi x 720 dpi (same as above), and 720 dpi x 720 dpi (same as above). If specialty paper is used as the print medium, the skipping procedure is dispensed with irrespective of the type of other print mode parameters. The reason is that specialty paper can rapidly absorb ink, making a skipping procedure unnecessary. However, the specifics of the skipping procedure are defined in the following manner when plain paper is used as the print medium. When dots adjacent to the inside of a contour line are involved, the skipping procedure is performed irrespective of other print mode parameters if the print medium is plain paper. This is the same skipping procedure as the one performed in accordance with the second working example above. Transverse contour lines are subjected to a skipping procedure when the print medium is plain paper and the print resolution in the direction of main scanning is 720 dpi. The reason that the skipping procedure is performed for a print resolution of 720 dpi × 720 dpi is that the printing device of the present working example is incapable of producing sufficiently small ink droplets required for filling in pixels with 720 dpi × 720 dpi. A dot pattern such as the one shown in Fig. 23 may, for example, be formed in such a case. Some of the dots belonging both to transverse contour lines and to longitudinal contour lines should preferably be skipped because sufficiently small ink droplets needed to fill in pixels are commonly difficult to obtain with an ink-jet printing device at a resolution greater than 1200 dpi x 1200 dpi. A longitudinal contour line is subjected to a skipping procedure only when the print medium is plain paper, the print resolution in the direction of sub-scan is 720 dpi, and the ink is black. The reason that a skipping procedure is performed for a black ink is that the black ink nozzle array is the only high-density nozzle array provided to the print head 28. With a black ink, high-speed printing is performed using the black ink nozzle array alone. Fig. 24 is a diagram depicting the relation between print resolution and the skipping procedure. The dot shown in the drawing is an ink dot obtained on the assumption that each dot is formed individually. The ink dot has dimension Rm in the direction of main scanning, and dimension Rs in the direction of sub-scan. The pixel shown in the drawing has dimension Pm in the direction of main scanning, and dimension Ps in the direction of sub-scan. The dimension Pm or Ps is the reciprocal of print resolution. For example, Pm is equal to 1/720 th of an inch when the print resolution is 720 dpi in the direction of main scanning. According to the present working example, the decision to skip some dots is made based on whether the value obtained by dividing the length of the ink dot by the length of the pixel is greater than a specific predetermined threshold Thm or Ths. As used herein, Thm is the threshold in the direction of main scanning, and Ths is the threshold in the direction of sub-scan. For example, skipping is performed if Rm/Pm is greater than the threshold Thm in the direction of main scanning. The threshold Thm corresponds to the first threshold referred to in the claims, and the threshold Ths corresponds to the second threshold referred to in the claims. Selecting a high threshold makes it less likely that spaces (voids) will form between dots but facilitates bleeding because of impaired skipping. Selecting a low threshold can further reduce bleeding but makes it more likely that voids will form. Setting the threshold Th to 2.0 allows skipping-induced voids to be removed substantially completely when images are printed on plain paper. Lowering the threshold Th to 1.8 is beneficial in the sense that the bleeding of contour lines can be further reduced while humanly perceivable voids are removed when images are printed on plain paper. It is assumed with regard to the printing device of the third working example that the same level is selected for the threshold Thm in the direction of main scanning as for the threshold Ths in the direction of sub-scan when images are printed on plain paper by a high-density nozzle array. The specifics of the skipping procedure thus defined apply to an entire print job. In step S505 of Fig. 19, the printer driver 96 generates print data that match the specifics of the skipping procedure selected for use in step S504. In step S506, the printer 20 prints images in accordance with the print data obtained from the computer 88. In the third working example, the specifics of the skipping procedure performed during actual printing are thus defined in accordance with the following three print mode parameters: print medium type, ink color, and print resolution. The resulting advantage is that an optimum skipping procedure suitable for a given print mode can be performed. As follows from the above description, the present invention entails adjusting dot data to achieve a systematic reduction in the amount of ink supplied to form, a contour line, and an approach should preferably be adopted configured to the amount of ink supplied to form the dots adjacent to the inside of the contour line is reduced in a systematic manner depending on the print medium used or other printing conditions selected. A method in which the specifics of the skipping procedure are defined in accordance with the print mode in the above-described manner can be cited as an example of the technique for varying the specifics of the skipping procedure with the print medium used or other printing conditions selected. F. Fourth Working Example This working example is different from the above-described working examples in that the size of the dots in the pixels adjacent to the inside of a contour line are reduced without skipping some of the pixels in the contour line. Bleeding can thus be reduced without creating excessive voids. Fig. 25 is a diagram outlining the printer adopted for the fourth working example of the present invention. A recording head 1101 (occasionally referred to as a ""print head"") is immovably mounted on a carriage 1102. The carriage 1102 can move in the course of main scanning along a guide shaft 1109 in the directions shown by arrows A and B. The main scanning is carried out by a carriage drive belt 1103, itself driven by a carriage drive motor 1104. A recording medium 1107 (occasionally referred to as ""print medium"") is fed in the course of sub-scan in the direction of arrow C. The medium is fed in the direction of sub-scan by a conveyance roller 1108, itself driven by a conveyance roller drive motor (not shown). The dot-forming ink is fed to the recording head 1101 through an ink supply tube 1106 from an ink supply tank 1105. The recording head 1101 ejects ink under the action of ejection drive elements. The recording head 1101 has 96 nozzles, arranged at a pitch of 1/360 th of an inch in the direction of sub-scan. As a result, the recording head 1101 can record at 360 dpi in a single main scan, and at 720 dpi in two main scans. The ink used in the present working example comprises at least water, a pigment, and a resin emulsion. Specifically, the ink can be prepared by adding purified water to a mixture obtained by mixing the following components in an appropriate manner: 6 wt% of carbon black as a pigment, 3 wt% of a styrene/acrylic acid ester copolymer as a resin emulsion, and 15 wt% of diethylene glycol as a moisturizing agent, as well as 0.1 wt% of Proxel, 1.5 wt% of a surfactant, and other components. The recording head 1101 deposits ink droplets on the recording medium 1107 by selectively ejecting these droplets from the nozzles in synchronism with the main scanning of the carriage 1102. When a main scan is completed, the recording medium 1107 is fed in the direction of sub-scan by the conveyance roller 1108. The desired printed image is formed on the recording medium by repeating such operations. According to a specific example, the recording head 1101 can eject an ink droplet every time a distance of 1/360 th of an inch is traveled in the direction of main scanning when the print resolution is 360 dpi. -Meanwhile, the recording medium 1107 is advanced 96/360 th of an inch in the direction of sub scan every time a main scan is completed. The reason that the recording head 1101 is advanced 96/360 th of an inch in the direction of sub-scan is that the head has 96 nozzles and can form 96 main scan lines in a single main scan. Fig. 26 is a block diagram outlining the printing device adopted for the fourth working example of the present invention. The printing device pertaining to the present working example comprises an external device 1220 whereby dot data for expressing the dot formation geometry are obtained from print image data for expressing the image to be printed, a recording data storage means 1201 for recording the dot data 1221 forwarded by the external device 1220, a contour line extraction means 1202 for extracting the outline of the printed image from the dot data 1221, a skipping means 1203 for skipping some of the dots in the pixels adjacent to the inside of the extracted contour line, fill-in means 1204 for filling in the pixels targeted for skipping, a band memory 1205 for storing the dot data 1223 deleted by the skipping means 1203 and the fill-in data 1224 produced by the fill-in means 1204, and a head drive means 1206 for generating drive signals in accordance with the data stored in the band memory 1205. As used herein, the term ""dot skipping"" refers to a procedure in which a pixel (recording pixel) with a dot is changed to a pixel (non-recording pixel) without a dot. The external device 1220 corresponds to the dot data generator referred to in the claims, the contour line extraction means 1202 corresponds to the contour line extractor referred to in the claims, and the skipping means 1203 and fill-in means 1204 correspond to the ink amount reducer referred to in the claims. The dot data 1221 forwarded by the external device 1220 are stored in the recording data storage means 1201. When printing is started, a CPU 1222 reads the dot data 1221 from the recording data storage means 1201 and forwards the result to the contour line extraction means 1202 and skipping means 1203. The contour line extraction means 1202 extracts a contour line from the dot data 1221, generates contour line data, and forwards the contour line data to the skipping means 1203. The skipping means 1203 performs a skipping procedure (that is, deletes dots from specific pixels) in accordance with the dot data 1221 and contour line data. The fill-in means 1204 receives data for expressing the deleted dots from the skipping means 1203. Contour lines may be extracted in the following manner. A contour line may, for example, be extracted using a known filter such as the first derivation filter shown in Fig. 27a. According to the present working example, a contour line may be extracted using a first derivation filter such as the Prewitt filter shown in Fig. 27b. Fig. 28 is a diagram depicting the process for extracting the contour line of text A according to the fourth working example of the present invention. Fig. 28a is a diagram depicting dot data for expressing text A. Fig. 28b is a diagram depicting the results obtained by extracting a contour line with a pixel width of 1 from the dot data shown in Fig. 28a. Specifically, the skipping means 1203 and fill-in means 1204 perform skipping and fill-in procedures in the following manner. According to the present example, an area whose width is equal to a single pixel and which is disposed on the inside of a pixel for forming a contour line is filled with smaller dots and is subjected to dot skipping. The skipping means 1203 receives contour line data from the contour line extraction means 1202. The contour line data contains dummy data 1701 for two pixels (one in front and one behind in the direction of main scanning in the area being recorded), as shown in Fig. 29. The presence of such dummy data allows the procedure to be started from pixel 1702, which is disposed at the edge of the recording area. Fig. 30 is a diagram depicting the progress of the skipping and fill-in procedures performed in accordance with the fourth working example of the present invention. Fig. 30a depicts the tenth line of data in the contour line data shown n Fig. 29. These data are processed in the following sequence. (1) For the data shown in Fig. 30a, the areas interposed between contour lines are blacked out. Data such as that shown in Fig. 30a are produced as a result. (2) The data shown in Fig. 30b are shifted two pixels to the left. Data such as that shown in Fig. 30c are produced as a result. (3) The data shown in Fig. 30b are shifted two pixels to the right. Data such as that shown in Fig. 30d are produced as a result. (4) A logical product of the data shown in Fig. 30c and the data shown in Fig. 30d is obtained. Data such as that shown in Fig. 30e are produced as a result. (5) A logical sum of the data shown in Fig. 30a and the data shown in Fig. 30e is obtained. Data such as that shown in Fig. 30f are produced as a result. (6) An exclusive-or logical sum of the data shown in Fig. 30b and the data shown in Fig. 30f is obtained. Data such as that shown in Fig. 30g are produced as a result. The dot data 1223 (Fig. 26) obtained as described above by performing the skipping procedure shown in Fig. 30f are sent and stored in the band memory 1205, as are the fill-in data 1224 shown in Fig. 30g. The head drive means 1206 generates a head drive signal and allows the recording head 1101 to operate in accordance with these data. Specifically, a drive signal for ejecting ink droplets designed to form large dots is generated in accordance with the dot data 1223 resulting from the skipping procedure shown in Fig. 30f, and a drive signal for ejecting ink droplets designed to form small dots is generated in accordance with the data 1224 shown in Fig. 30g. The recording head 1101 ejects large or small dots and forms characters or line drawings on the recording medium 1107 in accordance with these drive signals. A printed image such as the one shown in Fig. 31 is produced as a result. Adopting an approach in which the amount of ink supplied for the dots formed in the pixels inscribed in a contour line is reduced by shrinking the dots in this manner is advantageous because the bleeding of the contour line can be reduced without creating excessive voids. Although the present example was described with reference to a case in which a single pixel was selected as the width of the area filled in with smaller dots or subjected to dot skipping, it is also possible, for example, to adopt an arrangement in which the width is increased to two pixels. The pixel width can be adjusted by increasing the amount of shifting from two to three pixels when, for example, data such as that shown in Fig. 30c or 30d are generated. G. Modifications The present invention is not limited to the above-described working examples or embodiments and can be implemented in a variety of ways as long as its essence is not compromised. For example, the following modifications are possible. G-1. In the above-described working examples, a contour line constitutes a boundary with an area in which ink dots are completely absent. However, the contour line is not limited to this option alone and can be any discontinuity whose unique attributes define the area. For example, the contour line may visually define a boundary that divides different color tones. The present invention makes it possible to reduce bleeding from such outlines as well. This is because the bleeding from such outlines also has an adverse effect on picture quality. In such cases, some ink dots are skipped or fashioned to a different size in at least one such area. G-2. The amount of ink may also be reduced in accordance with print resolution. For example, it is possible to reduce the amount of ink only when the print resolution exceeds 600 dpi in the direction of main scanning and/or direction of sub-scan. This is because bleeding from contour lines increases with increased print resolution and becomes particularly pronounced at a resolution of 600 dpi or greater. G-3. Although the above working examples were described with reference to a case in which the print mode parameters used to define the specifics of a skipping procedure included print medium type, ink color, and print resolution, other possible examples may include those in which the specifics of the skipping procedure are defined based on the use of different types of ink, such as superhigh permeation ink and low permeation ink. Any approach can commonly be adopted as long as the specifics of the skipping procedure can be defined in accordance with the print mode parameters that affect the bleeding of contour lines. As used herein, the terms ""superhigh permeation ink"" and ""low permeation ink"" refer to the relative characteristics of such inks. Specifically, a superhigh permeation ink penetrates into a print medium faster than does a low permeation ink when equal amounts of both types of ink are fed in drops onto a standard print medium (plain paper, for example). An ink with a surface tension of less than about 40 × 10 -3 N/m at about 20°C may, for example, be used as superhigh permeation ink. An ink with a surface tension of greater than about 40 × 10 -3 N/m at about 20°C may be used as low permeation ink. Either dyes or pigments can be used as colorants for such superhigh or low permeation inks. G-4. Although the above working examples were described with reference to cases in which the type of print medium was specified by selecting the print mode, it is also possible to adopt an approach in which the type of print medium is specified by providing the printing device with a means for automatically specifying the type of print medium. It is commonly possible to adopt any arrangement in which the specifics of the skipping procedure are defined in accordance with the type of print medium. Examples of the means for automatically specifying the type of print medium include optical selection means for detecting reflected light and making a selection on the basis of the difference in optical reflectance between specialty paper and plain paper, bar code reading means for making a selection by reading a bar code provided in advance to a recording medium or packaging, and means for making a selection with the aid of an IC reader. Such means have the advantage of freeing the user from the need to specify the type of print medium, and the means for specifying the type of print medium by selecting the print mode have the additional advantage of being implemented in a simple structure. G-5. The above working example were described with reference to cases in which halftone data were processed, contour lines were extracted, and the amount of ink was reduced using the results. The method for extracting contour lines is not limited to this option alone, however. When, for example, images are printed using data for specifying contour lines (as is the case with outline data), it is possible to adopt an approach in which the amount of ink is reduced by the direct use of contour line data obtained from these outline data. Specifically, the present invention can be adapted to a technique for reducing the bleeding of contour lines by processing dot data for expressing the formation geometry of ink dots. Fig. 32 is diagram depicting a process in which text B is created with an outline font. Fig. 32a is a diagram depicting discreet points for forming the outline of text B. Complementing these dots with straight lines can yield data for expressing the contour lines of text B, as shown in Fig. 32b. Data for expressing text B such as the one shown in Fig. 32c can be further obtained by processing the data configured to the area inside these contour lines is blacked out. Data for expressing contour lines can thus be generated as print data without extracting the contour lines when a text is created with an outline font. The dot data generator functions as a contour line extractor when texts are created with an outline font. G-6. The present invention can be adapted not only to color printing but also to monochromatic printing. The invention can also be adapted to printing in which multiple gray scales are expressed by expressing a single pixel with a plurality of ink dots. Using the present invention with drum printers is yet another option. In a drum printer, the direction of drum rotation corresponds to main scanning; the direction of carriage travel, to sub-scan. Finally, the present invention can be adapted not only to ink-jet printers but also to any other common ink-jet recording device in which images are recorded on the surface of a print medium with the aid of a recording head having a plurality of nozzle arrays. G-7. In the above working examples, software can be used to perform some of the hardware functions, or, conversely, hardware can be used to perform some of the software functions. For example, some or all of the functions performed by the printer driver 96 shown in Fig. 2 or 20 can be performed by the control circuit 40 inside the printer 20. In this case, some or all of the functions performed by the computer 88, which is a print control device for compiling print data, can be performed by the control circuit 40 of the printer 20. When some or all of the functions of the present invention are performed by software, this software (computer programs) can be furnished after being stored on a computer-readable recording medium. As used herein, the term ""computer-readable recording medium"" is not limited to portable recording media such as floppy disks or CD-ROMs and also includes RAM, ROM, and other internal computer storage devices, as well as hard disks and other external storage devices immovably mounted in computers. G-8. According to the invention a method of printing by forming ink dots with a printing unit capable of printing images on a print medium with one of a plurality of print resolutions comprises the steps of: (a) generating dot data from image dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; (b) extracting a transverse contour line parallel to a main scan direction under a specific condition, the transverse contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a first value is greater than a predetermined first threshold, the first value being obtained by dividing a length of the specific type dot in a main scan direction by a pixel length in the main scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and (c) adjusting the dot data so as to regularly reduce an amount of ink for forming dots an the transverse contour line. The step (c) may include the step of adjusting the dot data so as to maintain the amount of ink for forming the specific dots at pixels, if at least one of two next pixels in the main scan direction to these pixels is not subject to dot formation. The print unit may be capable of printing images with a print resolution of 600 dpi or greater in the main scan direction; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink when printing is performed with a print resolution of 600 dpi or greater in the main scan direction. The first threshold may be 2.0; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink when the print medium is a plain paper. According to another embodiment the first threshold is 1.8; and the step(c) includes the step of adjusting the dot data so as to reduce the amount of ink when the print medium is a plain paper. The step (b) may include the step of further extracting a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and the dot data adjuster may be configured to adjust the dot data so as to further regularly reduce the amount of ink for forming dots an the longitudinal contour line. The print unit may be capable of printing images with a print resolution of 1200 dpi or greater in the main scan direction and/or sub-scan direction; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink for the dots an the transverse contour line and/or an the longitudinal contour line, when printing is performed with a print resolution of 1200 dpi or greater in the main scan direction and in the sub-scan direction. Furthermore, according to the invention a computer program product for causing a computer to generate print data to be supplied to a printing unit capable of printing images an a print medium with one of a plurality of print resolutions comprises a computer readable medium; and a computer program stored an the computer readable medium, the computer program comprising a first program for causing the computer to generate dot'data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; a second program for causing the computer to extract a transverse contour line parallel to a main scan direction under a specific condition, the transverse contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a first value is greater than a predetermined first threshold, the first value being obtained by dividing a length of the specific type dot in a main scan direction by a pixel length in the main scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and a third program for causing the computer to adjust the dot data so as to regularly reduce an amount of ink for forming dots an the transverse contour line. The third program may be configured to adjust the dot data so as to maintain the amount of ink for forming the specific dots at pixels, if at least one of two next pixels in the main scan direction to these pixels is not subject to dot formation. The print unit may be capable of printing images with a print resolution of 600 dpi or greater in the main scan direction; and the third program may be configured to adjust the dot data so as to reduce the amount of ink when printing is performed with a print resolution of 600 dpi or greater in the main scan direction. The first threshold may be 2.0; and the third program may be configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. According to another embodiment the first threshold is 1.8; and the third program is configured to adjust the dot data so as to reduce the'amount of ink when the print medium is a plain paper. The second program may be configured to further extract a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and the third program may be configured to adjust the dot data so as to further regularly reduce the amount of ink for forming dots an the longitudinal contour line. The print unit may be capable of printing images with a print resolution of 1200 dpi or greater in the main scan direction and/or sub-scan direction; and the third program may be configured to adjust the dot data so as to reduce the amount of ink for the dots an the transverse contour line and/or an the longitudinal contour line, when printing is performed with a print resolution of 1200 dpi or greater in the main scan direction and in the sub-scan direction. Moreover, according to the invention a method of printing by forming ink dots with a printing unit capable of printing images an a print medium with one of a plurality of print resolutions comprises the steps of: (a) generating dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; (b) extracting a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and (c) adjusting the dot data so as to regularly reduce the amount of ink for forming dots an the longitudinal contour line. The step (c) may include the step of adjusting the dot data so as to maintain the amount of ink for forming the specific dots at pixels, if at least one of two next pixels in the sub-scan direction to these pixels is not subject to dot formation. The print unit may be capable of printing images with a print resolution of 600 dpi or greater in the sub-scan direction; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink when printing is performed with a print resolution of 600 dpi or greater in the sub-scan direction. The printing unit may comprise a print head having at least one nozzle array in which a plurality of nozzles are aligned in the sub-scan direction at a nozzle pitch of 1/300th of an inch or less; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink when being ejected from the nozzle array. The second threshold may be 2.0; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink when the print medium is a plain paper. According to another embodiment the second threshold is 1.8; and the step(c) includes the step of adjusting the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing unit may comprise a print head having a plurality of nozzles and a plurality of ejection driving elements for causing ejection of ink droplets respectively from the plurality of nozzles, each nozzle being adaptable to form a selected one of N different dots having different sizes at one pixel area an the print medium, N being an integer of at least 2, the N different dots including a specific size dot that is one of comparatively large dots among the N different dots; and the step(c) may include the step of adjusting the dot data so as to reduce the amount of ink when the longitudinal contour line is formed with the specific size dot. The step (c) may include the step of adjusting the dot data so as to reduce the amount of ink when the print medium is a plain paper. The step (c) may include the step of adjusting the dot data so as to reduce the amount of ink by dot skipping. The step (c) may include the step of adjusting the dot data so as to reduce the amount of ink by reducing dot size. The step (c) may include the step of adjusting the dot data so as to reduce the amount of ink by selectively performing one of dot skipping and dot size reduction, depending on a pixel position of each dot within the specific image area. Furthermore, according to the invention a computer program product for causing a computer to generate print data to be supplied to a printing unit capable of printing images an a print medium with one of a plurality of print resolutions comprises a computer readable medium; and a computer program stored an the computer readable medium, the computer program comprising a first program for causing the computer to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; a second program for causing the computer to extract a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and a third program for causing the computer to adjust the dot data so as to regularly reduce the amount of ink for forming dots an the longitudinal contour line. The third program may be configured to adjust the dot data so as to maintain the amount of ink for forming the specific dots at pixels, if at least one of two next pixels in the sub-scan direction to these pixels is not subject to dot formation. The print unit may be capable of printing images with a print resolution of 600 dpi or greater in the sub-scan direction; and the third program may be configured to adjust the dot data so as to reduce the amount of ink when printing is performed with a print resolution of 600 dpi or greater in the sub-scan direction. The printing unit may comprise a print head having at least one nozzle array in which a plurality of nozzles are aligned in the sub-scan direction at a nozzle pitch of 1/300th of an inch or less; and the third program may be configured to adjust the dot data so as to reduce the amount of ink when being ejected from the nozzle array. The second threshold may be 2.0; and the third program may be configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. According to another embodiment the second threshold is 1.8; and the third program is configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing unit may comprise a print head having a plurality of nozzles and a plurality of ejection driving elements for causing ejection of ink droplets respectively from the plurality of nozzles, each nozzle beinq adaptable to form a selected one of N different dots having different sizes at one pixel area an the print medium, N being an integer of at least 2, the N different dots including a specific size dot that is one of comparatively large dots among the N different dots; and the third program may be configured to adjust the dot data so as to reduce the amount of ink when the longitudinal contour line is formed with the specific size dot. The third program may be configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The third program may be configured to adjust the dot data so as to reduce the amount of ink by dot skipping. The third program may be configured to adjust the dot data so as to reduce the amount of ink by reducing dot size. The third program may be configured to adjust the dot data so as to reduce the amount of ink by selectively performing one of dot skipping and dot size reduction, depending an a pixel position of each dot within the specific image area.";"A printing control apparatus for generating print data to be supplied to a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, the printing control apparatus comprising: a dot data generator configured to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; a contour line extractor configured to extract a transverse contour line parallel to a main scan direction under a specific condition, the transverse contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a first value is greater than a predetermined first threshold, the first value being obtained by dividing a length of the specific type dot in a -main scan direction by a pixel length in the main scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and a dot data adjuster configured to adjust the dot data so as to regularly reduce an amount of ink for forming dots on the transverse contour line. The printing control apparatus in accordance with claim 1, wherein the dot data adjuster is configured to adjust the dot data so as to maintain the amount of ink for forming the specific dots at pixels, if at least one of two next pixels in the main scan direction to these pixels is not subject to dot formation. The printing control apparatus in accordance with claim 1, wherein the print unit is capable of printing images with a print resolution of 600 dpi or greater in the main scan direction; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when printing is performed with a print resolution of 600 dpi or greater in the main scan direction. The printing control apparatus in accordance with claim 3, wherein the first threshold is 2.0; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing control apparatus in accordance with claim 3, wherein the first threshold is 1.8; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing control apparatus in accordance with claim 1, wherein the contour line extractor is configured to further extract a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and the dot data adjuster is configured to adjust the dot data so as to further regularly reduce the amount of ink for forming dots on the longitudinal contour line. The printing control apparatus in accordance with claim 6, wherein the print unit is capable of printing images with a print resolution of 1200 dpi or greater in the main scan direction and/or sub-scan direction; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink for the dots on the transverse contour line and/or on the longitudinal contour line, when printing is performed with a print resolution of 1200 dpi or greater in the main scan direction and in the sub scan direction. A method of printing by forming ink dots with a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, comprising the steps of: (a) generating dot data from image dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; (b) extracting a transverse contour line parallel to a main scan direction under a specific condition, the transverse contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a first value is greater than a predetermined first threshold, the first value being obtained by dividing a length of the specific type dot in a main scan direction by a pixel length in the main scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and (c) adjusting the dot data so as to regularly reduce an amount of ink for forming dots on the transverse contour line. A computer program product for causing a computer to generate print data to be supplied to a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, the computer program product comprising: a computer readable medium; and a computer program stored on the computer readable medium, the computer program comprising: a first program for causing the computer to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; a second program for causing the computer to extract a transverse contour line parallel to a main scan direction under a specific condition, the transverse contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a first value is greater than a predetermined first threshold, the first value being obtained by dividing a length of the specific type dot in a main scan direction by a pixel length in the main scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and a third program for causing the computer to adjust the dot data so as to regularly reduce an amount of ink for forming dots on the transverse contour line. A printing control apparatus for generating print data to be supplied to a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, the printing control apparatus comprising: a dot data generator configured to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; a contour line extractor is configured to extract a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and a dot data adjuster configured to adjust the dot data so as to regularly reduce the amount of ink for forming dots on the longitudinal contour line. The printing control apparatus in accordance with claim 10, wherein the dot data adjuster is configured to adjust the dot data so as to maintain the amount of ink for forming the specific dots at pixels, if at least one of two next pixels in the sub-scan direction to these pixels is not subject to dot formation. The printing control apparatus in accordance with claim 10, wherein the print unit is capable of printing images with a print resolution of 600 dpi or greater in the sub-scan direction; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when printing is performed with a print resolution of 600 dpi or greater in the sub-scan direction. The printing control apparatus in accordance with claim 12, wherein the printing unit comprises a print head having at least one nozzle array in which a plurality of nozzles are aligned in the sub-scan direction at a nozzle pitch of 1/300th of an inch or less; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when being ejected from the nozzle array. The printing control apparatus in accordance with claim 13, wherein the second threshold is 2.0; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing control apparatus in accordance with claim 13, wherein the second threshold is 1.8; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing control apparatus in accordance with claim 10, wherein the printing unit comprises a print head having a plurality of nozzles and a plurality of ejection driving elements for causing ejection of ink droplets respectively from the plurality of nozzles, each nozzle being adaptable to form a selected one of N different dots having different sizes at one pixel area on the print medium, N being an integer of at least 2, the N different dots including a specific size dot that is one of comparatively large dots among the N different dots; and the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when the longitudinal contour line is formed with the specific size dot. The printing control apparatus in accordance with claim 10, wherein the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink when the print medium is a plain paper. The printing control apparatus in accordance with claim 10, wherein the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink by dot skipping. The printing control apparatus in accordance with claim 10, wherein the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink by reducing dot size. The printing control apparatus in accordance with claim 10, wherein the dot data adjuster is configured to adjust the dot data so as to reduce the amount of ink by selectively performing one of dot skipping and dot size reduction, depending on a pixel position of each dot within the specific image area. A printing apparatus for forming ink dots with a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, the printing apparatus comprising: the print unit; and the printing control apparatus in accordance with any one of claim 1 to 7 and claim 10 to 20. A method of printing by forming ink dots with a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, comprising the steps of: (a) generating dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; (b) extracting a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and (c) adjusting the dot data so as to regularly reduce the amount of ink for forming dots on the longitudinal contour line. A computer program product for causing a computer to generate print data to be supplied to a printing unit capable of printing images on a print medium with one of a plurality of print resolutions, the computer program product comprising: a computer readable medium; and a computer program stored on the computer readable medium, the computer program comprising: a first program for causing the computer to generate dot data from image data indicative of a image to be printed, the dot data representing a state of dot formation at each pixel; a second program for causing the computer to extract a longitudinal contour line parallel to a sub-scan direction under a specific condition, the longitudinal contour line being a contour line of a specific type image area being composed of pixels at which specific type dots are to be formed according to the dot data, the specific condition being that a second value is greater than a predetermined second threshold, the second value being obtained by dividing a length of the specific type dot in a sub-scan direction by a pixel length in the sub-scan direction corresponding to a selected one of the plurality of print resolutions to be used by the printing unit; and a third program for causing the computer to adjust the dot data so as to regularly reduce the amount of ink for forming dots on the longitudinal contour line.";SATO AKITO, YAMASAKI KEIGO, SATO, AKITO, YAMASAKI, KEIGO;SEIKO EPSON CORP, SEIKO EPSON CORPORATION;2005.0;1524121
EP-1588712-A1;20051026.0;EP;A1;EN;20090605.0;new;34922926.0;A61K38;A01N37, A01N61, A61K39, C07H21, C07K1, C07K16, C12N5, C12P21, G01N33, 7A01N37;A01N37, A01N61, A61K38, A61K39, C07H21, C07K1, C07K14, C07K16, C12N1, C12N5, C12P21, G01N33;C07H  21/04, C07K  14/715, C07K  14/715B;Modulators of regulatory proteins;"A modulator of regulatory cellular events occurring intracellularly which are mediated by regulatory proteins containing a ""death domain"" motif is provided. The ""death domain"" is a regulatory portion of the regulatory proteins, and the modulator is capable of interacting with one or more ""death domain"" motifs contained in the regulatory proteins and affecting the regulatory action of one or more of the regulatory proteins. The modulator preferably is capable of interacting with ""death domain"" motifs with p55-TNF-R, FAS/APO1-R, NGF-R, MORT-1, RIP, TRADD, or ankyrin, as illustrated in the Figure. A method for producing the modulators is also provided. The modulators are useful for modulating functions mediated in cells by proteins containing the ""death domain"".";"Field of the Invention The present invention is generally in the field of regulatory proteins which exert their effects by intracellular signaling processes which are mediated by regulatory elements (domains or motifs) contained within the intracellular domains of these proteins. More specifically, the present invention concerns new modulators being proteins, peptides, antibodies or analogs or fragments of any thereof, and organic compounds which are capable of interacting with, or binding to, the newly discovered 'death domain' motif present in a wide range of related and unrelated proteins, for example, receptors of the TNF/NGF family such as p55 TNF-R, FAS-R, NGF-R. a related protein MORT-1, proteins known as TRADD and RIP and the unrelated protein ankyrin 1. These new modulators are capable of modulating or regulating the activity of the proteins which contain the 'death domain' motif. Background of the Invention and Prior Art There is a very large group of regulatory proteins which exert their regulatory effects on cells by way of intracellular signaling processes, mediated by regulatory portions or motifs contained within these proteins. Members of this group of proteins include, receptors belonging to the TNF/NGF family of receptors, such as, for example, the p55 and p75 TNF receptors (p55 and p75 TNF-Rs), the NGF receptor (NGF-R) and the Fas/APO1 protein (also called the FAS-ligand receptor or FAS-R, and hereinafter will be called FAS-R); these receptors being characterized by having an extracellular ligand-binding domain, a transmembrane domain and an intracellular (IC) domain, which intracellular domain or portions thereof is involved in the mediation of the intracellular signaling events initiated by the binding of the ligand to the extracellular domain. Other members of this group include various intracellular proteins, for example, the cytoskeleton-associated structural proteins, the ankyrins, which have a regulatory domain that is possibly involved in the ability of these proteins to associate with or bind to other cytoskeletal proteins, e.g. spectrin, or to other transmembrane proteins. Yet another member of this group is the recently identified MORT1 protein (also called HF1, see co-pending IL 112002 and IL 112692), which is capable of binding specifically to the intracellular domain of the FAS-R, and which is also capable of self-association and of mediating, in a ligand-independent manner, cytotoxic effects on cells. In MORT-1, a regulatory domain was also identified (see IL 112692). Tumor Necrosis Factor (TNF-α) and Lymphotoxin (TNF-β) (hereinafter, TNF, refers to both TNF-α and TNF-β) are multifunctional pro-inflammatory cytokines formed mainly by mononuclear phagocytes, which have many effects on cells (Wallach, D. (1986) in : Interferon 7 (Ion Gresser, ed.), pp. 83-122, Academic Press, London; and Beutler and Cerami (1987)). Both TNF-α and TNF-β initiate their effects by binding to specific cell surface receptors. Some of the effects are likely to be beneficial to the organism they may destroy, for example tumor cells or virus infected cells and augment antibacterial activities of granulocytes. In this way, TNF contributes to the defense of the organism against tumors and infectious agents and contributes to the recovery from injury. Thus, TNF can be used as an anti-tumor agent in which application it binds to its receptors on the surface of tumor cells and thereby initiates the events leading to the death of the tumor cells. TNF can also be used as an anti-infectious agent. However, both TNF-α and TNF-β also have deleterious effects. There is evidence that over-production of TNF-α can play a major pathogenic role in several diseases. Thus, effects of TNF-α, primarily on the vasculature, are now known to be a major cause for symptoms of septic shock (Tracey et al., 1986). In some diseases, TNF may cause excessive loss of weight (cachexia) by suppressing activities of adipocytes and by causing anorexia, and TNF-α was thus called cachetin. It was also described as a mediator of the damage to tissues in rheumatic diseases (Beutler and Cerami, 1987) and as a major mediator of the damage observed in graft-versus-host reactions (Piquet et al., 1987). In addition, TNF is known to be involved in the process of inflammation and in many other diseases. Two distinct, independently expressed, receptors, the p55 and p75 TNF-Rs, which bind both TNF-α and TNF-β specifically, initiate and/or mediate the above noted biological effects of TNF. These two receptors have structurally dissimilar intracellular domains suggesting that they signal differently (See Hohmann et al., 1989; Engelmann et al., 1990; Brockhaus et al., 1990; Loetscher et al., 1990; Schall et al., 1990; Nophar et al., 1990; Smith et al., 1990; and Heller et al., 1990). However, the cellular mechanisms, for example, the various proteins and possibly other factors, which are involved in the intracellular signaling of the p55 an p75 TNF-Rs have yet to be elucidated (In IL 109632 there are described for the first time, new proteins capable of binding to the intracellular domains of p55 and p75 TNF-Rs, these intracellular domains being called, respectively, p75IC and p55 IC). It is this intracellular signaling, which occurs usually after the binding of the ligand, i.e. TNF (α or β), to the receptor, that is responsible for the commencement of the cascade of reactions that ultimately result in the observed response of the cell to TNF As regards the above mentioned cytocidal effect of TNF, in most cells studied so far, this effect is triggered mainly by the p55 TNF-R. Antibodies against the extracellular domain (ligand binding domain) of the p55 TNF-R can themselves trigger the cytocidal effect (see EP 412486) which correlates with the effectivity of receptor cross-linking by the antibodies, believed to be the first step in the generation of the intracellular signaling process. Further, mutational studies (Brakebusch et al., 1992; Tartaglia et al., 1993) have shown that the biological function of the p55 TNF-R depends on the integrity of its intracellular domain, and accordingly it has been suggested that the initiation of intracellular signaling leading to the cytocidal effect of TNF occurs as a consequence of the association of two or more intracellular domains of the p55 TNF-R. Moreover, TNF (α and β) occurs as a homotrimer and as such has been suggested to induce intracellular signaling via the p55 TNF-R by way of its ability to bind to and to cross-link the receptor molecules, i.e. cause receptor aggregation. In co-pending IL 109632 and IL 111125, there is described how the p55IC and p55DD can self-associate and induce, in a ligand-independent fashion, TNF-associated effects in cells. Another member of the TNF/NGF superfamily of receptors is the FAS receptor (FAS-R) which has also been called the Fas antigen, a cell-surface protein expressed in various tissues and sharing homology with a number of cell-surface receptors including TNF-R and NGF-R. The FAS-R mediates cell death in the form of apoptosis (Itoh et al., 1991), and appears to serve as a negative selector of autoreactive T cells, i.e. during maturation of T cells, FAS-R mediates the apoptopic death of T cells recognizing self-antigens. It has also been found that mutations in the FAS-R gene ( lpr ) cause a lymphoproliferation disorder in mice that resembles the human autoimmune disease systemic lupus erythematosus (SLE) (Watanabe-Fukunaga et al., 1992). The ligand for the FAS-R appears to be a cell-surface associated molecule carried by, amongst others, killer T cells (or cytotoxic T lymphocytes - CTLs), and hence when such CTLs contact cells carrying FAS-R, they are capable of inducing apoptopic cell death of the FAS-R-carrying cells. Further, a monoclonal antibody has been prepared that is specific for FAS-R, this monoclonal antibody being capable of inducing apoptopic cell death in cells carrying FAS-R. including mouse cells transformed by cDNA encoding human FAS-R (Itoh et al., 1991). It has also been found that various other normal cells, besides T lymphocytes, express the FAS-R on their surface and can be killed by the triggering of this receptor Uncontrolled induction of such a killing process is suspected to contribute to tissue damage in certain diseases, for example, the destruction of liver cells in acute hepatitis. Accordingly, finding ways to restrain the cytotoxic activity of FAS-R may have therapeutic potential. Conversely, since it has also been found that certain malignant cells and HIV-infected cells carry the FAS-R on their surface, antibodies against FAS-R, or the FAS-R ligand, may be used to trigger the FAS-R mediated cytotoxic effects in these and thereby provide a means for combating such malignant cells or HIV-infected cells (see Itoh et al., 1991). Finding yet other ways for enhancing the cytotoxic activity of FAS-R may therefore also have therapeutic potential. In co-pending IL 109632, IL 111125 and IL 112002 there is described that the intracellular domain of FAS-R, the so-called FAS-IC, is capable of self-association and contains within this intracellular domain a region called the 'death domain' (DD) which is primarily responsible for the self-association of the FAS-IC. This 'death domain' shares sequence homology with the p55 TNF-R, 'death domain' (p55DD). It has been a long felt need to provide a way for modulating the cellular response to TNF (α or β) and FAS-R ligand, for example, in pathological situations as mentioned above, where TNF or FAS-R ligand is over-expressed it is desirable to inhibit the TNF- or FAS-R ligand- induced cytocidal effects, while in other situations, e.g. wound healing applications, it is desirable to enhance the TNF effect, or in the case of FAS-R, in tumor cells or HIV-infected cells it is desirable to enhance the FAS-R mediated effect. A number of approaches have been made by the present inventors (see for example. European Application Nos. EP 186833, EP 308378, EP 398327 and EP 412486) to regulate the deleterious effects of TNF by inhibiting the binding of TNF to its receptors using anti-TNF antibodies or by using soluble TNF receptors (being essentially the soluble extracellular domains of the receptors) to compete with the binding of TNF to the cell surface-bound TNF-Rs. Further, on the basis that TNF-binding to its receptors is required for the TNF-induced cellular effects, approaches by the present inventors (see for example IL 101769 and its corresponding EP 568925) have been made to modulate the TNF effect by modulating the activity of the TNF-Rs. Briefly, EP 568925 (IL 101769) relates to a method of modulating signal transduction and/or cleavage in TNF-Rs whereby peptides or other molecules may interact either with the receptor itself or with effector proteins interacting with the receptor, thus modulating the normal functioning of the TNF-Rs. In EP 568925 there is described the construction and characterization of various mutant p55 TNF-Rs, having mutations in the extracellular, transmembranal, and intracellular domains of the p55 TNF-R. In this way regions within the above domains of the p55 TNF-R were identified as being essential to the functioning of the receptor, i.e. the binding of the ligand (TNF) and the subsequent signal transduction and intracellular signaling which ultimately results in the observed TNF-effect on the cells. Further, there is also described a number of approaches to isolate and identify proteins, peptides or other factors which are capable of binding to the various regions in the above domains of the TNF-R, which proteins, peptides and other factors may be involved in regulating or modulating the activity of the TNF-R. A number of approaches for isolating and cloning the DNA sequences encoding such proteins and peptides; for constructing expression vectors for the production of these proteins and peptides; and for the preparation of antibodies or fragments thereof which interact with the TNF-R or with the above proteins and peptides that bind various regions of the TNF-R, are also set forth in EP 568925. However, no description is made in EP 568925 of the actual proteins and peptides which bind to the intracellular domains of the TNF-Rs (e.g. p55 TNF-R), nor is any description made of the yeast two-hybrid approach to isolate and identify such proteins or peptides which bind to the intracellular domains of TNF-Rs. Similarly, heretofore there has been no disclosure of proteins or peptides capable of binding the intracellular domain of FAS-R. Thus, when it is desired to inhibit the effect of TNF, or the FAS-R ligand, it would be desirable to decrease the amount or the activity of TNF-Rs or FAS-R at the cell surface, while an increase in the amount or the activity of TNF-Rs or FAS-R would be desired when an enhanced TNF or FAS-R ligand effect is sought. To this end the promoters of both the p55 TNF-R and the p75 TNF-R have been sequenced, analyze and a number of key sequence motifs have been found that are specific to various transcription regulating factors, and as such the expression of these TNF-Rs can be controlled at their promoter level, i.e. inhibition of transcription from the promoters for a decrease in the number of receptors, and an enhancement of transcription from the promoters for an increase in the number of receptors (see IL 104355 and IL 109633). Corresponding studies concerning the control of FAS-R at the level of the promoter of the FAS-R gene have yet to be reported. Further, it should also be mentioned that, while it is known that the tumor necrosis factor (TNF) receptors, and the structurally-related receptor FAS-R, trigger in cells, upon stimulation by leukocyte-produced ligands, destructive activities that lead to their own demise, the mechanisms of this triggering are still little understood. Mutational studies indicate that in FAS-R and the p55 TNF receptor (p55-R) signaling for cytotoxicity involve distinct regions within their intracellular domains (Brakebusch et al., 1992; Tartaglia et al., 1993; Itoh and Nagata, 1993). These regions (the 'death domains') have sequence similarity. The 'death domains' of both FAS-R and p55-R tend to self-associate. Their self-association apparently promotes that receptor aggregation which is necessary for initiation of signaling (see IL 109632, IL 111125 and IL 112002, as well as Song et al., 1994; Wallach et al., 1994; Boldin et al., 1995) and at high levels of receptor expression can result in triggering of ligand-independent signaling (IL 109632, IL 111125 and Boldin et al., 1995). The ankyrins constitute a family of proteins that control interactions between integral membrane components and cytoskeletal elements and are found in a wide range of tissues such as brain tissue and in erythrocytes, the erythrocyte ankyrin being the best characterized. The ankyrins are intracellular proteins associated with the cytoskeletal elements of the cell and have three domains : an upper domain involved in binding to the intracellular domains of transmembrane proteins, this upper domain containing the well-known repeats, the so-called ankyrin repeats: a middle domain which is involved in binding to spectrin, i.e. the binding of spectrin to transmembrane proteins via the ankyrins; and a C-terminal or lower (or third) domain, which is the regulatory domain that is capable of being phosphorylated, this domain regulating the activity of the other two domains when phosphorylated or dephosphorylated. This latter regulatory domain also has three parts: a middle part that can be deleted by alternative splicing naturally, and hence some ankyrins have this parts and others don't; and two other parts, less-well characterized (for a review on the ankyrins, see Lux et al., 1990 and Lambert and Bennett, 1993). It should be noted however, as is set forth hereinbelow, that in accordance with the present invention, it has been discovered that the upper part of the above noted regulatory (C-terminal) domain of ankyrin contains a so-called 'death domain' motif, which may function to mediate the binding of proteins together (activity of the first two ankyrin domains), or may function conformationally to regulate the ankyrin protein. The NGF-R is a low affinity NGF receptor which is not well characterized. The NGF-R is considered to be involved in growth regulation, such as its possible involvement in signaling intracellularly for NGF-induced effects. However, a recent publication discloses that overexpression of NGF-R in the absence of NGF can cause cell death. Thus, NGF-R appears to have a regulatory role in cell viability (see Rabizadeh et al. 1993). It should be noted however, as is set forth hereinbelow, that in accordance with the present invention, it has been discovered that the NGF-R contains a 'death domain' motif in its intracellular domain, which may be involved in the mediation of the intracellular events associated with the regulatory role played by NGF-R with regards to cell viability. MORT-1 is a recently discovered protein that binds to the intracellular domain of FAS-R, is capable of self-association and can activity cell cytotoxicity on its own. Hence, MORT1 is also a regulatory protein involved in intracellular signaling processes. It was also discovered that MORT-1 has a 'death domain' motif that is associated with its observed biological activity (see co-pending IL 112002 and IL 112692). Two further intracellular proteins RIP, (Stanger et al., 1995) and TRADD (Hsu et al., 1995), that bind to the intracellular domains of p55 TNF-R or FAS-R and apparently take part in the induction of their cytocidal effect, have recently been cloned. All three proteins, MORT-1, RIP and TRADD, were found to contain the sequence motif shared between the 'death domains' of the intracellular domains of p55-TNF-R and FAS-R. As in the receptors, the 'death domain' motifs (DD) in the three intracellular proteins seem to be sites of protein-protein interaction. The three proteins interact with the p55-TNF-R and FAS-R intracellular domains by the binding of their DDs to those in the receptors, and in both TRADD and RIP (though not in MORT-1) the DDs self-associate. It has now been found that MORT-1 and TRADD bind differentially to FAS-R and p55 TNF-R and also bind to each other. Moreover, both bind effectively to RIP Interference of the interaction between the above three intracellular proteins will result in modulation of the effects caused by this interaction. Thus, inhibition of TRADD binding to MORT-1 may modulate FAS-R - p55 TNF-R infraction. Inhibition of RIP in addition to the above inhibition of TRADD binding to MORT-1 may further modulate FAS-R - p55 TNF-R interaction. Monoclonal antibodies raised against the 'death domain' of the p55 TNF-R, specifically against the binding site or sites of TRADD and RIP can also be used to inhibit or prevent binding of these proteins and thus cause modulation of the interaction between the FAS-R and the p55 TNF-R. In a way analogous to that noted above in respect of TNF/TNF-R and FAS-ligand/FAS-R, there is also a need to provide a way for modulating the activity of the above noted proteins, i.e. ankyrin, NGF-R and MORT-1, namely, to inhibit their activity when it is associated with detrimental effects, e.g. disease/disorder-related cell cytotoxicity or conformational changes in cell-shape; or to enhance their activity when this is desired. e.g. for directed destruction of diseased cells, etc. In the co-pending applications, IL 109632, IL 111125, lL 112002 and IL 112692, there are described proteins which are involved in the modulation of the activity of receptors belonging to the TNF/NGF receptor family, these proteins being characterized by being capable of binding/associating with the intracellular domains of one or more of these receptors. The present invention concerns modulators such as proteins, peptides, antibodies and organic compounds which are capable of interacting/binding with one or more so-called 'death domain' motifs in the intracellular domains of proteins containing such motifs, these proteins being related, e.g. members of the TNF/NGF receptor family or proteins related thereto, e.g. MORT1, or unrelated proteins, e.g. ankyrins. These modulators are characterized by recognizing general structural features common to the 'death domain' motifs of the 'death domain' motif-containing proteins, and by also recognizing specific structural features present in each of the different 'death domain' motifs of these proteins. Accordingly, it is one aim of the invention to provide modulators, as noted above, capable of binding to or interacting with the 'death domain' motifs of one or more of the 'death domain' motif-containing proteins and thereby modulating the activity of these proteins. Another aim of the invention is to provide antagonists (e.g. antibodies) to one class of these modulators, namely the naturally-occurring proteins or peptides which bind to 'death domain' motif-containing proteins, and which antagonists may be used to inhibit the signaling process, when desired, when such 'death domain' motif-binding proteins or peptides are positive signal effectors (i.e. induce signaling), or to enhance the signaling process, when desired, when such 'death domain' motif-binding proteins are negative signal effectors (i.e. inhibit signaling). Yet another aim of the invention is to use such 'death domain' motif-binding proteins or peptides to isolate and characterize additional proteins or factors, which may, for example, be involved further downstream in the signaling process, and/or to isolate and identify other receptors further upstream in the signaling process to which these 'death domain' motif-binding proteins bind, and hence, in whose function they are also involved. Moreover, it is an aim of the present invention to use the above-mentioned 'death domain' motif-binding proteins as antigens for the preparation of polyclonal and/or monoclonal antibodies thereto. The antibodies, in turn, may be used for the purification of the new 'death domain' motif-binding proteins from different sources, such as cell extracts or transformed cell lines. Furthermore, these antibodies may be used for diagnostic purposes, e.g. for identifying disorders related to abnormal functioning of cellular effects mediated by the various proteins belonging to the group of'death domain' motif-containing proteins. A further aim of the invention is to provide pharmaceutical compositions comprising the above 'death domain' motif-binding modulators (proteins, peptides, organic molecules), and pharmaceutical compositions comprising the 'death domain' motif-binding protein or peptide antagonists, for the treatment or prophylaxis of conditions related to the activity of the 'death domain' motif-containing proteins, for example, such compositions can be used to enhance the TNF or FAS ligand effect or effects mediated by NGF-R, MORT-1, RIP, TRADD and ankyrin, or to inhibit the TNF or FAS ligand effect or effects mediated by depending on the above noted nature of the 'death domain' motif-binding modulators or antagonists thereof contained in the composition. A still further aim of the invention is to use the various 'death domain' motifs of the proteins containing them for the design and synthesis of complementary peptides and organic molecules which will be modulators of these proteins. Summary of the Invention The.present invention is based on the surprising and unexpected finding that there exists a so-called 'death domain' motif in a wide range of proteins some of which are related and others which are not related. For example, this 'death domain' motif has been found in p55 TNF-R, FAS-R, NGF-R, MORT1, RIP and TRADD which are related to each other, as well as in the unrelated protein, ankyrin 1. As noted above, the 'death domain' motif of the proteins containing this motif is located in the intracellular regulatory domain of these proteins. Hence, the 'death domain' motif appears to be involved in a regulatory function associated with cell viability (cell death) as well as cell shape/conformation, this function being effected at (i.e. in the case of receptors containing this motif) or close to (i.e. in the case of structural intracellular proteins, e.g. ankyrin) the cell surface. Moreover, the observation, in accordance with the present invention, that the 'death domain' motif is conserved amongst a wide range of related and non-related proteins indicates that this motif may have an important regulatory function. Accordingly, the present invention provides a modulator of regulatory cellular events occurring intracellularly that are mediated by regulatory proteins containing a 'death domain' motif which is a regulatory portion of said proteins, said modulator being capable of interacting with one or more of the 'death domain' motifs contained in said regulatory proteins and affecting the regulatory action of one or more of said regulatory proteins. In particular, the present invention provides : (i) a modulator wherein said modulator is selected from the group comprising naturally-derived 'death domain' motif-binding proteins and peptides and analogs and derivatives thereof capable of interacting with one or more of said 'death domain' motifs; (ii) a modulator wherein said modulator is selected from the group of synthetically produced complementary peptides, synthesized by using as substrates the 'death domain' motif sequences of said regulatory proteins containing 'death domain' motifs, said complementary peptides being capable of interacting with one or more of said 'death domain' motifs. (iii) a modulator wherein said modulator is selected from the group comprising antibodies or active fragments thereof capable of interacting with one or more of said 'death domain' motifs. (iv) a modulator wherein said modulator is selected from the group of organic compounds capable of interacting with one or more of said 'death domain' motifs, said organic compounds being derived from known compounds and selected by using said 'death domain' motifs as a substrate in a binding assay, or being synthesized using said 'death domain' motifs as a substrate for designing and synthesizing said organic compounds. (v) a modulator wherein said modulator is selected from the group of peptides or polypeptides derived from naturally occurring 'death domain' motif sequences, said peptides or polypeptides being capable of interacting with one or more of said 'death domain' motifs, and analogs and derivatives of said peptides or polypeptides capable of interacting with one or more of said'death domain' motifs. (vi) a modulator of any one of (i)-(v) wherein said modulator is further characterized by being capable of recognizing the general 'death domain' motif sequence features common to the 'death domain' motifs of'death domain' motif containing proteins, and being capable of recognizing one or more of the specific 'death domain' motifs of said proteins, said specific sequence features being specific to each 'death domain' motif sequence of each of said proteins. (vii) a modulator of any one of (i)-(vi) wherein said modulator is capable of interacting with one or more of the 'death domain' motifs contained within the proteins belonging to the group comprising p55 TNF-R, FAS-R, NGF-R, MORT-1, RIP, TRADD and ankyrin 1. (viii) a modulator of (vii) wherein said modulator is further characterized by being capable of interacting with common sequence features of the 'death domain' motifs of said group of proteins, said common sequence features comprising the group of common amino acid residues W (tryptophan), L (leucine), I (isoleucine), A (alanine), D (aspartic acid), E (glutamic acid), T (threonine), R (arginine) and Y (tyrosine) at the location within said 'death domain' motifs shown in Fig. 1. The present invention also provides a DNA sequence encoding a modulator being a protein, peptide or polypeptide or an analog of any one of (i), (ii) and (vii). An embodiment of the DNA sequence of the invention is a DNA sequence encoding a naturally derived protein or peptide selected from the group consisting of: (a) a cDNA sequence derived from the coding region of a native 'death domain' motif-binding protein or peptide. (b) DNA sequences capable of hybridization to a sequence of (a) under moderately stringent conditions and which encode a biologically active 'death domain' motif-binding protein or peptide; and (c) DNA sequences which are degenerate as a result of the genetic code to the DNA sequences defined in (a) and (b) and which encode a biologically active 'death domain' motif-binding protein or peptide. Other embodiments of the DNA sequence of the invention are : (i) DNA sequence encoding a 'death domain' motif-binding protein or peptide capable of binding to the 'death domain' motif of one or more of the proteins of the group comprising p55 TNF-R, FAS-R, NGF-R, MORT-1 and ankyrin 1. (ii) DNA sequence encoding a peptide or polypeptide derived from the naturally occurring 'death domain' motif sequence of the 'death domain' motif-containing proteins. (iii) DNA sequence encoding a peptide or polypeptide derived from the 'death domain' motif sequence of any one of the proteins of the group comprising p55 TNF-R, FAS-R, NGF-R, MORT-1, RIP, TRADD and ankyrin 1. Furthermore, there is also provided : (a) a protein, peptide or polypeptide and analogs of any one thereof encoded by a DNA sequence of the invention, said protein, peptide, polypeptide and analogs being capable of binding to or interacting with one or more of the 'death domain' motifs of one or more 'death domain' motif containing proteins. (b) a vector comprising a DNA sequence of the invention. (c) a vector of (b) capable of being expressed in a eukaryotic host cell. (d) a vector of (b) capable of being expressed in a prokaryotic host cell. (e) transformed eukaryotic or prokaryotic host cells containing a vector of (b), (c) or (d) (f) a method for producing the protein, peptide, polypeptide or analogs of (a) comprising growing the transformed host cells of (e) under conditions suitable for the expression of said protein, peptide, polypeptide or analogs, effecting post-translational modifications of said protein, peptide, polypeptide or analogs as necessary for obtention thereof and extracting said expressed protein, peptide, polypeptide or analogs from the culture medium of said transformed cells or from cell extracts of said transformed cells. (g) antibodies or active fragments or derivatives thereof, specific for the protein, peptide, polypeptide or analogs of (a). The present invention also provides a method for the modulation of the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising treating said cells with one or more proteins, peptides, polypeptides or analogs selected from the group consisting of the proteins, peptides, polypeptides or analogs of the invention (see (a) above), all being capable of binding to or interacting with the 'death domain' motif and modulating the activity of said 'death domain' motif-containing proteins, wherein said treating of said cells comprises introducing into said cells said one or more proteins, peptides, polypeptides or analogs in a form suitable for intracellular introduction thereof, or introducing into said cells a DNA sequence encoding said one or more proteins, peptides, polypeptides or analogs in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells. An embodiment of the above method is a method wherein said treating of said cells is by transfection of said cells with a recombinant animal virus vector comprising the steps of: (a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein (ligand) that is capable of binding to a specific cell surface receptor on the surface of said cell to be treated and a second sequence encoding a protein selected from the proteins, peptides, polypeptides and analogs of the invention, said protein, peptide, polypeptide or analogs, when expressed in said cells being capable of modulating the activity of said 'death domain' motif-containing protein; and (b) infecting said cells with said vector of (a). Another method of the invention is a method for modulating the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1,RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising treating said cells with antibodies or active fragments or derivatives thereof, of the invention (see (g) above), said treating being by application of a suitable composition containing said antibodies, active fragments or derivatives thereof to said cells, said composition being formulated for intracellular application. Yet another method of the invention is a method for modulating the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising treating said cells with an oligonucleotide sequence selected from a sequence encoding an antisense sequence of at least part of the sequence of the invention as noted above, said oligonucleotide sequence being capable of blocking the expression of at least one of the 'death domain' motif-binding proteins or peptides. An embodiment of the above method is a method wherein said oligonucleotide sequence is introduced to said cells via a virus vector as noted above wherein said second sequence of said virus encodes said oligonucleotide sequence. Other methods of the invention are : (i) a method for treating tumor cells or HIV-infected cells or other diseased cells, comprising: (a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein that is capable of binding to a specific tumor cell surface receptor or HIV-infected cell surface receptor or receptor carried by other diseased cells and a sequence encoding a protein selected from the proteins, peptides, polypeptides and analogs of the invention, said protein, peptide, polypeptide or analogs when expressed in said tumor, HIV-infected, or other diseased cell being capable of killing said cell; and (b) infecting said tumor or HIV-infected cells or other diseased cells with said vector of (a). (ii) a method for modulating the TNF or FAS-R ligand effect on cells mediaed by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising applying the ribozyme procedure in which a vector encoding a ribozyme sequence capable of interacting with a cellular mRNA sequence encoding a protein or peptide of the invention, is introduced into said cells in a form that permits expression of said ribozyme sequence in said cells, and wherein when said ribozyme sequence is expressed in said cells it interacts with said cellular mRNA sequence and cleaves said mRNA sequence resulting in the inhibition of expression of said protein or peptide in said cells. (iii) a method for isolating and identifying proteins, peptides, factors or receptors capable of binding to the 'death domain' motif-binding proteins or peptides of the invention, comprising applying the procedure of affinity chromatography in which said protein or peptide of the invention is attached to the affinity chromatography matrix, said attached protein is brought into contact with a cell extract and proteins, factors or receptors from cell extract which bound to said attached protein are then eluted, isolated analyzed. (iv) a method for isolating and identifying proteins, capable of binding to the 'death domain' motif-binding proteins or peptides of the invention, comprising applying the yeast two-hybrid procedure in which a sequence encoding said 'death domain' motif-binding protein is carried by one hybrid vector and sequence from a cDNA or genomic DNA library are carried by the second hybrid vector, the vectors then being used to transform yeast host cells and the positive transformed cells being isolated, followed by extraction of the said second hybrid vector to obtain a sequence encoding a protein which binds to said 'death domain' motif-binding protein. The present invention also provides a pharmaceutical composition for the modulation of the TNF- or FAS-R ligand- effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif comprising, as active, ingredient a modulator of the invention. Embodiments of the pharmaceutical compositions of the invention include : (i) a pharmaceutical composition for modulating the TNF- or FAS-R ligand- effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin I or by other proteins containing a 'death domain' motif, comprising, as active ingredient, a recombinant animal virus vector encoding a protein capable of binding a cell surface receptor and encoding a protein or peptide or analogs thereof of the invention. (ii) a pharmaceutical composition for modulating the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising as active ingredient, an oligonucleotide sequence encoding an anti-sense sequence of the sequence of the invention. A still further method of the invention is a method for isolating and identifying a protein capable of binding to the 'death domain' motifs of 'death domain' motif-containing proteins comprising applying the procedure of non-stringent southern hybridization followed by PCR cloning, in which a sequence or parts thereof of the invention is used as a probe to bind sequences from a cDNA or genomic DNA library, having at least partial homology thereto, said bound sequences then amplified and cloned by the PCR procedure to yield clones encoding proteins having at least partial, homology to said sequences of the invention. In addition, the present invention also provides a method for designing drugs that are capable of modulating the activity of 'death domain' motif-containing proteins, comprising the procedures described herein in Examples 3 and 4. Other aspects and embodiments of the present invention are also provided as arising from the following detailed description of the invention. It should be noted that, where used throughout, the following terms ""Modulation/Mediation of the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif' are understood to encompass in vitro as well as in vivo treatment. Moreover, where used throughout, the antibodies of the invention and the methods using these antibodies, include so-called ""humanized"" antibodies or the use thereof Brief Description of the Drawings Fig. 1 depicts schematically the sequence homology of the 'death domain' motif in MORT-1. p55 TNF-R, Fas/APO1 (FAS-R), low affinity NGF receptor (NGF-R) and the C-terminal part of the regulatory domain in ankyrin 1 (Ankyrin 1), as described in Example 1. Fig. 2 depicts interactions of the 'death domains' of the p55-R, Fas/APOI, MORT1, TRADD and RIP in a yeast two-hybrid test, and the effect of / pr cg -like mutations in these proteins on their interactions. Assessment of the interaction of Gal4 hybrid constructs encompassing the following human proteins, trunctated upstread to their DD motifs: p55-R (residues 326-426), FAS-R (residues 210-319), MORT-1 (residues 92-208), TRADD (residues 195-312) and RIP (residues 261-372), as well as of the following points mutants of these proteins: p55-R L35IN, FAS-R V238N, MORT-1 V121N, and RIP F308N, whose mutation sites within the DDs correspond to that found in the FAS-R of the lpr cg mice. Each cDNA insert was introduced both into the Gal4 DNA binding domain (DBD) and the Gal4 activation domain (AD) constructs (pGBT9 abd pGAD-GH), and the binding of the inserts in both constructs to all other inserts within transfected SFY526 yeasts was assessed by a β-galactosidase expression filter assay. The results are presented in terms of the time required for development of strong color. ND- not done. Fig. 3 is a diagrammatic illustration of the DD interactions observed in the yeast two-hybrid tests. The lengths and thicknesses of the arrose connecting the DD icons correspond to the intensity of the interactions, as observed in the experiment described in Fig. 2. Fig. 4 depicts interactions of MORT-1, TRADD and RIP within transfected HeLa cells. MORT-1 (nucleotides 19-753 in GenBank accession number U24231), fused at is N-terminus with the FLAG octapeptides, and the DDs of TRADD (amino acids 195-312) and of RIP (amino acids 261-372), fused at their N-termini either with the FLAG octapeptide or the HA epitope (Field et al., 1988), were expressed, either alone or in mixtures of two in HeLa celis and metabolically labeled with [ 35 S]-Cys and [ 35 S]-Met. Cross-immunoprecipitation of the co-expressed proteins was performed using the indicated antibodies. The proteins were analyzed by SDS-polyacrylamide gel electrophoresis (15% acrylamide), followed by autoradiography. In cell lysates containing MORT-1 and RIP co-immunoprecipitation of both proteins could be obtained using antibodies against either one of them. However, in lysates containing TRADD anmd RIP, co-immunoprecipitation of the two proteins was observed only when using antibody against RIP, and in lysates containing TRADD and MORT-1 - only with an antibody against TRADD, apparently due to steric hindrance. Detailed Description of the Invention The present invention relates, in one aspect, to novel proteins or peptides which are capable of binding to one or more 'death domain' motifs of 'death domain' motif-containing proteins by virtue of recognizing sequence features common to the 'death domain' motifs within these proteins. Hence the 'death domain' motif binding proteins or peptides are considered as mediators or modulators of this group of 'death domain' motif-containing proteins. This group of 'death domain' motif-containing proteins includes : (i) members of the TNF/NGF receptor family such as, for example, p55 TNF-R, FAS-R (Fas/APO1) and the low affinity NGF receptor (NGF-R); (ii) other related proteins such as, for example, the recently discovered protein called MORT-1 (or HF1) (for ""Mediator of Receptor-Mediated Toxicity"") which, amongst its characteristics, is capable of self-association and specific binding to the intracellular domain of FAS-R; as well as (iii) apparently non-related proteins such as, for example, the cytoskeletal protein ankyrin 1. The 'death domain' motif and some of its characteristics has been disclosed in respect of the p55 TNF-R, FAS-R and MORT-1 in the co-pending Israel Application Nos. 109632, 111125, 112002 and 112692. The 'death domain' motif present in NGF-R and ankyrin 1 has been discovered in accordance with the present invention (see Example 1). In the above noted co-pending applications there is described a number of proteins capable of binding specifically to the intracellular domains of p55-TNF-R and/or FAS-R, which proteins include MORT-1. However, in contrast, the present invention concerns, in this one aspect thereof, proteins or peptides which specifically bind to the 'death domain' motif of one or more of the above mentioned proteins belonging to the group characterized by having such a 'death domain' motif, the binding/interaction between the proteins or peptides of the invention and the 'death domain' motif being by virtue of sequence features common to the various 'death domain' motifs. Hence, the proteins or peptides of the invention are characterized by being capable of modulating or mediating the activity of one or more of the members of this group of proteins by recognizing features common to the 'death domain' motifs. Accordingly, included in the present invention is a large group of proteins or peptides which bind to the various 'death domain' motifs, in which some of the proteins or peptides bind specific 'death domain' motifs of specific proteins or receptors, while others bind more than one such motif of more than one such protein/receptor. From Fig. 1 it arises that common sequence features of the 'death domain' motifs in 'death domain' motif-containing proteins such as p55 TNF-R, FAS-R, NGF-R, MORT1 and ankyrin 1 include common amino acid residues (residues marked with black background) such as the W (tryptophan), L (leucine), I (isoleucine), A (alanine), D (aspartic acid) and E (glutamic acid), as well as T (threonine), R (arginine) and Y (tyrosine), at the location shown in Fig. 1. The proteins or peptides of the invention may be obtained as described in the above noted co-pending patent applications (see also Example 3), by use of the yeast two-hybrid procedure in which the 'death domain' motif of, for example, p55-TNF-R, FAS-R, MORT-1, NGF-R, ankyrin I will be used as probes or 'baits' to isolate from genomic or cDNA libraries, clones expressing proteins or peptides capable of binding to one or more of these 'death domain' motifs. Alternatively, a synthetic DNA sequence can be synthesized in which there is included all of the common sequence features of the 'death domain' motifs of p55-TNF-R, FAS-R, MORT-1, NGF-R, ankyrin 1 (see Fig. 1), to provide a common or ""universal"" 'death domain' motif sequence, which in turn can be used in the yeast two-hybrid procedure to isolate and identify clones from cDNA or genomic libraries which encode proteins or peptides capable of binding to this 'death domain' motif sequence. Other approaches for obtaining the proteins and peptides of the invention include the well known standard procedures such as, for example, affinity chromatography in which, for example, peptides or protein fragments having the 'death domain' motif sequence of p55 TNF-R, FAS-R, MORT1, NGF-R and ankyrin 1; or a synthetically produced 'death domain' motif peptide having common sequence features of all the aforesaid 'death domain' motifs (see Fig. 1), are attached to the chromatography substrate or matrix and are brought into contact with cell extracts or lysates (of human/mammalian origin) and thereby proteins or peptides are isolated which are capable of binding to one or more of these 'death domain' motifs. Likewise, other standard chemical and recombinant DNA procedures usually employed for isolating proteins or peptides capable of binding to a specific amino acid sequence ('death domain' motif sequence) can be employed to obtain the proteins and peptides of the invention. Thus, the present invention also concerns the DNA sequences encoding the proteins and peptides of the invention and the proteins and peptides encoded by these sequences. Moreover, the present invention also concerns the DNA sequences encoding biologically active analogs and derivatives of these proteins and peptides of the invention, and the analogs and derivatives encoded thereby. The preparation of such analogs and derivatives is by standard procedure (see for example, Sambrook et al., 1989) in which in the DNA sequences encoding these proteins, one or more codons may be deleted, added or substituted by another, to yield analogs having at least a one amino acid residue change with respect to the native protein. Acceptable analogs are those which retain at least the capability of binding to the 'death domain' motif of one or more of the members of the above mentioned group of 'death domain' motif-containing proteins, or which can mediate any other binding or enzymatic activity, e.g. analogs which bind the 'death domain' motif but which do not signal, i.e. do not bind to a further downstream receptor, protein or other factor, or do not catalyze a signal-dependent reaction. In such a way analogs can be produced which have a so-called dominant-negative effect, namely, an analog which is defective either in binding to the 'death domain' motif or in subsequent signaling following such binding. Such analogs can be used, for example, to inhibit the TNF, FAS-ligand-NGF-R-mediated, MORT-1-mediated and ankyrin 1-mediated effect by competing with the natural IC-binding proteins. Likewise, so-called dominant-positive analogs may be produced which would serve to enhance, for example, the TNF. FAS ligand. NGF-R-mediated. MORT-1-mediated and ankyrin 1- mediated effect. These would have the same or better 'death domain' motif-binding properties and the same or better signaling properties of the natural 'death domain' motif-binding proteins. Similarly, derivatives may be prepared by standard modifications of the side groups of one or more amino acid residues of the proteins, or by conjugation of the proteins to another molecule e.g. an antibody, enzyme, receptor, etc., as are well known in the art. The new 'death domain' motif-binding proteins and peptides of the invention, e.g. the proteins and peptides capable of binding one or more of the 'death domain' motifs of p55 TNF-R, FAS-R, MORT-1, NGF-R and ankyrin 1. as well as RIP and TRADD, have a number of possible uses, for example: (i) They may be used to mimic or enhance the function of TNF or FAS-R ligand, or the functions mediated by NGF-R, MORT-1, RIP, TRADD and ankyrin 1 or other proteins containing the 'death domain' motif, in situations where such an enhanced effect is desired such as in anti-tumor, anti-inflammatory, or anti-HIV or other disease/disorder applications where the enhanced activity is desired. In this case the proteins or peptides may be introduced to the cells by standard procedures known per se . For example, as the proteins or peptides are required to act intracellularly, i.e. bind/interact with intracellularly located 'death domain' motifs and it is desired that they be introduced only into the cells where their effect is wanted, a system for specific introduction of these proteins into the cells is necessary. One way of doing this is by creating a recombinant animal virus e.g. one derived from Vaccinia, to the DNA of which the following two genes will be introduced: the gene encoding a ligand that binds to cell surface proteins specifically expressed by the cells e.g. ones such as the AIDs (HIV) virus gp120 protein which binds specifically to some cells (CD4 lymphocytes and related leukemias), or a ligand that binds specifically to erythrocytes or nervous tissue (in the case of ankyrin 1), or a ligand binding specifically to cells characterized by expressing other members of the 'death domain' motif-containing group of proteins, e.g. those expressing MORT-1, RIP, TRADD, or any other ligand that binds specifically to cells carrying a TNF-R, FAS-R, or NGF-R such that the recombinant virus vector will be capable of binding such cells; and the gene encoding the new'death domain' motif-binding protein or peptide. Thus, expression of the cell-surface-binding protein on the surface of the virus will target the virus specifically to the tumor cell, HIV-infected cells or other cells, following which the 'death domain' motif-binding protein or peptide encoding sequence will be introduced into the cells via the virus, and once expressed in the cells will result in enhancement of, for example, the TNF, FAS-R ligand, NGF-R-mediated, MORT-1-mediated, RIP- and TRADD-mediated, or ankyrin 1-mediated effect leading to, for example, the death of the tumor cells or other TNF-R- or FAS-R- carrying cells it is desired to kill. Construction of such recombinant animal virus is by standard procedures (see for example, Sambrook et al., 1989). Another possibility is to introduce the sequences of the new proteins or peptides in the form of oligonucleotides which can be absorbed by the cells and expressed therein. (ii) They may be used to inhibit, for example, the TNF, FAS-R ligand, NGF-R-mediated, MORT1-mediated and aknyrin-1-mediated effect, e.g. in cases such as tissue damage in septic shock, graft-vs.-host rejection, acute hepatitis, or other diseases/disorders in which case it is desired to block the TNF-induced TNF-R, FAS-R ligand induced FAS-R or NGF induced NGF-R intracellular signaling or intracellular events mediated by MORT1, RIP, TRADD and ankyrin-1. In this situation it is possible, for example, to introduce into the cells, by standard procedures, oligonucleotides having the anti-sense coding sequence for these new proteins or peptides which would effectively block the translation of mRNAs encoding these proteins and thereby block their expression and lead to the above noted desired inhibition of the effects mediated by the 'death domain' motif-containing proteins. Such oligonucleotides may be introduced into the cells using the above recombinant virus approach, the second sequence carried by the virus being the oligonucleotide sequence. Another possibility is to use antibodies specific for these proteins or peptides to inhibit their intracellular signaling activity (via their binding to the 'death domain' motifs).Yet another way of inhibiting the TNT FAS-R ligand, NGF-R-mediated, MORT-1-mediated, RIP- and TRADD-mediated, or ankyrin-1-mediated effect or effects mediated by other 'death domain' motif-containing proteins, is by the recently, developed ribozyme approach. Ribozymes are catalytic RNA molecules that specifically cleave RNAs. Ribozymes may be engineered to cleave target RNAs of choice, e.g. the mRNAs encoding the new proteins or peptides of the invention. Such ribozymes would have a sequence specific for the mRNA of choice and would be capable of interacting therewith (complementary binding) followed by cleavage of the mRNA, resulting in a decrease (or complete loss) in the expression of the protein or peptide it is desired to inhibit, the level of decreased expression being dependent upon the level of ribozyme expression in the target cell. To introduce ribozymes into the cells of choice any suitable vector may be used, e.g. plasmid, animal virus (retrovirus) vectors, that are usually used for this purpose (see also (i) above, where the virus has, as second sequence, a cDNA encoding the ribozyme sequence of choice). Moreover, ribozymes can be constructed which have multiple targets (multi-target ribozymes) that can be used, for example, to inhibit the expression of one or more of the proteins or peptides of the invention (For reviews, methods etc. concerning ribozymes see Chen et al., 1992; Zhao and Pick, 1993; Shore et al., 1993; Joseph and Burke, 1993; Shimayama et al., 1993; Cantor et al., 1993; Barinaga, 1993; Crisell et al., 1993 and Koizumi et al., 1993). (iii) They may be used to isolate, identify and clone other proteins or peptides which are capable of binding to them. e.g. other proteins or peptides involved in the intracellular signaling process that are downstream of the 'death domain' motif-containing proteins. In this situation, these options, namely, the DNA sequences encoding them may be used in the yeast two-hybrid system (see Example 2, below) in which the sequence of these proteins or peptides will be used as ""baits"" to isolate, clone and identify from cDNA or genomic DNA libraries other sequences (""preys"") encoding proteins which can bind to these new 'death domain' motif-binding proteins. In the same way, it may also be determined whether the specific proteins or peptides of the present invention, namely, those which bind to the 'death domain' motif of p55 TNF-R, FAS-R, NGF-R, MORT-1 and ankyrin can bind to yet other receptors or proteins. Moreover, this approach may also be taken to determine whether the proteins or peptides of the present invention are capable of binding to other known receptors or proteins in whose activity they may have a functional role, i.e. other aas yet unidentified 'death domain' motif-containing receptors or proteins. (iv) The new proteins may also be used to isolate, identify and clone other proteins of the same class i.e. those binding to 'death domain' motifs of the various receptors or proteins listed above or to functionally related receptors or proteins, and involved in their modulation/mediation. In this application the above noted yeast two-hybrid system may be used, or there may be used a recently developed (Wilks et al., 1989) system employing non-stringent southern hybridization followed by PCR cloning. In the Wilks et al. publication, there is described the identification and cloning of two putative protein-tyrosine kinases by application of non-stringent southern hybridization followed by cloning by PCR based on the known sequence of the kinase motif, a conceived kinase sequence. This approach may be used, in accordance with the present invention using the sequences of the new proteins or peptides to identify and clone those of related 'death domain' motif-binding proteins or peptides also capable of binding to 'death domain' motif-containing receptors or proteins. (v) Yet another approach to utilizing the new proteins of the invention is to use them in methods of affinity chromatography to isolate and identify other proteins or factors to which they are capable of binding, e.g. other receptors related to TNF-Rs (TNF/NGF receptor superfamily) or other proteins or factors (e.g. related to MORT1, ankyrin 1) involved in the intracellular signaling or structural regulation process. In this application, the proteins of the present invention, may be individually attached to affinity chromatography matrices and then brought into contact with cell extracts or isolated proteins or factors suspected of being involved in the intracellular signaling or structural regulation process. Following the affinity chromatography procedure, the other proteins or factors which bind to the new proteins of the invention, can be eluted, isolated and characterized (vi) As noted above, the new proteins or peptides of the invention may also be used as immunogens (antigens) to produce specific antibodies thereto. These antibodies may also be used for the purposes of purification of the new proteins or peptides either from cell extracts or from transformed cell lines producing them. Further, these antibodies may be used for diagnostic purposes for identifying disorders related to abnormal functioning of, for example, the TNF, FAS-R ligand, NGF-R, MORT-1 or ankyrin 1 system, e.g. overactive or underactive TNF- or FAS-R ligand- induced cellular effect or NGF-R-, MORT-1- or ankyrin-1 mediated cellular effects. Thus, should such disorders be related to a malfunctioning intracellular signaling or structural regulation system involving the new proteins or antibodies, such antibodies would serve as an important diagnostic tool. In another aspect, the present invention relates to complementary peptides which may be synthesized by well known standard procedures of the art, that are capable of binding or interacting specifically with one or more of the 'death domain' motifs of the above mentioned group of'death domain' motif-containing proteins. These complementary peptides will be synthesized using, for example, the 'death domain' motif sequences of p55-TNF-R, FAS-R, MORT-1, RIP, TRADD, NGF-R. ankyrin 1. as substrates and synthesizing by standard chemical means peptides of sequence that are complementary to these 'death domain' motif sequences. A suitable complementary peptide is one that will be capable of binding to one or more of these 'death domain' motifs and thereby being capable of modulating or mediating the activity of'death domain' motif-containing proteins. The complementary peptides may be generated using as substrate one or more of the 'death domain' motif sequences set forth in Fig. 1 or may be generated using a synthetic peptide (see above) which has a sequence inclusive of all of the common sequence features of the known 'death domain' motif sequences, e.g. the above mentioned amino acid residues W, L, I, A, D, E, T, R and Y. The so-generated complementary peptides, and likewise, DNA sequences encoding them, which may be readily produced by standard procedures, may be employed, as noted above in any one of uses (i) - (vi), i.e. to enhance (gain-of-function) or inhibit the activity of proteins or receptors containing a 'death domain' motif, or may be used to generate specific antibodies thereto for modulation/mediation, isolation or diagnostic purposes. It should also be noted that included in the present invention are the antibodies (and their uses) specific to the proteins and peptides of the invention including the complementary peptides, as well as antibodies specific to the 'death domain' motif peptides themselves, e.g. those peptides shown in Fig. 1 which are the 'death domain' motifs of p55-TNF-R, FAS-R, MORT-1, NGF-R, ankyrin 1 and other proteins containing the 'death domain' motif These antibodies may be used for directly modulating/mediating the activity of proteins or receptors containing 'death domain' motifs or for isolation, identification and characterization (including diagnostic applications, as noted above) of other proteins and receptors containing such 'death domain' motifs. As regards the antibodies mentioned herein throughout, the term ""antibody"" is meant to include polyclonal antibodies, monoclonal antibodies (mAbs), chimeric antibodies, anti-idiotypic (anti-Id) antibodies to antibodies that can be labeled in soluble or bound form, as well as fragments thereof provided by any known technique, such as, but not limited to enzymatic cleavage, peptide synthesis or recombinant techniques. Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of animals immunized with an antigen A monoclonal antibody contains a substantially homogeneous population of antibodies specific to antigens, which populations contains substantially similar epitope binding sites. MAbs may be obtained by methods known to those skilled in the art. See, for example Kohler and Milstein, Nature, 256:495-497 (1975); U.S. Patent No. 4,376,110; Ausubel et al., eds., Harlow and Lane ANTIBODIES : A LABORATORY MANUAL, Cold Spring Harbor Laboratory (1988); and Colligan et al., eds., Current Protocols in Immunology, Greene publishing Assoc. and Wiley Interscience N.Y., (1992, 1993), the contents of which references are incorporated entirely herein by reference. Such antibodies may be of any immunoglobulin class including IgG, IgM, IgE, IgA, GILD and any subclass thereof. A hybridoma producing a mAb of the present invention may be cultivated in vitro, in situ or in vivo. Production of high titers of mAbs in vivo or in situ makes this the presently preferred method of production. Chimeric antibodies are molecules different portions of which are derived from different animal species, such as those having the variable region derived from a murine mAb and a human immunoglobulin constant region. Chimeric antibodies are primarily used to reduce immunogenicity in application and to increase yields in production, for example, where murine mAbs have higher yields from hybridomas but higher immunogenicity in humans, such that human/murine chimeric mAbs are used. Chimeric antibodies and methods for their production are known in the art (Cabilly et al., Proc. Natl. Acad. Sci. USA 81:3273-3277 (1984); Morrison et al., Proc. Natl. Acad. Sci. USA 81:6851-6855 (1984); Boulianne et al., Nature 312:643-646 (1984); Cabilly et al., European Patent Application 125023 (published November 14, 1984); Neuberger et al., Nature 314:268-270 (1985); Taniguchi et al., European Patent Application 171496 (published February 19, 1985); Morrison et al., European Patent Application 173494 (published March 5, 1986); Neuberger et al., PCT Application WO 8601533, (published March 13, 1986); Kudo et al., European Patent Application 184187 (published June 11, 1986); Sahagan et al., J. Immunol. 137:1066-1074 (1986); Robinson et al., International Patent Application No. WO8702671 (published May 7, 1987); Liu et al., Proc. Natl. Acad. Sci USA 84:3439-3443 (1987); Sun et al., Proc. Natl. Acad. Sci USA 84:214-218 (1987); Better et al., Science 240:1041-1043 (1988); and Harlow and Lane, ANTIBODIES :A LABORATORY MANUAL, supra. These references are entirely incorporated herein by reference An anti-idiotypic (anti-Id) antibody is an antibody which recognizes unique determinants generally associated with the antigen-binding site of an antibody. An Id antibody can be prepared by immunizing an animal of the same species and genetic type (e.g. mouse strain) as the source of the mAb with the mAb to which an anti-Id is being prepared. The immunized animal will recognize and respond to the idiotypic determinants of the immunizing antibody by producing an antibody to these idiotypic determinants (the anti-Id antibody). See, for example, U.S. Patent No. 4,699,880, which is herein entirely incorporated by reference. The anti-Id antibody may also be used as an ""immunogen"" to induce an immune response in yet another animal, producing a so-called anti-anti-Id antibody. The anti-anti-Id may be epitopically identical to the original mAb which induced the anti-Id. Thus, by using antibodies to the idiotypic determinants of a mAb, it is possible to identify other clones expressing antibodies of identical specificity. Accordingly, mAbs generated against the 'death domain' motif-containing peptides, 'death domain'-binding proteins or peptides, or 'death domain'-binding complementary peptides, analogs or derivatives thereof of the invention may be used to induce anti-Id antibodies in suitable animals, such as BALB/c mice. Spleen cells from such immunized mice are used to produce anti-Id hybridomas secreting anti-Id mAbs. Further, the anti-Id mAbs can be coupled to a carrier such as keyhole limpet hemocyanin (KLH) and used to immunize additional BALB/c mice. Sera from these mice will contain anti-anti-Id antibodies that have the binding properties of the original mAb specific for an epitope of the above proteins, peptides, analogs or derivatives. The anti-Id mAbs thus have their own idiotypic epitopes, or ""idiotopes"" structurally similar to the epitope being evaluated, such as GRB protein-α. The term ""antibody"" is also meant to include both intact molecules as well as fragments thereof, such as, for example, Fab and F(ab') 2 , which are capable of binding antigen. Fab and F(ab') 2 fragments lack the Fc fragment of intact antibody, clear more rapidly from the circulation, and may have less non-specific tissue binding than an intact antibody (Wahl et al., J. Nucl. Méd . 24:316-325 (1983)). It will be appreciated that Fab and F(ab') 2 and other fragments of the antibodies useful in the present invention may be used for the detection and quantitation of the 'death-domain'-binding proteins or peptides according to the methods disclosed herein for intact antibody molecules. Such fragments are typically produced by proteolytic cleavage, using enzymes such as papain (to produce Fab fragments) or pepsin (to produce F(ab') 2 fragments). An antibody is said to be ""capable of binding"" a molecule if it is capable of specifically reacting with the molecule to thereby bind the molecule to the antibody. The term ""epitope"" is meant to refer to that portion of any molecule capable of being bound by an antibody which can also be recognized by that antibody. Epitopes or ""antigenic determinants"" usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and have specific three dimensional structural characteristics as well as specific charge characteristics. An ""antigen"" is a molecule or a portion of a molecule capable of being bound by an antibody which is additionally capable of inducing an animal to produce antibody capable of binding to an epitope of that antigen. An antigen may have one or more than one epitope. The specific reaction referred to above is meant to indicate that the antigen will react, in a highly selective manner, with its corresponding antibody and not with the multitude of other antibodies which may be evoked by other antigens. The antibodies, including fragments of antibodies, useful in the present invention may be used to quantitatively or qualitatively detect the 'death domain' motif-binding proteins or peptides (including complementary peptides) in a sample or to detect presence of cells which express the 'death domain' motif-binding proteins or peptides of the present invention. This can be accomplished by immunofluorescence techniques employing a fluorescently labeled antibody (see below) coupled with light microscopic, flow cytometric, or fluorometric detection. The antibodies (or fragments thereof) useful in the present invention may be employed histologically, as in immunofluorescence or immunoelectron microscopy, for in situ detection of 'death domain' motif-binding proteins or peptides of the present invention. In situ detection may be accomplished by removing a histological specimen from a patient, and providing the labeled antibody of the present invention to such a specimen. The antibody (or fragment) is preferably provided by applying or by overlaying the labeled antibody (or fragment) to a biological sample. Through the use of such a procedure, it is possible to determine not only the presence of the 'death domain' motif-binding proteins or peptides, but also its distribution on the examined tissue. Using the present invention, those of ordinary skill will readily perceive that any of wide variety of histological methods (such as staining procedures) can be modified in order to achieve such in situ detection. Such assays for 'death domain' motif-binding proteins of the present invention typically comprises incubating a biological sample, such as a biological fluid, a tissue extract, freshly harvested cells such as lymphocytes or leukocytes, or cells which have been incubated in tissue culture, in the presence of a detectably labeled antibody capable of identifying the 'death domain' motif-binding proteins or peptides, and detecting the antibody by any of a number of techniques well known in the art. The biological sample may be treated with a solid phase support or carrier such as nitrocellulose, or other solid support or carrier which is capable of immobilizing cells, cell particles or soluble proteins. The support or carrier may then be washed with suitable buffers followed by treatment with a detectably labeled antibody in accordance with the present invention, as noted above. The solid phase support or carrier may then be washed with the buffer a second time to remove unbound antibody. The amount of bound label on said solid support or carrier may then be detected by conventional means. By ""solid phase support"", ""solid phase carrier"", ""solid support"", ""solid carrier"", ""support"" or ""carrier"" is intended any support or carrier capable of binding antigen or antibodies. Well-known supports or carriers, include glass, polystyrene, polypropylene, polyethylene, dextran, nylon amylases, natural and modified celluloses, polyacrylamides, gabbros and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material may have virtually any possible structural configuration so long as the coupled molecule is capable of binding to an antigen or antibody. Thus, the support or carrier configuration may be spherical, as in a bead, cylindrical, as in the inside surface of a test tube, or the external surface of a rod. Alternatively, the surface may be flat such as a sheet, test strip, etc. Preferred supports or carriers include polystyrene beads. Those skilled in the art will know may other suitable carriers for binding antibody or antigen, or will be able to ascertain the same by use of routine experimentation. The binding activity of a given lot of antibody, of the invention as noted above, may be determined according to well known methods. Those skilled in the art will be able to determine operative and optimal assay conditions for each determination by employing routine experimentation. Other such steps as washing, stirring, shaking, filtering and the like may be added to the assays as is customary or necessary for the particular situation. One of the ways in which an antibody in accordance with the present invention can be detectably labeled is by linking the same to an enzyme and use in an enzyme immunoassay (EIA). This enzyme, in turn, when later exposed to an appropriate substrate, will react with the substrate in such a manner as to produce a chemical moiety which can be detected, for example, by spectrophotometric, fluorometric or by visual means. Enzymes which can be used detectably label the antibody include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-5-steroid isomeras, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-6-phosphate dehydrogenase, glucoamylase and acetylcholinesterase. The detection can be accomplished by colorimetric methods which employ a chromogenic substrate for the enzyme. Detection may also be accomplished by visual comparison of the extent of enzymatic reaction of a substrate in comparison with similarly prepared standards. Detection may be accomplished using any of a variety of other immunoassays. For example, by radioactivity labeling the antibodies or antibody fragments, it is possible to detect R-PTPase through the use of a radioimmunoassay (RIA). A good description of RIA may be found in Laboratory Techniques and Biochemistry in Molecular Biology, by Work, T.S. et al., North Holland Publishing Company, NY (1978) with particular reference to the chapter entitled ""An Introduction to Radioimmune Assay and Related Techniques"" by Chard, T., incorporated by reference herein. The radioactive isotope can be detected by such means as the use of a γ counter or a scintillation counter or by autoradiography. It is also possible to label an antibody in accordance with the present invention with a fluorescent compound. When the fluorescently labeled antibody is exposed to light of the proper wavelength, its presence can be then detected due to fluorescence. Among the most commonly used fluorescent labeling compounds are fluorescein isothiocyanate, rhodamine, phycoerythrine, pycocyanin, allophycocyanin, o-phthaldehyde and fluorescamine. The antibody can also be detectably labeled using fluorescence emitting metals such as 152 E, or others of the lanthanide series. These metals can be attached to the antibody using such metal chelating groups as diethylenetriamine pentaacetic acid (ETPA). The antibody can also be detectably labeled by coupling it to a chemiluminescent compound. The presence of the chemiluminescent-tagged antibody is then determined by detecting the presence of luminescence that arises during the course of a chemical reaction. Examples of particularly useful chemiluminescent labeling compounds, are luminol, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester. Likewise, a bioluminescent compound may be used to label the antibody of the present invention. Bioluminescence is a type of chemiluminescence found in biological systems in which a catalytic protein increases the efficiency of the chemiluminescent reaction. The presence of a bioluminescent protein is determined by detecting the presence of luminescence. Important bioluminescent compounds for purposes of labeling are luciferin, luciferase and aequorin. An antibody molecule of the present invention may be adapted for utilization in an immunometric assay, also known as a ""two-site"" or ""sandwich"" assay. In a typical immunometric assay, a quantity of unlabeled antibody (or fragment of antibody) is bound to a solid support or carrier and a quantity of detectably labeled soluble antibody is added to permit detection and/or quantitation of the ternary complex formed between solid-phase antibody, antigen, and labeled antibody. Typical, and preferred, immunometric assays include ""forward"" assays in which the antibody bound to the solid phase is first contacted with the sample being tested to extract the antigen from the sample by formation of a binary solid phase antibody-antigen complex. After a suitable incubation period, the solid support or carrier is washed to remove the residue of the fluid sample, including unreacted antigen, if any, and the contacted with the solution containing an unknown quantity of labeled antibody (which functions as a ""reporter molecule""). After a second incubation period to permit the labeled antibody to complex with the antigen bound to the solid support or carrier through the unlabeled antibody, the solid support or carrier is washed a second time to remove the unreacted labeled antibody. In another type of ""sandwich"" assay, which may also be useful with the antigens of the present invention, the so-called ""simultaneous"" and ""reverse"" assays are used. A simultaneous assay involves a single incubation step as the antibody bound to the solid support or carrier and labeled antibody are both added to the sample being tested at the same time. After the incubation is completed, the solid support or carrier is washed to remove the residue of fluid sample and uncomplexed labeled antibody. The presence of labeled antibody associated with the solid support or carrier is then determined as it would be in a conventional ""forward"" sandwich assay. In the ""reverse"" assay, stepwise addition first of a solution of labeled antibody to the fluid sample followed by the addition of unlabeled antibody bound to a solid support or carrier after a suitable incubation period is utilized. After a second incubation, the solid phase is washed in conventional fashion to free it of the residue of the sample being tested and the solution of unreacted labeled antibody. The determination of labeled antibody associated with a solid support or carrier is then determined as in the ""simultaneous"" and ""forward"" assays. The new proteins and peptides of the invention once isolated, identified and characterized by any of the standard screening procedures, for example, the yeast two-hybrid method, affinity chromatography, and any other well known method known in the art, may then be produced by any standard recombinant DNA procedure (see for example, Sambrook, et al., 1989) in which suitable eukaryotic nr prokaryotic host cells are transformed by appropriate eukaryotic or prokaryotic vectors containing the sequences encoding for the proteins. Accordingly, the present invention also concerns such expression vectors and transformed hosts for the production of the proteins of the invention. As mentioned above, these proteins also include their biologically active analogs and derivatives, and thus the vectors encoding them also include vectors encoding analogs of these proteins, and the transformed hosts include those producing such analogs. The derivatives of these proteins are the derivatives produced by standard modification of the proteins or their analogs, produced by the transformed hosts. In another aspect, the present invention relates to the use of the various different 'death domain' motifs or the synthetically produced ""universal"" 'death domain' motif (having structural features common to many different 'death domain' motifs) as agents for enhancing (gain of function) the intracellular effect mediated by the natural 'death domain' motif-containing proteins. In this aspect the 'death domain' motifs will be used in the form of peptides containing all of the 'death domain' motif or active parts thereof and introduced into the cells as mentioned above (e.g. the vaccinia virus approach). In this regard it should be noted that the term 'death domain' was coined following the discovery (see the co-pending patent applications noted above) that this region of the intracellular domains of the p55 TNF-R and FAS-R was the region involved in the ligand-independent self-association and cell-cytotoxicity induction mediated by these receptors. In fact, the free 'death domain' of p55 TNF-R (p55DD) is capable of self-associating and inducing cell cytotoxicity. Further, upon discovery of the MORT1 protein which is a FAS-R binding protein, it was also found that this protein is capable of self-association and inducing, in a ligand-independent and FAS-R-independent manner, cytotoxic effects on cells. The MORT-1 protein was subsequently observed to contain a 'death domain' motif homologous to the 'death domains' or 'death domain' motifs of p55 TNF-R and FAS-R (see Fig. 1), which 'death domain' motif is involved in MORT1 association with FAS-R and is associated with the MORT1 protein's ability to induce cell cytotoxic effects. Thus, using the 'death domain' motifs of proteins such as p55-TNF-R, FAS-R and MORT1 and any other proteins involved in the induction of cytotoxic effects in the way described above, it is possible to enhance the cell cytotoxic effects normally mediated by the naturally-occuring counterparts of these proteins, i.e. it would be possible to enhance the killing of cells such as tumor cells, HIV-infected and other diseased cells, the killing of which is usuaiiy mediated by p55 TNF-R, FAS-R, MORT1, RIP or TRADD, by introducing into such cells the 'death domain' motifs of these receptors/proteins. Moreover, it is also possible to produce analogs of these 'death domain' motifs which will provide an even better enhancement of their action, i.e. enhanced cell cytotoxicity, these analogs having one or more amino acids added, deleted or replaced with respect to the naturally occuring sequences. In a similar fashion it is also possible by the means described herein above to introduce 'death domain' motifs or analogs thereof, of the NGF-R or ankyrin 1 into cells in which it is desired to enhance the intracellular effects mediated by NGF-R or ankyrin-1. Likewise, the present invention also relates to the specific blocking of the effects mediated by the 'death domain' motif-containing proteins by blocking the activity of the 'death domain' motifs of these proteins. e.g. by the introduction of anti-sense oligonucleotides into cells (as mentioned above) which would block the expression of the 'death domain' motifs. In yet another aspect of the invention there is provided organic compounds, e.g. heterocyclic compounds, which are capable of specifically binding to the 'death domain' motifs of one or more 'death domain' motif-containing proteins. These organic compounds are well known in the field of pharmaceuticals and are widely used as therapeutic agents which are capable of entering cells (hydrophobic/lipophilic compounds) and binding various intracellular proteins or intracellular portions of transmembrane proteins and thereby exerting their effect. These organic compounds may be readily screened and identified by using the 'death domain' motifs of the death domain motif-containing proteins, e.g. those of p55 TNF-R, FAS-R, NGF-R, MORT1, ankyrin 1, in standard affinity chromatography procedures or other methods well known in the art. It should also be mentioned, that the 'death domain' motif consists of both general structural features common to all of the various such motifs, i.e. a common scaffold, as well as specific structural features, specific to each of the 'death domain' motifs. Accordingly, a preferred drug or pharmaceutically active molecule according to the invention will contain, as active ingredient, naturally occurring proteins or peptides; synthetically produced proteins or peptides including complementary peptides; antibodies; or chemical compounds obtained by screening or design, all of which are characterized by being capable of recognizing the general 'death domain' features and one or more of the specific 'death domain' features. The present invention also relates to pharmaceutical compositions comprising recombinant animal virus vectors encoding the 'death domain' motif-binding proteins or peptides or the 'death domain' motif sequences themselves, which vector also encodes a virus surface protein capable of binding specific target cell (e.g. cancer cells) surface proteins to direct the insertion of the 'death domain' motif-binding protein or peptide sequences or the 'death domain' motif sequences into the cells. Likewise, the present invention also relates to pharmaceutical compositions comprising organic compounds capable of binding to 'death domain' motifs of'death domain' motif-containing proteins. The invention will now be described in more detail in the following non-limiting examples and the accompanying drawings: EXAMPLE 1 The 'death domain' motif common to the receptors p55 TNF-R, FAS-R and NGF-R and to the proteins MORT1 and ankyrin I Upon the discovery of MORT1 (see co-pending IL 109632, IL 112002 and 112692) it was also discovered that MORT1 contains a region having homology to the previously identified 'death domains' of p55 TNF-R and FAS-R (p55DD and FAS-DD, respectively), see IL 109632 and IL 111125). This surprising discovery of a'death domain' motif in a previously unknown protein led to a search for the existence of such a 'death domain' motif in other proteins. Surprisingly, such a 'death domain' motif was discovered in the low affinity NGF-R and in an apparently unrelated, cytoskeletal protein, ankyrin 1. The 'death domain' motifs of all these different proteins share a remarkable homology as is set forth schematically in Fig. 1, which shows a sequence comparison of the 'death domain' motifs of the p55 TNF-R, FAS-R, MORT1, low affinity NGF-R and the C terminal part of the regulatory domain in ankyrin 1 (all of human origin). The homology of these 'death domain' motifs was defined by the LINEUP and PRETTY programs of the GCG package. Identical and similar residues in three or more of the proteins are boxed. Gaps introduced to maximize alignment are denoted by dots. The significance of this homology was confirmed as follows : (a) Multiple alignment of the 'death domain' motif sequences, using the HSSP program of the PredictProtein Service (Sander and Schneider, 1991) showed sequence identities of 21-38% and sequence similarities of 30-48%. (b) Searching the Swiss-Prot data bank with a profile created (using the PILEUP, LINEUP and PROFILEMAKE programs of the GCG package) from consensuses of the 'death domain' motif sequences in the known p55 R and FAS-R (human, mouse, rat), NGF receptor (human, rat and chicken) and ankyrins (human and mouse ankyrin 1 and the human ankyrins c and g) sequences and in MORT1 yielded high scores only those sequences that were used for creating the profile (Zscores > 8.5 for all of them in search with the ""Bioaccelerator"" Compugen, Israel). The above homology search using the PredictProtein Service (PHDsec) and the PRODOM program of the GCG package revealed significant similarity between a region of approximately 65 residues in MORT1. within that part of the molecule that binds to FAS-R, and a region of that same length within the 'death domains' of FAS-R and p55-R, (Fig. 1) This part of the 'death domain' also shows similarity to a region in the intracellular domain of the low-affinity NGF receptor (Johnson et al., 1986), a receptor whose extracellular domain is known to contain another conserved sequence motif common to FAS-R. the TNF-Rs and other members of the TNF/NGF receptor family. It also revealed a previously-unnoticed similarity between this part of the 'death domain' and a conserved region in the ankyrins, which are structural proteins that link spectrin-based membrane skeletal proteins to the cytoplasmic domains of integral plasma membrane proteins (Lux et al., 1990, Lambert and Bennett, 1993). That region is located in the N terminal part of the ankyrin regulatory domain, just upstream to that part of the domain whose expression in subject to modulation by alternative splicing, and below the spectrin-binding and membrane binding domains. (The latter domain contains another known sequence motif - the 'ankyrin repeat'). The 'death domain' motif is distinct from the ankyrin repeat motif that is found in the membrane binding domain of the ankyrins. The finding of a 'death domain' motif in proteins having different intracellular effects suggests that this motif plays a more general role than that implied in the name 'death domain', i.e. this motif occurs in receptors such as p55 TNF-R, FAS-R and the related protein MORT1 which mediate cell cytotoxicity, as well as in the NGF-R which, when inducing death does so only in the absence of ligand (Rabizadeh et al., 1993) and in proteins such as the cytoskeletal ankyrins, not associated with cell cytotoxic effects. One kind of general activity of this 'death domain' motif, found so far in three of the proteins containing it, i.e. FAS-R, p55 TNF-R and MORT1 is the ability to self-associate or interact with other proteins that contain this motif. The discovery of the 'death domain' motif in such a wide range of different proteins provides the way for obtaining (as noted herein above and in Example 2 below) proteins or peptides capable of binding to the different (one or more) 'death domain' motifs, which proteins and peptides may be used as modulators/mediators of a wide group of regulatory proteins, be they cytokine receptors involved in cell cytotoxic (p55 TNF-R, FAS-R) or growth (NGF-R) effects or related proteins involved in cell cytotoxic effects (MORT1) or regulatory portions of structural proteins involved in the shape/conformational regulation of cells (ankyrins). In a similar fashion, the 'death domain' motifs of these various proteins may also be used directly for modulation/mediation of proteins containing such motifs. EXAMPLE 2 Interaction of 'death domains' of human p55 - TNF-R, FAS-R, TRADD, MORT-1 and RIP a) Experimental Procedures Two hybrid β -galactosidase expression tests - cDNA inserts were cloned by PCR either from the full-length cDNAs cloned previously in our laboratory, or from purchased cDNA libraries. Residue numbering in the proteins encoded by the cDNA inserts are as in the Swiss-Prot Data Bank. Point mutants were produced by oligonucleotide-directed mutagenesis (Kunkel, 1994). β-galactosidase expression in yeasts (SFY526 reporter strain (Bartel et al., 1993)) transformed with these cDNAs in the pGBT-9 and pGAD-GH vectors (DNA binding domain (DBD) and activation domain (AD) constructs, respectively) was assessed by a filter assay (Boldin et al., 1995). When expressed in the pGAD-GH vector, RIP and its DD had some cytotoxic effect on the yeasts, manifested in a low yield of yeast colonies. They did not have any such cytotoxic effect when expressed (to a lower extent) in the pGBT-9 vector. Induced expression, metabolic labeling and immunoprecipitation of proteins - Since the size similarity of the DDs makes it difficult to distinguish between them in gel electrophoresis, we chose to examine the interaction of MORT-1, TRADD and RIP by co-expressing the full-length MORT-1 protein with the DDs of TRADD and RIP. The proteins, N-linked to the FLAG octapeptide (Eastman-Kodak, New Haven, CT), or to an influenza hemagglutinin epitope (HA epitope, YPYDVPDYA (Field et al., 1988)) were expressed in HeLa cells, using a tetracycline-controlled expression vector, and labeled metabolically with [ 35 S]-Met (55 µCi/ml) and [ 35 S]-Cys (10 µCi/ml) (EXPRE 35 S 35 S Protein Labeling Mix, DuPont. Wilmington. DE), as described before (Boldin et al., 1995). The cells were then lysed in RIPA buffer (1 ml/5 x 10 5 cells) and the lysates were precleared by incubation with irrelevant rabbit antiserum (3 µl/ml) and Protein G Sepharose beads (Pharmacia, Uppsala, Sweden: 6- µl/ml). Immunoprecipitation was performed by 1 h. incubation at 4°C of 0.3 ml aliquots of lysate with mouse monoclonal antibodies (5 µg/aliquot) against the FLAG octapeptide (M2; Eastman Kodak). HA epitope (12CA5 (Field et al., 1988)), or the p75 TNF-R (#9; (Bigda et al., 1994)) as a control, followed by an additional 1 h. incubation with Protein G Sepharose beads (30 µl/aliquot). The immunoprecipitates were washed 3 times with RIPA buffer and analyzed by SDS-polyacrylamide gel electrophoresis. b) Evaluation The interactions of the DDs of human p55 TNF-R, FAS-R, TRADD. MORT-1 and RIP were evaluated first by a yeast two-hybrid test. The cDNAs encoding these domains were expressed as fusion proteins with the Gal4 DNA binding and activation domains (DBD and AD constructs) in the yeast SFY526 reporter strain, and the binding of these fusion proteins to each other was assessed by determining β-galactosidase expression by the yeasts. The results of these tests are summarized in Fig. 1 and illustrated diagrammatically in Fig. 3. The DDs of p55 TNF-R, FAS-R, TRADD and RIP were able to self-associate. The DD of MORT-1 lacked this ability, even though the full length MORT-1 protein does self-associate (Boldin et al., 1995), apparently through an interaction that involves the region upstream of its DD. The DD of TRADD bound to the DD of p55 TNF-R, but not to the DD of FAS-R, while the DD of MORT-1 behaved in the converse fashion. The DD of RIP, like the full length RIP protein (Stanger et al., 1995), was able to bind both to the DDs of FAS-R and p55 TNF-R. Binding was significantly weaker, though, than that of the DDs of TRADD and MORT-1 to these receptors. Although RIP wa initially identified by virtue of its binding in a two-hybrid screen to FAS-R (Stanger et al., 1995), this binding is quite weak, and could be observed only when the RIP DD was highly expressed in the yeasts, by introducing it into the AD construct. There was no measurable binding when the DD of RIP was introduced into the DBD construct, which has a lower expression effectivity. A longer RIP insert, corresponding to amino acids 161-372 in the protein, did not bind more effectively to FAS-R (not shown) Apart from their observed binding to the DDs of P55 TNF-R or FAS-P, the DDs of each of the three intracellular proteins tested bound also to each other. These interactions were all effective. Notably, the effectivity of binding of the DD of RIP to the DDs of MORT-1 and TRADD was significantly greater than that of its binding to the DDs of p55 TNF-R amd FAS-R. A similar pattern of interaction was observed in the HF7c yeast reporter strain, regularly used in inventors' laboratory for two-hybrid screens. Indeed, in a recent attempt to clone proteins that bind to MORT-1 by a two-hybrid screen, it was found that a significant proportion of the cloned cDNAs encode TRADD or RIP (not shown). In specificity tests for the two-hybrid assay, we did not observe binding of the DD motifs to any of a number of irrelevant proteins, including SNF1, the intracellular domain of the human p75 TNF receptor, lamin, cycline D and the DD of the rat low-affinity NGF receptor (not shown). To further assess the binding specificity, we introduced point mutations to the p55 TNF-R, FAS-R, MORT-1 and RIP DDs, at sites corresponding to that of I-225 in the mouse FAS-R sequence. A natrually occurring replacement mutation of this residue, found in lpr c g mice, abolishes signaling by FAS-R (Itoh and Nagata, 1993; Watanabe-Fukunaga et al., 1992) as well as its interaction with MORT-1 (Boldin et al., 1995; Chinnalyan et at., 1995). Mutation of the corresponding residues in the DDs of human p55 TNF-R (L351N) and FAS-R (V238N) had a similar effect. The mutated proteins were not able to self-associate, nor to bind to TRADD, MORT-1 or RIP Also, introduction of a replacement mutation to the DD of RIP at the site corresponding to that of the lpr c g mutation (F308N) resulted in loss of its ability to bind to FAS-R, MORT-1 and TRADD, as well as to self-associate, although the mutated protein bound to the normal RIP DD On the other hand, in MORT-1 the lpr c g like mutation (V121N) had only a limited effect. It resulted in less effective binding to FAS-R which, for some reason, was observed only when the mutated protein was introduced into the AD construct but not in the DBD construct. To test whether the interactions observed between TRADD, MORT-1 and RIP in the yeast two-hybrid tests occur also in eukaryotic cells, we co-expressed MORT-1 and the DDs of TRADD and RIP within transfected HeLa cells and attempted to immunoprecipitate them from the cell lysates. Immunoprecipitation resulted in precipitation of the co-expressed proteins, indicating that they bind to each other within the HeLa Cells (Fig. 4). Although the evidence is still largely indirect, TRADD, MORT-1 and RIP appear to play important roles in the initiation of the cytocidal effect of p55 TNF-R and FAS-R (Cleveland and Ihle, 1995). The binding of these proteins to the receptors, which occurs through their DDs, apparently is required for their contribution to the signaling. A recent study showing that stimulation of FAS-R in cells evokes binding of MORT-1 to this receptor suggests that the DD interactions observed within transfected yeasts also occur within the mammalian cells, and take part in the process of signaling induction (Kischkel et al., 1995). Although the DDs of all the proteins examined have the ability to bind to other DDs, there is clear specificity in this interaction. The DD of TRADD binds to that of p55 TNF-R, but not to the DD of FAS-R. The DD of MORT-1 binds to the DD of FAS-R, but does not bind to the DD of p55 TNF-R. This specificity in the action of proteins that take part in the signaling activity of p55 TNF-R and FAS-R may well contribute to the differences in function of the two receptors. In addition to their differential binding to the DDs of p55 TNF-R and FAS-R, the DDs of TRADD and MORT-1 also are able to bind effectively to each other, and both are capable of binding to the DD of RIP more effectively than do the DDs of FAS-R or p55 TNF-R. Thus, even though distinct, the signaling cascades affected by TRADD and MORT-1 may well turn to be coordinated through their mutual interactions. The nature of this coordination may vary, depending on the way in which the different interactions of the DD in a given protein affect each other. These interactions may occur together or be exclusive; they may also modulate each other. One possible way for such modulation is indicated by the occurrence in RIF of sequence motifs characteristic of protein kinases. If this protein indeed possesses protein kinase activity, it may turn to be capable of phosphorylating MORT-1 and TRADD upon binding to them, thereby modulating their function. One plausible consequence of the association of TRADD and MORT-1, and of the binding of RIP to both proteins, is integration of their effects, at least in part. This integration may account for the fact that cell death induction by p55 TNF-R and FAS-R exhibit, alongside distrinct features, also certain similarities; this could result also in sharing of other activities of the two receptors. EXAMPLE 3 Cloning and isolation of proteins which bind to the 'death domain' motifs of 'death domain' motif-containing proteins To isolate proteins interacting with the 'death domain' motifs of 'death domain' motif-containing proteins, for example, the 'death domain' motifs of p55 TNF-R, FAS-R, NGF-R, MORT1 and ankyrin 1, the yeast two-hybrid system (Fields and Song, 1989) may be used as described in co-pending Israel patent application Nos. 109632, 112002 and 112692. Briefly, this two-hybrid system is a yeast-based genetic assay to detect specific protein-protein interactions in vivo by restoration of a eukaryotic transcriptional activator such as GAL4 that has two separate domains, a DNA binding and an activation domain, which domains when expressed and bound together to form a restored GAL4 protein, is capable of binding to an upstream activating sequence which in turn activates a promoter that controls the expression of a reporter gene, such as lacZ or HIS3, the expression of which is readily observed in the cultured cells. In this system the genes for the candidate interacting proteins are cloned into separate expression vectors. In one expression vector the sequence of the one candidate protein is cloned in phase with the sequence of the GAL4 DNA-binding domain to generate a hybrid protein with the GAL4 DNA-binding domain, and in the other vector the sequence of the second candidate protein is cloned in phase with the sequence of the GAL4 activation domain to generate a hybrid protein with the GAL4-activation domain. The two hybrid vectors are then co-transformed into a yeast host strain having a lacZ or HIS3 reporter gene under the control of upstream GAL4 binding sites. Only those transformed host cells (cotransformants) in which the two hybrid proteins are expressed and are capable of interacting with each other, will be capable of expression of the reporter gene. In the case of the lacZ reporter gene, host cells expressing this gene will become blue in color when X-gal is added to the cultures. Hence, blue colonies are indicative of the fact that the two cloned candidate proteins are capable of interacting with each other. Using this two-hybrid system, the 'death domain' motifs may be cloned, separately, into the vector pGBT9 (carrying the GAL4 DNA-binding sequence, provided by CLONTECH, USA, see below), to create fusion proteins with the GAL4 DNA-binding domain. Once the sequence of the 'death domain' motif is known, e.g. those shown in Fig. 1, the DNA sequence encoding these motifs may be readily isolated and cloned, by standard procedures into the pGBT9 vector utilizing the vector's multiple cloning site region (MCS). The above hybrid (chimeric) pGBT9 vectors can then be cotransfected (separately, one cotransfection with each 'death domain' motif-containing hybrid together with a cDNA or genomic DNA library from human or other mammalian origin, e.g. a cDNA library from human HeLa cells cloned into the pGAD GH vector, bearing the GAL4 activating domain, into the HF7c yeast host strain (all the above-noted vectors, pGBT9 and pGAD GH carrying the HeLa cell cDNA library, and the yeast strain are purchasable from Clontech Laboratories, Inc., USA, as a part of MATCHMAKER Two-Hybrid System, #PT1265-1). The co-transfected yeasts are then selected for their ability to grow in medium lacking Histidine (His - medium), growing colonies being indicative of positive transformants. The selected yeast clones were then tested for their ability to express the lacZ gene, i.e. for their LAC Z activity, and this by adding X-gal to the culture medium, which is catabolized to form a blue colored product by β-galactosidase, the enzyme encoded by the lacZ gene. Thus, blue colonies are indicative of an active lacZ gene. For activity of the lacZ gene, it is necessary that the GAL4 transcription activator be present in an active form in the transformed clones, namely that the GAL4 DNA-binding domain encoded by one of the above hybrid vectors be combined properly with the GAL4 activation domain encoded by the other hybrid vector. Such a combination is only possible if the two proteins fused to each of the GAL4 domains are capable of stably interacting (binding) to each other. Thus, the His + and blue (LAC Z + ) colonies that are isolated are colonies which have been cotransfected with a vector encoding a 'death domain' motif and a vector encoding a protein product of, for example, human HeLa cell origin that is capable of binding stably to a 'death domain' motif The plasmid DNA from the above His + , LAC Z + yeast colonies can then be isolated and electroporated into E. coli strainHB101 by standard procedures followed by selection of Leu + and Ampicillin resistant transformants, these transformants being the ones carrying the hybrid pGAD GH vector which has both the Amp R and Leu 2 coding sequences. Such transformants therefore are clones carrying the sequences encoding newly identified proteins or peptides capable of binding to the 'death domain' motifs. Plasmid DNA was then isolated from these transformed E. coli and retested by : (a) retransforming them with the original 'death domain' motif-containing hybrid plasmids into yeast strain HF7 as set forth hereinabove. As controls, vectors carrying irrelevant protein encoding sequences, e.g. pACT-lamin or pGBT9 alone can be used for cotransformation with the 'death domain' motif-binding protein or peptide encoding plasmids. The cotransformed yeasts can then be tested for growth on His - medium alone, or with different levels of 3-aminotriazole; and (b) retransforming the plasmid DNA and original 'death domain' motif hybrid plasmids and control plasmids described in (a) into yeast host cells of strain SFY526 and determining the LAC Z + activity (effectivity of β-gal formation, i.e. blue color formation). It should be noted that the above noted β-galactosidase (β-gal) expression tests can also be done by a standard filter assay. EXAMPLE 4 Assessment of the involvement of sequence features characteristic of the 'death domain' motif in the binding of the cloned proteins The cDNA encoding the protein that contains the 'death domain' motif will be mutated at the various amino acids that constitute this motif. For example, tryptophan 380 in the intracellular domain of the human low-affinity nerve growth factor receptor (NGF-R) will be replaced with alanine. Such mutation can be performed, for example, by the Kunkel oligonucleotide-directed mutagenesis procedure. The mutated, as well as the wild-type proteins, can be produced in bacteria as fusions with Glutathione S-transferase (GST). The binding of the cloned protein in vitro to the GST fusion with the mutated NGF-R will be compared to its binding to the GST-wild type NGF-R intracellular domain fusion. Abolition of the binding by the mutation will indicate that the cloned protein indeed recognizes sequence features that are involved in the 'death domain' motif. A similar approach will be taken to assess the involvement of the sequence features characteristic of the 'death domain' in the function of other reagents that interact with proteins containing this motif, namely antibodies, peptides or organic compounds (See Example 4). EXAMPLE 5 Design of drugs that affect 'death domain' motif-containing proteins by virtue of their ability to interact with the 'death domain' Organic molecules or peptides that interact with the 'death domain' motif of one of the proteins containing this motif will be defined either by screening or by design. Further changes will then be introduced to this molecule to increase the effectivity of its interaction with that specific 'death domain' and the ability of the designed compound to affect (enhance or interfere with) the function of the protein containing the 'death domain'. Once creating such a molecule and defining the sequence feature of the 'death domain' which it recognizes (see Example 3) as well as the conformational features of the 'death domain' involved in this recognition (by NMR, X-ray crystallography, etc.), this knowledge can be applied as a starting point for designing drugs that will affect other proteins containing the 'death domain' motif To do so, one should introduce to the designed peptide or organic molecule, besides structural features that allow recognition of those structural features that are common to the 'death domain', also structural features that will dictate specific recognition of the specific 'death domain' containing protein. EXAMPLE 6 Analysis of the biological activity of the 'death domain' motif binding proteins , peptides, antibodies or organic molecules Once the 'death domain' motif binding proteins or peptides have been isolated, e.g. by the procedure of Example 1, they can be tested for their biological activity. In co-pending applications IL 109632, 111125, 112002 and 112692, there is described one such procedure which assays the effect of intracellular domain binding proteins of the cytotoxic effects mediated by the p55 TNF-R, FAS-R and MORT1 (HF1). Thus, using similar procedures it is possible to determine, firstly, the ability of such 'death domain' motif-binding proteins or peptides to associate in vitro with 'death domain' motif-containing proteins such as p55 TNF-R, FAS-R, NGF-R, MORT-1, RIP, TRADD and ankyrin 1, and secondly to assess in vivo, using standard cell cytotoxicity assays, whether such 'death domain' motif binding proteins or peptides are capable of enhancing or inhibiting the cell cytotoxicity induced by such receptors as p55 TNF-R or FAS-R or proteins such as MORT1. Likewise, the same tests may also be applied to assay organic compounds (obtained by screening or design, see Example 4); synthetically produced peptides (see Example 4); and antibodies, capable of binding to 'death domain' motifs. REFERENCES Barinaga, M. (1993) Science 262 :1512-4. Bartel, P.L. et al. (1993) Bio Techniques 14 :920-924. Beutler, B. and Cerami, C. (1987) NEJM, 316 :379-385. Bigda, J. et al. (1994) J. Exp. Med. 180 :445-460. Boldin, M.P. et al. (1995) J. Biol. Chem. 270 , 337-341. Boldin. M.P. et al. (1995) J. Biol. Chem. 270 , 387-391. Boldin, M.P. et al. (1995) J. Biol. Chem. 270, 7795-8. Brakebusch, C. et al. (1992) EMBO J., 11 :943-950. Brockhaus, M. et a1. (1990) Proc. Natl. Acad. Sci. USA, 87 :3127-3131. Cantor, G.H. et al. (1993) Proc. Natl. Acad. Sci. USA 90 :10932-6. Chen. C.J. et al. (1992) Ann N.Y. Acad. Sci. 660 :271-3. Chinnalyan, A.M. et al (1995) Cell 81 :505-512. Cleveland, J.L. and Ihle, J.N. (1995) Cell 81 :479-482. Crisell, P. et al., (1993) Nucleic Acids Res. (England) 21 (22):5251-5. Engelmann, H. et al. (1990) J. Biol. Chem., 265 :1531-1536. Field, J. et a!. (1988) Molec. Cell. Biol. 8 :2159-2165. Fields, S. and Song, O. (1989) Nature, 340 :245-246. Heller, R.A. et al. (1990) Proc. Natl. Acad. Sci. USA, 87 :6151-6155. Hohmann, H.-P. et al. (1989) J. Biol. Chem., 264 :14927-14934. Hsu, H. et al., (1995) Cell 81 : 495-504. Itoh, N. et al. (1991) Cell 66 :233. Itoh, N. and Nagata, S. (1993) J. Biol. Chem. 268, 10932-7. Johnson, D. et al. (1986) Cell 47 , 545-554. Joseph, S. and Burke, J.M. (1993) J. Biol. Chem. 268 :24515-8. Kischkel, F.C. et al. (1995) EMBO J. (in press) Koizumi, M. et al. (1993) Biol. Pharm. Bull (Japan) 16 (9):879-83. Kunkel, T.A. (1994) in Current Protocols in Molecular Biology, (Ausubel et al,.(eds)), pp. 8.1.1-8.1.6, Greene Publishing Associates, Inc. and Wiley & Sons, Inc., New York. Lambert, S. and Bennet, V. (1993) Eur. J. Biochem. 211 , 1-6. Loetscher, H. et al. (1990) Cell, 61 :351-359. Lux, S.E. et al. (1990) Nature 344, 36-42. Nophar, Y. et al. (1990) EMBO J., 9 :3269-3278. Piquet, P.F. t al. (1987) J. Exp. Med., 166 :1280-89. Rabizadeh, S. et al. (1993) Science 261 , 345-348. Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual , Cold Spring Harbor Laboratory Press. Cold Spring Harbor, NY Sander, C. and Schneider, R. (1991) Proteins 9 , 56-68. Schall, T.J. et al. (1990) Cell, 61 :361-370. Shimayama, T. et al., (1993) Nucleic Acids Symp. Ser. 29 :177-8 Shore, S.K. et al. (1993) Oncogene 8 :3183-8. Smith, C.A. et al. (1990) Science, 248 :1019-1023. Song, H.Y. et al. (1994) J. Biol. Chem. 269 , 22492-22495 Stanger, B.Z. et al. (1995) Cell 81 :513-523. Tartaglia. L. A. et al. (1993) Cell, 74 :845-853. Tracey, J.T. et al. (1987) Nature, 330 :662-664. Wallach, D. (1986) in: Interferon 7 (Ion Gresser, ed.), pp. 83-122, Academic Press, London Wallach, D. et al. (1994) Cytokine 6, 556. Watanabe-Fukunaga, R. et al. (1992) Nature, 356 , 314-317. Wilks, A.F. et al. (1989) Proc. Natl. Acad. Sci. USA, 86 :1603-1607. Zhao, J.J. and Pick, L. (1993) Nature (England) 365 :448-51. The following numbered paragraphs 1 to 36 define particular technical subject matter relating to this invention. Where, in a paragraph an earlier paragraph is referred to, this is done merely by stating the number of the earlier paragraph. 1. A modulator of regulatory cellular events occurring intracellularly that are mediated by regulatory proteins containing a'death domain' motif which is a regulatory portion of said proteins, said modulator being capable of interacting with one or more of the 'death domain' motifs contained in said regulatory proteins and affecting the regulatory action of one or more of said regulatory proteins. 2. A modulator according to 1 wherein said modulator is selected from the group comprising naturally-derived 'death domain' motif-binding proteins and peptides and analogs and derivatives thereof capable of interacting with one or more of said 'death domain' motifs. 3. A modulator according to 1, wherein said modulator is selected from the group of synthetically produced complementary peptides, synthesized by using as substrates the 'death domain' motif sequences of said regulatory proteins containing 'death domain' motifs, said complementary peptides being capable of interacting with one or more of said 'death domain' motifs. 4. A modulator according to 1, wherein said modulator is selected from the group comprising antibodies or active fragments thereof capable of interacting with one or more of said 'death domain' motifs. 5. A modulator according to 1, wherein said modulator is selected from the group of organic compounds capable of interacting with one or more of said 'death domain' motifs, said organic compounds being derived from known compounds and selected by using said 'death domain' motifs as a substrate in a binding assay, or being synthesized using said 'death domain' motifs as a substrate for designing and synthesizing said organic compounds. 6. A modulator according to 1, wherein said modulator is selected from the group of peptides or polypeptides derived from naturally occurring 'death domain' motif sequences, said peptides or polypeptides being capable of interacting with one or more of said 'death domain' motifs, and analogs and derivatives of said peptides or polypeptides capable of interacting with one or more of said 'death domain' motifs. 7. A modulator according to any one of 1-6, wherein said modulator is further characterized by being capable of recognizing the general 'death domain' motif sequence features common to the 'death domain' motifs of 'death domain' motif containing proteins, and being capable of recognizing one or more of the specific 'death domain' motifs of said proteins, said specific sequence features being specific to each 'death domain' motif sequence of each of said proteins. 8. A modulator according to any one of 1-7, wherein said modulator is capable of interacting with one or more of the 'death domain' motifs contained within the proteins belonging to the group comprising p55 TNF-R, FAS-R, NGF-R, MORT-1, RIP, TRADD and ankyrin 1. 9. A modulator according to 8, wherein said modulator is further characterized by being capable of interacting with common sequence features of the 'death domain' motifs of said group of proteins, said common sequence features comprising the group of common amino acid residues W (tryptophan), L (leucine), I (isoleucine), A (alanine), D (aspartic acid), E (glutamic acid), T (threonine), R (arginine) and Y (tyrosine) at the location within said 'death domain' motifs shown in Fig. 1. 10. A DNA sequence encoding a modulator being a protein, peptide or polypeptide or an analog of any thereof, according to any one of 1-3 and 6. 11. A DNA sequence according to 10 encoding a naturally derived protein or peptide selected from the group consisting of : (a) a cDNA sequence derived from the coding region of a native 'death domain' motif-binding protein or peptide; (b) DNA sequences capable of hybridization to a sequence of (a) under moderately stringent conditions and which encode a biologically active 'death domain' motif-binding protein or peptide; and (c) DNA sequences which are degenerate as a result of the genetic code to the DNA sequences defined in (a) and (b) and which encode a biologically active 'death domain' motif-binding protein or peptide. 12. A DNA sequence according to 10 or 11 encoding a 'death domain' motif-binding protein or peptide capable of binding to the 'death domain' motif of one or more of the proteins of the group comprising p55 TNF-R, FAS-R, NGF-R, MORT-1, RIP, TRADD and ankyrin 1. 13. A DNA sequence according to 10 or 11 encoding a peptide or polypeptide derived from the naturally occurring 'death domain' motif sequence of the 'death domain' motif-containing proteins. 14. A DNA sequence according to 13 encoding a peptide or polypeptide derived from the 'death domain' motif sequence of any one of the proteins of the group comprising p55 TNF-R, FAS-R, NGF-R, MORT-1, RIP, TRADD and ankyrin 1. 15. A protein, peptide or polypeptide and analogs of any one thereof encoded by a DNA sequence according to any one of 10-14, said protein, peptide, polypeptide and analogs being capable of binding to or interacting with one or more of the 'death domain' motifs of one or more 'death domain' motif containing proteins. 16. A vector comprising a DNA sequence according to any one of 10-14. 17. A vector according to 16 which is capable of being expressed in a eukaryotic host cell. 18. A vector according to 16 which is capable of being expressed in a prokaryotic host cell. 19. Transformed eukaryotic or prokaryotic host cells containing a vector according to any one of 16-24. 20. A method for producing the protein, peptide, polypeptide or analogs according to 15 comprising growing the transformed host cells according to 19 under conditions suitable for the expression of said protein, peptide, polypeptide or analogs, effecting post-translational modifications of said protein, peptide, polypeptide or analogs as necessary for obtention thereof and extracting said expressed protein, peptide, polypeptide or analogs from the culture medium of said transformed cells or from cell extracts of said transformed cells. 21. Antibodies or active fragments or derivatives thereof, specific for the protein, peptide, polypeptide or analogs according to 15. 22. A method for the modulation of the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP. TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising treating said cells with one or more proteins, peptides, polypeptides or analogs selected from the group consisting of the proteins, peptides, polypeptides or analogs according to 15, all being capable of binding to or interacting with the 'death domain' motif and modulating the activity of said 'death domain' motif-containing proteins, wherein said treating of said cells comprises introducing into said cells said one or more proteins, peptides, polypeptides or analogs in a form suitable for intracellular introduction thereof, or introducing into said cells a DNA sequence encoding said one or more proteins, peptides, polypeptides or analogs in the form of a suitable vector carrying said sequence, said vector being capable of effecting the insertion of said sequence into said cells in a way that said sequence is expressed in said cells. 23. A method according to 22 wherein said treating of said cells is by transfection of said cells with a recombinant animal virus vector comprising the steps of: (a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein (ligand) that is capable of binding to a specific cell surface receptor on the surface of said cell to be treated and a second sequence encoding a protein selected from the proteins, peptides, polypeptides and analogs according to 15. said protein, peptide, polypeptide or analogs, when expressed in said cells being capable of modulating the activity of said 'death domain motif-containing protein; and (b) infecting said cells with said vector of (a). 24. A method for modulating the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising treating said cells with antibodies or active fragments or derivatives thereof, according to 21, said treating being by application of a suitable composition containing said antibodies, active fragments or derivatives thereof to said cells, said composition being formulated for intracellular application. 25. A method for modulating the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising treating said cells with an oligonucleotide sequence selected from a sequence encoding an antisense sequence of at least part of the sequence according to any one of 10-14, said oligonucleotide sequence being capable of blocking the expression of at least one of the 'death domain' motif-binding proteins or peptides. 26. A method according to 25 wherein said oligonucleotide sequence is introduced to said cells via a virus of 23 wherein said second sequence of said virus encodes said oligonucleotide sequence. 27. A method for treating tumor cells or HIV-infected cells or other diseased cells, comprising: (a) constructing a recombinant animal virus vector carrying a sequence encoding a viral surface protein that is capable of binding to a specific tumor cell surface receptor or HIV-infected cell surface receptor or receptor carried by other diseased cells and a sequence encoding a protein selected from the proteins, peptides, polypeptides and analogs of 15 said protein, peptide, polypeptide or analogs when expressed in said tumor, HIV-infected, or other diseased cell being capable of killing said cell; and (b) infecting said tumor or HIV-infected cell or other diseased cells with said vector of (a). 28. A method for modulating the TNF or FAS-R ligand effect on cells mediaed by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, WORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising applying the ribozyme procedure in which a vector encoding a ribozyme sequence capable of interacting with a cellular mRNA sequence encoding a protein or peptide according to 15, is introduced into said cells in a form that permits expression of said ribozyme sequence in said cells, and wherein when said ribozyme sequence is expressed in said cells it interacts with said cellular mRNA sequence and cleaves said mRNA sequence resulting in the inhibition of expression of said protein or peptide in said cells. 29. A method for isolating and identifying proteins, peptides, factors or receptors capable of binding to the 'death domain' motif-binding proteins or peptides according to 15, comprising applying the procedure of affinity chromatography in which said protein or peptide according to 15 is attached to the affinity chromatography matrix, said attached protein is brought into contact with a cell extract and proteins, factors or receptors from cell extract which bound to said attached protein are then eluted, isolated analyzed. 30. A method for isolating and identifying proteins, capable of binding to the 'death domain' motif-binding proteins or peptides according, to 15, comprising applying the yeast two-hybrid procedure in which a sequence encoding said 'death domain' motif-binding protein is carried by one hybrid vector and sequence from a cDNA or genomic DNA library are carried by the second hybrid vector, the vectors then being used to transform yeast host cells and the positive transformed cells being isolated, followed by extraction of the said second hybrid vector to obtain a sequence encoding a protein which binds to said 'death domain' motif-binding protein. 31. A pharmaceutical composition for the modulation of the TNF- or FAS-R ligand-effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif comprising, as active, ingredient a modulator according to any one of 1-9. 32. A pharmaceutical composition for modulating the TNF- or FAS-R ligand- effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising, as active ingredient, a recombinant animal virus vector encoding a protein capable of binding a cell surface receptor and encoding a protein or peptide or analogs thereof according to 15. 33. A pharmaceutical composition for modulating the TNF or FAS-R ligand effect on cells mediated by p55 TNF-R and FAS-R, or the functions mediated in cells by NGF-R, MORT-1, RIP, TRADD, ankyrin 1 or by other proteins containing a 'death domain' motif, comprising as active ingredient, an oligonucleotide sequence encoding an anti-sense sequence of the sequence according to any one of 10-14. 34. A method for isolating and identifying a protein capable of binding to the 'death domain' motifs of 'death domain' motif-containing proteins comprising applying the procedure of non-stringent southern hybridization followed by PCR cloning, in which a sequence or parts thereof according to any one of 10-14 is used as a probe to bind sequences from a cDNA or genomic DNA library, having at least partial homology thereto, said bound sequences then amplified and cloned by the PCR procedure to yield clones encoding proteins having at least partial; homology to said sequences of 10-14. 35. A method for designing drugs that are capable of modulating the activity of 'death domain' motif-containing proteins, comprising the procedures described herein in Examples 3 and 4. 36. A method for modulating the concerted intracellular modulation resulting from the indirect interaction between the FAS-R and the p55 TNF-R via their cascading interaction of MORT-1 and TRADD, or MORT-1 and RIP, comprising treating cells with a modulator which will enhance or inhibit the MORT-1 - TRADD or MORT-1 - RIP mediated p55 5 TNF-R - FAS-R interaction.";An antibody specific to the death domain of a death domain-containing regulatory protein, or a fragment of a said antibody which is capable of binding said death domain, the regulatory protein being selected from the group consisting of MORT-1 and ankyrin 1. An antibody or fragment in accordance with claim 1, which is capable of binding to the death domain of both of said death domain-containing regulatory proteins. An antibody or fragment in accordance with claim 1, which is capable of binding to the death domain of at least one of said death domain-containing regulatory proteins and at least one regulatory protein selected from p55-TNF-R, FAS-R, RIP and TRADD. An antibody in accordance with any one of the preceding claims comprising a monoclonal antibody.;GONCHAROV TANYA M, METT IGOR, PANCER ZEEV, VARFOLOMEEV EUGENE E, WALLACH DAVID, GONCHAROV, TANYA M., METT, IGOR, PANCER, ZEEV, VARFOLOMEEV, EUGENE E., WALLACH, DAVID, Pancer, Zeev, Center of Marine Biotechnology;"YEDA RES & DEV, YEDA RESEARCH & DEVELOPMENT COMPANY, LTD., YEDA RESEARCH & DEVELOPMENT COMPANY, LTD.";2005.0;1588712