A contact lens (4) comprises a solid component capable of imparting shape and structure to said lens, and a liquid component, at least partially contained in the solid component, capable of favoring the compatibility between said lens and the eye of a user of said lens, wherein the liquid component comprises a solution capable of being used as a lachrymal substitute.

It is known that contact lenses, whether they are cosmetic or corrective, are widely used among the population. Among these, particular importance is given to contact lenses of the soft type, which, compared with the other types of lenses (rigid or semi-rigid) provide greater comfort in use.
This advantageous characteristic is provided by the high hydrophilic capacity of the lens which, containing a substantial percentage of water, permits greater compatibility between the lens and the eye, in addition to a greater deformability of the lens which allows it to adapt better to the surface of the eye.
Soft contact lenses are conventionally produced by means of a method which provides for a first step of obtaining a dry semi-manufactured product of lenticular shape and made of polymeric material, which may in turn be obtained by the polymerization of a monomer directly in a die (moulding technique), or by turning a disc of already polymerized material (turning technique).
Independently of the technique used for its preparation, the dry semi-manufactured product is then hydrated by immersion in a saline solution (known as a physiological solution) composed of around 1% by weight of sodium chloride in water. The polymeric material used is typically endowed with optimum hydrophilic properties, and is normally a polymeric mixture based on HEMA, so that a substantial amount of saline solution, between 25% and 75%, is absorbed in the dry semi-manufactured product.
The absorption of the liquid component, besides imparting to the lens the above-mentioned characteristics of compatibility and softness, also includes physical expansion of the dry semi-manufactured product, both radial and linear, thus determining both the final dimensions of the contact lens, and its optical properties.
The contact lens thus obtained thus comprises a solid component, defining the structural portion of the lens and composed of the polymeric material, and also a liquid component, composed of the saline solution, distributed almost uniformly in the solid component.
The marketing of the contact lens provides for the preparation of suitable packs, produced for example in the form of blister packs, in which the lenses are stored and maintained for the entire period between the end of the process of manufacturing same, and the first use thereof by a user.
The packs must therefore be arranged to maintain unaltered over time the mechanical, optical and dimensional characteristics of the lenses.
To this end, the packs typically comprise a support defining a container which is filled, at least partially, with physiological solution, in which the contact lens, in its turn, is immersed. The container is further conveniently closed by a membrane, generally constituted by a thin metallic sheet (known in the field as a "foil"), subsequently removable by the user in order to extract the lens from the container.
It is known that one of the major drawbacks arising from the use of contact lenses is represented by the sensation of ocular dryness, caused by the reduction or by the breakdown of the lachrymal film which surrounds and protects the cornea. This typically involves a sensation of discomfort and irritation which frequently forces the user to remove the lenses and which, in the long term, may also lead to changes in the lachrymal function and to other pathological disfunctions at the expense of the eye (such as, for example, corneal or conjunctival inflammation).
Also owing to this drawback, many persons are capable of wearing the contact lenses only for a very limited time or are even prevented from doing so.
In order to overcome this drawback, at least in part, various technical solutions have been developed and proposed.
A first of these solutions, for the formation of the solid component, provides for the use of polymers and/or copolymers having the highest possible hydrophilic properties. Such polymers and/or copolymers may be used for producing the entire solid component of the lens, or only as an outer coating of same. The use of such polymers, however, has a negative effect on the overall costs of production, but without succeeding in providing resolutory advantages with regard to the above-mentioned drawback. Moreover, such use may also turn out to be counter-productive in the case where the lens remains in the eye for a prolonged period, since the greater the amount of water released by the contact lens, the greater the variation in the dimensions thereof, with potential negative repercussions on its optical properties.
A second known solution is provided by the use of external solutions, known generically and overall as "lachrymal substitutes" ("artificial tears"). These latter are aqueous solutions comprising substances, generally polymers, the overall properties of which tend to reproduce, as far as possible, the properties of the natural lachrymal liquid.
In order that an aqueous solution can be defined as a lachrymal substitute, it must possess particular chemico-physical and rheological characteristics and bio-compatibility. In particular, specific and high visco-elastic and hydrophilic properties are required, as well as muco-adhesive properties (in order to remain attached for as long as possible to the mucinic component of the lachrymal film), mucomimetic properties (for simulating in the best possible manner the behaviour of the lachrymal film) and the ability to bathe the cornea, in addition, obviously, to general compatibility with the tissues of the eye.
The use of lachrymal substitutes provides for their addition as drops directly on to the eye to which the contact lens is fitted, so that the need to have recourse to this expedient is a not very pleasing eventuality to many people, without considering the further inconvenience of having to carry phials or containers with one. Moreover, the beneficial effect of the lachrymal substitutes is very limited over time, so that it is often necessary to have recourse to them several times a day and in all kinds of places.
In certain cases, provision is also made for the application of the lachrymal substitute to take place directly on the lens, both when worn and prior to its being fitted, but this expedient does not substantially modify the to picture described above. In fact, the absorption of the lachrymal substitute into the lens is limited to its outermost surface layers, and is therefore retained in very small amounts and thus with a beneficial effect necessarily limited over time.
The wider view of the technical field of reference of the invention is completed by contact lenses used as vehicles for the administration through the eye of drugs for therapeutic use. Such lenses, known also as "ophthalmic dressings", are typically contact lenses obtained in a quite conventional manner, to which are then added one or more drops of the drug to be administered. The effect of release of the drug has, however, a very limited duration. Some solutions for contact lenses are also known for use as ophthalmic dressings, in which an endeavour has been made to increase the duration of the release of the drug. One of these solutions provides for the interposition of a support soaked in the substance to be administered between a pair of contact lenses.

Contact lens, method for producing same, and pack for storage and maintenance of a contact lens


The present invention provides compositions and methods for the regulation of cytokine signaling through the Tumor Necrosis Factor (TNF) pathway. Specifically, the invention provides a novel gene, polypeptide and related compositions and methods for the regulation of ectodomain shedding. In preferred embodiments, methods and compositions for the regulation of TNF Type-1 Receptor ectodomain shedding are provided. The present invention finds use in therapeutics, diagnostics, and drug screening applications.

Aberrant regulation of cytokine signaling results in a wide variety of hyper-inflammatory, autoimmune and immune-deficiency pathological conditions. Cytokines are a large and diverse group of molecules which mediate interactions between cells, ultimately regulating the wide variety of cells of the immune repertoire. Cytokine signaling mediates numerous facets of normal immune system physiology, including development, response, activation, maintenance, memory and apoptosis (Roitt et al. (Eds.), Immunology, Fifth Edition, Mosby International Publishers [1998]).
Tumor Necrosis Factor
Tumor necrosis factor-α (commonly written as TNF, but also written as tumor necrosis factor or TNFα) is a multifunctional cytokine mediating pleiotropic biological functions in both health and disease states. TNF is secreted primarily by monocytes and macrophages, but can also be secreted by other cell types. The list of processes regulated by TNF is extensive, and includes inflammation, immunoregulation, cyytotoxicity and antiviral effects (See e.g., Vilcek et al, J. Biol. Chem., 266:7313–7316 [1991]). TNF plays an integral role in destroying tumors, mediating responses to tissue injury, and protecting hosts from infections by various microorganisms (Vassali, Ann. Rev. Immunol., 10:411–452 [1992]). TNF also induces the transcriptional activation of numerous genes, including NF-κB and AP-1, with the consequent expression of pro-inflammatory and immunoregulatory genes (Rothe et al., Cell 83:1243–124 [1995]; Varfolomeev et al., J. Exp. Med., 183:1271–1275 [1996]; Chinnaiyan et al., J. Biol. Chem., 271:4961–4965 [1996]; Hsu et al., Immunity 4:387–396 [1996]; and Hsu et al., Cell 84:299–308 [1996]). TNF-mediated NF-κB activation is also an important negative feedback mechanism regulating apoptosis (Beg and Baltimore, Science 274:782–784 [1996]; Van Antwerp et al., Science 274:787–789 [1996]; and Wang et al., Science 274:784–787 [1996]).
TNF in Disease
TNF has also been implicated in the pathogenesis of a variety of diseases and disorders. It is theorized that these pathologies result from the aberrant regulation of TNF activity, in which the pathologies manifest as a result of excessive or insufficient TNF activity. Among the activities for which TNF is most noted are its pro-inflammatory actions, sometimes termed the "acute phase immune response." Unfortunately, if not properly regulated, these proinflammatory responses can result in tissue injury and chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, septic shock, cachexia, autoirumune disorders, graft-versus-host disease and insulin resistance (Piguet et al., J. Exp. Med., 166:1280 [1987]; Pujol-Borrell et al., Nature 326:304–306 [1987]; Tracey et al., Nature 330:662–664 [1987]; Oliff, Cell 54:141–142 [1988]; Vilcek et al., J. Biol. Chem., 266:7313–7316 [1991]; and Eigler et al., Immunol. Today 18:487–92 [1997]). Excessive TNF activity results in the detrimental effects of an exaggerated immune response demonstrated in some of these diseases, exemplified by overstimulation of interleukin-6 and granulocyte/macrophage-colony stimulating factor (GM-CSF) secretion, enhanced cytotoxicity of polymorphonuclear neutrophils, prolonged expression of cellular adhesion molecules, induction of procoagulant activity on vascular endothelial cells, increased adherence of neutrophils and lymphocytes, and stimulation of the release of platelet activating factor from macrophages, neutrophils and vascular endothelial cells (Vassali, Ann. Rev. Immunol., 10:411–452 [1992]; Vilcek et al., J. Biol. Chem., 266:7313–7316 [1992]; and Barbara et al., Immunol. and Cell Biol., 74:434–443 [1996]).
Recent evidence also implicates TNF activity in the pathogenesis of many infections. TNF is thought to play a central role in the pathophysiological consequences of Gram-negative sepsis and endotoxic shock, including fever, malaise, anorexia, and cachexia (Beutler et al., Nature 316:552–554 [1985]; Bauss et al, Infect. Immun., 55:1622–1625 [1987]; Tracey et al., Nature 330:662–664 [1987]; and Vassali, Ann. Rev. Immunol., 10:411–452 [1992]). Because TNF can mimic many of the biological effects of endotoxin, it is theorized that TNF is a central mediator responsible for the clinical manifestations of endotoxin-related and other critical illnesses (Waage et al., Lancet 1:355–357 [1987]; Cerami et al., Immunol. Today 9:28 [1988]; Mitchie et al., N. Eng. J. Med., 318:1481–1486 [1988]; Revhaug et al., Arch. Surg., 123:162–170 [1988]; and Michie et al., Ann. Surg., 209:19–24 [1989]).
Tumor Necrosis Factor Receptor
The numerous biological effects of TNF are now known to be mediated by two transmembrane receptors, the 55 kilodalton Type I receptor (also written as "CD120a," and referred to herein as "TNFR1") and the 75 kilodalton Type II receptor (also written as "CD120b," and referred to herein as TNFR2). Although both TNFR1 and TNFR2 demonstrate strong affinity for TNFα, these two receptors demonstrate no apparent homology in their cytoplasmic (i.e., intracellular) domains. This fact is consistent with the observation that these two receptors transduce different signals to the nucleus via distinct signaling intermediates (Lewis et al., Proc. Natl. Acad. Sci. USA 88:2830–2834 [1991]; Tartaglia and Goeddel, Immunol. Today 13:151–153 [1992]; and Barbara et al., Imunol. Cell Biol., 74:434–443 [1996]).
Soluble TNF inhibitors have been identified in normal human urine, as well as in sera and other body fluids of patients with infectious, neoplastic and immunologic disorders. This observation ultimately led to the revelation that these soluble TNF inhibitors were actually the extracellular domains of TNF receptors derived by proteolytic cleavage of the transmembrane forms (Engelmann et al., J. Biol. Chem., 264:11974–11980 [1989]; Olsson et al., Eur. J. Haematol., 42:270–275 [1989]; Seckinger et al., J Biol. Chem., 264:11966–11973 [1989]; Engelmann et al., J. Biol. Chem., 265:1531–1536 [1990]; and Aderka et al., J. Exp. Med., 175:323–329 [1992]). In the case of the TNFR1, this proteolytic activity results in the cleavage and shedding of the extracellular N-terminal domain (also called the ectodomain). These free, soluble TNFR1 ectodomains ("sTNFR1s") have an affinity for TNF that is similar to that of intact membrane receptors. Due to this affinity, the free receptors are able to bind and sequester TNF, thereby inhibiting the biological action of TNF. Furthermore, the generation of sTNFR1 is also likely to suppress TNF signaling by reducing the number of functional TNF receptors acting at the cell membrane. The sTNFR1 ectodomains are also theorized to serve a more complex buffering function in the regulation of TNF activity (Aderka et al., J. Exp. Med., 175:323–329 [1992]; and Werb and Yan, Science 282:1279–1280 [1998]). The complexity of TNF signaling is fuirther illustrated by the observation that many of the stimuli that result in TNF release also result in the release of the soluble TNF receptor, suggesting that these soluble TNF inhibitors may serve as part of a regulated feedback mechanism to control TNF activity (Adreke et al., J. Exp. Med., 175:323–329 [1992]; and Porteu and Nathan, J. Exp. Med., 172:599–607 [1990]).
The importance of TNFR1 in the regulation of TNF activity in host defense, immunoregulation and development has been fuirther demonstrated in studies utilizing TNFR1 knockout mice. Mice deficient in TNFR1 show a variety of phenotypes, including phenotypes which mimic human immune disorders (Pfeffer et al., Cell 73:457–467 [1993]; Rothe, Nature 364:798–802 [1993]; Le Hir et al., J. Exp. Med., 183:2367–2372 [1996]; Matsumoto et al., Science 271:1289–1291[1996]; Mori et al. J. Immunol. 157:3178–3182 [1996]; Speiser et al., J. Immunol., 158:5185–5190 [1997]; Tkachuk et al., J. Exp. Med., 187:469–477 [1998]; and Kagi et al., J. Immunol., 162:4598–4605 [1999]).
The key role of TNFR1 shedding in the regulation of TNF bioactivity is highlighted by the association of germline mutations in TNFR1 extracellular domains with impaired TNFR1 shedding and autoinflammatory disease characterized by autosomal dominant periodic fever syndromes (McDermott et al., Cell 97:133–144 [1999]).
Other Mediators of Acute Phase Response
In addition to TNF, other cytokines have been implicated in the induction of the pro-inflammatory response (i.e., the acute phase immune response). These cytokines which demonstrate overlapping activities with TNF include the interleukins (e.g., IL-1 and IL-6) (Suffredini et al., J. Clin. Immunol., 19:203–214 [1999]).
IL-1 (consisting of both α and β forms) is an important proinflammatory cytokine which regulates the expression of a wide variety of target genes and proteins in nearly every cell type (Dinarello, Blood 77:1627–1652 [1991]; and Dinarello, The Cytokine Handbook (ed. Angus W. Thomson), 3rd edition, Academic Press, San Diego, p. 35–72 [1998]). The spectrum of IL-1-mediated biologic effects includes inflammatory, metabolic, physiologic, hematopoietic, and immunologic functions. IL-1 is thought to play a role in the pathogenesis of several disease states, including septic shock, rheumatoid arthritis, inflammatory bowel disease, myelogenous leukemia, diabetes mellitus, and atherosclerosis (Dinarello et al., N. Engl. J. Med., 328:106–113 [1993]).
IL-6 is also a multifunctional cytokine with pleiotropic pro-inflammatory effects (DiCosmo, et al., J. Clin. Invest., 94:2028–2035 [1994]; and Kishimoto et al., Blood 86:1243–1254 [1995]). For example, IL-6 plays an important role in regulating B cell immunoglobulin production, T-cell activation, growth and differentiation, hematopoiesis, hepatic acute phase reactions and osteoclast development (Hirano, The Cytokine Handbook (ed. Angus W. Thomson), 3rd edition, Academic Press, San Diego, p. 197–228 [1998]). Dysregulated production of IL-6 may contribute to the pathogenesis of a variety of inflammatory, neoplastic and autoimmune disorders, such as plasma cell neoplasia and Castleman's disease (Yoshizaki, et al., Blood 74:1360–1367 [1989]; and Hirano, Int. J. Cell Cloning 9:166–184 [1991]).
The signal transduction pathways utilized by TNF, IL-1 and IL-6 also show shared signaling intermediates. For example, both TNF and IL-1 can activate both NF-κB and AP-1, which are important pro-inflammatory transcription factors (Ashkenazi et al., Science 281:1305–1308 [1998]; and Dinarello, The Cytokine Handbook (ed. Angus W. Thomson), 3rd edition, Academic Press, San Diego, p. 35–72 [1998]). Similarly, IL-6 signaling uses components of the JAK-STAT pathway, which has also been reported to be induced by TNF (Guo et al., J. Immunol., 160:2742–2750 [1998]; and Hirano, The Cytokine Handbook (ed. Angus W. Thomson), 3rd edition, Academic Press, San Diego, p. 197–228 [1998]).
The cognate receptors for the IL-1 and IL-6 cytokines are known. There are two IL-1 receptor forms, type I and type II. There is a single IL-6 receptor, consisting of gp80 alpha chain and gp130 beta chain subunits, where ligand binding is mediated by the alpha subunit. The IL-1 and IL-6 receptors are also present as soluble forms analogous to the soluble form of TNFR1. Furthermore, it has been suggested that these receptors play a role in the regulation of IL-1 and IL-6 activity and pro-inflammatory response (Dower et al., J. Immunol., 142:4314 [1989]; Novick et al., J. Exp. Med., 170:1409 [1989]; Eastgate et al., FEBS Lett., 260:213 [1990]; Giri et al., J. Biol. Chem., 265:17416 [1990]; Symons et al., Cytokine 2:190 [1990]; Symons et al., FEBS Lett., 272:133 [1990]; Symons et al., J. Exp. Med., 174:1251–1254 [1991]; Mullberg et al., Biochem. Biophys. Res. Commun., 189:794 [1992]; Mullberg et al., Eur. J. Immunol., 23:473 [1993]; Svenson et al., Cytokine 5:427 [1993]; and Arend et al., J. Immunol., 153:4766–4774 [1994]).
Analogy between regulation of TNF and other cytokines is further illustrated by studies utilizing peptide-hydroxamate metalloprotease inhibitors. Specifically, the protease inhibitors TAPI (TNF-α protease inhibitor) and RU36156 have been reported to inhibit the proteolytic cleavage and shedding of both TNFR1 and IL-6R (Mullberg et al., J. Immunol., 155:5198–5205 [1995]; and Gallea-Robache et al., Cytokine 9:340–346 [1997]).
As discussed above, in view of the importance of TNF, IL-1 and IL-6 in both health and disease states, there exists a need for methods and compositions for the regulation of TNF, IL-1 and IL-6 cytokine activity. These methods and compositions will find use as therapeutic agents for the treatment of disease states.

Regulators of type-1 tumor necrosis factor receptor and other cytokine receptor shedding

The United States of America as represented by the Department of Health and Human Services


A pressure regulator for a fuel supply system of an internal combustion engine for regulating a fuel pressure, including a valve, having a valve ball forced against a valve seat into the closing position by the action of a valve leaf spring. With the valve open, at least some of the fuel flow that flows around the valve ball is deflected against an impact face coupled with the valve leaf spring for generating a flow force oriented counter to the closing force of the valve leaf spring. As a result, the pressure regulating performance of the pressure regulator is improved.

1 . Field of the Invention
The invention is directed to an improved pressure regulator for a fuel supply system of an internal combustion engine for regulating a fuel pressure, including a valve which includes a valve ball that is forced against a valve seat into the closing position by the action of a valve leaf spring.
2 . Description of the Prior Art
One pressure regulator of the type with which this invention is concerned is described by German Patent Disclosure DE 101 07 223A1, in which the valve leaf spring is pivotably supported, and one arm of the valve leaf spring toward the valve seat with respect to the pivotable support is braced on the valve ball, while one arm of the valve leaf spring located on the side opposite the valve seat is braced on a support body, in such a way that torque equilibrium prevails at the valve leaf spring. The prestressing force generated by the support body is transmitted by the valve leaf spring to the valve ball in the form of closing force. If fuel pressure that is high enough to generate a greater pressure force than the closing force acting on the valve ball prevails at the pressure input, then the valve ball lifts from the valve seat and opens a defined flow cross section, so that fuel can flow to the pressure outlet. SUMMARY AND ADVANTAGES OF THE INVENTION
Without the impact face according to the present invention, the force exerted by the valve leaf spring on the valve ball of the known regulator increases steadily as the flow becomes greater and consequently the valve ball stroke lengthens. Since an equilibrium of force or moment ensues at the valve leaf spring, the result is that with an increasing flow, the fuel pressure likewise increases, in a way that is unwanted for a pressure regulator.
As a result of the definitive characteristics of the invention a comparatively lesser increase in the characteristic pressure and flow curve of the pressure regulator is obtained; therefore even if the flow quantity increases, the set pressure becomes only slightly greater. When the valve ball has lifted from the valve seat, the deflection according to the invention of the fuel flow to the impact face creates a flow force that acts on the valve leaf spring counter to the closing force of the valve leaf spring and that is greater, the greater the flow through the valve of the pressure regulator. Thus with a greater flow and a consequent longer stroke of the valve ball, on the one hand the force exerted by the elastic valve leaf spring on the valve ball in the closing direction increases, but on the other hand, the contrary flow force on the valve leaf spring also increases, so that these forces at least partly compensate for one another. As a result, the influence of the stroke of the valve leaf spring and thus the influence of the flow on the pressure are advantageously less.
In a preferred embodiment, the impact face is formed by a portion of a lower face of the valve leaf spring, which portion is adjacent to a contact point of the valve ball with the valve leaf spring. This is especially advantageous in terms of production costs, since because of the integration of the impact face with the valve leaf spring, no additional components are necessary.
In order to deflect the fuel flow, flowing around the valve ball, onto the impact face at the valve leaf spring, the valve seat preferably has a cone angle in a range between 40° and 110°, preferably 60°.
In a further embodiment, the impact face is formed by a face that is defined at the valve ball and extends radially outward into the fuel flow. As a result, the fuel flow flowing around the valve ball can strike the impact face nearly perpendicularly, and this is an ideal state in terms of the flow force generated as a result.
In an especially preferred embodiment, the valve leaf spring is provided with at least one opening, which increases in cross section in a direction pointing away from a leaf spring bearing point. As a result, if the valve leaf spring bends, a substantially constant tension ensues over the length, and the spring constant of the valve leaf spring becomes relatively low; changes in the stroke of the valve ball therefore have a lesser effect on the pressure. In the preferred embodiment, in which the impact face is located on the valve leaf spring, the opening is located outside the impact face, in order not to hinder the buildup of the flow force.
A refinement provides that the valve leaf spring is embodied as rectangular and the opening is embodied as essentially triangular. The valve leaf spring is preferably supported tiltably at a pivot shaft, and one arm of the valve leaf spring is tensed against a prestressing spring for generating a force by which the other arm of the valve leaf spring holds the valve ball down in the valve seat. Then, both arms of the valve leaf spring are provided with at least one triangular opening, since they both contribute to the overall bending strength of the valve leaf spring.

Pressure regulator for a fuel supply system of an internal combustion engine


A motor assembly comprises a plurality of redundant bearings, a plurality of coaxial support elements, with at least one of the support elements rotatable about an axis of rotation, and an armature rotatably guided by the plurality of support elements to rotate about the axis of rotation. The bearings provide redundancy to continue armature rotation in the event one bearing fails.

1. Field of the Invention
This invention relates to electric systems, and more particularly to motor assemblies.
2. Description of the Related Art
Electric motor driven fans have become an integral part of design for thermal management in electronics. These fans, typically used to cool heat generating components in computer servers, personal computers (PCs) and other electronics, play a critical role in system reliability and longevity. Typical fans have stator windings ("stators"), a single bearing sleeve and a shaft. The stators induce rotor magnets ("rotors") on a blade assembly armature 130 to rotate, causing air movement through the fan. Various types of fans are used to cool heat generating components, including tube-axial, vane-axial, centrifugal, and blower fans. Regardless of the type of fan used, motor and bearing failures must be minimized to enhance reliability and longevity.
One approach to reduce the impact of motor and bearing failures is described by D. Kim et al. in U.S. Pat. No. 5,920,264. Thermal conditions around the system's cooled parts are monitored to provide a warning should overheating develop. When the temperature around the monitored parts increases past a predetermined level, an alarm sounds from a speaker so that a user can stop the power supplied to the system. Another solution is presented by S. Wrycraft in U.S. Pat. No. 6,011,689 in which an array of fans arranged in parallel cool components in a computer system. Each fan includes an airflow closure member that closes upon failure of the fan. The closure prevents cool air from escaping through the failed fan prior to flowing over a component to be cooled. In this manner, a fan suffering from a failed motor or bearing will not adversely affect the performance of the other fans in the array.
Another solution to reduce the impact of motor and bearing failures is to use multiple fans in series. Unfortunately, this arrangement produces undesirable turbulence noise and increased system impedance if one of the fans should fail. Fan redundancy, either with fans positioned in parallel or series, also reduces the space available for other components and increases system cost due to the increased parts count.
A need continues to exist, therefore, for a motor assembly with increased reliability and longevity without increasing noise, system cost or reducing space available for other components.

Motor assembly using redundant bearings and support elements

Hewlett-Packard Development Company, L.P.


A water-absorbing resin has a polymer molecular chain in which 50 mol % or more of repeating units in the chain are carboxy group-containing units, wherein the carboxy group neutralization ratio in the central part of the resin is 60 mol % or more and the carboxy group neutralization ratio on the external surface of the resin is 50 mol % or less. A method for producing the water-absorbing resin comprises polymerizing a monomer solution to form a polymer, drying the resulting polymer, and heat-treating the dried polymer, wherein the monomer solution contains a mixture comprising an alkali metal salt of an unsaturated carboxylic acid and an ammonium salt thereof, the percentage of the ammonium salt being more than 50 mol % of the mixture, and further contains a condensation crosslinking agent.

1. Field of the Invention
The present invention relates to a water-absorbing resin widely used in the sanitary material field such as disposable diapers and sanitary napkins, the agriculture and forestry field, the civil engineering field, and the like, and to a method for producing the same. In particular, the present invention relates to a water-absorbing resin for the sanitary material field such as disposable diapers and sanitary napkins requiring a high water absorption capacity, and to a method for producing the same. More particularly, the present invention relates to a water-absorbing resin excellent in the water absorption capacity under pressure and under no pressure, and to a method for producing the same.
2. Description of the Related Art
In recent years, water-absorbing resins which gelate by absorbing large amounts of water are developed as one of synthetic polymers and widely used in the sanitary material field such as disposable diapers and sanitary napkins, the agriculture and forestry field, the civil engineering field, and the like. Many kinds of water-absorbing resins are known as these water-absorbing resins, including, for example, a crosslinked partially neutralized polyacrylic acid (for example, refer to Patent Document 1), a hydrolysate of a starch-acrylonitrile graft polymer (for example, refer to Patent Document 2), a neutralized product of a starch-acrylic acid graft polymer (for example, refer to Patent Document 3), a saponified product of a vinyl acetate-acrylate copolymer (for example, refer to Patent Document 4), and a hydrolysate of an acrylonitrile copolymer or an acrylamide copolymer (for example, refer to Patent Document 5).
The properties that the above-described water-absorbing resins should have include a high water absorption capacity and an excellent absorption rate when these resins are brought into contact with aqueous liquid such as body fluid, liquid permeability, gel strength of a swelled gel, the absorbing amount to absorb water from a substrate containing an aqueous liquid, and the like. However, the relationship between these properties does not necessarily show a positive correlation, but physical properties, such as liquid permeability, gel strength, and absorption rate, tend to be reduced as the water absorption capacity increases.
A technique to crosslink the vicinity of the surface of a water-absorbing resin is known as a method for improving various water absorption properties of these water-absorbing resins while keeping them in balance, and various versions of the technique have been proposed so far.
For example, various methods in which the following crosslinking agents are used therein are known, including a method of using a polyhydric alcohol (for example, refer to Patent Documents 6 and 7), a method of using a polyvalent glycidyl compound, a polyvalent aziridine compound, a polyvalent amine compound, or a polyvalent isocyanate compound (for example, refer to Patent Document 8), a method of using a glyoxal (for example, refer to Patent Document 9), a method of using a polyvalent metal (for example, refer to Patent Documents 10 and 11), and a method of using a silane coupling agent (for example, refer to Patent Documents 12, 13, and 14).
Further, attempts to perform a uniform surface crosslinking by coating a crosslinking agent on a surface of a water-absorbing resin during crosslinking reaction are known, including a method in which an inert inorganic powder is present (for example, refer to Patent Documents 15 and 16), a method in which a dihydric alcohol is present (for example, refer to Patent Document 17), a method in which water and an ether compound are present (for example, refer to Patent Document 18), and a method in which phosphoric acid is present (for example, refer to Patent Document 19), when the crosslinking agent is added.
Furthermore, as an application of the above-described methods, a method is also known in which, for the purpose of reducing a residual monomer, a neutralized monomer having a specific composition is mixed with a crosslinking agent as described above and the surface crosslinking is performed during the heat treatment of the resulting mixture (for example, refer to Patent Documents 20, 21, and 22). There is also disclosed a method for producing a water-absorbing resin excellent in the water absorption rate and water absorption capacity under pressure by conducting polymerization in the presence of a blowing agent and subjecting the resulting polymer to surface crosslinking treatment (for example, refer to Patent Document 23).
However, although the balance of various properties of the water-absorbing resin is improved by these methods, it is not yet sufficient, and further improvement is required. In particular, when the property requirement of the water-absorbing resin used in the absorber for sanitary articles having a reduced thickness by using a large amount of water-absorbing resin, which represent a notable trend in recent years, is taken into account, the current state of affairs is that the conventional methods as described above have not yet provided such resins with a sufficient level of physical properties.
Moreover, the demand of disposable diapers for elderly people is increasing as the increase of average life in recent years. For a disposable diaper for elderly people, a water-absorbing resin having "an excellent absorption ratio under high loads so that the diaper can make full use of the absorption capability even when heavier loads are applied to it during the wearing thereof" is more strongly required because the loads applied to the disposable diaper are heavier and the amount excreted per one time is larger than in the case of disposable diapers for infants. In addition, reduction in thickness like underwear tends to be strongly required for the performance required for disposable diapers. A typical solution to the requirement is a method to reduce the amount of pulp in the absorber of the disposable diaper and use a large amount of water-absorbing resin (for example, refer to Patent Document 24). In such an absorber, the water-absorbing resin is in a dense state and liable to cause gel blocking. As a result, conventional water-absorbing resins are inconveniently liable to cause reduction in water absorption capacity under pressure. On the other hand, when crosslinking density is increased to ensure the water absorption capacity under pressure, there may be a problem of reduction in water absorption capacity under no pressure.
[Patent Document 1] Japanese Patent Laid-Open No. 55-84304
[Patent Document 2] Japanese Patent Publication No. 49-43395
[Patent Document 3] Japanese Patent Laid-Open No. 51-125468
[Patent Document 4] Japanese Patent Laid-Open No. 52-14689
[Patent Document 5] Japanese Patent Publication No. 53-15959
[Patent Document 6] Japanese Patent Laid-Open No. 58-180233
[Patent Document 7] Japanese Patent Laid-Open No. 61-16903
[Patent Document 8] Japanese Patent Laid-Open No. 59-189103
[Patent Document 9] Japanese Patent Laid-Open No. 52-117393
[Patent Document 10] Japanese Patent Laid-Open No. 51-136588
[Patent Document 11] Japanese Patent. Laid-Open No. 61-257235 [Patent Document 12] Japanese Patent Laid-Open No. 61-211305 [Patent Document 13] Japanese Patent Laid-Open No. 61-252212 [Patent Document 14] Japanese Patent Laid-Open No. 61-264006 [Patent Document 15] Japanese Patent Laid-Open No. 60-163956 [Patent Document 16] Japanese Patent Laid-Open No. 60-255814[Patent Document 17] Japanese Patent Laid-Open No. 1-292004[Patent Document 18] Japanese Patent Laid-Open No. 2-153903 [Patent Document 19] National Publication of International Patent Application No. 1996-508517[Patent Document 20] Japanese Patent Laid-Open No. 6-122707 [Patent Document 21] Japanese Patent Laid-Open No. 6-122708 [Patent Document 22] Japanese Patent Laid-Open No. 2004-315816 [Patent Document 23] National Publication of International Patent Application No. 1996-509521[Patent Document 24] Japanese Patent Laid-Open No. 06-057010

Water-absorbent polymer and process for producing the same


A preform suitable to be cured to form a friction element, such as clutch facing, is produced by winding a filament, or a tape containing curable material on to a surface of a rotating plate. The filament, or tape, is guided on to the surface by a guide which is movable in a plane. A signal, representative of the angular position of the plate, causes generation of a demand signal indicating the desired position of the guide. A closed loop control, controls the movement of the guide to give a predetermined winding pattern. The control causes the guide to move as a function of the demand signal and a feedback signal representative of the position of the guide. The curable material in the preform is then cured.

The present invention relates to the fabrication of friction elements and, in particular, to the winding of a filament, or a tape, into a generally disc-shaped preform suitable to be cured to form a friction element.
Disc-shaped friction elements, for example, are employed as the facings for clutches, the facing being secured to a backing plate, for example, by rivets. For convenience, hereinafter in this specification, reference is made only to a friction element comprising a facing for a clutch, but it will be understood that, where appropriate, such references to a facing for a clutch refer also to any friction element made by a similar process.
Many different compositions of the filaments, and tapes, have been used in winding such preforms, for example, a composition as disclosed in British patent specification No. 2,096,654.
In present methods of winding a filament, or a tape, into a generally disc-shaped preform, the filament, or tape, is guided on to a rotating face plate by a guide which is moved in a displacement plane around a path. The shade of the path is determined by a rotating cam. The winding pattern of the filament, or tape, on to the face plate can only be varied by changing the cam for one with a different profile and only relatively simple winding patterns are possible.
It is an object of the present invention to provide a method of winding a filament, or a tape, into a generally disc-shaped preform suitable to be cured to form a friction element which allows the preform to be wound without relying on the shape of a cam to determine the movement of the guide thereby enabling more complex and consistent winding patterns to be used.

Tape winding method and apparatus for forming friction elements


A dual head type magnetic disk according/reproducing apparatus, in which a magnetic disk is inserted and/or from which the magnetic disk is ejected, the magnetic disk having a first surface and a second surface each of which is segmented into a plurality of tracks, each track having a corresponding track number, the dual head type magnetic disk recording/reproducing apparatus includes a first magnetic head which reproduces an information signal from a first track on the first surface, a second magnetic head which reproduces an information signal from a second track on the second surface, a track number of the second track corresponding to that of the first track, and a predetermined number of tracks being between the first track and a radial location of the second track, a low pass filter, coupled to the first and second magnetic heads, to which the information signals reproduced by the first and second magnetic heads are supplied, and control means, coupled to the low pass filter, for adjusting a cut-off frequency of the low pass filter so that a resolution of the information signal reproduced at the first track and that of the information signal reproduced at the second track can be approximately equal to each other.

The present invention generally relates to magnetic disk recording/reproducing apparatus for recording and/or reproducing an information signal on and from a magnetic disk, and more particularly to a dual head type magnetic disk recording/reproducing apparatus for recording and/or reproducing the information signal on and from both sides of a flexible magnetic disk by a pair of magnetic heads.
Conventionally, there is a so-called dual head type magnetic disk recording/reproducing apparatus provided with a pair of magnetic read/write heads so as to perform recording and/or reproducing of an information signal on and from both sides of a flexible magnetic disk by respective heads. In such a magnetic disk recording/reproducing apparatus, the magnetic heads are provided such that one of the heads is offset in position relative to the other by about four to eight track pitches depending on the recording density in a moving direction of a carriage carrying the magnetic heads to avoid crosstalk between the information signals recorded on both sides of the magnetic disk.
In such an apparatus, even if a first track on the side O of the magnetic disk has the same track number as a second track on the side I thereof, a track radius of the first track differs from that of the second track. Responsive thereto, there appears a difference in resolution between the information signal reproduced from the side O and the information signal reproduced from the side I of the magnetic disk. This difference in the resolution becomes significant with increasing recording density and causes a problem in the recent magnetic disk recording/reproducing apparatus designed to operate with an increased recording density.

Dual head type magnetic disk recording/reproducing apparatus


The invention is A Soft, Tiny, Golf club-shaft Attachable Audio and Feel-Feedback Golf Swing Tuner of 1/10 Oz Weight. The golfer swings his club with the Tuner's soft 7 to 71/2 inches long, ulta-thin, tensilised polymeric foil, untwisted and elevated lengthwise parallel to the target side of the shaft by twin, resilient plastic end-piers snap-fitted onto the club head end of the shaft, and the foil resonates keeping pace with club-face motion. Golfer both hears that motion around him as specific "Go"/"No Go" humming, buzzing and clubshaft quivering signals that repeat when his swing repeats.

Most 6 and under handicap golfers whether or not the weight of the clubhead is balanced controllably as it swings around them. Occasionally their control wanes and the ball goes astray.
Less skilled players have extreme difficulty acquiring this tenuous "Feel of clubhead balance" without in swing "Go"/"No Go" club motion feedback.
The inventor's golf swing training machine U.S. Pat. No. 5,474,299 offers better swing feedback than standing machines of prior art. However it is not suited for swing practice after errant shots during play.
The Swing-Gyde Tm is a 12 inch club grip extension. The unit must be screw-clamped to the bottom of the grip after being first lined up with the clubface with the unit's arm-tip bearing on the golfer's forearm with the clubshaft cocked at 90 degrees. Once so mounted it does'nt help the golfer learn to balance the club for square-center face hits and it is too cumbersome for on course refresher swing practice.
The inventor's LittleBigShot Tm device lead to the present invention. The LBS clips to the target side of the clubshaft in seconds. Its backswing-top click and subtle downswing airspeed whistling are helpful feedback. Unfortunately its 2 Oz weight affects club balance.
A crude clubshaft-mounting outrigger swing feedback device by Simplicity Tm, composed of 2 thick rubber bands stretched around a rickety plastic bow, disappeared from the market along with its maker.
In use, inertia of the outrigger unit caused it to spin uselessly around the clubshaft even in chipping swings. Air speed hum of its bands was supposed to help a golfer pattern club swing motion correctly. The device failed to do its slated task even when secured to the shaft by tape. Its crude bands would hum indiscriminately however one induced them to start humming on the swinging club.
What golfer's need is a soft, tiny, 1/10 Oz. swing tuner that they can snap-fit onto their club-shaft and use within seconds for both practice and ball striking swings with irons or woods. And whose "Go"/"No Go" specific clubface motion feedback humming, buzzing and clubshaft quivvering signals, repeat when his swing repeats thereby prompting him to relax, feeling and dynamically balancing the clubhead throughout the swing, well enough to hit the golf ball solidly and squarely at the target.


A microprocessor based control system generates optimal field and armature currents for a separately excited DC motor. The current levels for the field and armature coils are set by feedback control. Armature and field current setpoints are established in accordance with tabulated values selected for providing a required torque and speed in an optimal fashion. A table of corresponding values of armature voltage is also maintained. If the actual armature voltage is below the calculated value, then the field current setpoint is boosted by an amount sufficient to optimize output torque.

This invention relates to a microprocessor based control system which provides optimal field and armature currents to control a separately excited direct current (DC) motor.
The use of microprocessor control for the purpose of independently controlling the field and armature currents in direct current motors to achieve maximum efficiency is described in an article by Soon Chan Hong and Min Ho Park in IEEE Transactions on Industrial Electronics, Vol IE-34, No. 4, November 1987.
One problem with microprocessor or computer control of separately excited motors results from the fact that the field flux expected from a given field current, as derived from the motor equations employed, is not always as expected. The actual field flux will differ due primarily to magnetic hysteresis in the field poles; thus, while the theory may predict optimal motor performance under given torque and speed conditions, in reality, the resulting efficiency is often less than expected or desired.

Control system for a separately excited DC motor


An abrasive plate having an abrasive surface for performing abrading applications is provided. The plate includes a base member having a substantially smooth surface with a plurality of holes formed therethrough. A plurality of pairs of spaced apart slots radiate outwardly from each of the holes to define tab members. The tab members may be selectively raised or deformed to protrude from the smooth surface to collectively form an abrasive surface. The number of tabs raised may be selected to control the coarseness of the surface.

1. Technical Field
The present disclosure relates generally to a unique surfacing tool. More particularly, the present disclosure relates to an abrasive metal plate adapted for use in a sanding machine, and to a method for producing an abrasive metal plate.
2. Background of Related Art
While sandpaper and similar materials are generally inexpensive, they become unserviceable through use in short periods of time. Sandpaper, for example, is easily ruptured as the abrasive particles attached to the base of the sandpaper become loosened, worn and clogged. The use of sandpaper with motor-powered tools exacerbates this problem in that due to the high speed of operation, most of the abrasive particles become quickly clogged with large amounts of wood flour or the particles become detached from the abrasive surface of the sandpaper.
To overcome this problem, abrasive metal sheets have been developed with integrally formed protrusions configured to perform abrading applications. For example, in U.S. Pat. No. 2,820,281, a metallic abrasive sheet is adapted to be used in the manner of sandpaper. The abrasive sheet is flexible so that it may be conformed to supporting blocks. Projections on an abrasive surface are formed by puncturing apertures in the sheet. In U.S. Pat. No. 3,545,308, a perforated abrasive metal sheet is provided for use with a reciprocating sander. The abrasive metal sheet is formed with generally rectangular shaped apertures which are punched in a metal sheet to form an abrasive surface. In U.S. Pat. No. 3,583,107, a flexible metal sheet is suggested for use with power sanders. Cutting edges for the sheet are formed by driving punches of various geometric shapes through the metal sheet.
While abrasive metal sheets have a service life greater than that of sandpaper, these sheets have been found to be more difficult than sandpaper to use with motor-powered sanders, e.g., random orbit sanders, vibratory sanders, etc. Because of the large number of protrusions in the metal sheet, the force transmitted from a surface being treated by the power sander through the plate is generally unbalanced. As such, the power sander has a tendency to pull in one direction as the sander is moved over the surface being treated, making it difficult for an operator to control the power sander and tiresome to operate the sander for sustained periods of time.
Accordingly, a need exists for an abrasive metal sheet adapted for use with motor-powered sanders that overcomes the above-noted disadvantages and is easy to make and use.


Methods of determining status of advertised system management server (SMS) packages at a client device include receiving a request for a determination of the status from a user at the client device. Responsive to the received request and without further input from the user a plurality of SMS packages that have been advertised to the client device may be identified, an installation status of the identified plurality of SMS packages may be determined and a graphical user interface (GUI) may be generated. The GUI lists the identified plurality of SMS packages and provides a visual indication of the determined installation status of the listed plurality of SMS packages. The generated GUI may be displayed to the user on a display of the client device.

The present invention relates to methods, systems and computer program products for monitoring computer systems and more particularly, for monitoring applications distributed to such computer systems.
Computer networks have grown increasingly complex with the use of distributed client/server applications, mixed platforms and multiple protocols all on a single physical backbone. The control of traffic on the networks is likewise moving from centralized information technology (IT) departments to distributed workgroups. The growing utilization of computer networks is not only causing a move to new, high-speed technologies but is at the same time making the operation of computer networks more critical to day-to-day business operations.
The growth in complexity and dependence on computer networks heightens the need for network management tools to design, build and maintain computer networks. The mix of protocols and vendors of installed hardware on many computer networks generally increases the difficulty of accomplishing network management. This problem may arise in planning or designing changes to a network, monitoring performance of a network, and testing the impact on performance of different hardware and software being installed on a network.
Systems management software has been proposed to assist in management of software installed on a managed computer network, which may allow an organization to control distribution of applications, updates to applications, security patches and the like across network devices supported by the organization from a centralized server location. For example, the system management server (SMS), available from Microsoft Corporation, is a software product for managing large groups of Windows-based computer systems including supporting distribution of software to supported devices by advertising available SMS packages to designated client devices and delivery of advertised SMS packages to client devices for installation.
SMS provides remote control, patch management, software distribution and hardware and software inventory functionality. SMS provides such functionality in a mobile environment through use of industry standards independent of connection or location, which may be advantageous for organizations supporting laptop computers and the like.
In particular, SMS provides for both deployment and monitoring of deployed security patches and the like from a central location to assist IT managers with assuring proper installation of advertised SMS packages. In addition, it is possible to obtain a report on advertised SMS packages at a client device having an SMS client application executing thereon. An example of such a report is seen in the graphical user interface (GUI) shown in FIG. 1. However, obtaining a report such as seen in FIG. 1 using SMS generally requires a sequence of user inputs and provides a display format that may be confusing to a typical user of a client device. As a result, in a typical implementation of SMS, the SMS client application is run in the background and a user of the client device may not even be aware that the SMS client application is executing on the client device, nonetheless how to obtain status information from the SMS client application.

Methods, systems and computer program products for determining installation status of SMS packages


Disclosed is a door catch that can help to prevent door sag, especially for heavy or tall residential or commercial doors, and provides for post-installation catch tension adjustment without removal or adjustment of mounting members. In one aspect, the door catch can include a ball catch base, a threaded ball plunger assembly, a catch bumper, and a bumper base. In another aspect, the catch bumper and the bumper base can optionally be combined into a single catch bar bracket. The ball plunger assembly is adjustably mounted within a threaded aperture of ball catch base. A ball captive in one end of the ball plunger assembly engages a detent in the catch bumper, or catch bar bracket, providing friction to hold the door open. The position of the ball plunger assembly can be adjusted vertically to increase or decrease the tension between the detent and the ball plunger assembly.

The present disclosure relates to door catches, and more particularly door catches utilizing a ball catch mechanism.
Door catches can generally be utilized to hold doors or similar structures in either an open or closed position. In addition, door catches used to hold a door or the like in an open position can be configured to prevent the door from hitting and damaging a wall and therefore can also perform the function of a doorstop.
Door catches come in a variety of different types. For example, roller catches, magnetic catches, hinge pin doorstops, kick down holders, j-hook catches, strike and catch automatic wall holders, and ball catches. One class of door catches relies on tension between two portions of the door catch to hold the door open.
One of the challenges in door catch design, is adjustment of catch tension, particularly for door catches that can be utilized to hold a door in the open position by relying on tension between two portions of the door catch. For example, catch tension adjustment sometimes requires that one of the mounting members be moved relative to the mounting surface. Alternatively, catch tension adjustment may require removal of one of the mounting members from the mounting surface. Either of these can be inconvenient for the installer or maintainer of the door. In many door catch designs, the installer or maintainer is required to drill new holes in order to adjust the position or catch tension. In these designs, micro-adjustments are not possible. Micro-adjustment of catch tension may be particularly important over time, as the door or doorframe shift and settle or as the door sags.


A label with which, among other things, vegetables, for instance vine tomatoes, fruit and house plants, can be supplied with information. The label is a three-dimensional object obtained by folding and gluing a punched or cut piece of paper, cardboard or another type of thin-walled material, which object can be attached to one or more branches of a vine of tomatoes and whereby at least one surface area of the three-dimensional object is visible in such a way that it can serve as an information-bearing surface.

The current technique of labelling vine tomatoes entails packaging the tomatoes in foil, possibly on a cardboard or synthetic tray and labelling the foil, by a self-adhesive label for instance. This is not the most durable way of coupling vine tomatoes with information. Labels are also used that are attached to one of the branches of a vine tomatoes by binding wire or cord.

Label for vegetables, fruit and house plants


A thermally imagable business record such as a form, tag, label or the like is provided in which selected areas of the record may be activated to form an image upon exposure to heat. In one embodiment, at least one selected area of a substrate surface contains a thermally imagable coating of initially colorless color formers and color developers while the remaining areas of the substrate are left uncoated. The substrate may be pre-coated to provide a smooth, non-porous base coat for the thermally imagable coating, and may also include a protective coating layer to protect the subsequently printed thermal image.

This invention relates to a thermally imagable business record, such as a form, label, tag, or the like, in which a selected area may be activated to form a thermal image. More particularly, the invention relates to a substrate containing a thermally imagable coating on at least one selected area of its surface while the remaining areas of the substrate are left uncoated.
In the field of product labeling, direct thermal printing has been a well-known means of non-impact printing. Direct thermal printers are capable of forming images by the application of heat to a substrate containing heat-reactive chemicals thereon. Typically, a substrate such as paper is coated with a coating of color forming and color developing reactants, which, when heated, combine to form a visible image. When such a coated substrate passes under the print head of a thermal printer, the areas containing the coating are activated by the heated print elements, forming images on the surface of the substrate.
Thermally imagable coatings provide a convenient method of providing computer generated data such as bar codes or serial numbers. Such information may be printed on business forms such as labels or tags. Thermally coated substrates have also been widely used as facsimile paper, bar code paper for point-of-sale (POS) systems, automatic ticket vending machines, and labels for food products. There are various compositions and methods of applying thermally sensitive coatings as described, for example, in U.S. Pat. Nos. 4,865,939, 4,861,749, and 4,894,359.
However, while the use of thermally imagable coatings is a convenient method of providing a printable surface, the present method of applying the coatings is to cover the surface of the substrate completely. This method is both expensive and wasteful as the thermally imagable coating is applied to areas of the substrate which are not subsequently imaged.
Further, as the application of thermally sensitive coatings requires sophisticated coating equipment and techniques, it has heretofore been impractical to apply the coatings only in selected areas or to apply the coatings at the same time a business record is manufactured. Additionally, as thermally imagable coatings are typically applied to a high volume of substrates which are widely distributed for different end uses, manufacturers have produced fully coated webs or sheets to accommodate the greatest number of end uses of the products.
Accordingly, there is still a need in the art for a thermally imagable business record, such as a form, label or the like, in which a thermally imagable coating may be applied in a cost effective manner to a selected area or areas of the form so that information is printed through the use of a thermal printer only at desired locations.

Business record having a thermally imagable surface


The present invention relates to a web-based financial management system for providing personalized financial coaching to a user. The system operates in a collaborative computing environment between the user and a financial advisor and comprises a service level subsystem and an advice generating subsystem. The service level subsystem allows the user to negotiate a service level agreement that defines the user's desired level of support and limits access to user provided information. The advice generating subsystem is coupled to the service level subsystem and includes one or more coaching engines that dynamically analyze the financial needs of the user in accordance with the user's service level agreement. Furthermore, the coaching engine provides customized financial advice tailored to the user's life intentions. The present invention also provides for a financial portfolio management subsystem enabling the user to model the effects of adding or deleting various securities and helping the user to better conform his portfolio to his level of risk tolerance and his investment style.

Financially prudent individuals develop financial plans that help them achieve their financial goals. Traditionally, many of these individuals have entrusted their financial plans to personal financial advisors.
More recently, however, some individuals have increasingly relied upon computer-based systems that organize their financial assets and liabilities and further provide them with a summary of their financial health. However, these systems tend to focus on the administrative aspects of financial planning without enabling the user to make reasoned choices about their financial futures. Furthermore, these systems are limited by their inability to dynamically analyze the financial goals. These limitations are counterproductive to the user's needs to develop and manage an integrated personal financial plan from an executive decision-making perspective.
Many existing financial management systems allow users to electronically organize their financial assets and liabilities. These systems typically focus on presenting the user with a summary of their financial transactions over a given period of time and their financial health, at a given instance. Furthermore, these systems typically rely on the user to continually update their personal financial data, although some systems allow access to user specific online data. As a result, these systems are merely data-driven calculators that are incapable of providing the user with meaningful financial coaching tailored to their financial intentions and expectations.
Similarly, some financial management systems present a static view of the user's financial health. These systems typically require the user to provide the most current financial data relating to their financial assets and liabilities. Consequently, when the user wishes to develop or update his or her financial plan, the user must input their most recent financial information. This problem is further exacerbated by the fact that these systems demand a lot of typing and guessing when the user enters financial data. This process is time-consuming and inefficient and does not promote an intuitive understanding of how complex financial variables interact to produce a sensible financial plan.
Another problem with many existing financial management systems is that the user is typically limited to managing the transactional details of their financial data. In these systems the user is shielded from the planning and deciding aspects of developing their financial plan. Accordingly, the user learns very little from the process and remains heavily dependent on the system to provide an accurate summary of their financial health. These limitations further exacerbate the potential lack of trust inherent within the relationship between the user and the financial management system.
Furthermore, many existing financial management systems merely project a future value of the user's financial portfolio without providing an indication of the likelihood of achieving that value. Thus, the user is left without any real sense of how to compare one financial plan to another. Consequently, these systems fail to foster a deeper understanding of the risks and/or rewards associated with reasoned financial planning. Furthermore, the user is left to his own devices to interpret the projected results of his financial model and thus leaves him dependent on a live advisor to guide him on how to resolve various financial issues.
On the other end, when users consult a financial advisor a major portion of their consultation time is spent on walking a user through setting up a financial plan. Only after the financial plan is set up and analyzed by the financial advisor, can the focus shift to possible problem areas. This process is time consuming, inefficient and very expensive. The same would apply to financial advisors helping customers with setting up an ideal portfolio, consistent with the customer's risk tolerance, investment style and market attitude. Again a great deal of the valuable and expensive advisor time is spent setting up a financial profile for the customer, whereas he should be focusing on specific recommendations to achieve specific user goals.
Currently, no web-enabled system exists that dynamically incorporates all of the user's financial assets and liabilities into an integrated summary of their health. Individuals do not want to focus on the transactional details of their financial information. Instead, individuals desire to assume an executive decision-making role in managing their financial life. A financial management system is needed where the user is provided with an integrated summary of their financial health and is given personalized financial coaching tailored to their financial goals and intentions. Furthermore, since automated coaching cannot completely replace a live advisor's expertise, experience and innovation in devising specific solutions to the user's problems, access to both automated and live coaching is desirable. However, live advising may be an expensive option due to the under-use of enabling technologies and the relative unavailability of economies of scale. Thus the use of a live advisor may only be feasible for individuals with high net worth and large portfolios. Furthermore, a live advisor is not available twenty four hours a day. No existing web-based system has combined the cost savings of an automated coaching with the expertise of a live advisor, promoting an inexpensive comprehensive financial modeling and counseling tool.

Financial modeling and counseling system


A method and an apparatus for scaling E-mail (electronic mail) address book databases for devices with limited storage capacity and synchronization of a first set of mail with a second set of mail at the message/folder level. A memory contains a mail subsetter for automatically generating a default personal address book and a mail synchronizer for application independent E-mail synchronization. A pseudo unique identification is generated for each message or folder in the mail boxes to be synchronized. An event log is then generated for each mail box. The memory also has a Synchronization mechanism for making the first set of data and the second set of data equivalent by using the information in the Change List generated by the Change Detection Mechanism. A processor runs the mail synchronizer.

1. Field of the Invention
The invention relates to E-mail (electronic mail) systems. More particularly, the present invention is related to the method and apparatus for scaling E-mail address book databases for devices with limited storage capacity.
2. Background
E-mail (electronic mail) is one of the most popular data use application for data and voice telephones, in particular, for cellular telephones. However, telephones are typically limited in storage capacity. An average advanced cellular phone (such as a SmartPhone) being designed has less than one mega byte (MB) of storage available for use by a user. In contrast, a typical electronic address database using corporate environments are very large.
Given the storage constraints of devices such as a SmartPhone and the desirability for access to a large electronic address database, it is desirable to have some type of a default personal address book. Currently, there are a couple of E-mail systems which may be used to offer some type of method for generating a default personal address book. However, neither of the systems are easy to use. For example, cc: Mail Mobile System from Lotus Development Corporation and cc: Mail Remote System from Lotus Development Corporation duplicate the address database (generally several mega-bytes in size) on a notebook PC (Personal Computer), or require the user to generate their own address book there is no subsetting offered by the systems. Additionally the E-mail systems do not work with devices with limited storage such as is found in SmartPhones.
MS Mail system from Microsoft allows subsetting using personal address books, however, with this method and apparatus, the user must manually select and move entries in the network database to his or her personal address book. Additionally, the method and apparatus clearly does not scale to large databases such as for corporations, where there may be a large number of employees. More specifically, manually finding, selecting and moving, for example one hundred people regularly from a large list of employees is not only inefficient and slow but ultimately unusable in a corporate or large organizational environment, e.g. with tens of thousands of employees.
Additionally, MS Mail does not provide synchronization for the personal address book and the network database. For example, if John Doe is in both a user's personal address book and in a network database and if John Doe's name is deleted from the network database, his name will remain in the user's personal address book. Hence, the user will not know that John Doe is no longer available until a mail is transmitted to him and the mail is returned as "undeliverable" or "user unknown".
CC: Mail from Lotus Development Corporation provides synchronization but it is very inefficient. Synchronization is performed on-line with CC: Mail, i.e. when a user is connected and requires that the entire database be reconciled. Exemplary circumstances requiring reconciliation include when new records are added such as for new employees, when records have been deleted such as to account for employee attrition, and when updates are made such as for changed telephone numbers. Scanning a large database for change takes tens of minutes and since synchronization must be performed periodically, use of CC: Mail Remote or Mobile in a large organizational environment becomes impractical.
Therefore it is desirable to have a method and an apparatus for scaling E-mail address book databases for devices with limited storage capacity by providing an easy to use method for generating default personal address books automatically and to provide an efficient method for keeping the personal address books synchronized with a main database.

Method and apparatus for scaling large electronic mail databases for devices with limited storage


In a storage apparatus comprising a communication interface that receives an I/O request sent from a host apparatus, a storage device controller that performs writing and reading of data with respect to a storage device, and a cache memory that stores data to be written in the storage device or data read from the storage device, a journal volume operated as a volume for which update writing is prohibited and write once is permitted is provided, on the basis of a storage area provided by the storage device, and a virtual volume is provided as a volume accessible from the host apparatus, the journal volume being the entity of the virtual volume, the virtual volume being a volume for which an attribute (Read/Add) that permits only reading and write once is settable.

In recent years, it is becoming important that juristic acts, financial reports, and the like have no fraudulence, i.e., tampering of data is prevented, in terms of the J-SOX (Sarbanes-Oxley) act, internal control, and the like. Accordingly, higher security is required for data handled by organizations such as corporations.
Concerning a security technique, Patent Citation 1, for example, describes that a tampering prevention attribute and an access authority attribute representing a deletion prohibition period are held as attributes and that the attributes are checked at the time of a data update request or a deletion request, in order to prevent fraudulent or erroneous update of data intended to be non-updatable by a person to which an update authority has been transferred or a person impersonating such a person.
Patent Citation 2 describes a technique for effectively using the capacity of a storage system in such a way that: an access control attribute is set for an arbitrary storage area of the storage system; and when an access request is received from a host computer, the access is not executed on condition that an access target according to the access request includes a predetermined storage area and that the access according to the access request is prohibited in accordance with the access control attribute set for the predetermined storage area.
Patent Citation 3 describes a technique for monitoring and archiving long term data regarding a storage system using a WORM (Write Once Read Many) storage medium in such a way that: a write-protection area is identified by using a volume ID and a start offset and an end offset of a protection area of a volume; and when an offset instructed by a write request of a host corresponds to one of the write-protection areas, the write request is ignored or an error message is returned.
Patent Citation 4 discloses a technique in view of following problems: WORM cannot be applied to a new file or a file during addition until all writings of data have been completed and the content of the file has been confirmed, so that data cannot be guaranteed for a file in which the content is not confirmed, e.g., a file during writing; whether or not WORM is to be applied to a file is managed in volume units, which is not user-friendly; whether or not WORM is to be applied is determined for the whole file, so that WORM cannot be applied to a part of data of a file. Patent Citation 4 describes that, when a write request with respect to a file stored in a storage apparatus is received from a client computer: an object management table of the target file is referred to; a WORM attribute of the file is checked; whether or not a range to be written is set as a WORM range is checked; and execution of the writing to the target file is performed on condition that the write range is not set as the WORM range, or update of a WORM range management table and setting for applying WORM to written data are performed on condition that WORM is set for the data to be written.
[Patent Citation 1]
    Japanese Patent Application Laid-open Publication No. 2004-86872[Patent Citation 2]    Japanese Patent Application Laid-open Publication No. 2006-127106[Patent Citation 3]    Japanese Patent Application Laid-open Publication No. 2005-267602[Patent Citation 4]    Japanese Patent Application Laid-open Publication No. 2006-92276

Storage apparatus, management apparatus, and method of controlling storage apparatus


Nitrogen atoms on the surface of a first body are terminated by hydrogen atoms after the surfaces of the first body and a second body to which it is to be bonded are cleaned. The surface of the first body terminated by the hydrogen atoms and the surface of the second body are bonded to each other so that hydrogen bonds are formed between the nitrogen atoms and the bonded hydrogen atoms on the surface of the first body and the atoms on the surface of the second body. Using these hydrogen bonds, the surface of the first body and the surface of the second body are strongly bonded to each other. When the surface of the second body is formed with nitride or oxide, strong hydrogen bonds of N--H .sup.- - - N or N--H .sup.- - - O are formed between the first body and the second body. Thus, the method does not require bonding under high temperature or high pressure.

1. Field of the Invention
The present invention relates to method for direct bonding a member having nitride surface to another member having a nitride or oxide surface. For the first member, a non-nitride member having its surface covered with nitride or a member entirely made of nitride can be used. As the other member, a member having its surface covered with nitride or oxide, a member entirely made of nitride or oxide, metal, a semiconductor material, ceramic, a polymeric compound or the like can be used. The direct bonding method is used to form a bond between a base and IC chips or sensors which have surfaces covered with a protective film such as Si.sub.3 N.sub.4 or TiN. Further, the direct bonding method is used for precisely bonding base to another member such as a super-hard member, a super-heat resisting member or the like.
2. Description of Related Art
A conventional method for direct bonding of two materials is disclosed in Japanese Unexamined Patent Publication No. hei 6-302486. In the conventional direct bonding method, hydroxide groups are chemically adsorbed on the surface of a member in a vacuum atmosphere, then two members are pressed together tightly so that two materials are directly bonded through the use of hydrogen bonds between the surfaces of the two members.
However, in the above-described method, it is necessary to adsorb hydroxide groups to the surface of one bonding member, that is, it is a necessary condition that the surface can be oxidized. Because nitride does not adsorb hydroxide groups, a nitride member or a member covering the surface with nitride is not used as a member for adsorbing hydroxide groups. Thus, it is impossible to form a bond between two members having a nitride body or nitride cover film on the surface, or between such a nitride member and another member such as a metal and semiconductor member without adsorbing hydroxide groups.
As a conventional method of bonding nitride and metal, metal atoms are driven into the surface of a nitride member at a high energy so that the surface of nitride is metallized. Then, the nitride and metal are compressed at a high pressure of above 100 MPa to tightly contact one another, or an insert member which conforms to both bonding members is sandwiched between the nitride member and the metal member, and the two bonding materials are pressed together at a high temperature.
As described above, the conventional method does not directly bond between the nitride members or between the nitride member and a non-metal member. Further, in the bonding method of nitride and metal, the metal for bonding must have good ductility, the method requires a high temperature of direct lower melting point and a high pressure of above 100 MPa.
Thus, in the above-described bonding methods, the size and the shape of bonding member and bonding precision have limits. Particularly, when metal and a member which is made with nitride material having a complex shape at the microscopic level are bonded, deformations and cracks are generated in this member after bonding so that the method cannot be used for precise bonding.

Method for direct bonding nitride bodies


A filter member includes a first lead terminal, an optical filter, and a first mold member, and a light incidence surface and a light emission surface of the optical filter is exposed from the first mold member. A sensor member includes an IR sensor element, a second lead terminal and a second mold member. A light-receiving surface of the IR sensor element is exposed from the second mole member. The filter member is disposed on the sensor member so that the light emission surface of the optical filter faces the light-receiving surface of the IR sensor element in the sensor member.

Patent Literature (PTL) 1 discloses examples of this kind of related art. In the publication, as illustrated in FIGS. 2A to 2C, an infrared sensor is disclosed which has a structure in which a sensor element equipped with an optical filter only transmitting infrared rays is covered with a resin except for the light-receiving surface. The sensor element is a quantum-type photodiode generating a photovoltaic effect using an infrared ray. In addition, the optical filter has a function of only transmitting an infrared ray having a specific wavelength.

Infrared sensor and method for manufacturing same, filter member for infrared sensor, and photocoupler


A high performance digital signal processor includes a bidirectional communication port for communication with an external device. The bidirectional communication port includes a first transmitting circuit for transmitting to the external device a first clock on a first control line in a transmit mode and for transmitting data words on plural data lines in synchronism with the first clock, and a first receiving circuit for receiving a first acknowledge signal on a second control line in the transmit mode. The communication port further includes a second receiving circuit for receiving a second clock on the second control line in a receive mode and for receiving data words on the data lines in synchronism with the second clock, and a second transmitting circuit for transmitting a second acknowledge signal on the first control line in the receive mode. The communication port further includes switching means for switching between the transmit mode and the receive mode.

A digital signal computer, or digital signal processor (DSP), is a special purpose computer that is designed to optimize performance for digital signal processing applications, such as, for example, fast Fourier transforms, digital filters, image processing and speech recognition. Digital signal processor applications are typically characterized by real time operation, high interrupt rates and intensive numeric computations. In addition, digital signal processor applications tend to be intensive in memory access operations and to require the input and output of large quantities of data. Thus, designs of digital signal processors may be quite different from those of general purpose computers.
One approach that has been used in the architecture of digital signal processors to achieve high speed numeric computation is the Harvard architecture, which utilizes separate, independent program and data memories so that the two memories may be accessed simultaneously. This architecture permits an instruction and an operand to be fetched from memory in a single clock cycle. Current architectures integrate the computation unit and the memory on a single integrated circuit, or chip, to provide a self-contained, high performance digital signal processor.
One important aspect of DSP chips is external communication. Because the DSP processes the large quantities of data, it is necessary to transfer data to and from the internal memory and the computation unit of the DSP chip efficiently and at high speed. The DSP chip typically includes a parallel external bus for communicating with a host computer, an external memory and other external devices such as, for example, an analog-to-digital converter. The external bus may also be used to interconnect two or more DSP chips in a multiprocessor configuration, or cluster, for increased computational capability. The bus architecture provides the ability to transfer information between devices at high speed.
Despite the capabilities provided by the external bus, a need frequently exists for high speed, point-to-point communication between digital signal processors in a multiprocessor configuration or between a digital signal processor and an external device, such as an analog-to-digital converter. The point-to-point communication link may be used for transferring the large quantities of data typically involved in DSP computations without using the external bus, which may be required for other operations.
One well-known approach to point-to-point data transmission is serial communication, wherein data is transmitted serially on a single data line. This technique is efficient with respect to cabling and connections to the DSP chip but is limited in the rate at which data can be transferred.
Parallel data transfer techniques provide the highest speed. However, where multiple communication ports are required, the number of connections to the DSP chip is excessive, and the number of conductors required for each port must be minimized.
A point-to-point communication system for a digital signal processor is disclosed in U.S. Pat. No. 5,619,720 issued Apr. 8, 1997 to Douglas Garde et al. The disclosed communication port is bidirectional and transfers nibbles of four bits at a time on four data lines. While this approach provides highly satisfactory performance, communication with the external device on the external bus of the digital signal processor is required to change the direction of transmission. This approach may produce delays and is relatively complex.
Accordingly, there is a need for improved high speed, point-to-point communication apparatus. The communication apparatus should require a small number of conductors, should be capable of transferring large quantities of data at high speed with minimum overhead and should permit the direction of transmission to easily be changed.

Bidirectional communication port for digital signal processor


A mobile satellite navigation receiver for calculating an offset between a local positioning system and a wide-area satellite positioning system is presented. The mobile satellite navigation receiver determines a first solution of a position of the mobile satellite navigation receiver relative to a first local positioning system, wherein the first local positioning system includes one or more reference receivers at known locations. The mobile satellite navigation receiver determines a second solution of the position of the satellite navigation receiver relative to a wide-area differential satellite positioning system. The mobile satellite navigation receiver then calculates an offset between the first solution and the second solution.

The global positioning system (GPS) uses satellites in space to locate objects on earth. GPS uses L-band signals from the satellites, which are tracked by a GPS receiver and used to determine the position of the GPS receiver. Currently, two types of GPS measurements are available within a civilian GPS receiver for each carrier signal of each GPS satellite that is being tracked. The two types of GPS measurements are pseudorange, and integrated carrier phase. These two types of measurements are available on each of two carrier signals, L1 and L2, with frequencies of 1.5754 GHz and 1.2276 GHz, respectively. The wavelengths of these two frequencies are 0.1903 m and 0.2442 m, respectively. The pseudorange measurement (or code measurement) is a basic GPS observable that all types of GPS receivers can make. It utilizes the C/A or P pseudorandom codes modulated onto the carrier signals. The pseudorange measurement records the apparent time taken for the relevant code to travel from the satellite to the receiver, i.e., the time the signal arrives at the receiver according to the receiver clock minus the time the signal left the satellite according to the satellite clock. The carrier phase measurement is obtained by integrating a reconstructed carrier of the signal as it arrives at the receiver. Thus, the carrier phase measurement is also a measure of a transit time difference as determined by the time the signal left the satellite according to the satellite clock and the time it arrives at the receiver according to the receiver clock. However, because the initial number of whole cycles in transit between the satellite and the receiver when the receiver starts tracking the carrier phase of the signal is not known, the transit time difference obtained from the carrier phase will typically be in error by multiple carrier cycles, i.e., there is a whole-cycle ambiguity in the carrier phase measurement.
The range or distance between a GPS receiver and each of a multitude of satellites is calculated by multiplying each signal's travel time by the speed of light. These ranges are usually referred to as pseudoranges (false ranges) because the receiver clock generally has a significant time error which causes a common bias in the measured range. This common bias from receiver clock error is solved for along with the position coordinates of the receiver as part of the normal navigation computation. Various other factors can also lead to errors or noise in the calculated range, including ephemeris error, satellite clock timing error, atmospheric effects, receiver noise and multipath error. In standalone GPS navigation, where the receiver obtains code and/or carrier-phase ranges from multiple satellites without the benefit of corrections from any reference stations, the receiver is very limited in methods available to reduce the errors or noises in the ranges.
To eliminate or reduce systematic errors, differential operations are typically used in GPS applications. Differential GPS (DGPS) operations typically involve one or more reference receivers located at known sites (sometimes called base stations) together with a communication link between the user receiver and the reference receivers. The reference receivers are used to generate corrections associated with some or all of the above error types and these corrections are sent to the user receiver over the communication link. The user receiver then applies the corrections to its own measurements or position and thereby obtains a more accurate computed position. The corrections from a respective reference receiver can be in the form of corrections to the reference receiver position determined at the reference site or in the form of corrections to the specific GPS satellite clock and/or orbit. Differential operations using carrier-phase measurements are often referred to as real-time kinematic (RTK) positioning/navigation operations.
The fundamental concept of Differential GPS (DGPS) is to take advantage of the spatial and temporal correlations of the errors inherent in the GPS measurements. Thus, the corrections cancel or significantly mitigate most of the noise sources in the pseudorange and/or carrier phase measurements. The amount of mitigation depends upon the correlation between the error sources at the user and reference receiver. While the GPS satellite clock timing error, which appears as a bias on the pseudorange or carrier phase measurement, is perfectly correlated between the reference receiver and the user receiver, most of the other error factors are either not correlated or the correlation diminishes as a function of distance between them.
To overcome the error sources within the DGPS system in wide-area applications, various regional, wide-area, or global DGPS (sometimes referred to as WADGPS) techniques have been developed. The typical WADGPS includes a network of multiple reference stations in communication with a computational center or hub. Error corrections are computed at the hub based upon the known locations of the reference stations and the measurements taken by them. The computed error corrections are then transmitted to users via a communication link such as satellite, phone, or radio. By using multiple reference stations, WADGPS provides more accurate estimates of the error corrections.
A number of different techniques have been developed to obtain high-accuracy differential navigation using the GPS carrier-phase measurements. The technique with the highest accuracy is the RTK technique, which yields a typical accuracy of about one-centimeter. In order to obtain that accuracy, however, the whole-cycle ambiguity in the differential carrier-phase measurements must be determined. When the distance between the user receiver and the reference receiver (baseline distance) is short, the RTK technique is highly advantageous because in this case, the whole-cycle ambiguity can be resolved not only accurately but also quickly. On the other hand, when the baseline distance is more than a few tens of kilometers, it may become impossible to determine the whole-cycle ambiguity and the normal RTK accuracy cannot be achieved. Another limitation of the RTK technique is that it requires a local radio link to be maintained between the reference receiver and the navigation receiver to supply timely correction or measurement data.
The WADGPS techniques that employ a carrier-phase differential method can also achieve very high navigational accuracy. The WADGPS differential techniques are also typically characterized by reliable long distance low-frequency communication links or by reliable satellite communication links. Thus, corrections can generally be communicated to navigation receivers without significant interruption. However, the WADGPS techniques usually treat the whole-cycle ambiguities as a real-valued (non-integer) variable and solve for a "floating ambiguity," which is usually very poorly defined until measurement data covering a time interval of significant satellite geometry change have been obtained. Thus, in a WADGPS application, a time interval as long as one or two hours may be required to solve for the "floating ambiguity" with sufficient accuracy to yield a navigated position with an accuracy of less than (i.e., better than) 10 centimeters.

Navigation receiver and method for combined use of a standard RTK system and a global carrier-phase differential positioning system


The invention provides a non-invasive technique for the differential detection of multiple genotypes and/or mutations for a plurality of target genes in a biological sample containing genetic material from different genomic sources. Methods are conducted using multiplex amplification of a plurality of target sequences from the biological sample, and sequencing is used to detect and enumerate genetic mutations and chromosomal abnormalities at the single nucleotide level.

Fetal DNA shed from the placenta is detectable in maternal blood at levels between 3% and 6% of total DNA. Thus, a number of PCR based fetal genetic screens have been described (e.g., gender, Rh, and thalassemia. However, traditional techniques are limited for at least two primary reasons: first, PCR assays trade sensitivity for specificity, often making it difficult to identify particular mutations, and second, aneuplodies, such as Down's Syndrome, cannot be detected by conventional PCR in a heterogeneous sample.
One way to avoid the problems of PCR-based assays is through large amounts of DNA using highly scalable techniques. Such digital analysis approaches involve the separation of extracted genomic material into discrete subsamples so that target sequence detection is binary (0, 1). For example, digital PCR allows amplification of single molecules, followed by quantitative analysis. Digital PCR typically requires limited dilution of a nucleic acid in a multi-well format followed by amplification of nucleic acids in the wells.
Digital PCR has been applied to fetal diagnostics in order to detect fetal mutations with specificity and sensitivity beyond that of conventional PCR. However, such methods are optimized for analyzing a single target in a biological sample, and moreover, the sample is consumed without interrogating the identity of other targets in the sample. Furthermore, digital PCR is limited to optical detection. Thus, multiplex analysis using digital PCR is not feasible, as it would be difficult to distinguish between optical signals for multiple targets in a given well. Additionally, conventional digital analysis does not allow for the detection of fetal single nucleotide polymorphisms (SNPs), which could be informative regarding a broad spectrum of diseases or conditions in the fetus. Thus, there is a need for improved methods for non-invasive, prenatal screening for multiple genotypes and/or mutations on many different targets genes at the single nucleotide level.

Method of simultaneously screening for multiple genotypes and/or mutations