A polymeric piezoelectric material including a polylactic acid molded article having been uniaxially drawn to an extent causing no fibrillation. The piezoelectric material exhibits piezoelectric properties equal to or higher than those of electret type or polypeptide type piezoelectric materials while having high enough mechanical strength to be processed into various articles ranging from films to profiles depending on the end use.

Known piezoelectric polymers include a polypeptide type, such as poly(.gamma.-benzyl L-glutamate); an electret type, such as polyvinyl chloride; and a ferroelectric substance type, such as polyvinylidene fluoride, a vinylidene fluoridetrifluoroethylene copolymer, and a vinylidene cyanide-vinyl acetate copolymer. The most typical among them is a film of polyvinylidene fluoride, which has already been put to practical use in ultrasonic transducers (see JP-A-55-151896 and JP-A-56-112200 (the term "JP-A" as used herein means an "unexamined published Japanese patent application")).
Polyvinylidene fluoride, a vinylidene fluoridetrifluoroethylene copolymer, and a vinylidene cyanide-vinyl acetate copolymer, which are synthetic polar piezoelectric polymers of the ferroelectric substance type, are oriented by drawing and the application of an electrical field. The mechanism of retention is spontaneous polarization or freeze-polarization, and the orientation state is uniaxial polar orientation. A drawing treatment and a polarizing treatment are required before these materials exhibit piezoelectric properties. In particular, polyvinylidene fluoride has the highest piezoelectric properties. However, it has a dielectric constant of 13, which is relatively high as compared with other polymeric materials, so that the piezo g-constant (open circuit voltage per unit stress) obtained by dividing a piezo d-constant by a dielectric constant is not so great. Therefore, it has somewhat poor sound-to-electricity transformation efficiency, although it has satisfactory electricity-to-sound transformation efficiency.
Films of electret type polymers, such as polyvinyl chloride, are endowed with piezoelectric properties by orientation of the polar groups by polarizing treatment. Piezoelectricity of these materials is not as high as the polymers of the ferroelectric substance type.
To the contrary, artificial oriented films of naturally-occurring polymer-related substances, such as poly(.gamma.-benzyl L-glutamate) which are of the polypeptide type, DNA, and polyhydroxybutyrate, have their orientation controlled by dynamic drawing. The mechanism of retention is a crystal structure, and the state of orientation is uniaxial orientation with no polarity. These films exhibit piezoelectric properties without being subjected to polarizing treatment in such a manner that polarization takes place in the z direction upon application of shear in the xy directions. However, since they have a molecular structure in which a main chain helix is surrounded by a long side chain, their piezoelectric properties are of the relaxation type and are not so strong. Further, since the mechanical strength of these materials themselves is insufficient, it is difficult to obtain rigid piezoelectric materials of irregular shape.
With respect to the artificial oriented film of polyhydroxybutyrate, there is a research report that piezoelectricity of the film wound around a fractured part of a bone is advantageous of for acceleration of the initial ossification (Shigeru Harada, et al., The 12th Research Meeting on Bone and Electrical Stimulation, No. 8 (1985)). However, the fact that the film has small piezoelectric constants d'.sub.14 of about 1.3 (pC/N) and e'.sub.14 of 3.5 to 4.0 (mC/m.sup.2) at room temperature and 10 Hz leaves doubt as to whether the piezoelectricity of the film makes a true contribution to the ossification in the initial stage. Even if it does, it seems that a remarkable effect on the acceleration of ossification would hardly be produced. Further, the artificial oriented film of polyhydroxybutyrate so slowly degrades in a living body that it remains unabsorbed for a long time even after a fracture completely heals. Besides, the safety of polyhydroxybutyrate in a living body has not yet been confirmed.


Various methods and systems for calculating ranks of importance of nodes of an enterprise are described. A plurality of relations may be accessed, wherein each relation of the plurality of relations comprises an indication of two nodes of a plurality of nodes, and an indication of a relationship between the two nodes. A matrix may be created using the plurality of relations. The matrix may be processed using the Perron-Frobenius theorem. The plurality of nodes of the enterprise may be ranked according to importance, wherein each node is either a user or an item.

When a person uses a search engine, she may be looking for specific topics, files, or persons, to name only a few examples. Whether she is searching the Internet, a hard drive, or an enterprise's network, many results may be provided to the person. While these results may be in some way related to the search terms provided by the person, the results may contain at least some obscure recommendations that are unlikely to be desired by the person. One possible way of providing more relevant results is by organizing or filtering the results according to a calculated level of importance of each result. Therefore, a result determined to have a higher importance level may be presented to the person ahead of a result that has a lower importance level.


A novel method of treating and preventing diseases is provided. In particular, compositions and methods of blocking diseases associated with aberrant levels of nitric oxide and facilitated by a serine proteolytic (SP) activity are disclosed, which consist of administering to a subject a therapeutically effective amount of a compound having a serine protease inhibitory activity. Among effective compounds are xcex11-antitrypsin and synthetic drugs mimicking some or all of the actions of xcex11-antitrypsin.

The present invention relates to compositions and methods for inhibition of nitric oxide (NO), and to therapeutic treatment of diseases or disorders that involve inappropriate or detrimental NO activity. Thus, the invention relates to modulation of cellular activities, including macrophage activity, endothelial cell function, and the like. The present invention also relates to substances exhibiting inhibitory activity toward nitric oxide-associated diseases, which are facilitated by serine protease activity. More particularly, the inhibitory compounds comprise naturally occurring and man-made serine protease inhibitors and antagonists.
2.1. Serine Proteases
Serine proteases serve an important role in human physiology by mediating the activation of vital functions. In addition to their normal physiological function, serine proteases have been implicated in a number of pathological conditions in humans. Serine proteases are characterized by a catalytic triad consisting of aspartic acid, histidine and serine at the active site.
The naturally occurring serine protease inhibitors are usually, but not always, polypeptides and proteins which have been classified into families primarily on the basis of the disulfide bonding pattern and the sequence homology of the reactive site. Serine protease inhibitors, including the group known as serpins, have been found in microbes, in the tissues and fluids of plants, animals, insects and other organisms. Protease inhibitor activities were first discovered in human plasma by Fermi and Pemossi in 1894. At least nine separate, well-characterized proteins are now identified, which share the ability to inhibit the activity of various proteases. Several of the inhibitors have been grouped together, namely xcex11-proteinase inhibitor, antithrombin III, antichymotrypsin, C1-inhibitor, and xcex12-antiplasmin, which are directed against various serine proteases, i.e., leukocyte elastase, thrombin, cathepsin G, chymotrypsin, plasminogen activators, and plasmin. These inhibitors are members of the xcex11-proteinase inhibitor class. The protein xcex12-macroglobulin inhibits members of all four catalytic classes: serine, cysteine, aspartic, and metalloproteases. However, other types of protease inhibitors are class specific. For example, the xcex11-proteinase inhibitor (also known as (xcex11-antitrypsin or AAT) and inter-alpha-trypsin inhibitor inhibit only serine proteases, xcex11-cysteine protease inhibitor inhibits cysteine proteases, and xcex11-anticollagenase inhibits collagenolytic enzymes of the metalloenzyme class.
Human neutrophil elastase (NE) is a proteolytic enzyme secreted by polymorphonuclear leukocytes in response to a variety of inflammatory stimuli. The degradative capacity of NE, under normal circumstances, is modulated by relatively high plasma concentrations of xcex11-antitrypsin. However, stimulated neutrophils produce a burst of active oxygen metabolites, some of which (hypochlorous acid for example) are capable of oxidizing a critical methionine residue in xcex11-antitrypsin. Oxidized xcex11-antitrypsin has been shown to have a limited potency as a NE inhibitor and it has been proposed that alteration of this protease/antiprotease balance permits NE to perform its degradative functions in localized and controlled environments.
xcex11-Antitrypsin is a glycoprotein of MW 51,000 with 417 amino acids and 3 oligosaccharide side chains. Human xcex11-antitrypsin was named anti-trypsin because of its initially discovered ability to inactivate pancreatic trypsin. Human xcex11-antitrypsin is a single polypeptide chain with no internal disulfide bonds and only a single cysteine residue normally intermolecularly disulfide-linked to either cysteine or glutathione. The reactive site of xcex11-antitrypsin contains a methionine residue, which is labile to oxidation upon exposure to tobacco smoke or other oxidizing pollutants. Such oxidation reduces the biological activity of xcex11-antitrypsin; therefore substitution of another amino acid at that position, i.e. alanine, valine, glycine, phenylalanine, arginine or lysine, produces a form of xcex11-antitrypsin which is more stable. xcex11-Antitrypsin can be represented by the following formula:
Ciliberto, et al. in Cell 1985, 41, 531-540. The critical amino acid sequence near the carboxyterminal end of xcex11-antitrypsin is shown in bold and is pertinent to this invention.
The C-terminus of human xcex11-antitrypsin is homologous to antithrombin (ATIII), antichymotrypsin (ACT), C1-inhibitor, tPA-inhibitor, mouse anti-trypsin, mouse contrapsin, barley protein Z, and ovalbumin. The normal plasma concentration of ATT ranges from 1.3 to 3.5 mg/ml although it can behave as an acute phase reactant and increases 3-4-fold during host response to inflammation and/or tissue injury such as with pregnancy, acute infection, and tumors. It easily diffuses into tissue spaces and forms a 1:1 complex with a target protease, principally neutrophil elastase. Other enzymes such as trypsin, chymotrypsin, cathepsin G, plasmin, thrombin, tissue kallikrein, and factor Xa can also serve as substrates. The enzyme/inhibitor complex is then removed from circulation by binding to serpin-enzyme complex (SEC) receptor and catabolized by the liver and spleen. Humans with circulating levels of xcex11-antitrypsin less than 15% of normal are susceptible to the development of lung disease, e.g., familial emphysema, at an early age. Familial emphysema is associated with low ratios of xcex11-antitrypsin to serine proteases, particularly elastase. Therefore, it appears that this inhibitor represents an important part of the defense mechanism against attack by serine proteases.
xcex11-Antitrypsin is one of few naturally occurring mammalian serine protease inhibitors currently approved for the clinical therapy of protease imbalance. Therapeutic xcex11-antitrypsin has been commercially available since the mid 80s and is prepared by various purification methods (see for example Bollen et al., U.S. Pat. No. 4,629,567; Thompson et al., U.S. Pat. Nos. 4,760,130; 5,616,693; WO 98/56821). Prolastin is a trademark for a purified variant of xcex11-antitrypsin and is currently sold by Bayer Company (U.S. Pat. No. 5,610,285 Lebing et al., Mar. 11, 1997). Recombinant unmodified and mutant variants of xcex11-antitrypsin produced by genetic engineering methods are also known (U.S. Pat. No. 4,711,848); methods of use are also known, e.g., (xcex11-antitrypsin gene therapy/delivery (U.S. Pat. No. 5,399,346 to French Anderson et al.).
The two known cellular mechanisms of action of serine proteases are by direct degradative effects and by activation of G-protein-coupled proteinase-activated receptors (PARs). The PAR is activated by the binding of the protease followed by hydrolysis of specific peptide bonds, with the result that the new N-terminal sequences stimulate the receptor. The consequences of PAR activation depend on the PAR type that is stimulated and on the cell or tissue affected and may include activation of phospholipase Cxcex2, activation of protein kinase C and inhibition of adenylate kinase (Dery, O. and Bunnett, N. W. Biochem Soc Trans 1999, 27,246-254; Altieri, D. C. J. Leukoc Biol 1995, 58, 120-127; Dery, O. et al. Am J. Physiol 1998, 274, C1429-C1452).
2.2. Nitric Oxide (NO)
Nitric oxide (NO), also known as endothelium-derived relaxing factor (EDRF), is a potent vasodilator, oxidant, and neurotransmitter produced by many different types of cells and tissues, such as endothelium, macrophages and neuronal cells reviewed by Patel R. P., et al. in Biochim Biophys Acta 1999, 1411, 385-400; Lowenstein, C. J. and Snyder, S. H. in Cell 1992, 70, 705-707; Nathan, C. in FASEB J. 1992, 6, 3051.
A presently dominant theory based on DNA analyses holds that the NO synthase enzymes (NOS) exist in at least three isoforms, namely, neuronal constitutive NOS (N-cNOS) which is present constitutively in neurons, endothelial constitutive NOS (E-cNOS) which is present constitutively in endothelial cells, and inducible NOS (iNOS) which is expressed following stimulation by cytokines and lipopolysaccharides in macrophages and many other cells. (see Beck, K. F. et al. in J. Exp Biol 1999, 202, 645-53; Kirkeboen, K. A. and Strand, O. A. in Acta Anaesthesiol Scand 1999, 43, 275; Wood, E. R. et al. in Biochem Biophys Res Commun 1993, 191, 767-74; Lowenstein C. J. et al. in Proc. Natl. Acad. Sci. USA, 1993, 90, 9730). Among these three isoforms, N-cNOS and E-cNOS are calcium-dependent whereas iNOS is calcium-independent (Nathan, C. in FASEB J. 1992, 6, 3051). NO synthesized by nitric oxide synthase from arginine and oxygen is also an important signal transducing molecule in various cell types (Nathan, 1992, supra). In macrophages NO has assumed, under certain situations, the role of a cytotoxic agentxe2x80x94a reactive nitrogen intermediate that is lethal to cancer cells and microorganisms. The release of nitric oxide is also involved in other acute and chronic inflammatory diseases. These diseases include but are not limited to diseases such as, for example, acute and chronic infections (viral, bacterial and fungal), acute and chronic bronchitis, sinusitis, and upper respiratory infections, including the common cold; acute and chronic gastroenteritis and colitis; acute and chronic cystitis, and urethritis; acute and chronic dermatitis; acute and chronic conjunctivitis; acute and chronic serositis (pericarditis, peritonitis, synovitis, pleuritis and tendinitis); uremic pericarditis; acute and chronic cholecystitis; acute and chronic vaginitis; drug reactions; insect bites; bums and sunburn.
Released NO combines very rapidly with superoxide to form peroxynitrite (ONOOxe2x88x92xe2x80xa2), a reactive tissue damaging nitrogen species thought to be involved in the pathology of several chronic diseases. Peroxynitrite nitrates tyrosine residues and inactivates xcex11-antitrypsin (Rehman, A. et al. in Br J Pharmacol, 1997, 122, 1702). This mechanism is postulated to be responsible for xcex11-antitrypsin inactivation by cigarette smoke (Pryor, W. A. et al., in Chem Biol Interact 1985, 54, 171). Nitric oxide inhibits iron-containing enzymes important in respiration and DNA synthesis. Peroxynitrite decomposes to the reactive NO2 and hydroxyl radicals, and NO stimulates ADP-ribosylation of various proteins including glyceraldehyde-3-phosphate dehydrogenase, with consequent inactivation.
Van Molle and colleagues have shown that the acute phase protein xcex11-antitrypsin inhibits the cellular lethality induced by tumor necrosis factor (TNF) both in normal mice and in mice sensitized with galactosamine but similar apoptosis of hepatocytes induced by anti-Fas remained unaffected. Molle W. et al. in J Immunol 1997, 159, 3555. However, xcex11-antitrypsin did not affect the induction by TNF of NO Van Molle, ibid. In contrast, Bratt and colleagues have shown that TNF injury was not prevented by xcex11-antitrypsin (Bratt, J. and Palmblad, J. in J Immunol 1997, 159, 812).
Many proteins are reported to modulate NO production. Macrophage deactivating factor and TGF-xcex2 partially blocked NO release by macrophages activated with xcex3-interferon (xcex3-IFN or IFN-xcex3) and TGF-xcex1 (transforming growth factor-xcex1), but not when activated by xcex3-IFN and lipopolysaccharide (LPS or endotoxin) (Ding, A. et al., in J. Immunol. 1990, 145, 940). Epidermal growth factor can suppress both NO and H2O2 production by keratinocytes (Heck, D. E. et al., in J. Biol. Chem. 1990, 267, 21277). Incubation of LPS-activated peritoneal neutrophils with IL-8 blocks both the release of NO and NOS induction at the transcriptional level (McCall, T. B. et al., in Biochem. Biophys. Res. Commun. 1992, 186, 680).
TGF-xcex21 and 12-O-tetradecanoylphorbol-13-acetate (i.e., phorbol myristyl acetate or PMA) inhibit LPS and xcex3-IFN-induced NO synthesis in mouse bone marrow cells (Punjabi, C. J. et al., in J. Immunol. 1992, 149, 2179). In contrast, in bovine pigmented retinal epithelial cells TGF-xcex2 increases the NO production, as measured by nitrite, attributable to treatment with LPS and xcex3-IFN. In this system both fibroblast growth factor (FGF)-1 and FGF-2 inhibit nitrite production, likely by inhibiting the induction of NOS mRNA at the transcriptional level (Goureau, O. et al., in Proc. Natl. Acad. Sci. U.S.A. 1993, 90, 4276). Insulin-like growth factor 1 reduces the amount of NO produced by the action of IL-162  on vascular smooth muscle cells (Schini et al. in Circ Res 1994, 74, 24). The fact that so many agents can modulate NO activity by increasing or inhibiting NO production suggests that NO production may be important in many different contexts.
The overproduction in the body of nitric oxide (NO) and/or peroxynitrite (ONOOxe2x88x92xe2x80xa2) has been suggested by some to be a contributing factor to diseases that are immune-mediated and/or inflammatory. In a clinical study the levels of IL-6, IL-1xcex2, NO and xcex11-antitrypsin were shown to be involved in the pathogenesis of scorpion envenomation and correlated with the severity of envenomation (Meki, A. R. et al. in Toxicon 1998, 36, 18519). An extensively used model system to study multiple sclerosis, an example of a disease treated by the present invention, is experimental allergic encephalomyelitis (EAE) in rats and mice. (Popko B. and Baerwald, K. D. in Neurochem Res 1999, 24, 331; Smith, M. E. in Neurochem Res 1999, 24, 261).
Thus, the prior art taught that NO metabolites inactivate xcex11-antitrypsin. Also taught was that in certain clinical situations NO levels tended to rise concomitantly along with increase in xcex11-antitrypsin levels, although the AAT activity may have been reduced. However, the prior art failed to recognize that xcex11-antitrypsin might in fact prevent NO synthesis. The present inventor discovered that therapeutic and physiological levels of xcex11-antitrypsin can efficiently block xcex3-IFN- and LPS-induced NO synthesis. This invention addresses a long-felt need for safe and effective amelioration of many diseases related to nitric oxide-caused damage.
The present invention is directed to a method for treating a disease or disorder involving an excess activity of nitric oxide (NO) in an animal subject. The method of the invention comprises administering a therapeutically effective amount of an agent that reduces NO levels, to an animal subject suspected of having a disease or disorder involving excess nitric oxide. In a preferred embodiment the agent can be xcex11-antitrypsin. In addition, peptides of interest are homologous and analogous peptides. While homologues are natural peptides with sequence homology, analogues will be peptidyl derivatives, e.g., aldehyde or ketone derivatives of such peptides. Typical examples of analogues are TLCK or TPCK. Without limiting to xcex11-antitrypsin and peptide derivatives of xcex11-antitrypsin, compounds like oxadiazole, thiadiazole, CE-2072, UT-77, and triazole peptoids are preferred. The agent that reduces NO levels can also be an xcex11-antitrypsin-like agent, an inhibitor of elastase, or an inhibitor of proteinase-3. The xcex11-antitrypsin-like agent can include, but is not limited to, small organic molecules including naturally-occurring, synthetic, and biosynthetic molecules, small inorganic molecules including naturally-occurring and synthetic molecules, natural products including those produced by plants and fungi, peptides, variants of xcex11-antitrypsin, chemically modified peptides, and proteins. An xcex11-antitrypsin-like agent has the capability of inhibiting the proteolytic activity of trypsin, elastase, kallikrein, and/or other serine proteases.
A general method of treating a mammal suffering from a pathological condition that is mediated by endogenous serine protease or serine protease-like activity is contemplated as well, which comprises administering a therapeutically effective amount of a substance exhibiting mammalian xcex11-antitrypsin or xcex11-antitrypsin-like activity. The pathological condition can be precipitated at least in part by abnormal nitric oxide levels.
Also a method is provided of inhibiting bacterial colonization in a host, which comprises administering to a mammal susceptible to bacterial colonization an effective amount of a substance exhibiting mammalian xcex11-antitrypsin or xcex11-antitrypsin-like activity. Without limiting to xcex11-antitrypsin, the substance may be a compound that inhibits proteinase-3, cathepsin G, or elastase.
Also contemplated is a method of preventing a deficiency of functional endogenous xcex11-antitrypsin levels in a patient susceptible to an infection that is mediated by endogenous host serine protease or serine protease-like activity, by treating with a pharmaceutical composition in a pharmaceutically acceptable carrier comprising effective amounts of a substance exhibiting mammalian xcex11-antitrypsin or xcex11-antitrypsin-like activity. In addition, to reduce ischemia-reperfusion injury associated with administration of thrombolytics, a combination of serine protease inhibitor, and a thrombolytic agent such as tissue plasminogen activator, urokinase, streptokinase, or combinations or complexes thereof can be administered. The pharmaceutical composition can be a peptide or a small molecule, which exhibits xcex11-antitrypsin or xcex11-antitrypsin-like activity.
It should be apparent that in addition to these preferred embodiments a method is contemplated which consists of treating an individual having a pathological condition caused, in whole or part, by nitric oxide release. In accordance with this embodiment, a method of inhibiting nitric oxide release is provided wherein the target of the therapy is a cell and one will contact such cell with an effective amount of a compound having xcex11-antitrypsin activity.
According to the invention, the peptide can be protected or derivitized in various ways, e.g., N-terminal acylation, C-terminal amidation, cyclization, etc. In a specific embodiment, the N-terminus of the peptide is acetylated.
The invention further provides pharmaceutical compositions comprising such agents. In yet a further embodiment of the invention, the pharmaceutical composition also comprises a vasoconstrictor effective to increase blood pressure in an animal.
It is therefore the goal of the present invention, in its broadest aspect, to provide methods of treating diseases dependent on the action of NO and proteases. Accordingly, it should be recognized that this invention is applicable to the control of catalytic activity of serine proteases in any appropriate situation including, but not necessarily limited to, medicine, biology, agriculture, and microbial fermentation.
Accordingly, it is therefore the overall object of the present invention to provide compounds that exhibit inhibitory activity toward serine proteases.
It is an object of the present invention to provide clinically acceptable serine protease inhibitors with recognized utility and exhibiting relatively high activity at relatively low concentrations.
It is yet another object of the invention to provide means of regulating nitric oxide release by compounds having xcex11-antitrypsin activity.
These and other objects and advantages of the present invention will be recognized by those skilled in the art from the following description and illustrative examples.
FIG. 1 illustrates the effect of xcex11-antitrypsin on NO release upon induction with LPS and xcex3-IFN.
FIG. 2 illustrates the effect of xcex11-antitrypsin on induction of iNOS protein by LPS and xcex3-interferon.
FIG. 3 illustrates an electrophoretic mobility shift assay of NF-xcexaB on gel electrophoresis demonstrating inhibition of NF-xcexaB activation due to the presence of xcex11-antitrypsin.
FIG. 4 illustrates the inhibition of elevated NO levels, measured as NO2xe2x88x92, by CE-2072.
FIG. 5 illustrates the inhibition of p-ERK expression by xcex11-antitrypsin (AAT).
FIG. 6 illustrates the effect of xcex11-antitrypsin on cytomegalovirus replication.
FIG. 7 illustrates the effect of xcex11-antitrypsin on herpes simplex infection.

Inhibitors of serine protease activity, methods and compositions for treatment of nitric-oxide-induced clinical conditions

Trustees of University of Technology Corporation


A non-planar, stepped NROM array is comprised of cells formed in trenches and on pillars that are etched into a substrate. Each cell has a plurality of charge storage regions in its nitride layer and a pair of source/drain regions that are shared with adjacent cells in a column. The source/drain regions, formed in the pillar/trench sidewalls, couple the column cells serially into bitlines. The rows of the array are each coupled by a wordline. A second set of trenches separates the columns of cells.

Memory devices are typically provided as internal, semiconductor, integrated circuits in computers or other electronic devices. There are many different types of memory including random-access memory (RAM), read only memory (ROM), dynamic random access memory (DRAM), synchronous dynamic random access memory (SDRAM), and flash memory.
Flash memory devices have developed into a popular source of non-volatile memory for a wide range of electronic applications. Flash memory devices typically use a one-transistor memory cell that allows for high memory densities, high reliability, and low power consumption. Common uses for flash memory include personal computers, personal digital assistants (PDAs), digital cameras, and cellular telephones. Program code and system data such as a basic input/output system (BIOS) are typically stored in flash memory devices for use in personal computer systems.
FIG. 1 shows a cross-section of a typical prior art NROM array. The array is comprised of a silicon substrate 100 with a gate oxide layer 101 formed over the substrate 100. A silicon nitride layer 102 is formed over the gate oxide 101. Each transistor 140–142 is comprised of two charge storage regions 110 and 111 in the nitride layer 102. An intergate insulator 107 is formed over the nitride layer 102 prior to forming the control gate/wordline 120–122 of each transistor 140–142 over the intergate insulator 107 and substantially between the source/drain regions 130–133.
The minimum feature size of the transistors 140–142 of FIG. 1 is described by F. The density is therefore one bit for each 4F2 units surface area. This is typically described as a density of 4F2/bit.
As computers become smaller and their performance increase, the computer components should also go through a corresponding size reduction and performance increase. To accomplish this, the transistors can be reduced in size. This has the effect of increased speed and memory density with decreased power requirements.
However, a problem with decreased flash memory size is that flash memory cell technologies have some scaling limitations due to the high voltage requirements for program and erase operations. As MOSFETs are scaled to deep sub-micron dimensions, it becomes more difficult to maintain an acceptable aspect ratio. Not only is the gate oxide thickness scaled to less than 10 nm as the channel length becomes sub-micron but the depletion region width and junction depth must be scaled to smaller dimensions.
For the reasons stated above, and for other reasons stated below which will become apparent to those skilled in the art upon reading and understanding the present specification, there is a need in the art for a memory device having increased memory density and performance.

High density stepped, non-planar nitride read only memory


A merge support system includes a first detection unit and a second detection unit for detecting a position and a speed of an approaching vehicle in a traffic on a main lane and a position and a speed of a subject vehicle, an information provision unit for providing information for a driver of the subject vehicle and a control unit for calculating a merge speed of the subject vehicle relative to the traffic on the main lane and a merge position relative to the traffic on the main lane. The control unit calculates the merge speed and the merge position on the main lane based on the position and the speed of the approaching vehicle and the subject vehicle, and the control unit controls the information provision unit for providing a calculation result of the merge speed and the merge position for the driver of the subject vehicle.

In recent years, a specific type of navigation system is used to navigate a vehicle when the vehicle is merging from an onramp into a through traffic on a main lane of an expressway or the like. For example, Japanese patent document JP-A-H11-86192 discloses a technique that facilitates a smooth merging of a subject vehicle by reporting to a driver of the subject vehicle a position and appearance of an approaching vehicle in the through traffic on a main lane. In addition, the navigation system in the above disclosure provides for the driver of the subject vehicle a predicted position of the approaching vehicle at a certain period of time after an initial report of the position and appearance of the approaching vehicle.
However, the driver of the subject vehicle has to determine a merge speed by him/herself based on the information provided by the navigation system. That is, the driver has to decide the merge speed by him/herself based on the predicted position of the approaching vehicle provided by the navigation system. In addition, the driver has to find an appropriate merge timing and/or a merge position at the same time for merging. Therefore, the driver of the subject vehicle has to process a large amount of information for merging operation provided by the navigation system at his/her own cost. In other words, the navigation system leaves a huge load on the driver's disposal even when it provides navigation information for merging into the traffic on the main lane.


A magnetic recording medium is provided, which includes a recording layer formed in a concavo-convex pattern to achieve high areal density and can ensure good recording and reproduction characteristics so as to provide high reliability. The magnetic recording medium has a substrate and a recording layer formed in the predetermined concavo-convex pattern over the substrate. The recording layer has a non-recording element and recording elements. The non-recording element is formed as convex portion of the concavo-convex pattern at an outer circumferential end and/or an inner circumferential end. The recording elements are formed as convex portions of the concavo-convex pattern in a region other than a region where the non-recording element is arranged. The magnetic recording medium further has a non-magnetic material with which concave portions of the concavo-convex pattern are filled and which covers the non-recording element, and a protective layer formed over the recording layer and the non-magnetic material.

1. Field of the Invention
The present invention relates to a magnetic recording medium including a recording layer formed in a concavo-convex pattern, and a magnetic recording and reproduction apparatus.
2. Description of the Related Art
Conventionally, in a magnetic recording medium such as a hard disk, a non-magnetic protective layer is formed over a recording layer in order to protect the recording layer against abrasion caused by contact with a magnetic head and corrosion caused by oxygen and the like in an atmosphere. A lubricating layer is further formed on the protective layer. The protective layer can be formed by a vapor deposition method such as CVD (chemical vapor deposition). The lubricating layer can be formed by dipping or the like.
On the other hand, in the magnetic recording medium, various types of development such as miniaturization of magnetic particles forming the recording layer, change of a material for the magnetic particles, and miniaturization of head processing have been made to largely improve areal density of the recording layer. The improvement of the areal density is expected to continue. However, problems of the limitation of the magnetic head processing, erroneous recording of information onto a track adjacent to a target track caused by broadening of a magnetic field of the recording head, crosstalk during reproduction, and other problems have been made apparent. Therefore, the improvement of the areal density by the conventional development approach has reached the limit. Thus, a magnetic recording medium in which a recording layer is formed in a predetermined concavo-convex pattern, such as a discrete track medium and a patterned medium, has been proposed as a candidate of a magnetic recording medium that can further improve the areal density (see Japanese Patent Laid-Open Publication No. Hei 7-129953, for example).
In the discrete track medium and the patterned medium, it is desirable to fill concave portions of the concavo-convex pattern with a non-magnetic material so as to flatten a surface of the medium from a viewpoint of stable flying of the magnetic head (see Japanese Patent Laid-Open No. 2000-195042, for example). Moreover, it is also preferable in the discrete track medium and the patterned medium to form a protective layer and a lubricating layer over the recording layer in order to protect the recording layer against abrasion caused by contact with the magnetic head and corrosion caused by contact with oxygen and the like in the atmosphere.
However, when the protective layer is formed by CVD or the like, an object to be processed in a shape of a circular disk is held by jigs or the like at several portions, e.g., three portions at an outer circumferential end or an inner circumferential end. Thus, particles forming the protective layer are not sufficiently supplied to a region around the portion held by the jigs. Therefore, the thickness of the protective layer in that region becomes insufficient or no protective layer is formed in that region. Since the outer circumferential end and the inner circumferential end of the magnetic recording medium are usually non-recording regions, corrosion of the recording layer in the region in which the thickness of the protective layer is not enough does not directly cause a problem in recording and reproduction. However, the corrosion of the recording layer may progress from the region in which the thickness of the protective layer is not enough to other regions so as to degrade the recording and reproduction characteristics. Thus, there is a reliability problem.
On the other hand, the protective layer can be deposited on the entire surface of the object to be processed by forming the protective layer to some degree, removing the object to be processed from the jigs, holding the object to be processed again at other portions by the jigs, and further depositing the protective layer. However, the reliability problem remains in this case because the protective layer is thinner around the portions held by the jigs. Moreover, a method is considered which forms the protective layer to be thick on the entire surface of the object to be processed including a recording region in such a manner that the protective layer having a sufficient thickness is surely formed at and around the portions held by the jigs. However, in case of a magnetic recording medium such as a discrete track medium and a patterned medium, for which areal density of 200 Gbpsi or more is expected, a guideline that a magnetic gap between an upper surface of the recording layer and a magnetic head is set to 15 nm or less is issued. Thus, when the protective layer is formed to be excessively thick even by several nanometers, the magnetic gap becomes too large. This may degrade the recording and reproduction characteristics.
Alternatively, as described in Japanese Patent Laid-Open Publication No. 2000-195042, the non-magnetic material with which the concave portions are filled may also be formed on the convex portions and the protective layer may be formed on the non-magnetic material. In this case, the magnetic gap also becomes too large as in the case where the protective layer is formed to be excessively thick, when the non-magnetic material is formed in sufficient thickness at and around the portions held by the jigs. Thus, the recording and reproduction characteristics may be also degraded in this case.

Magnetic recording medium and magnetic recording and reproduction apparatus


A communication system and method that translates a first plurality of information symbols into a plurality of code words, transmits the plurality of code words through a communication channel receives the plurality of code words transmitted through the communication channel, deciphers the plurality of code words transmitted through the communication channel into a second plurality of information symbols that correspond to the first set plurality of information symbols, wherein the plurality of code words are derived from a reverse dynamical flow within a first neural network.

1. Field of the Invention
The present invention relates to error control coding systems and methods, and, more particularly, including the generation and decoding of pseudo-random code word messages such as would be useful for increasing the reliability of tranferring information over noisy communication channels.
2. Description of the Related Art
Thermodynamics teaches that statistical fluctuations in the energy of media and systems cause a positive probability of errors being introduced in the process of transferring information from one point to another point. Information must be assembled, codified by symbols, encoded for transmission, converted into a physical signal, transported across a distance, received, decoded, and passed on to a user. At any stage in an electronic version of a communication process, transient errors due to temperature, cosmic rays, communication medium noise, receiver noise figure, and faulty apparatus and their components may occur. Noise in received signals, rather than apparatus failure, constitutes the primary factor limiting the performance of modern communication systems. Noise prevents the receiver(demodulator) from distinguishing one message(waveform) from another, thereby introducing uncertainties about the true nature of the information being received. It is therefore a problem to communicate reliably information in the presence of masking noise.
When the transmission of message information is accompanied by errors, the receiver of the information must perform operations that correct the errors so that an uncorrupted message can be presented to the user. for the correction process to be successful, it must be the case that not all possible received messages can be treated as valid, for otherwise the receiver would be incapable of distinguishing a valid message M1, from a corrupted valid message M2 wherein the corruption of M2 produced an apparent message identical to M1. Thus, the ability of a receiver to correct for errors introduced during transmission implies that redundant information must be added to valid messages so that the receiver can detect and possibly correct at least some errors. The added redundancy effectively lowers the rate at which useful message information can be transferred so that it is an advantage of error correction methods to be as efficient as possible without sacrificing error correcting ability.
Two primary methods currently exist for minimizing the impact of errors in electronic communication. In the first method, the energy per unit of information transferred is increased to the point where the raw signal to noise ratio exceeds the minimum value required for a tolerable rate of error production. In the second method error-control encoding techniques are used to add extra units of information the the message so that a receiver can detect and correct errors that occur at some maximum rate. Cost savings through the use of low-energy error control methods can be significant relative to the first method, even though an added complexity to the transmitter and receiver apparatii is required. The second error control method is the most widely used for the transfer and storage of digital information.
It is well known to encode the intelligence of information and transmit the encoded information to the receiver. Encoding normally adds redundant information to the message so that the receiver can detect, and in many cases correct, faulty received information. Simple error detectors and correcters are conventionally available for correcting minor errors. However, where the encoded message accumulates more than a couple of errors, such equipment is ineffective to correct errors.
In recent decades, much of the art in the field of error-control coding has addressed two essential problems; that of finding classes of code words that yield good error-control performance at various lengths, and then designing fast and cost effective circuitry to carry out the electronic control of errors.
In practice, a message to be transmitted by electronic means is encoded into a potentially long sequence of information symbols called bits by an error-control circuit, and then into a transmitted modulated waveform. A demodulation of this waveform at the receiver provides a sequence of bits to the error-control circuitry which uses the code word bits to make the best estimate of the message that was originally encoded.
One widely used method of makin gaccurate valid message ideification is to associate each of the possible information units in a message with a unique code word designed to facilitate the detection and correction of message transmission errors. In binary error-control coding, the error-control circuitry accepts information bits at a rate Rs, adds the desired level of redundancy, and then generates code word bits at a higher rate Rc. In a block encoder, successive k-bit blocks of binary information are converted into successive n-bit blocks where n.gtoreq.k. The n-bit block is referred interchangibly to as the code word, or code block, or block code word. When encoding using a convolution code, the encoder accepts information as a continuous stream of bits, and generates a continuous stream of output code bits at a higher rate. The number of information bits used by the encoder in generating each output code bit is called the constraint length of the code.
Examples of often employed block codes include the parity check codes, product codes, binary repetition codes, binary hamming codes. Most of the successful block codes are called cyclic codes such as the Bose-Chaudhuri-Hocquenghem codes because their well defined algebraic structure makes practical the contruction of low cost encoders and decoders using straighforward electronic means. However, all of these codes an all convolution codes suffer from an inability to correct errors when the error rate is very high in relation the message transmission rate. Good codes and circuitry exists for controlling small numbers of errors per code word received, but none of these conventional approaches have solved the problem of detecting and correcting errors when the probability of an error in a code word bit position is above a few percent. It is therefore a problem in the prior art to provide a method for correcting high rates of communication errors in a practical manner.
The Channel Coding Theorem first proven by Shannon states that every channel of communication has a channel capacity C, and that for any information transfer rate R<C there exists code words of block length n that can be transferred at rate R such that the probability of incorrectly interpreting a message, P(E), is bounded by EQU P(E).ltoreq.2.sup.-nEb(R)
where Eb(R) is positive and is determined the physical and noise properties of the channel. This theorem implies that for any symbol transmission rate less than C, it is possible to reduce the probability of miscorrecting the errors in a noisy message to any degree required, even if the error rate is very high. In practice the symbol transmission rate is held fixed while the length of the encoded message (code word) is increased in length. The lower error rate is thus offset by the need to add more and more redundant symbols to the basic message to provide the information needed to correct errors, but there is no reason in principle that prevents the correction of arbitrarily high error rates. This result is valid for both fixed length, Block codes, and fixed constraint length, Convolution codes.
It is important to observe that very noisy channels require the use of very long code words, even for very simple messages. For example, even though each of the 26 letters of the english alphabet may be represented by a unique sequence of 5 binary (zeros and ones) bits, successful communication of a sequence of such characters over a noisy channel may require the encoding, transmission, reception and decoding of code words of tens or even hundreds of bits in length per character transferred.
Unfortunately, no general theory exists which specifies the construction of code words for very noisy communication channels. Moreover, as the length of code words increase, the burden and complexity of the encoder and decoder circuitry is also increased at least proportionately. It is in general quite difficult to construct efficient encoders and decoders of long code words using conventional methods, even if the expected error rates are small.
However, Shannon's main theorem of information theory proves that it is possible to signal reliably through the use of random encodings of message symbols. Consider the encoding of information using randomly selected binary code words of n bits in length. There are 2.sup.n such code words that can be selected, but if it is desired to guard against a large number of simultaneous errors in the communication process, then the admissible code words must be chosen to be very dissimilar so that they can be easily distinguished even when masked by noise. For binary code words, a measure of this similarity is called the "Hamming Distance." The hamming distance between any pair of code words of the same length is simply the total number of bit positions in which the code words are dissimilar. For example, the two code words, (1011100) and (0011110) have a Hamming distance between them of 2.
Code words consisting of long, random strings of zeros and ones symbols may be associated with valid messages. And because such bit strings are random and thus nearly uncorrelated (orthogonal), these special code words give the receiver the best chance of recovering from high levels of added noise.
One method of selecting a set of random code words for error-control encoding is to select each word by random coin tossing. That is, each bit in each code word is obtained by flipping an unbiased coin until all code words have been generated. The set of code words are then shared between the sender and receiver so that the sender and receiver share an identical table that associates a unique message symbol with a unique code word.
We can imagine the code words as points in an n-dimensional space of possible code words. We assume that the minimum Hamming distance between any pair of code words in the code word set is at least D.sub.min. By the law of large numbers there is, for a sufficiently large code word size n, an arbitrarily small probability that the received message will lie at or beyond a Hamming distance (D.sub.min -1)/2 from one of the uncorrupted code words as long as EQU D.sub.min >2ne+1,
where e is the probability of a random error at any bit position in the received message. Thus, if the receiver-decoder assumes that the codeword that is most similar to the received code word is in fact the actual code word sent, then up to ne errors in the received word can be corrected with high probability.
The method of using randomly selected code words to encode information to be sent over noisy channels seems attractive and easily implementable due to their simplicity of generation. However, the use of random code words places a severe burden on the communication equipment since the random nature of the code words does not admit to a simpler mathematical representation of the code words other than simple tabulation. Unlike all code word types used in practice, random codes have no inherent pattern that can be used to simplify the encoding and decoding apparatus; no formula or pattern exists for computing the code words for each message. Moreover, the decoding apparatus must be relatively complex since the code lengths required to correct errors in very noisy channels must be very large. For although only a small number of valid code words may exist in the code word set, the number of possible messages that could be received is equal to the total number of possible code words that exist for codes of a given length. Thus the transmitter must select by table lookup one of 2.sup.S code words to encode one of 2.sup.S message symbols, and the receiver must provide an apparatus for decoding one of 2.sup.n possible receiver message patterns. Due to these factors the use of random encoding has been abandoned or unused by the art in favor of the use of highly structured code word sets that can be more easily generated and decoded.
Attempts to understand the functioning of the human brain have led to various "neural network" models in which large numbers of neurons are interconnected with the inputs to one neuron including the outputs of many other neurons. These models roughly presume each neuron exists in one of two states (quiescent and firing) with the neuron's state determined by the states of the input connected neurons (if enough connected neurons are firing, then the original neuron should be in the firing state); and the thrust of the models is to perform computations such as pattern recognition with the neural networks.
J. Hopfield, Neural Networks and Physical Systems with Emergent Collective Computational Abilities, 79 Proc. Natl. Acad. Sci. USA 2554 (1982) describes a neural network model with N neurons each of which has the value -1 or 1 (corresponding to the quiescent and firing states), so the state of the network is then a N-component vector V=[V.sub.1, V.sub.2, . . . , V.sub.N ] of -1's and 1's which depends upon time. The neuron interconnections are described by a matrix T.sub.i,j defining the influence of the j.sup.th neuron on the i.sup.th neuron. The state of the network evolves in time as follows: for each i, the i.sup.th neuron has a fixed threshold .theta..sub.i and readjusts its state V.sub.i randomly in time by setting V.sub.i equal to -1 or 1 depending on whether EQU .SIGMA..sub.j T.sub.i,j V.sub.j -.theta..sub.i
is negative or positive. All neurons have the same average rate of readjustment, and the readjustments define a dynamical flow in state space. With the assumption that T.sub.i,j is symmetric, the potential function EQU .SIGMA..sub.i .SIGMA..sub.j T.sub.i,j V.sub.i V.sub.j
can be used to show that the flow of the network is to local minima of the potential function. Further, with a given set of s uncorrelated N-component binary (-1, 1) vectors, U.sup.1, U.sup.2, . . . , U.sup.8, a T.sub.i,j can be defined by ##EQU1## and the corresponding network with the thresholds .theta..sub.j set equal to 0 has these U.sup.k as the fixed points of the flow and thus stable states of the network. Such a network can act as a content-addressable memory as follows: the memories to be stored in the network are used to construct the U.sup.k and hence T.sub.i,j, so the stored memories are fixed points of the flow. Then a given partial memory is input by using it to define the initial state of the network, and the state will flow usually to the closest fixed point/stable state U.sup.k which is then the memory recalled upon input of the partial memory. This is the correlation used for decoding messages with the stable states corresponding to valid messages.
Further analysis and modified network models appear in, for example, J. Hopfield et al, Computing with Neural Circuits: A Model, 233 Science 625 (1986) and J. Hopfield, Neurons with Graded Response Have Collective Computational Properties like Those of Two-State Neurons, 81 Proc. Natl. Acad. Sci. USA 3088 (1984). FIG. 1 shows a simple neural network made from standard electronic components.
D. Ackley et al, A Learning Algorithm for Boltzmann Machines, 9 Cognitive Science 147 (1985) describe neural networks with additional adjustment mechanisms for the neurons which analogize thermal fluctuations; this permits escape from local minima of the potential function. However, this disrupts the flow to fixed points for memory recall of the Hopfield type neural networks.

Error control codeword generating system and method based on a neural network


Disclosed are monoesters, inner complex salts or monoester salts of hexahydro-β-acid, and application thereof as animal feed additives. The compounds as shown in formula (I), (II) and (III) show low toxicity or non-toxicity to animals, and have higher stability and better growth promotion effects than those disclosed in other patents, which make them more suitable to be applied as growth promoters used in feed and have a very good application prospect in cultivation industry.

A plurality of US patents, such as U.S. Pat. No. 8,197,863B2, U.S. Pat. No. 8,012,516B2, US20080213342A1, US20060269588, US20040219240, U.S. Pat. No. 7,090,873, US20060134248, US20110311663, U.S. Pat. No. 7,553,504, US20130018106 and U.S. Pat. No. 6,251,461, and as plurality of European patents, such as EP2606742A1, EP1542543B1, EP2429311A2 and EP1722635B1, have disclosed the application of hops acids and hydrogenated β-acids as substitutes for antibiotic growth promoters used in feed.
However, recited in the above-mentioned patents is the application of extracts from hops or hops acids (e.g. a mixture of α-acids and β-acids) as feed additives those already included in the Chinese Feed Additive Catalogue but only serve as condiment for feed. Secondly, the grounds of the patents are mainly results of trial in vitro rather than feeding trial. What's more, there is no data so far, to demonstrate safety and stability of these natural products, or the salts and ester thereof, as animal feed additives.
Hexahydro-β-acids are also mentioned in the above-mentioned patents, but application of the esters, salts or ester salts thereof as animal feed additives has not been reported so far.

Monoesters, inner complex salts or monoester salts of hexahydro-beta-acid and application thereof as animal feed additives

GUANGZHOU INSIGHTER BIOTECHNOLOGY CO., LTD.


A method for maintaining a material data blockchain (MDC) is disclosed. The method includes receiving a material data block (MDB), wherein the MDB includes a metadata portion and a payload portion. The method further includes extracting a first sequence from the metadata portion and generating a genomic engagement factor (GEF) based on the sequence, a genomic differentiation object assigned to the creator VDAX, and genomic regulation instructions (GRI) that are maintained by the creator VDAX. The method further includes generating a creator value corresponding to the MDB based on the first GEF and the MDB and digitally signing the MDB with the creator value. The method includes providing the unnotarized MDB to one or more notary cohorts; and receiving a respective notary value from each of the notary cohorts, wherein each notary value is generated using respective GRI and genomic differentiation object maintained by a respective notary.

The requirement to distinguish the Noble from the Nefarious has grown in urgency as the ARPAnet community of adjunct-nodes breached their perimeter into a world-wide-web comprised of virtual digital ecosystems supported by an interoperable Digital Monoculture. By the time the material consequences faced by this new machine-connected-world became apparent, first responder technologies (e.g., Firewalls, Analytics, Forensics, PM, Proxies, and Monitoring) were already relegated to network perimeter patrol and rapid recovery services.
Experts broadly agree cryptography offers the only provable machine-connected-world security solution. Quantum, Homomorphic, and Obfuscation-based cryptographic research have garnered huge investment but no more than hoped for impact. Nevertheless, the most essential but indomitably complex of all cryptographic disciplines—hyper-scalability—remains unattended. Efforts to update PM to post quantum status abound, even as its linear scalability perseveres.
Applicant has developed and has disclosed herein, Cyphergenics (CG) technologies, which comprehensively resolves the heretofore intractable hyper-scalability dilemma, descriptions of which are disclosed in this document. As will be discussed, Cyphergenics enables unlimited deployment of cryptographic-based digital ecosystem security for di minimis overhead and bandwidth, while fully preserving interoperability. Importantly, hyper-scalability directly facilitates functional homomorphic cryptography and functional indistinguishable obfuscation.


A data processing system and method of preparing a presentation-ready document are described. In response to receipt of a document description that includes at least one Page Description Language (PDL) instruction and specifies both fixed data and variable data, the one or more PDL instructions are processed to produce separate presentation-ready images of the fixed data and the variable data. In addition, a bookticket specifying an arrangement of the presentation-ready images of the fixed data and the variable data is automatically generated. In response to receipt of the bookticket, a presentation-ready document is built that includes the presentation-ready images of the fixed data and the variable data in the arrangement specified by the bookticket. In one embodiment of the present invention, the document description specifies the fixed data of the document utilizing a PDL form operator.

1. Technical Field
The present invention relates in general to document presentation and in particular to the generation of a presentation-ready document within a data processing system. Still more particularly, the present invention relates to a data processing system and method for efficiently generating a presentation-ready document including both fixed and variable data, wherein a user is not required to manually specify how the fixed and variable data are to be merged.
2. Description of the Related Art
Many industries, for example, the publishing and direct marketing industries, rely heavily on high-speed, high-resolution, large-capacity printing. These industries often make use of so-called Print On Demand (POD) presentation environments that are capable of producing over 400 pages per minute (100 pages per minute in full color) at resolutions of 600 dots per inch or greater. The high performance requirements of a POD presentation environment necessitate the transfer of massive amounts of data to the printhead--on the order of 30 MB per second.
Information to be presented within a POD presentation environment is typically formatted as a document, which comprises both the collection of data objects that constitute the document's content and the resources and formatting specifications that dictate the processing functions to be performed on that content. Documents are constructed of one or more pages, and the pages in turn are made up of data objects such as bar code objects, graphics objects, image objects and presentation text. Each data object has associated layout information that directs the placement and orientation of the data object on the page, as well as the page width, page depth, and other format parameters. In addition to fixed data objects such as presentation text, which may be common to multiple copies of a document, POD architectures also typically support variable data objects, which can be unique to each copy (and each page of each copy) of a document.
Conventional POD presentation environments have typically handled documents including variable data inefficiently. For example, assume that a user desires to produce 100 copies of a one page document for which the fixed data objects in each copy are identical and the variable data objects in each copy are unique. In a conventional POD presentation system, the user first prepares, utilizing a desktop publishing or word processing application, a one page document including both the fixed data and a designation of a variable data area in which variable data objects are to be presented. The user also prepares either a second document or additional pages of the first document that specify the variable data objects. In response to an output command, the application merges the fixed and variable data objects into a lengthy Page Description Language (PDL) file, which specifies the content and format for each of the 100 pages to be printed. The PDL file is then transmitted to a Raster Image Processor (RIP) within the POD presentation system, which executes (hereinafter referred to as "rips") the PDL instructions within the document file in order to obtain 100 pages of dot patterns that are to appear on the physical print medium. Thereafter, the dot patterns are applied to the print medium by the printhead.
Although this prior art method of presenting documents including variable data is relatively simple from the user's perspective, it unnecessarily limits the performance of a POD presentation system by requiring the RIP to repetitively process the fixed data appearing on each of the 100 pages. In order to address this inefficiency, custom applications such as MERGEDOC (available from International Business Machines (IBM) Corporation of Armonk, N.Y.) were developed that permit a user to generate two separate PDL files: a fixed data object file and a variable data object file. In addition, such custom applications provide facilities that enable the user to manually build a "bookticket" that specifies how the fixed and variable data objects are to be merged. In POD presentation systems that employ a custom application, the manually-generated bookticket and the two PDL files are transmitted to the RIP, which processes each of the fixed and variable data objects once and stores the resulting dot patterns. The RIP then merges the variable data objects with the fixed data objects in accordance with the bookticket prepared by the user in order to obtain a presentation-ready document. Although custom applications enhance presentation efficiency by eliminating the need to rip fixed data objects multiple times, the use of custom applications entails a large amount of additional user input in order to specify how the fixed and variable data objects are to be merged.
As should thus be apparent, it would be desirable to provide an improved method and system for presenting documents within a POD presentation environment. In particular, it would be desirable to provide a method and system for automatically generating a presentation-ready document that do not require the user to manually build a bookticket specifying the manner in which the fixed and variable data are to be merged.

Data processing system and method for Preparing a presentation-ready document that produces separate images of fixed and variable data and a bookticket specifying an arrangement of such images

International Business Machines Corporation


A tooth brush holder adapted to contain at least one tooth brush is provided with a switch and circuitry such that when the tooth brush is removed from the holder a sound producing device is actuated which device can continue to produce sound for at least a predetermined time. In one preferred form of the invention, the sound producing device may incorporate an audio chip on which a pre-recorded message is located and, in a second form, may include a recordable chip recorded by a user or some other person. The apparatus may be provided with a control apparatus to monitor the amount of time the toothbrush has been removed from the holder to insure that proper brushing has taken place. If the toothbrush is replaced in the holder before the predetermined time period has elapsed, a warning message or tone (and/or light) may be activated advising the user that more brushing is needed. An indicator may be activated to alert a parent or other adult that brushing has not occurred (or has not occurred by a certain time of day) or that brushing was inadequate. If the toothbrush is replaced after the predetermined time period has elapsed (and/or message has been played) an audio or visual reward may be generated. An audio message praising the child may be played (e.g., song or the like) and/or other stimuli may be used (e.g., lights in eyes may flash, animated character elements may move).

With the advent of fluoridated toothpaste and fluoridated water, the incidence of cavities in children and adults has dropped dramatically. However, the need for proper oral hygiene remains paramount. Proper brushing insures that cavities will remain few, and moreover, reduces the likelihood of gum diseases such as gingivitis and the like.
Parents may not have sufficient time or energy to properly supervise their children's brushing habits on a regular basis. Children, even after being instructed in proper brushing techniques, may lapse into a more lackadaisical schedule without constant supervision and instruction from adults. The reasons are relatively simple. Tooth brushing is a relatively boring and unpleasant task, and children have largely short attention spans. As a result, a child is often likely to be distracted by a television programme, video game, or the like, and may foreshorten brushing, if not foregoing it altogether.
There have been proposed many different forms of tooth brush holders which are normally adapted to be connected to a vertical surface although, in some cases, they are associated with a glass and these have, quite generally, served their primary purpose quite effectively. One such prior art toothbrush holder, Gertler, U.S. Pat. No. 4,285,151, goes one step further by providing a recorded message which is played when a toothbrush is removed from the holder.
The recorded message in Gertler may comprise a melody or message or combination, which may be used to encourage proper oral hygiene (Gertler, Col. 3, lines 28-35). However, the apparatus of Gertler has some limitations. In particular, gertler uses a primitive recording disk or tape which may only play one message. Moreover, the primitive on/off switch of Gertler only serves to initiates playback of the message when brushing starts. If the toothbrush is replaced prematurely, the message continues to play to the end of the melody or message in progress.
Moreover, the apparatus of Gertler is rather bulky, relying upon a recording disk system located in the base. In a typical bathroom, shelf or counter space at a vanity or sink may be at a premium, and consumers may dislike clutter in the bathroom. The large base of Gertler may occupy too much space to make the apparatus acceptable to consumers.


A technique for easily making modifications to a graphical user interface (GUI). XML files each containing different rules for making a tree display are easily written by code developers. The files are merged into a document object model (DOM) stored in memory. The GUI display presentation can thus be easily updated by the code developers by modifying the rules stored in the DOM by merging additional XML files containing rule additions, deletions and/or modifications into the DOM. The DOM is parsed for certain object classes for which object instances are needed. The object instances having certain display properties are retrieved from the system or network with which the GUI is operative and are combined with certain display attributes or display rules stored in the DOM. The object instances including their display properties and attributes are returned to the GUI to be displayed on the terminal screen in accordance therewith.

1. Field of the Invention
The present invention relates to computer program product, methodology, systems, and/or apparatus for making modifications to a Graphical User Interface (GUI) display and, more particularly, relates to a technique for allowing such modifications to be made in an extremely convenient and efficient manner because the code underlying the display is not modified.
2. Description of Prior Art
Most people who interact with the world of computers, computer networks, computer storage systems, etc., can probably be classified as users of this technology. Many, if not most of us, own personal computers (PCs) or use them at our jobs. We are Internet subscribers or users, and we take convenient advantage of technological advances which have been provided for us. We are enjoying the benefits of the computer revolution. However, there is a group set apart from ordinary users, a special subset of users who are also developers of this technology who have necessary skills and training to perform successfully in this competitive development activity. That subset of individuals (computer scientists, computer programmers, code developers, computer technologists, etc.) is constantly challenged. They are normally under great pressure to produce new product offerings having enhanced features within constraining deadlines, and the amazing growth of the computer industry is to a large extent a result of efforts by these individuals to meet these goals within these deadlines. Accordingly, these individuals, and perhaps software developers in particular, are strongly motivated to find ways or techniques to make their tasks easier.
One category of tasks confronting certain software developers is the category of modifying a large body of complex code that has been developed by a large developer team over a long period of time into a substantially fixed body of code. Any modification of that type of code usually ripples throughout the entire body of that code causing severe rework problems. These modifications can be inordinately frustrating and can take immense amounts of time to accomplish. In certain software development environments not only can there be many different products under development at the same time, but the specifications of these products may be continuously changing or evolving. Accordingly, there is a need to react quickly to these changes in direction to the product lines. When there are severe pressures to meet deadlines on a number of different development fronts, the last thing a development team needs is the large headache of rewriting one or more large bodies of code.
One example of this kind of complex code is that which controls the terminal screen presentation on a GUI in a computer system or computer network. The network may, for example, be part of a storage network or storage area network (SAN). And, the screen presentation may include toolbars with accompanying menus and menu items as well as displays such as graphs, maps or trees. Examples of these kinds of presentations and techniques for enabling them are disclosed in U.S. patent application Ser. No. 09/916,102 filed Jul. 26, 2001, entitled: "Plug and Play Interface for User Actions", having inventors Munish T. Desai, Brian R. Gruttadauria and Andreas L. Bauer, assigned to the assignee of the present invention, and hereby incorporated by reference herein in its entirety.
In one of those displays to which the term "tree" presentation or display is applied, one element in the tree is visually connected from another element in the tree somewhat reminiscent of a tree-branching, giving rise to the term. This display would be familiar to users of various commercially-available software packages, such as Microsoft's Windows Explorer® software. The element at treetop is normally called a "root node" or "parent" and elements connected directly below and from that root node are termed "children" of that root node. Children of that root node's children are "grandchildren" of the root node, etc., comprising the "descendents" of that root node. Any child node in the descendent hierarchy can be selected or considered as a "local root node" for its descendents. These displayed nodes, which are visible to computer users, are normally constructed within the computer system or network as software "objects" which are then handled or controlled by object-oriented software running in the system or network.
A typical computer network being used today that can run object oriented software is a client-server network, the client being the user (GUI) or workstation and the server being software (discrete or distributed throughout the network) which serves the client. In this network, a computer system can employ one or more object-oriented computer languages such as C++, XML (eXtensible Markup Language), JAVA, and/or others. Briefly, an object, in computer software terms, is a dedicated area of memory which can be thought of as an impervious container holding both data and instructions within itself, both defining itself and its relationships to other objects in the computer system or network. Such object or node can send and receive messages to and from other objects, respond and react to such messages (e.g. commands) but shall normally be impervious to internal scrutiny. For example, in a computer data storage system (a kind of computer) each object (system object) may describe or relate to a specific tangible detail in the storage system or in the storage system's processor (e.g., details such as those describing or relating to aspects of operation of the processor's cooling-fan, power switch, cache memory, power supply, disk drive interface, individual disks, etc.). These tangible objects (nodes) within the storage processor in the storage system can send messages to each other within the storage system and to other objects outside the storage system over the network with which they are operatively coupled. The relationship between these specific objects in the storage processor is usually visualized or characterized as the tree to which reference was earlier made. In this tree, many children may typically hang from the same parent. In addition to these kinds of tangible objects, logical units (LUNs) are other nodes or objects that can be contained within a tree. Also, the storage processor itself and/or the storage system itself can be objects and interact as individual nodes, respectively, with other nodes in their network.
The tree relationship of these node objects may be displayed in tree fashion on the terminal screen of the GUI. This display is controlled, in part, by a large, fixed body of complex code which "paints" this tree display on the terminal screen, and to which reference was made hereinabove. What is needed, therefore, is a convenient and efficient technique for use by software developers to modify their complex code responsive to requests by customers or to their own company directives, as new functionality which was not part of the original, arduous code development is discovered/developed and is sought to be added to the original. Embodiments of the present invention satisfy this need otherwise left unsatisfied by the prior art.

Technique for graphical user interface modification


A method for cleaning a heat exchanging coil in an air conditioning unit using a low-pressure cleaning system to remove foreign particles that have accumulated on the heat exchanging coil. The low-pressure cleaning system discharges air at a low pressure, high velocity, and a high volume in order to clean the heat exchanging coil. Further, the low-pressure cleaning system can inject a substance into the discharge air flow to aid in cleaning the heat exchanging coil.

Air conditioning systems, such as roof top units that cool the air inside a building, rely on the efficient transfer of heat from a refrigeration fluid to the air through heat exchangers. Heat exchangers generally comprise a "heat exchanging coil" comprising one or more tubes interconnected by a plurality of thin metal fins that serve to increase the surface area of the tubes that is exposed to the air. As compressed refrigeration fluid passes through the tubes, a fan draws unfiltered air through the fins and around the tubes to facilitate cooling of the refrigeration fluid inside the tubes. The unfiltered air tends to carry dirt and debris from the surrounding environment, some of which becomes trapped in the spaces between the tubes and the fins. The efficiency of a heat exchanging coil in transferring heat from a refrigeration fluid to the air depends on how freely the air moves through the spaces between the tubes and the fins. If the spaces between the tubes and the fins are clogged by dirt and debris, the efficiency of a heat exchanging coil drops significantly.
Regular maintenance of the heat exchanging coil is important to maintain efficient heat transfer. Traditionally, heat exchanging coils are cleaned in a variety of ways, including, but not limited to, the use of high pressure "pressure washers." Pressure washers force high-pressure (1000 pounds per square inch ("psi") or higher) air or water through a small, usually hand-held nozzle that directs high-pressure air or water toward the heat exchanging coil to blow dirt and debris from the spaces between the tubes and the fins. The effective cleaning area of the air or water stream is approximately the size of the small nozzle orifice, which may be one-eighth inch to three-eighths of an inch (⅛–⅜″) in diameter in some cases. Significant labor costs are incurred when using small orifice, high-pressure nozzles because of the number of passes that must be made by the operator to clean a desired region of the heat exchanging coil.
The use of water-based pressure washers has several disadvantages. Water-based pressure cleaners typically require even higher pressures than do air-based pressure cleaners, because water has a much higher drag coefficient than air and is more difficult to "push" through a typical heat exchanging coil. Moreover, the large volume of water gallons per minute typically needed to clean a heat exchanging coil can cause damage to other components of an air conditioning system, which could lead to an electrical short in the circuitry of the air conditioning system. Further, the use of a large volume of water can cause damage to an adjacent building or other surrounding materials near the air conditioning system that is being cleaned. In order to prevent this damage, significant labor time is required to mask-off air conditioner components and the surrounding building to prevent or limit water damage during water-based cleaning of a heat exchanging coil.
Any type of high-pressure cleaning method can cause damage to a heat exchanging coil because the high pressure tends to bend the fins and/or fold the fins over, which closes the space between the tubes and the fins and leads to a loss of heat exchanger efficiency. In addition, high pressure water cleaning methods always impose extreme force on the coil bundle which can loosen the tight fit between the fin and tube causing reduced efficiency and mechanical damage. Thus, there is a need for an improved system for cleaning heat exchanging coils that reduces the labor time required to clean a coil, reduces the risk of damage to the coil fins, reduces the labor time needed to mask and clean a coil, and reduces the possibility of damage to the building on which the heat exchanging coil is installed.

Low-pressure cleaning system using high velocity high volume air


The present invention relates to isolation and characterization of novel nucleotide sequences from rice tungro bacilliform virus (RTBV) showing promoter activity in plants. The present invention further relates to the analysis of the functional domains of RTBV promoters by fusing full-length and deleted versions of the RTBV promoter sequences with the bacterial reporter gene GUS. The invention also relates to the study of the expression of the reporter gene in various tissues of transgenic rice and tobacco plants during different stages of development. The present invention also describes an RTBV promoter and its deletions which function in a constitutive or tissue-specific manner to drive the expression of the heterologous nucleic acid sequences in both monocot and dicot plants, cells and tissues.

Rice is considered to be the most important food crop in the world as it is the primary source of dietary calories to majority of human beings. To continue providing adequate calories and to improve the quality of rice-based food in the coming years for the growing population of rice-eaters, the rice plant has to be improved in order to increase yields by exploiting hybrid vigor, to withstand unfavorable conditions like pests, diseases, drought, flooding, salinity and extreme temperatures and to incorporate added nutrients. For a majority of these improvements, genes taken from other organisms, commonly known as transgenes, have to be introduced and expressed in rice.
From agronomic point of view, to generate superior rice varieties, multiple genes conferring desirable genetic traits need to be introduced into the same transgenic background. Accomplishing gene pyramiding, however, is not as easy.
In order to ensure stable expression of the transgenes, they have to be fused to specific DNA elements known as promoters, which function as controlling units for the generation of mRNA from genes, the most important stage of gene expression. These sequences are essentially regulatory in nature, in the sense they initiate the process of transcription and may regulate the rate of transcription. A relatively small number of promoters have been commonly used for expressing transgenes in plants. Additionally, the number of promoters which can drive high levels of constitutive expression in both dicot and monocot plants are even fewer. Also, there are just a handful of promoters driving tissue- or organ-specific expression. The current scientific challenge therefore, lies in the identification of novel regulatory elements to introduce greater versatility in terms of attaining desired spatio-temporal mRNA expression patterns.
Studies have shown that using the same promoter to drive the expression of two distinct heterologous genes in the same plant can lead to gene silencing. This problem can, however, be circumvented by using different promoters for each of the heterologous gene. Hence, there is a need for identifying new promoters which can show tissue- and/or development-specific expression, and can be used for transgene expression in various plants. This document provides such information on a new promoter identified and characterized from the rice tungro bacilliform virus (RTBV), isolated and modified from virus infected rice plants growing in fields in West Bengal, India.
The Cauliflower mosaic virus 35S promoter (CaMV 35S) and its derivatives are among the most commonly used promoters for this purpose. The CaMV 35S is active in dicots, but its relative strength is substantially lower in monocots than in dicots. Other dicot promoters have also been used for monocot transformation, but activity tends to be lower for monocot promoters (Wilmink et al., 1995). Several promoters have been identified to drive a high level of transgene expression in monocots, for example, the rice Act1 promoter (McElroy et al., 1991), the rice rbcs promoter (Kyozuka et al., 1993), the maize Ubi1 promoter (Toki et al., 1992; Cornejo et al., 1993) and the rice cytochrome C gene promoter OsCc1 (Jang et al., 2002). Of these, only the CaMV 35S (Terada and Shimamoto, 1990), rice Act1, maize Ubi1 and rice OsCc1 are constitutive in nature. Only a few tissue-specific promoters have been identified in rice. For example, rice seed storage protein glutelin (Gt1) promoter has been used to express transgenes in rice seeds (Ye et al., 2000) and rice Glu-B1 promoter has been used for endosperm-specific expression of soybean ferritin gene (Goto et al., 1999). Some of the other characterized promoters in rice include, the potato pin2 promoter which has been shown to be wound inducible (Xu et al., 1993), the maize Adh1 promoter which is strongly induced in roots under anaerobic conditions (Kyozuka et al., 1991) and the maize pep and rbcS promoters which are mesophyll specific (Matsuoka et al., 1994).
Beachy, Roger N. and Bhattacharyya, Maitrayee have identified and characterized a promoter from RTBV, isolated from Philippines (U.S. Pat. No. 5,824,857). The utility of the promoter was implicated in driving vascular specific expression in transgenic plants. However, the present study deals with the identification and characterization of a promoter fragment from RTBV, isolated from West Bengal, India, which has no significant homology to the previously-characterized RTBV promoter. The DNA sequence of this full-length clone has been deposited in the EMBL Sequence Database and has been assigned the following accession number: AJ314596, but no function to the DNA sequences was assigned earlier. The present invention deals with the identification of new promoters from RTBV (West Bengal isolate) and their use for transgene expression in plants.


A space saver pillow system comprises a space saver pillow and a bag. The space saver pillow includes a fill and a covering surrounding and enclosing the fill. The fill of the space saver pillow is adapted to generally rebound back to its natural state after being compressed. The bag encloses the space saver pillow and an amount of air. The space saver pillow enclosed in the bag is compressed no more than about 80% of its original size.

Businesses and individuals often times look for ways to reduce storage and packing space whether it be for storage and/or mass shipment of products. The need for space is especially true in the health care industry where it is particularly necessary for organizations such as hospitals and nursing homes to store a large number of supplies, such as new and clean pillows. However, storage space in these facilities is usually far from plentiful and some products, such as pillows, tend to take up quite a bit of space.
In relation to pillows, the above-identified issues have been addressed in the past by rolling and/or compressing pillows. However, various additional issues arise when rolling a pillow. For example, difficulties have been encountered in producing a smooth, uniform roll that is compact and stable. Some pillow arrangements are difficult to secure and stabilize in the rolled-up configuration. Compressing pillows (i.e., by vacuum packing) typically allows one to reduce the size of the pillow more so than rolling the pillow. However, in doing so, a different set of problems arise. Specifically, due to the amount of compression and the fill material typically used in pillows, the pillow typically becomes over-compressed. Upon decompression, the ability of the pillow to rebound back to its original shape is hindered and the pillow often times remains deformed in shape.
Accordingly, to meet the need for a pillow which can significantly be reduced in size without compromising the integrity and ability of the pillow to rebound back to its original shape upon decompression, the present inventors have developed a pillow and method of compression which addresses these issues.

This patent is subject to a terminal disclaimer.

Space saver pillow system and method for making the same


A method of manufacturing gem decorated articles, typically jewelry, includes the steps of: using a first mold which has a mold cavity with one or more gem portions for receiving one or more gems and duplicates a model of the article; positioning one or more gems in the mold gem portion(s) of the mold; forming a temporary bond between the gem(s) and the mold gem portion(s) of the mold to maintain the gem(s) in place in the mold gem portion(s) during formation of a wax model including the gem(s); introducing a molten, hardenable wax material into the mold; cooling the wax material to form a wax model reproduction of the article with the gem(s) set therein; ending the temporary bond between the gem(s) and the mold gem portion(s) of the mold; removing the wax model with the set gem(s) from the mold; applying an investment material about the wax model with the set gem(s) and hardening the investment material to form a second mold; removing the wax material from the second mold; introducing a molten metal into the second mold; hardening the metal through cooling to form an article with the gem(s) preset therein; and removing the article from the second mold. If needed, insecurely set gems can be adhesively bonded to the wax model and wax projections can be used to facilitate the removal of the gems with the wax model from the first mold.

The present invention relates to a method of making articles of jewelry with one or more gems set in a metal support or setting and, more specifically, to a method of making articles of jewelry wherein one or more gems are properly set into the articles of jewelry during the casting of the metal support or setting.
Articles of jewelry are commonly formed by casting a precious metal support or setting and thereafter manually placing a gem or gems in position on the precious metal support or setting and anchoring the gem or gems in place in or on the precious metal support or setting, e.g. by hammering and moving metal or by bending prongs or other anchoring elements over facets of the gem or gems. A great deal of time and skill is required to properly orient and anchor the gem or gems in place, especially when several gems are being set in the support or setting. Thus, this procedure of making or manufacturing articles of jewelry greatly increases the cost of making or manufacturing such articles of jewelry and frequently, if one or more gems are not properly anchored in the support or setting, the gems become loose and are lost or the article of jewelry must be repaired.
U.S. Pat. No. 4,154,282; issued May 15, 1979; inventor, Herbert Kull; (hereinafter the "Kull Patent") discloses a method of manufacturing articles of jewelry with a single gem set in the precious metal support during the casting process. While an improvement over the method of making such articles of jewelry described above, the method of manufacturing articles of jewelry disclosed in the Kull Patent still presents manufacturing problems. As pointed out in U.S. Pat. No. 4,392,289; issued Jul. 12, 1983; inventor Franck Michaud; (hereinafter the "Michaud Patent"), the method described in the Kull Patent presents a problem with respect to maintaining the gem in its proper position and orientation during the formation of the wax model reproduction of the article of jewelry, especially when several gems are being set in the wax model reproduction. In the Kull Patent method of making an article of jewelry, a high degree of care must be exercised in closing the open rubber mold, after the gem(s) have been positioned in the open rubber mold, to keep from displacing the gem(s) prior to injecting the wax material to form the wax model reproduction, especially when several gems are being set in the wax model. The displacement of the gem(s), prior to the formation of the wax model reproduction, is not apparent until the wax model has been removed from the rubber mold thereby necessitating the removal of the gem(s) from the wax model after the wax model has been formed, the discarding of the wax model, and the repositioning of the gem(s) in the rubber mold to again attempt to form a wax model of the article of jewelry with the gem(s) properly positioned and oriented in the wax model.
The Michaud Patent attempts to solve the problem of gem displacement by forming rubber molds, from the article of jewelry to be reproduced, with opposing undercut grooves located in the sidewalls of the seats of each gem setting to engage portions of the girdles of the gems as the means of securing or anchoring the gems in the wax material model. An elastic wax material is introduced into the rubber mold to form the wax model. After the elastic wax model is removed from the rubber mold, the gems are "snapped" into their set position in the seats of the elastic wax model with the girdle of the gem in the opposed undercut grooves.
The method set forth in the Michaud Patent may solve some of the problems associated with the method disclosed in the Kull Patent. However, there has remained a need for a method of making such articles of jewelry which assures the accurate placement and orientation of the gems in the article of jewelry: without restricting the article of jewelry to those wherein each gem of the article is positioned relative to the precious metal support and other gems so that the mold can be provided with a seat with undercut grooves to hold each gem; and without requiring the sizes or dimensions and shapes of the gem girdles to be uniform.
Almost all diamonds and other gems are individually cut by hand and polished. Accordingly, the shapes and dimensions or sizes of the girdles of these hand cut gems differ. Even with respect to gems which are categorized as the same in dimensions or size and shape, there will be at least slight differences in the thicknesses or other dimensions of the girdles and the shape of the girdle will vary with some gems having a more sharply defined girdle and other gems having a more rounded girdle. Thus, when these gems are "snapped" into the undercut grooves, even for gems categorized as having the same size or dimensions and shape, there will be differences in the sizes or dimensions and shapes of the gems which will cause at least some of the gem seats to be expanded more than adjacent gem seats. While the wax materials used in processes, such as the Michaud process, may be somewhat elastic, in most instances the wax materials are not elastic enough to compensate for the over expansion of one gem seat (by the insertion of a gem) relative to adjacent gem seats. Accordingly, gems, having smaller dimensions or sizes and shapes, inserted into these adjacent gem seats will not be securely held in place. This problem is amplified when gems of different sizes and shapes are to be mounted adjacent each other in such a setting. There has also been a need to provide a method of making such articles of jewelry without requiring the use of elastic wax materials.

Method of casting metal around gems to form articles of jewelry