A method of enhancing tolerance of a porcine transplant in a xenogeneic recipient by administering porcine bone marrow cells to the recipient and of enhancing proliferation and engraftment of the porcine bone marrow cells by exposing said cells to at least one substantially pure porcine cytokine and porcine cytokines that are substantially free of other porcine proteins and preferentially enhance the proliferation and engraftment of porcine bone marrow cells in the presence of bone marrow cells of other species. Protein and DNA sequence(s) for such porcine cytokines.

Organ procurement currently poses one of the major problems in organ transplantation, as the number of patients requiring transplants far exceeds the number of organs available. Xenotransplantation may provide a solution to this problem. Phylogenetically, non-human primates are the most closely related species to humans and might therefore represent the first choice as donors. In 1969, Reetsma et al. achieved the first successful kidney human xenograft from a chimpanzee (Reetsma, K. et al., 1964, Ann. Surg. 160:384). However, the potential utilization of primate donors is limited by insufficient numbers, legal and ethical considerations, and the potential for transmitting dangerous viral diseases. Swine represent one of the few large animal species in which breeding characteristics make genetic experiments possible, making it possible to develop MHC homozygous lines of miniature swine. Miniature swine can be maintained at maximum adult weights of 200 to 300 lbs and are anatomically and physiologically close to humans. Therefore the organs of miniature swine seem appropriate for use as xenografts for human beings of all ages.
Tolerance to self major histocompatibility (MHC) antigens occurs during T cell maturation in the thymus (McDuffie et al., J. Immunol. 141:1840, 1988). Exposure of the immune system to MHC antigens during ontogeny can cause the immune system to lose reactivity to those antigens, thus leaving the animal specifically tolerant into adult life (Billingham et al., 1953, Nature 172:603). Transplantation immunologists have sought means of inducing tolerance in adult animals by production of lymphohematopoietic chimeras. The induction of tolerance across MHC barriers in adult mice by whole body irradiation (WBI) and bone marrow transplantation (BMT) has been studied extensively in murine models (Hayfield et al., 1983, Transplan. 36:183; Mayumi et al., 1989, J. Exp. Med. 169:213; Sykes et al., 1988, Immunol. Today 9:23).
The use of MHC mismatched BMT as a means of inducing tolerance to organ grafts can be accompanied by several major disadvantages: the preparative regimen involves lethal irradiation, with its inherent risks and toxicities; clinical applicability is limited by the fact that most potential recipients do not have an appropriate MHC-matched donor, and BMT across MHC barriers causes severe graft-vs-host-disease (GVHD). Removing the T lymphocytes in allogeneic bone marrow inocula (Rodt et al., 1971, Eur. J. Immunol. 4:25) to prevent GVHD is associated with increased rates of engraftment failure (Martin et al., 1988, Bone Marrow Transplant 3:445; O'Reilly et al., 1985, Transplant. Proc. 17:455; Soderling et al., 1985, J. Immunol., 135:941). While these drawbacks are generally considered acceptable for the treatment of otherwise lethal malignant diseases, they would severely limit the application of MHC mismatched BMT as a preparative regimen for organ transplantation, in which non-specific immunosuppressive agents, while not without major complications, are effective.
Use of a relatively non-toxic, non-myeloablative preparative regimen for bone marrow engraftment and specific transplantation tolerance has been applied to the concordant rat to mouse species combination (Sharabi, Y. et al., 1990, J. Exp. Med. 172:195-202). The treatment involved administration of monoclonal antibodies to eliminate mature T cell subsets (CD4 and CD8) as well as NK cells (NK1.1). These monoclonal antibodies permitted engraftment of xenogeneic bone marrow after only a sub-lethal (300 rads) dose of WBI and a local dose of 700 rads thymic irradiation. The resulting lymphoid reconstitution was superior to that of previously mixed xenogeneic chimeras prepared by lethal irradiation and reconstitution with mixtures of T cell-depleted syngeneic and xenogeneic bone marrow (Sharabi, Y., et al., 1990, J. Exp. Med. 172:195-202; Ildstad, et al., 1984, Nature 307:168-170) as recipients did not suffer toxic effects from the preparative regimen. In addition, attempts have been made to lengthen the survival of skin allografts in primates and man by intravenously administering a polyclonal preparation of horse anti-human antithymocyte globulin (ATG). The ATG was injected simultaneously with and on days immediately following grafting (Cosimi, A. B. et al., 1970, Surgery. 68:54-61).
It has been recognized that the use of swine organs for xenogeneic transplantation to humans is facilitated by inducing tolerance (i.e., reducing the severity of and/or eliminating any immunological response to the transplant) to swine tissue using swine bone marrow. The swine bone marrow cells (BMC) can be transplanted to the recipient's marrow and engraft there. Engraftment, as used herein, refers to implantation or transplantation of porcine BMCs into a xenogeneic recipient or host such that the porcine BMCs proliferate, differentiate and function as bone marrow in the recipient. The porcine bone marrow can be introduced before transplantation of the swine organ, contemporaneously with the organ transplantation, or both. In this context, contemporaneously or substantially contemporaneously contemplates introduction during the same operative procedure or as part of preoperative preparation.
In accordance with the present invention, it has been recognized by the inventors that it would be highly desirable to promote the engraftment of the porcine bone marrow and that cytokines which have an effect on marrow engraftment are highly species specific in their effect. In accordance with the invention, the inventors recognized the deficiency that porcine cytokines effective to promote porcine bone marrow engraftment had not been identified, isolated, characterized or produced, such as by recombinant techniques and that such was highly desirable for use in the above and other applications.
Accordingly, other principal aspects of the invention are porcine cytokines that preferentially enhance the proliferation and engraftment of porcine bone marrow cells in the presence of bone marrow cells of other species, DNA sequences therefor and DNA molecules for expression of these porcine cytokines. More particularly, the invention provides porcine chimeric enhancement factors ("CHEFs") that are porcine analogs of interleukin-3 (hereinafter "CHEF-1"), granulocyle-macrophage colony stimulating factor (hereinafter "CHEF-2") and stem cell factor (hereinafter "CHEF-3") as well as combinations of these novel porcine cytokines with each other and with other porcine cytokines, such as porcine leukemia inhibitory factor (hereinafter "porcine LIF"). The porcine cytokines of the invention are contemplated to encompass the protein whether purified from native origin, expressed by recombinant methodologies or chemically synthesized.
As will be explained in more detail below, the porcine bone marrow that is preferentially stimulated by the porcine cytokines in the recipient prepares the recipient for the tissue or organ transplantation by inducing tolerance at both the B-cell and T-cell levels. Preferably, the bone marrow cells include immature cells (e.g., undifferentiated hematopoietic stem cells; these cells can be separated out of the bone marrow prior to administration), or a complex bone marrow sample including such cells can be used.
Preferred embodiments include those in which: swine of the same immunological profile are the donor of both the tissue or organ to be transplanted and the bone marrow; the recipient mammal is a primate, preferably a human; and the swine is a partially or completely inbred strain, e.g., a miniature swine. In a preferred embodiment of the method of use, the recipient is irradiated with low dose radiation prior to introducing the bone marrow, preferably with radiation of more than 100 rads and less than 400 rads.


An optical disk recording medium includes a single layer disk substrate having a hub provided on one side which includes a circular magnetic plate for effecting chucking of the optical disk. On the opposite side of the disk substrate a reinforcing plate is attached for reducing disk warpage during chucking, loading etc. The circular magnetic plate includes a centering opening for disk chucking, while a center opening of the reinforcing plate is larger in diameter than the centering opening. The reinforcing plate covers a central opening formed in the disk substrate and includes a boss portion which is projected into the opening. A groove is provided in the reinforcing plate at the outer circumference of the boss portion for retaining excess adhesive when the substrate is affixed to the reinforcing plate.

1. Field of the Invention
The present invention relates generally to an optical data recording medium. Particularly, the present invention relates to a readable/writable optical disk which is supported on a rotatable disk table when in use.
2. Description of the Related Art
In optical disk technology, a small laser spot is utilized for reading and/or writing high density information data to a recording playback layer of the disk material. Generally, three types of such disks are available, read only, write once read many and rewritable.
For many types of data which may now be accessed by computer users, such as coded data, audio data and graphic data, an erasable rewritable type of optical or magneto optical disk is the most useful.
Referring to FIGS. 5 and 6, a conventional example of such type of magneto optical disk will be discussed hereinbelow.
FIG. 6 shows a cross-sectional view of the conventional magneto-optical disk of FIG. 5 as supported on a disk table 6 of a disk drive (not shown) for carrying out reading/writing operations. The disk 1 comprises a disk substrate 2 both sides of which have an opening 2a formed at a center portion thereof. The disk substrate is formed of a combustible plastic resin generally molded by injection of the resin through the central openings. At one side of the disk substrate a circular plastic hub 3 having an installation groove 3a formed at an inner peripheral side thereof is provided.
Within the hub 3, retained by the installation groove 3a, a circular mounting plate 4 having a center opening 4a is provided. The center opening 4a allows insertion of an output shaft 5 of a spindle motor (not shown) of the disk drive (not shown) for rotatingly driving the magneto-optical disk 1.
The disk table 6 supporting the disk 1 is comprised of a table body 7 including an annular portion 7a and an annular disk support portion 7b of the table body 7, the disk support portion 7b being effective for determining correct positioning of the disk 1. The lower portion of the table body 7 is inset with a circular yoke 8 and, set between the yoke 8 and the circular mounting plate 4 an annular magnet 9 is disposed for effecting high speed rotation of the disk 1 according to operation of the spindle motor (not shown).
In addition, disposed around an outer periphery of the annular disk support portion 7b a friction ring 10, formed of rubber or the like, is provided for preventing slipping of the disk 1 when loaded on the disk table 6.
According to the above arrangement, when the disk substrate 2 is set on the table body 7 such that the circular mounting plate 4 is engaged by the magnetic force of the magnet 9 and the output shaft 5 of the spindle motor (not shown) is inserted into the centering opening 4a of the circular mounting plate, the outer circumference of the output shaft 5 is in touching contact with the inner cirumference of the centering opening 4a.
Such a conventional magneto-optical disk as described above has been disclosed, for example, in Japanese Utility Model 62-80240.
Increased demand for such variable magnetic overwriteable disk systems has been forecast, thus systems having advantages including low cost, simple single layer construction etc., are desired.
In such an optical disk system as described above, the disk substrate is generally formed of a polycarbonate resin, or the like, according to this, in order to minimize occurence of comma type aberration, a substrate thickness of 1.2 mm is set. At this, a flexibility or resilience of the substrate is lowered considerably. The effect of this is that when the hub 3 is chucked in the table body 7, the disk substrate 2 abuts the annular disk support portion 7b of of the table body 7 under pressure such that warpage of the disk substrate may easily occur.
A degree of warpage to which the substrate 2 is susceptible is directly connected to the resilience or flexibility of the substrate material.
At this, flexibility is proportional to thickness to the third power. That is, if theoretically, the warpage of a single layer substrate is expressed as S.sub.1 and of a two layer substrate as S.sub.2, comparatively; S.sub.1 =2.sup.3 .times.S.sub.2, i.e. S.sub.1 =8.times.S.sub.2.
Accordingly, such warpage, particularly in a single layer substrate type disk, cannot be ignored as this will have an adverse effect on data reading and writing operations and degrade disk performance.
Thus it has been required to provide an optical disk by which warpage of a substrate portion of the disk is prevented and degrading influence of warpage on data reading and writing operations is prevented.


An apparatus for determining the timing of an internal combustion engine having a crankshaft, a camshaft, and a plurality of cylinders each having an electronically controlled fuel injector is disclosed. A crankshaft sensing device monitors the rotation of the engine crankshaft and responsively produces a crankshaft pulsetrain. Additionally, a camshaft sensing device monitors the rotation of the engine camshaft and responsively produces a camshaft pulsetrain. An engine control receives the crankshaft and camshaft pulsetrains, and responsively determines the period of each pulse, determines the rotational position of the crankshaft and camshaft, and produces an inject signal relative to one of the crankshaft and camshaft pulsetrains to the fuel injector in order to initiate fuel injection.

The timing of an internal combustion engine must be accurately controlled so that emissions are minimized and so that the engine runs at peak efficiency. In compression type diesel engines, ignition occurs upon injection of fuel into a cylinder containing air that has been compressed by a piston which is movable in the cylinder. The "timing" of such an engine is defined as the time at which a fuel injector is operated to inject fuel into the cylinder relative to the time at which the piston reaches a position known as "top dead center" in the cylinder that has reached the end of the piston stroke. Current state of the art engines typically include electronically controlled fuel injectors, which provides for efficient engine operation at maximum power.
In such engines that utilizes electronic fuel injectors, the position of the piston within the cylinders relative to top dead center must be measured. These measurements must be accurate in order to maximize engine operating efficiency. However, once the highly accurate measurement system fails, the entire engine control will shutdown. Consequently, it is desirable to introduce redundancy into the system in order to prevent catastrophic failure of the engine control system.
The present invention is directed toward overcoming one or more of the problems as set forth above.

Engine timing apparatus and method of operating same


In one aspect, the present invention provides methods for suppressing cracking, stem browning, and water loss in fruit or vegetables, such as cherries. The methods comprise applying to fruit or vegetables an amount of a wax emulsion effective to suppress cherry cracking, stem browning, and water loss. The wax emulsion used in the methods of the invention typically comprises a matrix of complex hydrocarbons, one or more emulsifying agents, and water. In some embodiments, the wax emulsion comprises from about 0.125% to about 25% (weight/weight) of carnauba wax, from about 0.1% to about 16% (weight/weight) of oleic acid, and from about 0.03% to about 6% (weight/weight) of morpholine, and from about 53% to about 99.7% (weight/weight) of water. In some embodiments, the wax emulsions further comprise one or more osmoregulators.

Sunburn has been a problem for apple growers for at least 75 years, but its incidence has increased in recent years with the widespread use of dwarfing rootstocks and high-density plantings. Many cultivars (e.g., 'Fuji,' 'Granny Smith,' 'Jonagold,' 'Gala,' and 'Braeburn') are susceptible to sunburn. Prominent growers have indicated that sunburn may be the most significant cullage or quality problem in the industry. Trees are smaller and fruit are more exposed to solar radiation making fruit more susceptible to sunburn.
There is no adequate product on the market today for preventing sunburn damage. Many growers use overhead evaporative cooling or shadecloth to reduce sunburn in their apple orchards. Evaporative cooling decreases the temperature of the fruit and helps protect the fruit from sunburn (Parchomchuk, P. and Meheriuk, M., "Orchard cooling With Pulsed Overtree Irrigation to Prevent Solar Injury and Improve Fruit Quality of 'Jonagold' Apples," HortScience 31:802–804 (1996)). However, growers are concerned about several deleterious effects on fruit trees and soil (Warner, G., "Overhead Cooling May Not Be Total Sunburn Cure," Good Fruit Grower 46(12):20–21 (1995)). The shadecloths cost several thousand dollars per acre to install, and frequently interfere with normal color development of fruit. Uniform shade causes an undesirable alteration in the growth habit of apple trees and significantly reduces fruit production (Warner, G., "Cooling Problems Prompt Growers To Try Covers," Good Fruit Grower 46(12):24–25 (1995); Warner, G., "Growers Test Shade Cloths To Reduce Fuji Sunburn," Good Fruit Grower 46(17):55–63 (1995); Warner, G., "What Shade Do Cloths Provide, What Do You Need?", Good Fruit Grower 46(17):50–53 (1995)). Problems with these approaches confirm that new treatments are needed to lower fruit temperature, but not interfere with color development or fruit production.
In 1986 and 1987, Sibbett et al. ("Effect Of A Topically Applied Whitener On Sun Damage To Granny Smith Apples," California Agriculture 45(1):9–10 (1991)) in California attempted to solve the problem by applying a commercial whitener (Sunguard) to Granny Smith apples. The whitener had been developed for walnuts. They concluded from their experiments that Granny Smith apples could not be protected from sunburn by up to four topical applications of this particular whitening agent.
Miller Chemical & Fertilizer Corp. (Hanover, Pa.) markets an anti-transpirant concentrate called VAPOR GARD, and claims in its advertisements that the product reduced sunburn cullage by 30% in their trials. Transpiration is important to plant leaves, as evapotranspiration serves to cool the leaves and protects the leaves from heating to temperatures that are deleterious. Fruits have much lower transpiration rates than do leaves, but it seems likely that applying an anti-transpirant to fruit would exacerbate a situation in which there is already too much thermal energy.
Myhob, Guindy, and Salem in Egypt (Bulletin of Faculty of Agriculture, University of Cairo, 47(3):457–469 (1996)) reported that Agricultural GatCool significantly reduced sunburn as compared to controls sprayed with water on Balady mandarin fruits. duToit in South Africa (Citrus and Subtropical Fruit Research Institute Information Bulletin No. 80:8–9 (1979)) reported that spraying Koolcote on pineapple trees decreased fruit flesh temperatures by 2–3 degrees Celsius.
Lipton and Matoba (HortScience 6(4):343–345 (1971)) reduced sunburn of 'Crenshaw' melons by whitewashing fruit with a suspension of aluminum silicate.
Ing (Good Fruit Grower 49(6):58 (1998)), commenting on unpublished field trials, reports that the application of kaolin to apple fruits not only acts as an insect repellent, but also lowers canopy temperature, increases fruit size, and may reduce sunburn. However, as noted by 1 ng, application of kaolin to fruit surfaces is problematic. To achieve an insecticidal result, large amounts of kaolin (50 to 100 pounds per acre) must be applied to the fruit trees. Current kaolin formulations are reported to suffer from substantial application problems such as excessive foaming and "globbing" in spray tanks. (Good Fruit Grower 49(6):58 (1998)). Furthermore, kaolin powders are easily washed off by rain, thus necessitating multiple applications in order to maintain beneficial effects. (Good Fruit Grower 49(6):58 (1998); see also Washington State University Cooperative Extension Area Wide IPM Update 3(4): 1(1998)).
Sekutowski et al. (U.S. Pat. No. 5,908,708) developed a protective water resistant coating that was formulated as an aqueous dispersion of particulate matter having a hydrophobic outer surface in a low boiling point organic liquid, such as methanol. The particulate matter of the Sekutowski et al. coating can be any finely divided hydrophobic particulate solids including minerals, such as calcium carbonate, mica, talc, kaolin, bentonites, clays attapulgite, pyrophyllite, wollastonite, silica, feldspar, sand, quartz, chalk, limestone, precipitated calcium carbonate, diatomaceous earth and barytes. One agricultural use of the Sekutowski et al. aqueous dispersions is to provide tree leaves with a water resistant coating by spraying the formulation onto the surface of the leaves. The water resistant coating is thought to reduce plant disease and insect damage. However, one major problem with the Sekutowski et al. formulation is the use of large volumes of organic liquids such as alcohols, ketones and cyclic ethers that are highly flammable and pose other health risks to workers during spray application.
Protective formulations which additionally function as pesticides in plant crops would be a valuable addition to Integrated Pest Management (IPM) practices providing "soft" suppression of pests without disrupting natural control processes. Desirable formulations would be expected to be non-toxic to mammals and thus safe for applicators and farm workers. Application of the protective formulations by commonly employed horticultural spray operations invariably involves treatment of foliage and fruit or vegetable. It is therefore important to develop new formulations that have protective properties against sunburn to fruits and vegetables as well as against damage caused by insects that inhabit both foliage and fruit.
Rain-induced cherry cracking is one of the most serious problems to the sweet cherry industry around the world. Cracking of cherries induced by rain is often the greatest single cause of fruit cullage. Cherry cracking has been studied for several decades (Verner & Blodgett (1931) Univ. Idaho Agr. Expt. Sta. Bull. 184; Verner (1938) Proc. Amer. Soc. Hort. Sci. 36:271–74, Verner (1939) Proc. Wash. State Hort. Assoc. 35:54–57; Ackley (1956) Inst. Agr. Sci. State Coll. of Wash. Expt. Publ. 53; Christensen (1972) Acta Agr. Sand. 22:153–161; Andersen & Richardson (1982); Glenn & Poovaiah (1989) J. Amer. Soc. Hort. Sci. 114:781–788; Beyer et al. (2002) Hort. Sci 37(4): 637–641), but the phenomenon is not yet well understood.
It is generally thought that cherry cracking occurs as a result of direct water absorption through the fruit skin (Kertesz & Nebel (1935) Plant Physiol. 10:763–777; Verner (1939) Proc. Wash. State Hort. Assoc. 35:54–57; Westwood & Bjomstad (1970) Proc. Oregon Hort. Soc. 61:70–75; Christensen (1972) Acta Agr. Sand. 22:153–161; Beyer & Knoche (2002) J. Amer. Soc. Hort. Sci. 127(3):325–332; Beyer et al. (2002) Hort. Sci. 37(4): 637–641). Consequently, factors affecting permeability of the skin are of major importance in determining fruit resistance to water injury. Penetration of the cuticle, which occurs by diffusion or by mass flow through cuticular cracks and other surface structures, may be important in determining whether cherries are susceptible to cracking (Anderson & Richardson (1982) J. Amer. Soc. Hort. Sci. 107:441–444; Glenn & Poovaiah (1989) J. Amer. Soc. Hort. Sci. 114:781–788). Calcium is known to decrease hydraulic permeability of cell membranes and is reported to decrease water absorption in sweet cherries (Verner (1939) Proc. Wash. State Hort. Assoc. 35:54–57).
Some treatments have been demonstrated to reduce cherry cracking in some instances (see, e.g., Verner (1939) Proc. Wash. State Hort. Assoc. 35:54–57; Callan (1986) J. Amer. Soc. Hort. Sci. 111(2):173–175; Lang & Hayden (1996) Proc. Wash. State Hort. Assoc. 92:283–28; Lang et al. (1997) Good Fruit Grower 48(12):27–30; Fernandez & Flore (1998) Acta Horticulturae 468:683–689; Lang et al. (1998) Acta Horticulturae 468:649–656; Lang & Flore (1999) Good Fruit Grower 50(4):34–38; Heacox (2001) Fruit Grower 121(4):16). However, the applicability of these treatments in cherry production is limited due to variable or inconsistent results, mechanical problems, or phytotoxicity related to repeated applications (see, e.g., Koffman et al. (1996) Plant Protec. Quart. 11(3):126–30). Part of the variability in results has been attributed to differences in temperature at various sites, as temperature strongly influences natural fruit cracking (i.e., higher temperatures induce more cracking). In addition, cultivars appear to differ in their susceptibility to rain-induced cracking (King & Norton (1987) Fruit Varieties J. 41:83–84; Lang et al. (1997) Good Fruit Grower 48(12):27–30).
Fruit coating waxes have been used on many crops including apples, avocados, citrus, cucumbers, eggplant, peaches, sweet peppers, and tomatoes (Hagenmaier & Shaw (1992) J. Amer. Soc. Hort. Sci. 117(1):105–109). Many studies have investigated water loss during storage (Hagenmaier & Shaw (1992) J. Amer. Soc. Hort. Sci. 117 (1):105–109. One study investigated the effects of antitranspirants and wax coatings that contained vegetable oil emulsions, shellac emulsions, or polysaccharide-protein-oil emulsions on cherries (Lidster (1981) J. Amer. Soc. Hort. Sci. 106:478–480). Some treatments reduced water loss after harvest, however, the antitranspirant treatments were deemed to be unacceptable for commercial use as they left an objectionable sticky residue.
In summary, there is a lack of adequate means to prevent sunburn and insect damage to fruit and vegetable crops. Thus, there is a strong need in agricultural markets for an inexpensive and effective composition that prevents sunburn, repels deleterious insects, is long lasting, and is relatively amenable to easy application by growers and commercial applicators. There is also a need for reliable methods for protecting cherries from the damaging effects of rainfall and for commercially acceptable methods for suppressing water loss from cherries.

Compositions and methods for suppressing cracking and water loss from cherries

Washington State University Research Foundation


A method for transporting a substrate is provided. In this method, a non-Newtonian fluid is provided and the substrate is suspended in the non-Newtonian fluid. The non-Newtonian fluid is capable of supporting the substrate. Thereafter, a supply force is applied on the non-Newtonian fluid to cause the non-Newtonian fluid to flow, whereby the flow is capable of moving the substrate along a direction of the flow. Apparatuses and systems for transporting the substrate using the non-Newtonian fluid also are described.

A substrate, such as a semiconductor wafer, can be moved from one location to another location by a variety of methods. For example, mechanical rollers are typically used in semiconductor manufacturing systems to move the substrate within the system. Specifically, a substrate may be placed between rollers such that the tapered surfaces of the rollers catch the edges of the substrate. To move the substrate, the rollers rotate to push the substrate towards a direction of the rotation. The problem with rollers, and other mechanical devices, is that the mechanisms associated with the rollers can be complicated. Furthermore, rollers must make contact with the substrate to move the substrate. Such contact can exert considerable stress on the substrate, which may lead to the degradation of the substrate.
Water also has been used to move a substrate. For example, the substrate can be placed in a flow of water to move the substrate in a direction of the flow. The problem with using water to transport the substrate is that the substrate can sink and stick to a bottom surface, thereby impeding transport of the substrate. When the substrate is stuck to a surface, the substrate cannot easily be dislodged. The substrate sinks to the bottom because water cannot support the substrate. Accordingly, the use of water to transport the substrate can be unreliable and the substrate is prone to being stuck at the bottom.
In view of the foregoing, there is a need to provide a simpler and more reliable method and apparatus to transport the substrate.

Method and apparatus for transporting a substrate using non-Newtonian fluid


Devices and methods for treating spinal disorders and associated discomfort therefrom. In one embodiment, an interspinous implant device is configured for distracting an adjacent pair of spinous processes while permitting relative flexion, lateral bending and side rotation motions between the vertebrae joined to the adjacent pair of spinous processes. A method of treating spinal disorders and associated discomfort therefrom, includes inserting an interspinous device between a pair of adjacent spinous processes such that a superior portion of the device contacts an inferior surface of the relatively superior spinous process of the pair, and an inferior portion of the of the device contacts a superior surface of the relatively inferior spinous process of the pair; and distracting the superior and inferior portions, relative to one another, thereby distracting the spinous processes, whereby vertebrae integral with the spinous processes retain capability of flexion, lateral bending and side rotation motions, relative to one another, after the distraction has been performed.

With the aging of the population there has occurred an increase in the incidences of degenerative diseases of the spine and this trend is expected to continue with the continuing increase in the percentage of elderly people in the population. Spinal stenosis is one of the most frequent forms of spinal degenerative disease observed. One conventional treatment of spinal stenosis has been laminectomy and decompression of neurologic structures and fusing the treated vertebrae if instability exists. Many potentially negative side effects are inherent in this form of treatment, including profuse bleeding, substantial risk of infection, potential nerve damage sometimes leading to paralysis and/or bladder/bowel dysfunction, dural tears, persistent fluid leakage, arachnoiditis, continuing chronic pain, non-union (if fusion is performed), fusion hardware failure, donor site pain, adjacent segment disease, long operation times, and substantial operation costs.
There are inherent general risks of the surgical procedure and medical risks including, but not limited to: bleeding, infection, nerve or vessel damage, risks of anesthesia, death, need for further surgery, iatrogenic instability, epidural hematoma, failure or implants and/or associated hardware, misplacement of implants and hardware, migration of implants and hardware, heart attack, stroke, deep venous thrombosis, pulmonary embolism, spinal cord and nerve damage, reflex sympathetic dystrophy, sexual dysfunction, positioning problems, brachial plexus injuries, traction injuries, swallowing difficulties, problems with vocal cords, airway obstruction, postoperative swelling, need for prolonged intubation, persistent dural fistula, paralysis, blindness, no relief of current symptoms, possible development of new symptoms, possible worsening of current symptoms, possible need for intraoperative change of procedure, possible need for fusion of the spine as determined intraoperatively, and other rare risks not named above. The need for fusion of the spine can be sometimes first recognized intraoperatively, when a spinal fusion was not originally planned to be performed, but when instability or iatrogenic instability is encountered during the procedure that would make the spine unstable if the fusion were not performed. The risks, benefits, alternatives and risks of the alternatives are discussed with the patient, so that the patient understands the risks of the procedure to be performed and elects to proceed.
Other types of implants have been developed to distract the spinous processes without the performance of laminectomy or fusion to increase the space for existing nerves to thereby relieve pain. Implantation of these implants typically require a large incision and dissection on both sides of the spinous processes. Multiple steps of dilation and distraction are performed prior to implantation of the implant in order to final provide a sufficient interspinous space to wedge the implant between the spinous processes. Examples of implants of these types are described in U.S. Pat. Nos. 5,645,599; 6,149,652; 6,514,256; 6,695,842; and 6,761,720. Further, many of these devices are rigid, inflexible and non-adjustable wedge-like implants that require dissection of muscle tissue and/or ligaments such as the supraspinous ligament and interspinous ligament.
In view of these and other drawbacks with using currently existing spine treatments and inter-spinous implants, there is a continuing need for improved procedures and implants to treat disorders of the spine and pain associated therewith, and particularly for treatment of degenerative spine disorders, in the elderly as well as in any other vertebrate patients. It would be further advantageous to provide implants that are implantable via minimally invasive procedures, to reduce trauma, risks of infection and costs relative to those associated with currently available procedures. Still further, it would be desirable to provide such implants to be removable (i.e., explanted), if desired, by minimally invasive procedures. The ability to adjust the amount of distraction between the spinous processes, both during initial implantation and at a later time after completion of the implantation procedure, would also be desirable.

Interspinous dynamic stabilization implant and method of implanting


Method, apparatus, and system, including computer program products, implementing and using techniques for determining a periodic cycle of time series data. A frequency spectrum of the data is provided. The frequency spectrum is processed using at least one of the following steps, resulting in a processed frequency spectrum: filtering the frequency spectrum for reducing noise of the data, truncating the frequency spectrum at low frequencies, and weighting high frequency contributions over low frequency contributions of the frequency spectrum. A periodic cycle is extracted based on the processed frequency spectrum.

The invention relates to time series analysis, and in particular to determining a periodic cycle of time series data. Apart from identification and estimation of a stable and accurate model, time series modeling consists of calculating some periodic cycles or seasonality patterns which are comprised in the time series data. For such analyses it is known in the art to use additional seasonally-lagged regressors in an equation (seasonal autoregressive integrated moving average (ARIMA) models), introducing additional dummy variables into some trend equation before the (non-)linear estimation of its coefficients, or iterative correction of the forecasted value with respect to its recent seasonal counterpart (exponential smoothing).
In seasonal data, there is a cyclical data pattern. For example, quarterly gross domestic product (GDP) data are characterized by some decline in the winter quarter (with less activity in construction and agriculture sector), and some decline as summer holiday effect. It can be expected a cycle of four observations, on top of an upward-sloping trend and variable-length business cycle. Monthly unemployment data are characterized by a cycle of twelve, with some activity decline in the winter and school graduates entering the labor market in the summer. Heaviness of traffic is possibly to be determined by three cycles, e.g. daily: rush hours and night, weekly: no rush hours on the week-end and annual: long week-ends, national holidays, summer holidays etc. The exact cycle lengths depend here on time intervals of measurement.
A problem may arise when this cycle length is not known (or not so obvious) in advance. Another question is whether the seasonality of the data is significant at all. If not, introducing seasonal parameters into the model could account for over fitting the data. The time series analysis methods developed as part of e.g. Intelligent Miner time series functionality do support versions both with and without seasonality, but it is still needed to decide whether to use it and what the cycle length is.
State of the art time series analysis software, e.g. SPSS, Statistica, Eviews, Stata and the like, normally requires seasonality cycle length, e.g., twelve for monthly data, as an input parameter. Besides, the user is often asked whether his data are quarterly, monthly etc. and the program sets then the parameter to four, twelve, etc., respectively. Other programs also provide tools graphically supporting an expert user when taking decision as to seasonality length.

This patent is subject to a terminal disclaimer.

Method, data processing program and computer program product for determining a periodic cycle of time series data

International Business Machines Corporation


In a liquid crystal display device using uniaxially drawn polymer film as a phase difference plate, as the elevation angle becomes wider, the difference between the retardation of the phase difference plate and the retardation of the liquid crystal display panel becomes larger, and the optical compensation relation is broken, and the viewing angle becomes narrower. To solve this problem, uniaxially drawn polymer films are prepared separately from polycarbonate and polystyrene which differ in the optical properties, and they are disposed as the optical compensation plate at the front side and back side of a liquid crystal cell, or they are laminated and disposed at the front side and back side of a liquid crystal cell.

1. Field of the Invention
The present invention relates to a liquid crystal display device with a color compensation function by having liquid crystal molecules oriented by twisting 90 degrees or more (supertwisted) as a display medium.
2. Description of the Prior Art
Generally a supertwisted nematic (STN) liquid crystal display device is colored in yellow-green or blue color, but the color is corrected by using an optical compensating plate and a bright and sharp black/white display is obtained. Accordingly, the display quality is enhanced, and it can be used as the display element for a word processor, a computer and other business machines.
As the color-compensated supertwisted liquid crystal display device, a two-layer supertwisted liquid crystal display device is known well, in which the coloring occurring in the first layer (a driving panel) is corrected in the second layer (optical compensating panel) to realize a colorless display. This structure requires two liquid crystal panels, as compared with the single-layer supertwisted liquid crystal display device, and the thickness of the display device increases, which adds to the weight. To solve this problem, using a phase difference plate composed of a uniaxially drawn polymer film as the optical compensating plate, a thin and light-weight supertwisted liquid crystal display device has been developed. This phase difference plate is, however, manufactured by drawing a polymer film, and differs in the optical properties between the film drawing direction and its orthogonal direction, and therefore as compared with the two-layer supertwisted liquid crystal display device, the color change due to the azimuth or elevation angle is larger in the supertwisted liquid crystal display device of phase difference plate type; that is, the viewing angle is narrower.
It is because of its optical anisotropy that a uniaxially drawn polymer film is used as a phase difference plate. That is, between the polymer film drawing direction and its orthogonal direction, the refractive index is different (birefringence). The retardation (.DELTA.n.d) given by the product of this refractive anisotropy .DELTA.n and the film thickness d is a physical quantity that brings about phase difference of the light occurring when passing through the film, and the change of this due to elevation angle differs between the drawing angle and its orthogonal direction. For example, in a phase difference plate made of polycarbonate, as the elevation angle becomes larger, the retardation decreases in the drawing direction and increases in the orthogonal direction. As a result, when combined with a liquid crystal display panel, if the optical compensation relation is perfect in the normal direction, as the elevation angle becomes larger, the difference between the retardation of the phase difference plate and the retardation of the liquid crystal panel becomes larger, and the optical compensation relation collapses. In other words, a color change occurs, and the contrast ratio is lowered, and therefore the viewing angle is narrowed.

Liquid crystal display device with positive and negative compensating films each with its optical axis parallel to the surface


A document image management system and associated method for integrating the operations of various independent software applications and the reuse of data entries within an enterprise, to increase productivity and promote a flexible method for the visualization of complete and coordinated information contained on a plurality of form pages. To this end, the system and method use an electronic checklist that enables the automated population of data fields in the checklist, and the reuse of the collected data in other applications. The system further includes additional tools that use the knowledge information to enable an efficient use of the knowledge within an enterprise, including the ability to develop a context for, and visualization of such knowledge.

Corporate entities typically collect, manage, and review massive amounts of information electronically on a daily basis. Such information is comprised of structured, numerical data, and unstructured text documents, wherein separate data entry forms often require duplicate information within their fields, such as "customer name," "customer number," "customer address," and so forth.
These processes are usually cumbersome and error-prone due to manual updates to related data and documents. The high error rates are caused by missing or wrong key information (e.g., customer number). In addition, there may be data inconsistencies. For example, a customer's name may not match the customer's assigned number.
These processes also tend to be user-unfriendly, hampering workflow and decision making due to their lack of integrating textual and numerical information. They further lack in efficiency, since duplicate information fields are entered and re-entered manually. Re-keying of certain data, such as customer number or contract number, in an order entry or contract management application, presents another set of issues, namely reduced productivity and increased possibility of data entry errors.
Furthermore, these processes are inflexible in handling data changes during the information gathering stage. A minimal change, for instance, to the "customer name" may induce a series of changes everywhere the "customer name" field appears in the document, requiring modifications of yet other relational documents.
It would therefore be desirable to have a system that addresses and resolves these concerns.

System and method for facilitating document imaging requests


A method and system for containing escaping hydrocarbon fluid from a well pipe of a production well. Suppression of the hydrocarbon fluid to a level below the breach location using a control fluid allows the breach to be repaired through the installation of a containment sleeve at the location of the breach. After collecting the escaping hydrocarbon fluids with a containment sleeve, the hydrocarbon fluid is routed to a collection reservoir from which it may be easily recovered without causing environmental damage. This process occurs with minimal downtime of the production well with the added environmental benefit of remediation of earth contaminated by the hydrocarbon breach.

1. Field of the Invention.
The present invention relates to the field of crude oil production and, more specifically, to a system and method for collecting hydrocarbon fluid that is escaping through a breach in a well pipe of a hydrocarbon producing well. The terms "hydrocarbon producing well," "hydrocarbon well," "oil well," and "well" are used synonymously in this application.
2. Background of the Invention.
A typical hydrocarbon production well includes a production pipe nested within a casing pipe that provides support to the borehole of the well. While the production pipe communicates hydrocarbons to the surface, surrounding casing pipes primarily serve to reinforce the main borehole. Casing pipe, or casing, is an essential component of the well completion. For example, the casing prevents the formation wall from caving into the wellbore. Moreover, the casing provides a way for a well operator to control formation fluids and pressure as the well is drilled. A casing pipe must operate in a difficult environment and is subjected to a variety of forces and corrosive chemicals.
Generally, the production pipe and casing pipes are made of steel, which is susceptible to oxidation and corrosion over time that may cause the oil well to leak hydrocarbon fluids or gases through the casing pipes and into the surrounding earth. These leaked hydrocarbons may eventually surface at ground level and, as they move through the earth, cause a harmful environmental impact to surface and underground water and soil, as well as wildlife, during migration to the surface. Furthermore, any leaking oil translates to lost revenue and reduced efficiency of the well, especially when is a large volume of producer. Not surprisingly, the larger the breach in a casing pipe, the more revenue is lost.
Traditional methods for addressing this problem required the well operator to stop production and withdraw the leaking casing or production pipe from the well to seal the breach. Not only is this undesirable because of the lost revenue due to a production stop, but this can potentially create an economic disincentive for even repairing the smaller leaks; in other words, it may be more profitable to continue production despite the presence of a small leak in the casing rather that cease producing long enough to repair the leak. Such economic disincentive may make economic sense, but would not make environmental sense, as the surrounding earth, nearby water sources, and the wildlife ultimately pay a heavy price.
A review of the prior art in the field reveals other attempts at maintaining the integrity of well casing. Some inventions merely test the physical integrity of the production tubing or casing without repairing the breach. For example, U.S. Pat. No. 5,267,469 provides a method for testing the physical integrity of casing by applying a test pressure to the inner annular space of the wellbore and monitoring the test pressure for a pressure drop. By measuring the pressure in a sealed-off portion of the well annulus—the area between the production tubing and casing—and applying a known test pressure, the pressure can be monitored. Any drop in the test pressure indicates a breach in either the production tubing or the casing. The patent makes no provision, however, for repairing any such breach.
U.S. Pat. No. 3,194,310 discloses both locating and repairing the leak. A breakable capsule containing a sealing compound is disposed into the well to the position of the breach. After sealing the tubing both above and below the breach, the capsule is broken to allow the sealant to flow around the tool and be contained between the seals. Importantly, however, the production tubing must be removed from the well—and thus production substantially disrupted—to use the tool and method taught to seal a breach in the casing pipe.
Similarly, U.S. Pat. No. 3,364,993 also teaches a method of well casing repair in which the method of repairing a leak in a well pipe comprises placing an expansible patch around the breach, inflating the patch by injecting fluid into the patch to expand and set the patch against the breach. As with U.S. Pat. No. 3,194,310, though, this method disrupts the production piping within the well.

System and method for collecting escaping hydrocarbons from a breached well pipe


A radiation image-pickup device includes: a plurality of pixels each configured to generate signal charge based on radiation; and a field effect transistor used to read the signal charge from each of the plurality of pixels, wherein the field effect transistor includes a semiconductor layer including an active layer and a low concentration impurity layer formed to be adjacent to the active layer, and a first and a second gate electrode disposed to face each other with the active layer interposed therebetween, and one or both of the first and the second gate electrodes are provided in a region not facing the low concentration impurity layer.

The present disclosure relates to a radiation image-pickup device suitable for, for example, X-ray photography for medical application and nondestructive inspection, and to a radiation image-pickup display system using such a radiation image-pickup device.
Radiation image-pickup devices obtaining an image signal based on, for example, radiation such as X-rays have been proposed (for example, see Japanese Unexamined Patent Application Publication Nos. 2008-252074 and 2004-265935).

Radiation image-pickup device and radiation image-pickup display system

Sony Semiconductor Solutions Corporation


A semiconductor film formation device has: a reaction vessel that includes a gas flow path to allow source gas to pass through and a substrate mount site provided in the gas flow path to mount a substrate; a temperature control means that is disposed opposite to the substrate mount site and close to the reaction vessel to control the internal temperature of the reaction vessel; and a thermal conductivity adjusting member that is disposed between the reaction vessel and the temperature control means. The thermal conductivity adjusting member has a section with a thermal conductivity different from the other section along the gas flow path.

1. Field of the Invention
The invention relates to a semiconductor film formation device and, particularly, to a semiconductor film formation device that is provided with a temperature control means to control the internal temperature of reaction vessel to offer a good evenness in film thickness and composition ratio.
2. Description of the Related Art
Conventionally, the CVD (chemical vapor deposition) method is used to grow a semiconductor film on the surface of a wafer. In the CVD method, source gases supplied into a reaction vessel react with each other on the surface of a substrate disposed in the reaction vessel and its reacted product is deposited on the substrate while being grown as a semiconductor film. It is desired that the semiconductor film thus produced has a good evenness in thickness, composition and impurity distribution. Such evenness is influenced by conditions of gas flow and temperature distribution in the reaction vessel. Thus, it is important to finely control these conditions to have a semiconductor film with good evenness.
Japanese patent application laid-open No. 4-132213 discloses a semiconductor film formation device that the internal temperature distribution of reaction vessel is controlled by providing pipes for coolant in the wall of reaction vessel and by separately setting the temperature or flow rate of coolant to be supplied through the pipes.
However, the conventional semiconductor film formation device has problems as below.
The device is complicated in its structure since it needs to provide pipes for coolant in the wall of reaction vessel. Therefore, the manufacturing cost must be increased.
Further, the device is complicated in its operation since it needs to separately set the temperature or flow rate of coolant to be supplied through the pipes. Therefore, the operating or maintenance cost must be increased.


In an analytical instrument having a radiation detector, such as an electron microscope with an X-ray detector, a thermoelectric element (such as one or more Peltier junctions) is driven by a cooling power supply to cool the detector and thereby decrease measurement noise. Oil condensates and ice can then form on the detector owing to residual water vapor and vacuum pump oil in the analysis chamber, and these contaminants can interfere with measurement accuracy. To assist in reducing this problem, the thermoelectric element can be powered in the reverse of its cooling mode, thereby heating the detector and evaporating the contaminants. After the detector is cleared of contaminants, it may again be cooled and measurements may resume. Preferably, the thermoelectric element is heated by a power supply separate from the one that provides the cooling power, though it can also be possible to utilize a single power supply to provide both heating and cooling modes.

Various instruments for analyzing the characteristics of materials rely on sensors for at least a portion of their measurement operations, with these sensors being chilled to low temperatures to enhance measurement accuracy (e.g., by decreasing electronic "noise"). As an example, electron microscopes often include an X-ray detector (such as a silicon sensor) mounted at the end of an elongated probe or other mount, often called a "cold finger," which is situated next to a specimen to be analyzed. The cold finger is chilled to cryogenic (ultralow) temperatures, usually by a Dewar system utilizing liquid nitrogen coolant, though some systems use a standard refrigeration cycle for cooling (i.e., evaporative cooling). Additionally, one provider (Thermo Electron, Madison, Wis., USA) has long provided thermoelectric (Peltier) cooling of detectors. During operation, as the specimen is bombarded by electrons from the microscope's electron beam, it emits X-rays which are picked up by the detector. The detector measurements can be processed to provide information regarding the specimen's material and other characteristics.
These arrangements suffer from the unfortunate disadvantage that while cooling of the detector enhances measurement quality, cooling also increases the possibility that the detector will be fouled (and its measurements skewed) owing to water/oil condensation, and ice formation, on the cooled detector. Moisture and oil are often present in the analysis chamber wherein the specimen and detector are located, with the oil originating from the vacuum pumping system. While they can be diminished by steps such as evacuating the analysis chamber so the specimen and detector are in vacuum (a common step), ice and oil condensates still tend to collect on the detector owing to factors such as residual gas within the analysis chamber and moisture release from the specimen. Some detectors and mounts are partially insulated from the analysis chamber by a surrounding shell about the mount and/or a window between the chamber and the detector; however, even these arrangements tend to accumulate ice and oil on the shell and/or window. Additionally, while windows help protect detectors from contamination, they can also block lower-energy emissions that could otherwise be usefully detected by the detector.
As discussed in U.S. Pat. Nos. 4,931,650 and 5,274,237, the foregoing difficulties have led to the development of a variety of corrective devices and methodologies. Both patents describe the use of periodic warm-up cycles wherein the mount and detector are allowed to warm up to drive off water. U.S. Pat. No. 4,931,650 assists such a procedure by incorporating a resistive heater for warming the detector, and U.S. Pat. No. 5,274,237 has a portion of the analysis chamber about the detector at a cooler temperature so that the bulk of any ice will form away from the detector. However, it would be useful to have further arrangements available for avoiding detector ice contamination in electron microscopes and other analytical instruments.

Deicing of radiation detectors in analytical instruments

Thermo Electron Scientific Instruments LLC


A method and apparatus for transferring a pre-molded film into a cavity by the following steps. A robotically controlled arm having a loader receives flexible film. The loader by two moveable end portion and a main portion there between. The pre-molded film is transferred onto the loader. The end portions are retracted so that the loader is in a retracted position. The loader is moved to a position within a cavity. The cavity has an opening that is larger then the loader when the loader is in the retracted position. The film is transferred to the cavity by aligning the film with corresponding three-dimensional contours on the cavity. The edge portions are extended so that essentially the entire surface of the film contacts the cavity. The loader is withdrawn from the cavity by first retracting the end portions and removing the loader.

1. Field of the Invention
Present invention is directed to a method and apparatus for transferring a pre-molded film into a mold. More specifically, the present invention is directed to providing a robotically controlled moveable arm to transfer a flexible, pre-molded film into an injection-molding tool.
2. Description of the Related Arts
It is known to manufacture injection molded articles in an injection molding press. Generally, the robotically controlled arm manipulates a device called an unloader to remove articles manufactured in the press. The unloader secures the molded article by vacuum and lifts the molded article from the core portion of the mold.
It is also known to manufacture molded articles using flexible films wherein the film is placed within a mold cavity and a polymer is injected behind the film to heat and soften the film backing. The film backing fuses to the polymer to form a molded article. An example of this type of method is taught in U.S. Pat. No. 3,668,034. One difficulty in manufacturing molded articles using pre-molded flexible films, is properly positioning the flexible film within the molds so that it is free of wrinkles or creases and is precisely positioned in the cavity to register with the cavity contours to form the desired article. Heretofore, proper placement of the pre-molded film within the cavity has been a major stumbling block to widespread application of pre-molded films. The problem is especially acute when handling thin pre-molded films for large automotive applications such as bumper facias, instrument panels and door panels. The entire surface area of the film must be properly positioned within the cavity to produce a defect-free article. Slight misalignments will cause wrinkles or defects and make the article unusable.
It is necessary to precisely place the film between the operable core and cavity pieces of a molding press. Because these operable pieces open and close, it is advantageous to provide a mechanism which allows the pre-molded film to be robotically placed within the mold rather then manual placement by an operator. It is a further desired result of the present invention to utilize the existing equipment for removing the molded article from the core, in the method for placing the pre-molded film within the mold. It is also desired that the method and apparatus utilize existing molding equipment to the maximum extent possible. This includes utilizing a mold press and core with a limited opening there between. It is further desirable to manufacture an article in a tool that is subject to "die-lock" conditions. Die-lock conditions occur when the molded article has a dimension greater than the opening of the mold. Die-lock prevents the article from being removed from the cavity after the molding operation. Utilizing die-lock conditions enables the manufacture of parts with covered edge portions or flanges.
A variety of methods are known for removing articles from molds that are subject to die-lock, however, a method of placing flexible films within a cavity that is subject to die-lock has not been shown. It is yet another desired object of the present invention to provide a method and apparatus for placing a pre-molded film into a cavity that is subject to die-lock conditions. It is further desirable to precisely position a pre-molded film within a cavity so that edge portions are placed within the cavity and a flange portion is formed behind the edge portion.
It is known to form a covered edge using in-mold films. An example of this construction is illustrated in U.S. Pat. No. 5,599,608. A film having a re-entrant edge portion is placed within a mold. A cavity is moved to contact the core. The core engages the re-entrant portions and folds them within the cavity. Molten plastic is injected into the cavity and the combination of closing the mold combined with the pressure the molten plastic material forces the re-entrant edge portions against the cavity wall to form the covered edge of the molded article. The method described in U.S. Pat. No. 5,599,608 is limited to forming an edge portion having a width equal to the thickness of the substrate. This is useful when forming a part having a covered edge, but not useful when forming a part having a covered flange portion. A flange creates a space behind the flange known as an undercut. The U.S. Pat. No. 5,599,609 patent does not teach forming parts having an undercut.
These deficiencies and problems are overcome by the present invention.

Method of transferring a pre-molded film into a mold


A voting server transmits a list of plaintext and encrypted voting data obtained by encrypting the plaintext to a voter terminal, and the voter terminal a selected encrypted candidate name corresponding to the plaintext elected by the voter to an encryption server. The encryption server returns encrypted voting data obtained by re-encrypting the encrypted candidate name to the voter terminal, and the voter terminal transmits the encrypted voting data received from the encryption server for voting. Decryption of the encrypted voting data is performed by an anonymous decryption system. The voter terminal certifies the voter to an authentication server, and affixes a digital signature to the encrypted voting data based on a common-key authentication base, transmitting the same to the voting server.

An anonymous electronic voting system is a system that electronically realizes uninscribed secret vote effected through a network, fore example. Examples of the conventional anonymous electronic voting system are described in Patent Publication 1 and a non-Patent Publication 1. In the following description, the "vote" includes a vote for electing a candidate from among candidates set beforehand, as well as a questionnaire etc. which allows a free description. In addition, the "candidate" and "candidate name" are directed not only to a candidate and a candidate name in an election, but also to an element (item) or an element name (item name) in a case wherein the element or element name are selected by the intention of the voter from an assembly.
As shown in FIG. 28, a conventional anonymous electronic voting system includes an anonymous decryption system 900 configured by a window center 901 and a plurality of decrypting shuffle centers 902, and a vote management center (voting server) 910 to which each voter will access. The anonymous decryption system 900 is provided in order to keep the secrecy of vote, and is used for outputting the decrypted result while securing secrecy for the correspondence between the voter and the encrypted voting data.
The conventional anonymous electronic voting system having such a configuration operates as follows.
First, the window center 901 and the decrypting shuffle center 902 create public information of the system, such as an encryption key for voting, and transmit the same to the vote management center 910, which notifies each voter of the public information.
After the voting period starts, each voter encrypts own voting contents based on the public information, to create an encrypted voting contents, and also creates a digital signature of the voter, transmitting the encrypted voting contents and the digital signature to the vote management center 910. At this stage, each voter creates the encrypted voting contents and the digital signature in the own client terminal, and transmits the encrypted voting contents and the digital signature to the vote management center 910 from the own client terminal through a variety of networks. The vote management center 910 verifies the received digital signature, examines the voting right of the voter based on the list of electorate names, and accepts the received, encrypted voting contents after confirming that there is no duplication of the vote.
After the voting period expires, the vote management center 910 finishes registration of the votes, and transmits the list of the encrypted voting contents received between the start and the end of the voting period to the window center 901 of the anonymous decryption system 900. The window center 901 decrypts the list of the encrypted voting contents through the decrypting shuffle center 902, permutes the voting contents in the list to obtain the list of plaintext voting contents, and returns the list of the plaintext voting contents to the vote management center 910.
The vote management center 910 tallies (sums up) the voted results based on the list of the plaintext voting contents received from the window center 901.
Patent Publication 1: JP-2002-237810A
Patent Publication 2: JP-2001-251289A
Patent Publication 3: JP-2002-344445A
Non-Patent Publication 1: "Realization of Large-scale Electronic Voting System using Shuffling" on second meeting of Information Processing Society of Japan, March, 2001, by SAKO, Kazue etc. including other six members.

Anonymous electronic voting system and anonymous electronic voting method


The present invention includes a toothbrush having a handle attached to a head. The head may rotate positions relative to the handle to improve brushing of both teeth and tongue of a user.

1. Field of the Invention
This invention relates generally to dental care apparatuses, and particularly relates to a toothbrush having a handle and pivoting head of cleaning elements, such as, for example, bristles, tufts, and the like. Toothpaste is applied to the cleaning elements and then inserted into the mouth of a user in order to brush the user's teeth and tongue.
2. Description of the Related Art
Conventionally, a toothbrush comprises a handle and a head attached to the handle. Sometimes the handle and the head are a single piece, but may be separable as well.
Typically, the head of the toothbrush includes fixed cleaning elements extending outwardly from at least one side of the head of the toothbrush. Throughout the prior art, there have been attempts to alter the flexibility, movement, and form of these cleaning elements.
For example, U.S. Pat. No. 5,491,866 describes an articulate toothbrush having a pivot joint connecting the handle and the head.
U.S. Pat. Nos. 3,214,776 and 5,813,075 disclose a toothbrush having a manual provision for rotating the head of a toothbrush clockwise or counterclockwise relative to the handle. In other words, when looking at the toothbrush from a top view, the head twists clockwise and counterclockwise around longitudinal sides of the handle.
There are additional dental hygiene considerations beyond merely cleaning one's teeth. Many individuals also enjoy cleaning one's tongue. However, the conventional shape of a toothbrush head being substantially rectangular with the longitudinal sides parallel to the toothbrush handle makes it somewhat difficult to properly clean one's tongue. Having the longitudinal sides of the toothbrush head being perpendicular to the handle makes cleaning the tongue easier and more efficient.
A toothbrush head with the longitudinal sides of the toothbrush head being perpendicular to a central axis of the handle makes properly brushing one's teeth difficult though.
Thus, what is desired is a toothbrush in which the head may pivot such that the longitudinal sides of the toothbrush head may be substantially parallel to the handle, substantially perpendicular to the handle, and any desired angle between.


A vehicle fault determination device includes a relay, a vehicle configuration circuit, and a control section. The relay is connected to a power source. The vehicle configuration circuit is supplied with power from the power source via the relay. The control section determines whether the relay is faulty while controlling the relay and the vehicle configuration circuit. The control section includes first and second ports. The first port outputs a control signal to a coil portion of the relay. The second port is connected to a contact portion of the relay via the vehicle configuration circuit. The second port serves as an input port when the fault determination is made and as an operation port when the vehicle configuration circuit is controlled. Thus, the number of parts is keep to a minimum to increase the number of dedicated ports for determining whether the relay is faulty.

1. Field of the Invention
The present invention relates to a vehicle fault determination device. More particularly, to a fault determination method of a relay connected to a power source.
2. Description of Background Art
In a vehicle having an electric actuator, it has been proposed to provide a fail-safe relay between a power source and the electric actuator to positively shut off power in the event of a non-functional condition. Because of its configuration, a relay may become stuck due, for example, to welding of its contact portion. For this reason, a technique has been proposed to determine whether the contact portion is in such a non-functional condition. See, for example, Japanese Patent No. 3097723.
To provide a relay, a signal output is required to control the operation thereof. As a result, a control section needs an output port to control the relay. To determine whether the relay is faulty, an input port is required in addition to the output port. The input port is used to receive a signal that indicates the ON/OFF state of the relay during a fault determination test. The number of ports that can be accommodated in the control section is limited. Increasing the number of dedicated ports restricts the degree of freedom in designing the control section.


In various embodiments, a secure optical communication system is disclosed. Such a system may include a photon-pair generation circuit configured to generate pairs of photons with each photon pair including a first-channel photon and a second-channel photon, a transmitting circuit configured to receive first-channel photons, and modulate the first-channel photons according to a stream of data using a first optical circulator to produce first-modulated photons, and a receiving circuit configured to receive second-channel photons, pass the second-channel photons through a complementary optical circulator to produce second modulated photons, and detect relative timing between the first-modulated photons and the second modulated photons to recover the stream of data.

1. Field
This disclosure relates to secure optical communications systems.
2. Background
Secure communication systems are a cornerstone of government, business and military interests. Generally, secure communications are established by applying an encryption to a given message to produce an encrypted message, transmitting the encrypted message to a remote location, and decrypting the encrypted message at the remote location.
Unfortunately, the encryption and decryption processes can be computationally expensive, and they are by no means absolutely secure. Further, increasing the level of encryption involves increasing the level of computation and decreasing data transmission efficiency.
Regardless of whatever level of encryption may be used, a threat to the security of any transmitted information may be posed by the possible construction of a quantum computer. If such a computer is eventually constructed, then a known algorithm may be run on such a computer that will enable the computer to "break" virtually every modern data encryption technique in a very short time. Thus, new technology directed to secure data communications may be desirable.

The United States of America as represented by Secretary of the Navy


A utility vehicle comprising a device for displaying a portion on a screen, the portion being concealed by an object at least in part, and the object being arranged between the portion and a vehicle driver and the screen being arranged between the vehicle driver and the object, the portion being in a region that is recorded by a camera setup, the device having a determination device that is provided and set up to determine a position of at least one eye of the vehicle driver and a position of the screen, the determination device determining the position of the portion in the recorded region using the position of the eye and the position of the screen, and this portion being represented by the screen.

Camera systems are known from the prior art, particularly from security technology or surveillance technology, by means of which, regions that are to be monitored can be displayed on monitors and thus monitored. However, in this case, not only a concealed part of the recorded region is displayed, but rather the entire recorded region. Likewise, no field of application in the agricultural sector for making regions that are concealed—for example by accessory equipment or parts of the vehicle—visible to a vehicle driver, is known from the prior art.

Device and method for displaying regions including a portion on a screen that is concealed by an object


A serial multiplier for multiplying two n-bit numbers is provided in which a shift register having a total of n destructive read out cells contains a separate bit of a first multiplicand in each cell. A string of (2n-1) non-destructive read out cells is provided to receive the second multiplicand. Each of the first n cells of the string of non-destructive readout cells contain a separate bit of the second multiplicand. Each bit of the first multiplicand is serially multiplied with the series of bits of said second multiplicand. After each such multiplication, each bit of the second multiplicand is moved to the next adjacent cell. The partial product of the multiplication is stored in a string of 2n T flip-flop cells. Each of the T flip-flop cells has a carry path to the next adjacent T flip-flop cell. Timing means are provided to regulate and initiate the multiplication.

1. Field Of The Invention
The present invention relates to the field of multiply-accumulators, and more particular, to the field of multiply-accumulators utilizing single-flux-quantum logic circuits.
2. Description of Related Art
High speed digital signal processing is becoming increasingly important for advanced electronic applications. High speed digital signal processing is crucial for the realization of digital bandpass interpolation filters for wide band rf systems. Josephson-junction based logic offers the potential for orders of magnitude improvement in both speed and power over equivalent semiconductor based circuits.
By utilization of a circuit architecture known as Modified Variable Threshold Logic (MVTL), an 8-bit processor was capable of operating at clock speeds of up to one gigahertz with 12 mW of power dissipation. In the MVTL circuit architecture, information is stored as voltages across Superconducting Quantum Interference Devices (SQUIDs). Although the performance of the MVTL circuit is impressive, such a circuit does not take full advantage of the inherent speed of Josephson junctions. The operating speed of MVTL circuits is limited by the use of latching gates which require an active reset in switching from a logical "ONE" to a logical "ZERO".
Recently, circuit designs for a logic family have been described in which the binary information is stored as magnetic flux in superconducting loops. Information is transmitted within such a circuit in the form of voltage pulses. Because a single-flux-quantum, .PHI..sub.0 (.PHI..sub.0 =2.07 mV.ps), is used to denote each binary "ONE", this circuit architecture is referred to as Rapid Single Flux Quantum (RSFQ) logic. Clock rates of up to 200 GHz have been projected for such circuits with orders of magnitude improvements in power dissipation over MVTL circuits. In addition, the operating margins of RSFQ circuits are larger than for comparable MVTL circuits.
In Likharev and Semenov, "RSFQ Logic/Memory: A New Josephson-junction Technology for Sub-Terahertz-Clock-Frequency Digital Systems," IEEE Trans. on Applied Superconductivity, Vol. 1, pp. 3-28 (March 1991) an RSFQ serial multiplier is disclosed which is formed of various logic elements including non-destructive readout (NDRO) cells, destructive readout (DRO) cells, and one-bit full adders (FA). A block diagram of this multiplier 10 is shown in FIG. 1.
To multiply two n-bit numbers, A and B, in multiplier 10 [A=(a.sub.n-1, a.sub.n-2, . . . , a.sub.0) and B=(b.sub.n-1, b.sub.n-2, . . . , b.sub.0)], the digits of B are first read into the NDRO cells 12 using a series of timing pulses T.sub.B. Each NDRO cell 12 will contain a separate bit of the B multiplicand. Multiplication is accomplished by multiplying each bit of the A multiplicand with the series of bits of the B multiplicand loaded into the NDRO cells 12. During such multiplication, the state of a.sub.i sets the DRO cells 14. If a.sub.i =1, a pulse is sent to the set inputs of the DRO cells 14. If a.sub.i =0, no pulse is sent. A timing pulse T.sub.A is used to read out the DRO cells 14, with the output (a.sub.i) triggering the NDRO cells 12 in the event a.sub.i =1. In this way, the partial product [p.sub.i =a.sub.i .times. B=(a.sub.i b.sub.n-1 +a.sub.i b.sub.n-2 +. . . +a.sub.i b.sub.0)] is generated in the string of full adders 16.
The pulse T.sub.A also outputs the sum bits of the full adders 16 to redirect the carry bits to inputs on the same adders. The DRO cells 14 are then set by the next bit (a.sub.1) of the A multiplicand and the procedure is repeated. At each pulse T.sub.A, one bit of the product (p.sub.i) emerges from the full adder 16 string. After 2n cycles, the multiplication is complete. Projected performance of multiplier 10 is 0.5 billion multiplications per second for 32-bit.times.32-bit multiplications.
While RSFQ logic offers high-speed and low-power operation, and although all of the required logic elements have been successfully modeled, this architecture still lacks a reliable single-bit full adder 16. Full adders 16 proposed to date have proved to have limited operating margins, particularly for reset. Since the one-bit full adder 16 is a basic building block of a serial multiplier 10, this poses a serious limitation. Consequently, there is a need for a serial multiplier which does not rely on a full adder cell which nevertheless offers the benefits of RSFQ digital processing with added reliability.


In accordance with an embodiment of the present invention, a first asynchronous transfer mode network is provided, adapted to couple with a first entity external to the network, the first entity having a fourth port and a fifth port. The network has a first port. The network also has a second port coupled to the first port by a first permanent virtual connection, and the second port is coupled to the fourth port via a first interface. The network also has a third port coupled to said first port by a second permanent virtual connection, and the third port is coupled to the fifth port via a second interface. Packets are sent between the first port and the second port via the first permanent virtual connection, and between the second port and the fourth port via the first interface until a failure is detected, the failure occurring at the first interface, the second port, or the fourth port. After a failure is detected, packets are sent between the first port and the third port via the second permanent virtual connection, and between the third port and the fifth port via the second interface.

An asynchronous transfer mode network ("ATM network") is made of a plurality of switches, each of which is coupled directly to at least one other switch. The points at which data enters and exits a switch are referred to as "ports."
ATM networks use virtual connections to send data across the network. A virtual connection is basically a path or a circuit between two switches in an ATM network that may be routed through any number of intermediate switches. Before sending a data packet to the next switch along the virtual connection, a switch attaches a header to the data packet that contains a virtual channel identifier and a virtual path identifier ("VCI/VPI"), which allows the next switch along the virtual connection to identify which virtual connection the packet is traversing. The VCI/VPI is unique to a particular virtual connection along a particular leg of the connection, but need not remain constant between different legs, i.e., the VCI/VPI may be changed at each switch.
A virtual connection may be set up for a particular data transmission having multiple data packets, such that each data packet in the transmission is sent along the virtual connection, which is then deactivated once the transmission is complete. Alternatively, a virtual connection may be a permanent virtual connection ("PVC"), which is used for multiple data transmissions.
Failures within an ATM network are typically resolved by a network management system ("NMS"). Each switch in the network is in contact with the NMS, and reports failures to the NMS. When a failure within the network is reported, the NMS reroutes virtual connections around the failure. The NMS may also have the capability to detect failures at the boundary or outside of the NMS's ATM network, but is typically not able to resolve such failures, particularly when networks made by different vendors are involved. Such a failure might occur at an interface, which is used to couple the ATM network to an entity external to the network, or at a port to which the interface is coupled. After such a failure is detected, the NMS may declare the interface and any PVC coupled to the interface in a failed state. Once a failed state is declared, manual intervention may be required to restore the PVC.
As ATM networks grow in popularity and are used in a wider variety of applications, interfaces between ATM networks and entities external to the ATM network are being created and used with increasing frequency. Accordingly, there is an increasing need for a way to resolve failures at these interfaces and the ports to which they are coupled.
Physical layer protection is one method of resolving failures at interfaces between networks, and the ports to which the interfaces are coupled. For example, an active interface between networks may be associated with a second interface reserved for use in case the active interface fails. This second interface may remain inactive until there is a failure, or the same data may be transmitted along both interfaces simultaneously such that a failure in one does not prevent transmission along the other. However, this type of physical layer protection approximately doubles the bandwidth required for a particular data transmission between networks, as it requires one interface to be dedicated to protection for each active interface. Alternatively, a single interface between networks may have a Y-cable or other means of splitting the signal at one or both ends, such that a failure after the split does not prevent transmission. However, this type of physical layer protection also uses excess bandwidth in that it requires four ports, two active and two dedicated to protection, for each active interface. In addition, this type of physical layer protection does not protect against a failure along the interface where the signal is not split.

Asynchronous transfer mode layer automatic protection switching mechanism for ATM permanent virtual connections


In a state where a process gas including SF.sub. 6 and O.sub. 2 is supplied in a chamber, a laser light irradiator provided outside the chamber irradiates a laser light onto a substrate. At the portion of the substrate onto which the laser light is irradiated, the material that makes up the substrate is excited and converted into a gaseous substance by reacting with the process gas. The temperature of the substrate placed on a stage is kept at a predetermined temperature since a temperature adjuster supplies a chiller to a coolant flow passage provided inside the stage.

1. Field of the Invention
The present invention relates to a processing device and a processing method for a substrate such as a semiconductor substrate.
2. Description of the Related Art
A method using a dicing saw which is rotated at a high speed is widely used as a method of applying some process, for example, dividing to a substrate such as a semiconductor substrate. According to this method, a substrate in a state of being adhered on an adhesive sheet is cut by a dicing saw made of a diamond blade, etc.
There is a kind of semiconductor element called MEMS (Micro Electro Mechanical System) element. The MEMS element comprises a mechanical structure which is formed on a surface of a semiconductor substrate in which circuit elements are formed. The MEMS element is used for an electronic component and a mechanical component necessary for many types of electronic systems and electronic optical systems. For example, an optical switching element having a movable cantilever can be cited as the MEMS element.
In the process of manufacturing a component comprising the MEMS element, a chip (die) of the MEMS element is cut out from a substrate by the above-described method, likewise a substrate of an ordinary element. However, a mechanical structure is exposed on the surface of the MEMS element substrate, and this causes the following problems if the above-described conventional processing method is used.
First, in case of a cutting process using a dicing saw, minute cutting dust produced from cutting stick to the mechanical structure, causing a fear that the function of the mechanical structure might be damaged. For example, if minute cutting dust enter a space between a cantilever and the surface of a substrate, the switching function of a switching element might be harmed.
Second, in order to prevent cutting dust from sticking and a substrate from being overheated, pure water is supplied, in the cutting process, to where the substrate and a dicing blade contact each other and therearound. Because of this, the mechanical structure, which is exposed on the surface of the substrate might be damaged by the flow of the water.
Third, the function of the mechanical structure might be damaged by the surface tension of the water when the water evaporates. For example, if a cantilever is stuck on the surface of a substrate, the switching function of a switching element might be damaged.
As described above, in a case where a substrate on which an MEMS element is formed is processed by utilizing the above-described conventional method, there is a danger that the mechanical structure exposed on the surface of the substrate and its function might be damaged. This might damage the reliability of substrate processing, and cause a decrease in the yield.
Problems similar to those described above happen not only when processing an MEMS element substrate, but also applying a process such as cutting to a substrate on whose surface a fine structure is formed.

Substrate processing device and processing method


The binding specificity of the murine OKT3 has been transferred into a human antibody framework in order to reduce its immunogenicity. This "humanized" anti-CD3 mAb (gOKT3-5) was previously shown to retain, in vitro, all the properties of native OKT3, including T cell activation which has been correlated, in vivo, with the severe side-effects observed in transplant recipients after the first administration of the mAb. Disclosed is a single amino acid mutation from a leucine to a glutamic acid at position 235 in the Fc receptor (FcR) binding segment of the gOKT3-5 mAb to produce Glu-235 mAb. Also disclosed is an amino acid mutation from the contiguous phenylalanine at position 234 to a leucine (Leu-234).

OKT3 is a murine monoclonal antibody (mAb) which recognizes an epitope on the .epsilon.-subunit within the human CD3 complex (Salmeron, 1991; Transy, 1989; see also, U.S. Pat. No. 4,658,019, herein incorporated by reference). In vitro studies have demonstrated that OKT3 possesses potent T-cell activating and suppressive properties depending on the assay used (Landgren, 1982; Van Seventer, 1987; Weiss, 1986). Binding of OKT3 to the T-cell receptor (TcR) results in coating of the TcR and or modulation, thus mediating TcR blockade, and inhibiting alloantigen recognition and cell-mediated cytotoxicity. Fc receptor-mediated cross-linking of TcR-bound anti-CD3 mAb results in T-cell activation marker expression, and proliferation (Weiss, 1986). Similarly, in vivo administration of OKT3 results in both T-cell activation and suppression of immune responses (Ellenhorn, 1992; Chatenoud, 1990). Repeated daily administration of OKT3 results in profound immunosuppression, and provides effective treatment of rejection following renal transplantation (Thistlethwaite, 1984).
The production of an immune response to rodent mAbs is a major obstacle to their therapeutic use. Several groups have reported attempts to circumvent this problem by reconstructing the rodent antibody genes by replacing immunogenic murine constant region sequences by the equivalent human antibody sequences (reviewed in Adair, 1992). In cases such as these, there is still the potential to mount an immune response against the variable region. In a further extension of the procedure, the variable region framework regions have been replaced with equivalent sequences from human variable region genes. From an examination of available X-ray structures of antigen-antibody complexes (reviewed in Poljak, 1991) it is probable that only a small number of antibody residues make direct contact with antigen. Other amino acids may contribute to antigen binding by positioning the contact residues in favorable configurations and also by inducing a stable packing of the individual variable domains, and stable interaction of the light and heavy chain variable domains. The antibody domains have been the subject of detailed examination and much has been published about the organization of the variable regions (see for example, Looney, 1986, and references therein) which can be applied to the design of the humanized antibody.
The use of OKT3 is limited by problems of "first dose" side effects, ranging from mild flu-like symptoms to severe toxicity, which are believed to be caused by lymphokine production stimulated by OKT3. Although successful reuse of OKT3 has been reported (Woodle, 1991) it is complicated by a human anti-mouse antibody (HAMA) response (Ortho Health Center Transplant Study Group, 1985), a proportion of the response being directed to the variable region of the antibody (Jaffers, 1984). While low titre HAMA may present no significant problem, some patients do develop high titre anti-isotype and/or anti-idiotype responses. These can result in specific inactivation and/or the rapid clearance of the drug.
Early data on the utility of chimeric antibodies (Morrison, 1984) in which the coding sequences for the variable region of the mAb are retained while the coding sequences for the constant regions are derived from human antibody, suggests that the HAMA response may indeed be reduced; however, a HAMA response to the murine variable region may still emerge (reviewed by Adair (Adair, 1992)) and more recently the humanization process has been taken further by substituting into a human antibody those amino acids in the variable regions believed to be involved in antigen binding to give a fully humanized antibody (Reichman, 1988).
A major concern is that the humanized antibody will still be immunogenic because of the presence of the non-CDR residues which need to be transferred in order to regenerate suitable antigen binding activity, in addition to any antiparatope antibodies that may be generated. To date two humanized antibodies, CAMPATH-1H and Hu2PLAP, have been administered to patients (LoBuglio, 1989). Both of these antibodies used the rodent amino acid sequences in complementarity determining regions (CDRs) as defined by Kabat (1987), along with the rodent framework residues at position 27, where the amino acid is buried, and position 30 where the residue is predicted to be solvent accessible near CDR1. In both cases no specific immune response to initial treatments with the administered antibody was noted, although responses to a second course of treatment was seen in one study using CAMPATH-1H for the treatment of rheumatoid arthritis (Frenken, 1991). There have been no reported clinical studies using humanized antibodies in which other non-CDR solvent-accessible residues have also been included in the design.
The interactions of various cell surface proteins such as T-cell receptor/CD3 complex (TCR/CD3), MHC, CD8, ED45 and CD4 have been shown to be important in the stimulation of T-cell responses (Floury, 1991, Swartz, 1985, Strominger, 1980, Weiss, 1988). Two of these molecules, CD4 and CD3 have been found to be physically associated on the T-cell (Saizawa, 1987, Anderson, 1988, Rojo, 1989, Mittler, 1989, Dianzani, 1992). This association is critical to T-cell receptor mediated signal transduction, in part due to their associated kinase and phosphatase activities (Ledbetter, 1990). Molecules which can interrupt or prevent these interactions (i.e. antibodies) are currently recognized as therapeutically useful in the treatment of kidney allograft rejection (Ortho Multi Center Transplant Group, 1985). A modification of antibody treatment, one in which several of the T-cell surface proteins are directly bound together by one antibody might prove useful in current immunotherapy protocols. In addition to blocking cell adhesion or cell to cell interaction, antibodies which are capable of cross-linking several cell surface proteins may result in stimulation of T-cell activity or induction of aberrant signalling, and thus produce modulation of the immune response (Ledbetter, 1990).
Bringing together molecules involved in T-cell activation such as CD3 and CD4, or CD3 and CD8, may be a potent method for immunoactivation. Previous studies have shown that cross-linking CD3 and CD4 with heteroconjugates composed of anti-CD3 and anti-CD4 antibodies result in a greater stimulation of Ca.sup.2+ flux than that observed with CD3 cross-linked to itself or simultaneous cross-linking of CD3 and CD4 by separate reagents (Ledbetter, 1990). Similarly, cross-linking CD3 and CD8 with immobilized antibody mixtures resulted in synergistic effects on T-cell proliferation and interleukin 2 (IL-2) receptor expression (Emmrich, 1986 and 1987). These studies taken together point to a critical role for the interaction of CD3 with CD4/8 in T-cell activation.
The immunomodulatory effect of cross linking various T-cell surface molecules can be both immunosuppressive and immunostimulatory. Linkage of CD4 with itself or other T-cell surface molecules has been shown to result in a different pattern of protein phosphorylation compared to cross-linking CD3 to itself (Ledbetter, 1990). This aberrant signalling may result as a consequence of binding both CD3 and CD4 simultaneously by a single cross-linking reagent. Previous studies have shown that pretreatment of T-cells with antibody to cross-link CD4 to itself before anti-CD3 treatment inhibits T-cell activation and promotes apoptosis (Newell, 1990). These results would argue that a reagent that crosslinks CD4 with CD3, or other T-cell surface molecules, could be a potent immunosuppressant by virtue of inappropriate signalling through the TCR/CD3 complex.

Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies