Methods and compositions are provided for facilitating gene therapy procedures involving the transduction of target cells with retroviral vector particles in the presence of complement containing body fluids. The reduction of levels of galactose alpha (1,3) galactosyl epitopes on the retroviral vector particles and/or the blockade of antibody binding to such epitopes have been found to render the particles less sensitive to inactivation by complement mediated mechanisms, and to thus allow transduction in the presence of complement containing body fluids. Means are provided for obtaining such reductions.

I. Retroviruses
The Retroviridae virus family encompasses all viruses containing an RNA genome and producing an RNA-dependent DNA polymerase (reverse transcriptase). In broadest overview, the life cycle of a retrovirus comprises entry of an infectious retroviral particle into a host cell, integration of the virus' genetic information into the host cell's genome, and production of new infectious retroviral particles by the biosynthetic machinery of the infected host cell. More specifically, upon entering a cell, a retroviral particle initiates a series of interactive biochemical steps that result in the production of a DNA copy of the virus' RNA genome and its integration into the nuclear DNA of the cell. This integrated DNA copy is referred to as a provirus and can be inherited by any daughter cells of the infected cell like any other gene. Genes contained within the integrated provirus may be expressed in the host cell.
All retroviral particles share common morphological, biochemical, and physical properties, including:
(1) A linear, positive-sense, single-stranded RNA genome composed of two identical subunits and making up about 1% of the mass of the virus. PA0 (2) At least three types of proteins encoded by the viral genome, i.e., gag proteins (the group antigen internal structural proteins), pol proteins (the RNA-dependent DNA polymerase and integrase proteins), and env proteins (the viral envelope protein or proteins). These proteins together make up about 60%-70% of the mass of the virus. PA0 (3) Lipid derived from the cell membrane of an infected cell making up about 30%-40% of the mass of the virus. PA0 (4) Carbohydrate associated with the env proteins, making up about 2-4% of the mass of the virus. PA0 (5) An overall spherical morphology with variable surface projections. PA0 (6) An isocahedral capsid structure containing a ribonucleoprotein complex within an internal nucleoid or nucleocapsid shell. PA0 (1) Gal .alpha.(1,3) Gal .beta.(1,4) GlcNAc, PA0 (2) Gal .alpha.(1,3) Gal .beta.(1,4) Glc, PA0 (3) Gal .alpha.(1,3) Gal .beta., and PA0 (4) Gal .alpha.(1,3) Gal.
In addition to genes encoding the gag, pol, and env proteins, the genome of the retrovirus includes two long terminal repeat (LTR) sequences, one at each end of the linear genome. These 5' and 3' LTRs serve to promote transcription and polyadenylation of viral mRNAs. Adjacent to the 5' LTR are sequences necessary for reverse transcription of the viral genome (the tRNA primer binding site) and for efficient encapsulation of viral RNA into particles (the Psi site). Other genes may also be found between the 5' and 3' LTRs of the retroviral genome.
If heterologous genes are inserted in between the 5' and 3' LTRs of a retroviral genome, which is then packaged into a functional retroviral particle, the resulting recombinant retroviral particle is capable of carrying the heterologous genes into a host cell. Upon integration of the recombinant retroviral genome into the host cell's genome as part of the proviral DNA, the heterologous genes may be expressed.
These properties and capabilities have led to the development of retroviral vectors, retroviral packaging and producer cells, which are typically prepared from cells of murine origin, and retroviral vector particles (collectively referred to as retroviral transduction systems) as efficient means of stably introducing exogenous genes of interest into mammalian cells. Certain retroviruses have been engineered to produce non-infectious retroviral transduction systems that are especially useful in the field of gene therapy. See, for example, Anderson, 1992; Miller, 1992; Mulligan, 1983; Mann, 1983; Cone and Mulligan, 1984.
II. Gene Transfer by Retroviral Transduction
Retroviral transduction systems of the type discussed above are able to introduce recombinant nucleic acid molecules into mammalian target cells, and to efficiently integrate DNA molecules containing some or all of the genetic information (sequence) of the introduced recombinant nucleic acid molecule into the genome of the target cell so that the introduced genetic material is replicated and is stably and functionally maintained (and any encoded gene products are expressed) in the cell without the danger of the production of replicating infectious virus. See, for example, Ausubel, et al., Volume 1, Section III (units 9.10.1-9.14.3), 1992.
Retroviral vector particles are particularly useful for genetically modifying mammalian cells, including human cells, because the efficiency with which they can transduce target cells and integrate their genetic information into the target cell genome is higher than that achievable using other systems of introducing exogenous genetic material into cells. Other advantages associated with the use of retroviral vector particles as gene therapy agents include stable expression of transferred genes, capacity to transfer large genes, and lack of cellular cytotoxicity. Additionally, retroviral vector articles may be constructed so as to be capable of transducing mammalian cells from a wide variety of species and tissues.
Successful gene transfer by transduction with a retroviral vector particle (RVVP) requires: 1) incorporation of a gene of interest into a retroviral vector; 2) packaging of a vector-derived viral genome into a RVVP; 3) binding of the RVVP to the target cell; 4) penetration of at least the RNA molecules comprising the viral genome into the target cell (generally associated with penetration of the RVVP and uncoating of the RVVP); 5) reverse transcription of the viral RNA into pre-proviral cDNA; 6) incorporation of the pre-proviral cDNA into preintegration complexes, 7) translocation of the preintegration complexes into the target cell nucleus, 8) generation of stable proviral DNA by integration of the pre-proviral cDNA into the host genome (typically mediated by the viral integrase protein); and 9) expression of the gene of interest. In the in vivo setting (and in some ex vivo settings), the RVVP must survive in the extracellular fluids of the host organism in an active state for a period sufficient to allow binding and penetration of the host target cell by the RVVP.
Gene Therapy: There is active research, including clinical trial research, on treatment of disease by introduction of genetic material into some of the cells of a patient. A variety of diseases may be treated by therapeutic approaches that involve stably introducing a gene into a cell such that the gene may be transcribed and the gene product may be produced in the cell. Diseases amenable to treatment by this approach include inherited diseases, particularly those diseases that are caused by a single gene defect. Many other types of diseases, including acquired diseases, may also be amenable to gene therapy. Examples of such acquired diseases include many forms of cancer, lung disease, liver disease, and blood cell disorders. See Anderson, 1992; Miller, 1992; and Mulligan, 1993.
Delivery of the gene or genetic material into the cell is the first critical step in gene therapy treatment of disease. A variety of methods have been used experimentally to deliver genetic material into cells. Most research has focused on the use of retroviral and adenoviral vectors for gene delivery. As discussed above, RVVPs are particularly attractive because they have the ability to stably integrate transferred gene sequences into the chromosomal DNA of the target cell and are very efficient in stably transducing a high percentage of target cells. Accordingly most clinical protocols for gene therapy use retroviral vectors (see, for example, Miller, 1992; and Anderson, 1992).
Most gene therapy protocols involve treating target cells from the patient ex vivo and then reintroducing the cells into the patient. Patients suffering from several inherited diseases that are each caused by a single gene defect have already received gene therapy treatments. Such treatments generally involve the transduction of the patient's cells in vitro using RVVPs designed to direct the expression of therapeutic molecules, followed by reintroduction of the transduced cells into the patient. In many cases such treatments have provided beneficial therapeutic effects.
For many diseases, however, it will be necessary to introduce the gene into the target cell in situ, because the target cells cannot be removed from and returned to the body. In other cases, cells that are removed from the patient must be maintained in the presence of body fluids until being returned to the body. Stem cells, particularly hematopoietic stem cells, are an especially important type of target cell for gene therapy of inheritable and acquired blood disorders. Such cells are intrinsically unstable in vitro, and tend to differentiate into cells that are less attractive targets for gene therapy, especially when they have been washed free of the fluids that surround them in vivo and transferred into body-fluid-free tissue culture media or the like.
Accordingly, it is desirable to transduce stem cells as quickly as possible, and ex vivo treatment of such cells with RVVPs is best carried out in the cells natural milieu, i.e., in cells that have not been washed or otherwise removed from the body fluids in which they are obtained, e.g., hematopoietic stem cells in bone marrow aspirates. In the case of stem cells in bone marrow, current medical procedures for bone marrow transplant involve mixing an ex vivo bone marrow aspirate (which is inevitably obtained as a mixture of bone marrow and blood) with an anticoagulant, typically heparin, and tissue culture medium. The condition of such cells, that have been removed from the body but kept in diluted or undiluted fluids of their natural milieu, is referred to hereinafter as the "ex vivo unwashed state".
III. The Humoral Immune System and Retroviral Vector Particles
A longstanding problem associated with the use of RVVPs as gene therapy vectors in cells in vivo or in cells in the ex vivo unwashed state relates to the inactivation of many retroviruses (and RVVPs derived therefrom) by the body fluids (e.g., blood, bone marrow, lymph) of many primates, including Old World monkeys, apes, and humans. Indeed, it has been known for almost two decades that certain retroviruses are rapidly inactivated in human serum (Welsh et al., 1975), as well as serum from nonhuman primates (Welsh et al., 1976). This problem has precluded the use of such RVVPs for gene therapy in vivo or in the ex vivo unwashed state.
The humoral immune system, and particularly the complement system has long been implicated in the serum mediated inactivation of retroviruses, as serum deficient in C2, C4 or C8 does not cause the detectable release of reverse transcriptase from retroviral virions (Welsh et al., 1975; Cooper, et al., 1976). The protection of active retroviral particles from human complement is thus necessary for the use of the RVVPs to mediate gene therapy in human cells in vivo or in the ex vivo unwashed state. Accordingly, to date, gene transfer by retroviral transduction has been, for the most part, limited to cells that were removed from the extracellular fluids of the host organism (i.e., ex vivo cells that are not in the ex vivo unwashed state) and thus were not subjected to complement attack. This limitation has represented a significant shortcoming of this technology.
The need for methods allowing transduction of primate cells in situ, in vivo, or in the ex vivo unwashed state has resulted in the development of methods designed to prevent the inactivation of retroviruses by human and other primate sera. Such methods have included the removal of cells from the extracellular fluids of the host organism, as discussed above, as well as the masking of virion structures that can activate complement activity by administration of isolated C1s and/or C1q complement subcomponents, as discussed below under the subheading "The Direct C1 Binding Mechanism".
Significantly, with regard to the present invention, no previous methods for allowing transduction of primate cells in situ, in vivo, or in the ex vivo unwashed state have included methods or compositions for preventing antibody binding to alpha galacotsyl epitopes on virion cell surface molecules.
The Direct C1 Binding Mechanism: Retroviruses that are sensitive to human serum have been reported to activate the human classical complement pathway by a mechanism that involves an antibody independent process. This process is found in many primates and is generally not present in other mammals (see Cooper, et al., 1976). This mechanism is activated when complement component C1 binds to retroviral virions directly and triggers the classical complement pathway, just as the pathway is normally activated by an antigen-antibody complex (Bartholomew, et al., 1978). The complement cascade then causes the eventual destruction and elimination of the virus. Prior to the present invention, it has generally been believed in the art that this mechanism provides the major, if not the only, means by which retroviral virions are destroyed by the humoral immune system.
Complement component C1 is a large complex protein composed of 3 subunits designated C1q, C1s, and Clr. C1q is itself composed of 18 polypeptide chains of three different types designated A, B, and C. Six molecules each of chains A, B, and C compose the C1q subunit. There are two molecules each of the C1s subunit and the Clr subunit that associate with C1q to form the C1 complement component. The C1q subunit contains multiple identical binding sites for the complement binding regions of immunoglobulin molecules, which regions are only exposed upon the formation of an antigen-antibody complex. In the classical pathway, the binding of C1q to these regions of antigen-bound antibody molecules causes a conformational change in the Cl complex resulting in the enzymatic activation of C1 to yield an active serine protease. The C1s and C1q subunits both have a molecular weight of approximately 85 kDa, and each is cleaved to smaller molecular weight forms of approximately 57 kDa and 28 kDa during activation of the C1 complex. The 57 kDa forms of C1s and C1q present in the activated C1 complex contain the protease activity.
In the activation of the classical complement pathway by retroviruses via direct binding of C1, the C1q subunit of Cl binds directly to at least one site on the retroviral virion. In the case of Moloney murine leukemia virus, the pl5E viral protein has been identified as the C1 binding receptor. See Bartholomew, et al., 1978. In contrast to the antibody-mediated classical complement pathway, binding by both the C1q subunit and the C1s subunit of the Cl complex is required for complement activation by retroviral particles via this mechanism. Furthermore, the C1s subunit and C1q subunit must bind the viral particle when they are present in a functional Cl complex in order for complement activation to occur by this mechanism. See Bartholomew, et al., 1980.
The C1s subunit is also believed to have a specific binding site for retroviral coat proteins. It has been shown, using inactive retrovirus, that pre-binding with C1s blocks the subsequent activation of the complement cascade by the retrovirus in vitro. See Bartholomew, et al., 1980.
Co-pending U.S. patent application Ser. No. 08/098,944 ("the '944 application"), filed Jul. 28, 1993 in the name of James M. Mason and entitled "Pre-binding of Retroviral Vector Particles with Complement Components to Enable The Performance of Human Gene Therapy In Vivo," discuses the use of free C1q or free C1s to block the subsequent binding and/or activation of the C1 complex by active retrovirus particles including RVVPs.
As described therein, C1s or C1q or a combination thereof are incubated with the RVVPs in vitro to form complexes with the particles. This complex formation blocks the binding sites for C1s and/or C1q and thereby protects the particles from subsequent inactivation or lysis when the RVVPs are exposed to complement. As further described therein, blockade of intact C1 binding to RVVPs can be achieved by the use of fragments of antibodies that bind the viral envelope proteins of RVVPs but lack complement binding regions.
As disclosed in the '944 application, the use of these methods improves the survival of RVVPs in human serum, but does not completely inhibit retroviral inactivation. The incomplete nature of the inhibition of retroviral inactivation by these methods have heretofore been unexplained.
Many gene therapy methods require very high titers of transducing RVVPs in order to be practiced effectively. The methods of the '944 application are of limited efficacy, as they do not provide a sizable inhibition of complement mediated RVVP inactivation, and thus may not provide high enough titers of RVVPs in vivo or in the ex vivo unwashed state for the effective practice of all such gene therapy methods.
Thus, a need continues to exist for methods to control complement-mediated destruction of RVVPs. The present invention provides new methods and compositions that can be used in conjunction with, or as an alternative to other methods of protecting RVVPs from inactivation by complement such as the blockade of intact C1 binding to RVVPs as disclosed in the '944 application. The methods and compositions of the present invention thus allow the practice of more efficient gene therapy procedures in vivo, in situ, and in the ex vivo unwashed state.
IV. The Complement System
The complement system acts in conjunction with other immunological systems of the body to defend against intrusion of cellular and viral pathogens. There are at least 25 complement proteins, which are found as a complex collection of plasma proteins and membrane cofactors. The plasma proteins (which are also found in most other body fluids, such as lymph, bone marrow, and cerebrospinal fluid) make up about 10% of the globulins in vertebrate serum. Complement components achieve their immune defensive functions by interacting in a series of intricate but precise enzymatic cleavage and membrane binding events. The resulting complement cascade leads to the production of products with opsonic, immunoregulatory, and lytic functions.
The complement cascade progresses via the classical pathway or the alternative pathway. These pathways share many components, and, while they differ in their early steps, both converge and share the same terminal complement components responsible for the damage and destruction of target cells and viruses.
The classical complement pathway is typically initiated by antibody recognition of and binding to an antigenic site on a target cell. This surface bound antibody subsequently reacts with the first component of complement, C1, which, as discussed above, includes subunits C1s, Clr, and C1q.
The C1q subunit of C1 mediates the binding of C1 both to antigen-antibody complexes and to retroviruses, although, in the case of direct binding to retroviruses, the C1s subunit also has a binding function. The bound C1 undergoes a set of autocatalytic reactions that result in the activation of the Clr subunits, which in turn proteolytically activate the C1s subunits, altering the conformation of C1 so that the active C1s subunits are exposed on the exterior of C1, where they can interact proteolytically with complement components C2 and C4.
C1s cleaves C2 and C4 into C2a, C2b, C4a, and C4b. The function of C2b is poorly understood. C2a and C4b combine to form the C4b,2a complex, which is an active protease known as the C3 convertase. C4b,2a acts to cleave C3 into C3a and C3b. C3a is a relatively weak anaphylatoxin. C4a is a stronger anaphylatoxin, and can induce degranulation of mast cells, resulting in the release of histamine and other mediators of inflammation.
C3b has multiple functions. As opsonin, it binds to bacteria, viruses and other cells and particles and tags them for removal from the circulation. C3b can also form a complex with C4b,C2a to produce C4b,2a,3b, or C5 convertase, which cleaves C5 into C5a (another anaphylatoxin), and C5b. C5b combines with C6 yielding C5b,6, and this complex combines with C7 to form the ternary complex C5b,6,7. The C5b,6,7 complex binds C8 at the surface of a cell membrane. Upon binding of C9, the complete membrane attack complex (MAC) is formed (C5b-9) which mediates the damage and lysis of foreign cells, microorganisms, and viruses.
A more complete discussion of the classical complement pathway, as well as a detailed description of the alternative pathway of complement activation, which pathway has also been implicated in the inactivation of RVVPs by human complement, can be found in Roitt, et al., 1988.
V. Galactose Alpha (1,3) Galactosyl Epitopes
Natural human antibodies are preformed antibodies that bind to epitopes of foreign antigens (xenoepitopes). Several recent studies have convincingly demonstrated that the galactose alpha (1,3) galactosyl carbohydrate epitopes, also referred to as Gal .alpha.(1,3) Gal epitopes, are major xenoepitopes recognized by natural human antibodies (see Sandrin, et al., 1993A; Sandrin, et al., 1993B; copending U.S. patent application Ser. No. 08/214,580, entitled "Xenotransplantation Therapies", filed by Mauro S. Sandrin and Ian F. C. McKenzie on Mar. 15, 1994; copending U.S. patent application Ser. No. 08/278,282, entitled "Methods for Reducing Hyperacute Rejection of Xenografts", filed Jul. 21, 1994 in the names of Mauro S. Sandrin, William L. Fodor, Russell P. Rother, Stephen P. Squinto, and Ian F. C. McKenzie; and PCT publication No. 93/03735, entitled "Methods and Compositions for Attenuating Antibody-Mediated Xenograft Rejection"). In addition, it has been suggested that galactose alpha (1,3) galactosyl epitopes on certain DNA viruses may be involved in triggering immune responses (Repik et al., 1994).
Galili and colleagues have shown that a large proportion of IgG (1%) in human serum is directed against the galactose alpha (1,3) galactosyl epitopes expressed as part of a variety of glycosylated molecules found on both cell surfaces and on secreted glycoproteins (Galili et al., 1984; and Thall and Galili, 1990). This disaccharide epitope is found in all mammals except humans and Old World primates, and naturally occurring preformed anti-.alpha.(galactosyl antibodies e.g., anti-galactose alpha (1,3) galactose antibodies--i.e., antibodies that bind specifically to galactose alpha (1,3) galactosyl epitopes--are found only in humans and Old World primates, i.e., those species that do not themselves express the epitope (Galili et al., 1987 and Galili et al., 1988).
The ability of different monosaccharides and oligosaccharides to inhibit the interaction of naturally occurring preformed human antibodies with pig cells and to prevent the antibody-dependent and complement-mediated damage and lysis of pig cells has been examined (Sandrin et al., 1993A; Sandrin et al., 1993B; PCT publication No. 93/03735, supra; and copending U.S. patent application Ser. No. 08/214,580, supra).
Inhibition of the binding of such antibodies to xenogeneic cells was obtained with galactose, or with moieties containing terminal galactose in an alpha linkage but not a beta linkage. Various carbohydrates have also been shown to contain the target epitopes for several types of naturally occurring preformed human antibodies with other specificities (e.g., ABO blood group antibodies). However, no monosaccharide tested, other than those containing the galactose alpha (1,3) galatosyl epitope, had any inhibitory effect on the binding of naturally occurring preformed human antibodies to xenogeneic cells. Identical inhibition results were obtained when individual human serum samples from blood group A, B, AB or O individuals were used (Sandrin et al., 1993A and Sandrin et al., 1993B).
Similarly, Cooper and colleagues have demonstrated that, of a total of 132 carbohydrates screened for binding to preformed naturally occurring human IgG and IgM antibodies, each of the four carbohydrate molecules that they found could bind such antibodies contained a terminal alpha galactose (Good et al., 1992). The four carbohydrates were:
Sugars such as melibiose (a disaccharide containing a terminal galactose in an alpha (1,3) linkage) coupled to a carrier such as SEPHAROSE can be used to purify anti-galactose alpha (1,3) galactose antibodies (Galili et al, 1984 and Galili et al., 1985). In some antibody absorption experiments, human serum was passed over the carrier-sugar matrix in order to prepare serum from which the antibodies reactive with the sugar were removed. The results of testing the cytolytic activity of the sera prepared in these experiments indicate that the majority of the cytotoxic antibodies were removed from the serum by these means (Sandrin et al., 1993A; Sandrin et al., 1993B).
In sum, the results of the sugar inhibition studies, the studies of the binding of antibodies to galactose alpha (1,3) galatosyl epitope-containing molecules, and the studies of the absorption of antibodies by melibiose-SEPHAROSE, all lead to the conclusion that galactose alpha (1,3) galactosyl epitopes are amongst the most important epitopes detected by naturally occurring human antibodies.
Inhibitors of Glycosylation
Glycosylation of retroviral proteins, including the glycosylated envelope protein (gp70), is a dynamic process involving the host cell translational machinery. Mature glycoproteins which contain asparagine linked (N-linked) oligosaccharides fall generally into three categories, depending on the oligosaccharide side chains of their carbohydrate moieties: high mannose, complex, and hybrid types. These side chain oligosaccharides are added to nascent proteins through a well characterized biosynthetic pathway (for review see Kornfeld and Kornfeld, 1985).
This pathway is initiated with the addition of a glucosylated high mannose oligosaccharide precursor, (Glc).sub.3 (Man).sub.9 (GlcNAc).sub.2. This high mannose precursor is trimmed by various glucosidases and mannosidases as the protein traverses the rough endoplasmic reticulum and golgi apparatus, respectively. When high mannose oligosaccharide side chains are not trimmed by the mannosidases, the high mannose type side chain results. When high mannose oligosaccharide sides chains are trimmed by the mannosidases and are subsequently modified to contain glucosamine, fucosyl, galactosyl, and other side chain additions, the complex type side chain results. Intermediates between these two end products are termed hybrid side chains.

Methods and compositions for protecting retroviral vector particles and producer cells from inactivation by complement via reduction of the expression or recognition of galactose alpha (1,3) galactosyl epitopes


A credit card and money carrying device comprising an endless band of elastic material, a plate member folded around the elastic band and crimped providing engagement of the crimped portion of the plate member into the elastic band.

The present invention is directed towards a new and improved credit card and money carrying device for holding foldable currency and credit type cards or identification cards together in a convenient, easy to use arrangement.
Money clips have been used for a long time to hold folded currency and are designed to be carried in a pants or jacket pocket or other area. These money clips are fashioned from a single piece of bent or formed metal stock generally in the form of a spring clip and are available in plated or solid precious metals, stainless steel, bronze or nickel.
The demise of popularity for the money clip in the past decade can be directly attributed to the demand for and growth in the use of credit cards and the accompanying need to conveniently and securely carry on one's person. This change has been brought about by the emergence of the credit card and its impact on society, banking and the very nature of monetary transactions. The credit card has now become a standard item for most adults in the United States. Each card complies with a defacto standard with respect to size, shape, dimensions and weight. The proliferation of these credit card sized devices hall led to the adoption of the same sized devices for use in a wide array of identification cards. These include ATM cards, bank cards, phone cards, driver's licenses, smart keys and other identification cards.
Most money clips do not adequately accommodate credit cards and other types of cards, many which were originally designed prior to the widespread use of credit and other type cards. Those that do often pose the disadvantage of added weight and bulk caused by the need for a heavy spring attachment to keep the cards in place.
The primary carrying device for credit cards and money for men and women has been in the form of a wallet or small pocketbook. With the attire which has been adopted by the public in casual, business or formal dress, wallets and pocketbooks have become bulky and in some instances uncomfortable when driving distances, or sitting in a theatre or restaurant. Furthermore, changes in the money and banking industry including the widespread use of the automated teller machines and consumer credit cards have changed the way people organize, handle and carry their money. Checkbooks are not as frequently used and cash can easily be obtained from a cash machine with a credit card. Women do not desire to carry a purse around with them which is clearly visible and can be easy target for a thief or placed aside and forgotten or displaced. It is now common to carry a small amount of money, the primary means for purchase or lease being credit which increases personal security as there is less to steal and less personal monetary risk. In addition to the monetary loss risk, a disturbing influence has cropped up in society which is directed toward personal risk in that persons with bulging pockets or pocketbooks may be subject to brutal attack and suffer physical and physiological harm through street attacks and robbery.
While money clips are a convenient way to carry folded money, they do not work very well in carrying credit cards, driver's licenses or other card identifications as the same tend to fall out of money clips or are bent, scratched, broken or destroyed by the money clip while being carried or removed.
It is estimated that by 1995 smart card technology will become common place providing yet another card sized identification device able to contain important personal information ranging from health information to banking, credit, telephone and other data.
These factors combine to create the need for a carrying device that can accommodate denominational money bills as well as a wide variety of credit card sized items. The carrying device should be capable of being carried in any pocket and also be capable of carrying up to ten different cards and a quantity of bills.
A number of patents have been obtained to attempt to provide a suitable currency or a credit card and identification carrier for individuals. U.S. Pat. No. 5,077,869 is directed towards a credit card/money clip device with a folded metal clip member adapted to hold folded currency and a T-shaped elastic band fastened to the clip member to retain credit cards and identification cards. U.S. Pat. No. 4,675,953 discloses a money clip with a base and operative clip member mounted to the base. The clip member has a pair of semi-elastic legs terminated in opposed staggered but parallel journals, pivotally mounted in bearings to provide offset parallel pivotal axes. The semi-elastic legs flex and cross through an over-center plane between a closed, clamping position and an inoperative open position. U.S. Pat. No. 3,555,623 discloses a paper money clip made of a length of spring wire in the form of a rectangular cylindrical helix on which is mounted a carrier plate. A resilient pad is secured to the coin facing surface of the carrier plate and functions with the bent over ears of the carrier plate to retain coins. U.S. Pat. No. 3,861,002 discloses a money clip constructed of a double clip member of spring wire or sheet spring material. A central clip element is common to both elements of the double clip which holds the money in place while allowing removal of a single bill from a stack of paper money. U.S. Pat. No. 3,623,193 discloses a money clip with a rectangular coiled spring structure held in place by an outer ring and inner disc medallion. The coiled spring has sufficient resiliency to open and close. U.S. Pat. No. 3,596,757 discloses a coin holding device, in combination with a paper money clip mounted within the framework of a paper money clip. The money clip is of the type having a rectangular helix of spring wire which functions to hold the paper money. The housing of the coin holder contains a resilient bowed plate which serves as a bias element for the coins and also encloses two legs of the money clip allowing the money clip and coin holding device to be operated independently of the other. U.S. Pat. No. 4,540,034 discloses a money clip mounted in a wallet, the clip being formed from resilient material and formed with two arms connected by a flexure section, the arms holding currency by virtue of a flexural torquing deformation around an axis through the flexure section.
As a result of the present need, the present invention is directed towards a new and improved credit card and money carrying device for conveniently carrying a number of credit sized cards, identification cards and folding monies in a convenient, easy manner in a pants pocket, shirt pocket or the like.


There are provided measures for improved service continuity with mobile edge computing. Such measures exemplarily comprise detecting a handover of a communication endpoint from a first gateway to a second gateway, determining, whether an ongoing mobile edge computing related application session of said communication endpoint is routed by said first gateway, checking, upon positive result of said determining, whether said ongoing mobile edge computing related application session fulfills a predetermined condition, and initiating, upon positive result of said checking, a swap of said ongoing mobile edge computing related application session from said first gateway and a first mobile edge computing entity connected to said first gateway to said second gateway and a second mobile edge computing entity connected to said second gateway.

The present specification generally relates to measures considering/enabling session continuity in mobile edge computing scenarios in case of handover between gateways and/or mobile edge computing entities. Mobile edge computing (MEG) is a network architecture (concept), in which applications are run and related processing tasks are performed closer to the cellular customer by pushing applications, data and computing power (services) away from centralized points to the logical extremes of a network. By running applications and performing related processing tasks closer to the cellular customer, network congestion may be reduced and applications may perform better. MEC technology is designed to be implemented at/near the cellular base stations.
MEC may support different kinds of connectivity scenarios. Applications and services offered by a MEC server may be used by 3rd Generation Partnership Project (3GPP) mobile network users/subscribers either in sessions between a terminal (e.g. user equipment (UE)) and an MEC server or as intermediate data flow manipulators in sessions between a UE and e.g. the internet.
MEG may support different mobility scenarios. For example, a UE may move from a MEC server to another MEC server. It may be assumed that, depending on the case and/or conditions, the internet protocol (IP) address of the UE may change or stay unchanged during mobility.
MEC may work both in the forthcoming 5th Generation (5G) environment and in the current 3GPP evolved packet core (EPC) environment. It is further conceivable that MEC may work in any future 3GPP mobile network environment.
For MEC, two architecturally different implementations may be considered. Namely, one architectural implementation with a MEG server/platform residing between the evolved NodeB (eNB, eNodeB) and Serving Gateway (S-GW)/Packet data network Gateway (P-GW), the other with the S/P-GW residing between the eNB and the MEC server/platform.
The latter implementation may be easily implementable in virtualized networks (as opposed to current non-virtualized, EPC based networks with physical S/P-GWs) and may be compatible with 5G ponderings with different levels of gateways (local, regional, central).
In a further architectural variation, the Gateway-(GW) and MEC-functionalities may be integrated in the same platform, e.g. as virtual network functions (VNF) running on the same physical platform.
Concerning the architectural implementation where the S/P-GW resides between the eNB and MEC server/platform, or the GW and MEG functionalities are integrated in the same platform, problems regarding optimal session continuity arise in mobility scenarios where a UE moves from the area of a P-GW (that has allocated an IP address from its own address range to the UE) connected to a MEC server/platform to the area of another P-GW connected to another MEC server/platform.
In particular in case the optimal session continuity requires the change of the MEC server/platform during an ongoing application session, a mere distributed mobility management and/or routing based mobility may be insufficient.
In particular, it cannot be assumed that all applications tolerate a change of an IP address during an ongoing application session. Accordingly, when a need arises to move an ongoing application session from the area of a MEC server to the area of another MEC server, further problems and complications may be caused by the uniqueness of IP addresses of MEG applications in the network.
Hence, there is a need to provide for improved service continuity with mobile edge computing.

Methods, apparatuses and computer program product for improved service continuity with mobile edge computing


A solar power generator includes a support, a plurality of first electrodes disposed on one side of the support, a solar cell module mounted to the support, and a plurality of second electrodes disposed on the opposite side of the support. The solar cell module is electrically connected to a pair of the first electrodes via a transmission line for module connection. Three pairs of the second electrodes are electrically connected one-to-one to three pairs of the first electrodes via a transmission line for passage of current. Three of the second electrodes are electrically connected to one of the first electrode via the transmission line for passage of current.

A solar array wing includes a plurality of solar panels to generate power required by a satellite. Each of the panels is connected to the body of the satellite by wiring in order to supply power generated in each of the panels to the body of the satellite. That is, a transmission line is installed at the back of each of the panels for allowing passage of current from the panel placed on the outer side. The area of installation of the transmission line varies from panel to panel so that wiring design specific to each panel is required. The larger the number of types of drawings, the longer the time required for designing and the greater the risk of occurrence of a problem due to design and manufacturing errors. This also applies to a solar array wing including a plurality of solar array blankets instead of the plurality of solar panels, as in a solar array wing described in Patent Literature 1.
In order to disuse the transmission line as described above, a solar array wing described in Patent Literature 2 connects solar cells in series by integrated inner current conduction path system and outer current conduction path system. Specifically, the series circuit of solar cells extends across a plurality of solar array blankets in the direction of expansion thereof and makes a U-turn at a position farthest from the body of the satellite via wiring of the outer current conduction path system. The series circuit of solar cells then extends across the plurality of solar array blankets again in the direction of expansion thereof and is led to a processing system of the body of the satellite via wiring of the inner current conduction path system. The solar cells are connected in series within the same module or connected in series between different modules by contact welding.

Solar power generator, solar array wing, and space structure


A vertical lift mechanism (100, 100a, 100b) including: a lift support assembly (102) comprising an upper frame member (104), a lower frame member (106), the upper frame member is movable between a lowered position and a lifted position. The lift support assembly additionally includes a support mechanism (150) that holds and maintains the alignment between the upper frame member and a lower frame member as well as a powering unit to cause movement of the upper frame.

The present invention generally relates to lifting mechanisms generally including lifts, jacks, and lift or lifting platforms, each of these terms are used interchangeably herein.
Industrial lifting platforms provide a powerful mechanism to lift and or otherwise orientate machinery, manufactured parts, pallets, boxes and the like. These devices also serve as adjustable platforms for operators as well. The prior art including U.S. Pat. No. 7,070,167, shows a variety of different types or classes of industrial lifts including stationary lifts, mobile lifts, lifts with fixedly secured platforms as well as lifts with platforms capable of tilting about a horizontal axis as well as rotating about a vertical axis. Each of these lifts is built to a fixed design to achieve a basic purpose and is not convertible or reconfigurable from one class of lift to another.
The manufacturer, distributor or customer of these various lifts must maintain and/or purchase an extremely large inventory of fully assembled lifts or parts therefor to enable the manufacture, assembly and use of a large set of products. The present invention has as one of its goals the reduction of inventoried parts while still enabling the assembly of a wide variety of lifts including those mentioned above. The present invention shows how the above mentioned lifts can be assembled utilizing modularity which permit for example starting with one type of basic lift and converting or reconfiguring its purpose and functionality.
More particularly, the present invention comprises in a first embodiment: a vertical lift including an upper frame member, a lower frame member, and the upper frame member is movable by a powering unit between a lowered position and a lifted position. The lift additionally includes a support mechanism that maintains the alignment of the upper frame member and a lower frame member. The powering unit is also referred to as a force generating subassembly. As can be appreciated the support mechanism can also be part of the power unit.
In the illustrated embodiment the support mechanism comprises a plurality of scissor mechanisms which primarily serve to support the upper frame and to maintain the alignment between the upper and lower frames. In the illustrated embodiment the scissor mechanisms are part of a lift support assembly and as such the illustrated lift is often referred to as a scissor lift. The powering unit or force generating subassembly in some of the illustrated embodiments is achieved by a plurality of inflatable chamber's (which resemble tires, air bags or bellows) that act directly between the upper and lower frames. The invention encompasses other support mechanisms and powering units. The lift is configured to accept one of a plurality of modular element or units to vary the functionality of the lower frame member and/or the upper frame member creating various lifts to provide commercial and functional flexibility and easily meet varying customer demand. In the illustrated embodiments the lift has a one-to-one ratio lift, with high lifting capacity, employing air bag (bellows) having diameters of up to 0.76 m (30 inches) to achieve a low profile, rapidly responsive lift. The lift is engineered to maximize structural strength and reduce cost by optimally placing steel elements in critical locations throughout the lift as opposed to increasing the size and weight of all of the components.


A compensator lens is driven by a second driving means such that the rear end of the focal depth of an object image at infinity coincides with a surface of image-formation irrespective of the movement of a variable lens when the object image is photographed. With this arrangement, the whole range of the focal depth can be effectively utilized, so that the range of photographing can be enlarged without focussing immediately after the power source is turned on as compared with the conventional zoom lens system. That is, even an object disposed at a close distance can be photographed without focussing as compared with the conventional zoom lens system which can utilize only the substantially half length of the focal depth. Furthermore, even when the object disposed at the closest distance is photographed, focussing can be made in a short period of time as compared with the conventional zoom lens system.

1. Field of the Invention
This invention relates to a zoom lens system, and more particularly to a zoom lens system suitable for a video camera.
2. Description of the Related Art
As methods of correcting the movement of focus, the zoom lens system has heretofore included an optical compensation type and a mechanical compensation type.
The optical compensation type is of a type for unifying the movement of movable lenses, in which the mechanism is simplified, however, such disadvantages are presented that the lenses become larger in the whole size and the focussing is easily shifted. In contrast thereto, in the mechanical compensation type, the movable lenses move differently from one another, whereby a cam mechanism is required and the lenses become complicated in construction, however, the focussing is not shifted during the zooming and the lenses can be rendered compact in size. Because of the above-described reasons, the zoom lens system of the mechanical compensation type is most widely used.
In the zoom lens system of the mechanical compensation type, a group of variable lenses is moved to change the focal distance, whereby the shift of focussing caused by the movement of the variable lenses is corrected by the movement of a group of compensator lenses, so that, even the group of variable lenses is moved, the shift of focussing on a surface of image-formation is not caused as a whole.
Furthermore, in recent years, according to the mechanical compensation type, a group of focus lenses is disposed in the rear of the group of compensator lenses, whereby the group of focus lenses is moved, so that the range of photographing is enlarged and an object disposed at the closest distance can be focussed. Incidentally, the group of focus lenses is driven independently of the group of variable lenses and the group of compensator lenses, or a value of delivery thereof is mechanically and electrically controlled on the basis of information of the focal distance.
As shown in FIG. 9, in the conventional zoom lens system, a moving locus of the group 4 of the compensator lenses is regulated such that a light flux 2 of an object at infinity, which falls into a group 1 of variable lenses, can be made to focus at a surface 3 of image-formation, and a home position of a group 5 of focus lenses is such that the above-described light flux 2 can be made to focus at the surface 3 of image-formation.
Accordingly, the conventional zoom lens system utilizes only a range of S1.about.S2, which is substantially the half length of the focal depth, whereby, the range, within which focussing is made, is narrow when the power source is turned on, and, when an object disposed at a close distance, which is out of the range, is taken, the object is made to focus at a position shifted rearwardly of the rear end S2 of the focal depth. Because of this, the group 5 of focus lenses moves to a position where focussing is made, whereby much time is taken before focussing, thus presenting the disadvantage that the image is blurred during the photographing time.
Even when the image is blurred during the photographing time, if the zoom lens system applicable to the VTR camera for photographing the movie is used, then the image can be edited after taking, thereby presenting no problem. However, when the zoom lens system is applied to the VTR integrated with a camera, in which the image cannot be edited, a special device is required for removing the blurred image.


An air conditioner support system is provided including a pair of suspenders each with a horizontally oriented member coupled to a respective side of a window. Coupled to the horizontally oriented member is a truss. Next provided is a support plate assembly including a pair of extendible plates. In use, such support plate assembly is engaged with the suspenders for supporting an air conditioner thereon.

1. Field of the Invention
The present invention relates to window shelves and more particularly pertains to a new window shelf for allowing the installation of a window shelf from within a house and does not inflict damage by way of tools or fasteners on the window.
2. Description of the Prior Art
The use of window shelves is known in the prior art. More specifically, window shelves heretofore devised and utilized are known to consist basically of familiar, expected and obvious structural configurations, notwithstanding the myriad of designs encompassed by the crowded prior art which have been developed for the fulfillment of countless objectives and requirements.
Known prior art window shelves include U.S. Pat. No. 4,510,852; U.S. Pat. No. 4,869,451; U.S. Pat. Des. 288,570; U.S. Pat. Des. 266,827; U.S. Pat. No. 4,862,812; and U.S. Pat. No. 5,112,015.
While these devices fulfill their respective, particular objectives and requirements, the aforementioned patens do not disclose a new window shelf. The inventive device includes a pair of suspenders are provided each including a vertically oriented member and a horizontally oriented member in the form of an angle iron. The angle iron has a vertical extent with an inboard end perpendicularly coupled to a bottom end of the vertically oriented member and extended outwardly therefrom. Associated therewith is a horizontal extent defining an inwardly extending ledge. Also included is truss having a first end coupled to an outboard end of the angle iron and a second end coupled to a top end of the vertically oriented member. A vertical slot is formed in the vertically oriented member adjacent the top end thereof. A foot is integrally coupled to the horizontal extent of the angle iron adjacent the inboard end thereof. Such foot extends inwardly from the respective angle iron with a pad lining a bottom surface thereof. Next provided is a pair of ears each having an L-shaped configuration. Each ear is defined by a first plate and second plate. The second plate is integrally coupled perpendicularly with respect to the first plate. Further, the second plate has a lip extending therefrom in a direction opposite from that which the first plate extends. In use, the first plate of each ear is coupled on opposite sides of a window with padding situated therebetween. As such, the second plate extends outwardly from a wall in which the window resides and the lip extends inwardly towards the window. By this structure, the slots of the suspenders may be engaged with the lips of the ears such that the feet of the suspenders rest on a window stool. As shown in FIGS. 1 and 2, an extendible support plate assembly is provided including a pair of rectilinear plates. Such plates include a rectilinear first plate with a top face, a bottom face, a front face, and a rear face defining a pair of open ends. Also included is a rectilinear second plate with a top face, a front face, and a rear face defining a pair of open ends and an open bottom. Formed on the top face of both plates is a plurality of linearly aligned apertures. Preferably, such apertures are located adjacent the associated front face of the plates. During use of the present invention, the second plate may be slidably inserted within the first plate such that at least one of the apertures of each plate are aligned thereby allowing the securement of the relative positions of the plates via a pin. Note FIG. 2. This allows the support plate assembly to be supported by the ledges of the suspenders.
In these respects, the window shelf according to the present invention substantially departs from the conventional concepts and designs of the prior art, and in so doing provides an apparatus primarily developed for the purpose of allowing the installation of a window shelf from within a house and does not inflict damage by way of tools or fasteners on the window.

Window shelf for supporting an air conditioner


A composition comprising doxepin, or a pharmaceutically acceptable salt, or prodrug thereof, and a compound that enhances sleep onset, sleep maintenance or reduces early morning awakenings. These compositions are useful for treating multiple manifestations of insomnia.

Sleep is essential for health and quality of life. Insomnia is a growing health problem in the United States. It is believed that more than 30-45 million people suffer from chronic insomnia and up to an additional 70 million people suffer from some form of insomnia each year. Insomnia is a condition characterized by difficulty falling asleep (sleep onset), waking frequently during the night (fragmented sleep), waking too early (premature final awakening), and/or waking up feeling un-refreshed. In the National Sleep Foundation's (NSF) Sleep in America Poll 2005, 42% of survey respondents reported that they awoke frequently during the night, 22% of adults reported waking too early and not being able to return to sleep and 38% reported waking and feeling un-refreshed.
Sleep maintenance difficulty is the most commonly reported symptom in primary care patients with chronic insomnia, and is the most common insomnia complaint in depressed patients, medically ill populations, especially those with pain symptoms, and in the elderly.
Medications commonly used to treat sleep disorders, such as insomnia, include sedative antidepressants, antihistamines, antipsychotics, benzodiazepines, non-benzodiazepine GABA modulators and a recently approved melatonin receptor agonist. Benzodiazepines enhance the activity of gamma amino butyric acid (GABA), the main inhibitory neurotransmitter of the central nervous system, resulting in activation of GABA receptors which favors sleep.
Unfortunately, many of these existing medications have very undesirable side effects, including abnormal thinking and behavioral changes such as decreased inhibition, hallucinations, complex behaviors such as sleep driving, amnesia, anxiety, suicidal thinking; withdrawal symptoms; CNS depressant effects; impaired motor or cognitive performance (particularly in the elderly); bad taste; headaches; parasomnias such as sleep walking; anaphylactic and anaphylactoid reactions; weight gain; or result in rebound insomnia or tolerance.
In addition, existing sleep medications have failed to satisfactorily treat sleep disorders. For example, although benzodiazepines and other GABA modulators, as well as melatonin receptor agonists, promote sleep onset, they have limited effectiveness in promoting a full night's sleep into the 7th and 8th hours of the night and have no demonstrated benefit in reducing early awakenings.
Embodiments of the present invention relate to the use of doxepin in combination with other drugs to provide safer and improved sleep therapies.

This patent is subject to a terminal disclaimer.

Methods of treating insomnia using a combination therapy of low-dose doxepin and zolpidem


A single shaft shifting mechanism (300) is provided having supports (310, 312), independent of the shift shaft (106), for supporting the weight of the shift forks (302, 304, 306) to minimize frictional contact between the shift shaft and the shift forks.

1. Field of the Invention
The present invention relates to single shaft shifting mechanisms of the type comprising a selectively axially and rotationally movable shift shaft and a plurality of shift forks having hubs with through bores for receiving the shaft for rotational and/or axial movement relative thereto. In particular, the present invention relates to a single shaft shifting mechanisms of the type described wherein the shift forks are partially or entirely supported by support members independent of the shift shaft to minimize frictional resistance to relative axial and/or rotational movements of the shift shaft relative to the hubs of the shift forks.
2. Description of the Prior Art
Single shaft shifting mechanisms for selectively engaging and disengaging a selected one of three or more selectable transmission ratios are known in the prior art, as may be seen by reference to U.S. Pat. Nos. 4,621,537 and 4,920,815, the disclosures of which are incorporated herein by reference.
While these prior art single shaft shifting mechanisms have been well received, they are subject to improvement, as the weight of the shift forks, in large part, are supported by the shift shaft, which may result in objectionable frictional resistance to relative rotational and/or axial movement between the shift shaft and the shift fork hubs.


A sensing element of an oxygen sensor is controlled to keep a target impedance for maintaining activation temperature of the oxygen sensor. As the sensing element deteriorates, its internal impedance increases and power supply to a heater for heating the sensing element increases. The oxygen sensor temperature rises excessively above an activation temperature. To restrict excessive temperature rise, the target impedance is altered when the supply power to the heater exceeds a predetermined reference. The target impedance may be increased with increase in the power supply to the heater. Alternatively, the heater supply power is limited to a predetermined maximum for restricting excessive temperature rise.

1. Field of the Invention
The present invention relates to an apparatus and method for controlling oxygen sensor heating to restrict sensor deterioration caused by excessive heating.
2. Description of Related Art
Many modern air-fuel ratio control systems for engines use a current limiting type oxygen sensor (oxygen concentration detector) which produces current proportional to oxygen concentration in exhaust gas.
This type of oxygen sensor is incapable of producing current proportional to the oxygen concentration until activated at predetermined temperature (activation temperature). Therefore, to maintain the activation of the oxygen sensor, power supply to a heater for heating the oxygen sensor is controlled in response to temperature of the sensing element in the oxygen sensor (element temperature feedback control).
The feedback control for the oxygen sensor temperature is based on the sensing element impedance which varies with temperature. The target impedance is set to the impedance at which the activation temperature is attained.
Internal impedance of the sensing element increases as the oxygen sensor deteriorates. Therefore, even when the temperature of the oxygen sensor is above the activation temperature, the supply power to the heater (heater supply power) will be increased to attain the target impedance because the impedance of the sensing element increases by deterioration. The temperature of the oxygen sensor will accordingly rise. Further, when the oxygen sensor operating characteristics change due to sensor deterioration or the sensor environment (e.g., engine exhaust gas temperature) changes, the heater supply power will become unstable and cause excessive heating of the sensing element. Thus, this temperature rise will adversely promote deterioration of the oxygen sensor.

Apparatus and method for controlling oxygen sensor heating


Method, systems, and apparatus to facilitate navigation in a known environment. Communication and tracking between a receiver device and one or more beacons are provided to identify a current position of the receiver device. A direction to a next waypoint of a current path is determined based on the identified current position and a haptic feedback system is signaled to provide continuous haptic feedback to orient a user in the identified direction.

The present invention relates to the electrical, electronic and computer arts, and more specifically, to a spatial guidance system for individuals.
One of the biggest challenges for visually impaired persons is achieving independent mobility, typically using reference locations to navigate within a familiar environment. These reference points range from the location and position of furniture within a space to trees, park benches, and lampposts located outdoors. Typically, reaching each reference point conveys both that one is moving in the right direction and what to expect going forward, in terms of the next expected reference point. It often happens, however, that between leaving one reference point and reaching the next, a visually impaired person can miss the next reference point and become disoriented due to taking a wrong turn, making a slight deviation in direction, and the like. Guiding the visually impaired person back to her or his last reference point (or to the nearest reference point) is often required to enable him or her to recognize where she or he is and to reorient his or her intended direction.

Spatial guidance system for visually impaired individuals

International Business Machines Corporation


A system and method are disclosed for the automatic and transparent repair of IP multicast sessions. The invention is a system and method for the repair of IP multicast sessions. In one aspect of the invention the method repairs a multicast session in a network, beginning with the step of sending a request message from a source to a subscription server in the network, requesting a repair service for an original multicast session originated by the source. The method continues by sending an enabling signal from the subscription server to a plurality of retransmit servers in the network, to buffer data traffic from the original multicast session, in response to the request. The method continues by buffering a copy of the data traffic at each of the plurality of retransmit servers and monitoring errors in each copy. The method continues by automatically selecting with the plurality of retransmit servers at least one retransmit server from among the plurality, having a minimum of the errors in its respective copy. The method concludes by sending the respective copy to a repair server in the network to enable the repair server to provide a repaired multicast session derived from the respective copy.

IP multicasting provides an efficient way for a source to send a stream of User Datagram Protocol (UDP) packets to a set of recipients. The source sends only one copy of each packet to an IP network, such as the Internet, for example. The routers in the IP network do the work required to deliver that packet to each recipient. Various IP multicast routing protocols can be used in an IP network. These allow the routers to communicate with each other so that the multicast datagrams are sent only to those subnetworks with receivers that have joined a multicast session.
A multicast session is identified by an IP address and port number. The IP address is a Class D address in the range from 220.127.116.11 to 184.108.40.206. IP multicasting is more efficient than unicasting for group communication. Unicasting requires that the source send a separate copy of each datagram to each recipient. This requires extra resources at the source and in the IP network and is wasteful of network bandwidth.
Some useful background references describing IP multicasting in greater detail include: (1) Kosiur, D., xe2x80x9cIP Multicasting: The Complete Guide to Corporate Networksxe2x80x9d, Wiley, 1998; (2) Maufer, T., xe2x80x9cDeploying IP Multicast in the Enterprisexe2x80x9d, Prentice-Hall, 1997; (3) Deering, S., xe2x80x9cHost Extensions for IP Multicasting,xe2x80x9d Network Working Group Request for Comments Internet RFC-1112, August 1989;. (4) Waitzman, D., Partridge, C., Deering, S., xe2x80x9cDistance Vector Multicasting Routing Protocol,xe2x80x9d Network Working Group Request for Comments Internet RFC-1075, November 1988; (5) Schulzrinne, H., Casner, S., Frederick, R., Jacobson, V., xe2x80x9cRTP: A Transport Protocol for Real-Time Applications,xe2x80x9d Network Working Group Request for Comments Internet RFC 1889, Jul. 18, 1994. The IP multicast protocol set forth in the IETF RFC 1112 xe2x80x9cHost Extensions for IP Multicastingxe2x80x9d is the standard protocol for enabling hosts to establish and conduct IP multicast sessions on the Internet. The IETF RFC 1075, xe2x80x9cDistance Vector Multicast Routing Protocol (DVMRP),xe2x80x9d describes a protocol for propagating routing information among multicast-enabled routers.
The multicast backbone on the Internet (Mbone) is an extension of the Internet backbone to support IP multicasting. The Mbone is formed collectively by the portion of the network routers in the Internet backbone that are programmed to perform the IP multicast routing protocol. Those routers in the Internet backbone that are programmed to handle IP multicast sessions, as well as unicast sessions, are referred to herein as multicast-enabled routers. The Mbone is a virtual network that is layered on top of sections of the physical Internet. It is composed of islands of multicast-enabled routers connected to each other by virtual point-to-point links called xe2x80x9ctunnels.xe2x80x9d The tunnels allow multicast traffic to pass through the non-multicast-enabled routers of the Internet. IP multicast packets are encapsulated as IP-over-IP, so that they look like normal unicast packets to the intervening routers. The encapsulation is added upon entry to a tunnel and removed upon exit from a tunnel. This set of multicast-enabled routers, their directly connected subnetworks, and the interconnecting tunnels define the Mbone. For additional details, see (1) Comer, Douglas E. Internetworking with TCP/IP: Volume 1xe2x80x94Principles, Protocols, and Architecture, Third Edition. Englewood Cliffs, N.J.: Prentice Hall, 1995; (2) Finlayson, Ross, xe2x80x9cThe UDP Multicast Tunneling Protocolxe2x80x9d, IETF Network Working Group Internet-Draft, published Sep. 9, 1998, http://search.ietf.org/internet-drafts/draft-finlayson-umtp-03.txt; and (3) Eriksson, Hans, xe2x80x9cMBone: The Multicast Backbone,xe2x80x9d Communications of the ACM, August 1994, Vol.37, pp.54-60.
Since the multicast-enabled routers of the Mbone and the non-multicast-enabled routers of the Internet backbone have different topologies, multicast-enabled routers execute a separate routing protocol to decide how to forward multicast packets. The majority of the Mbone routers use the Distance Vector Multicast Routing Protocol (DVMRP), although some portions of the Mbone execute either Multicast OSPF (MOSPF) or the Protocol-Independent Multicast (PIM) routing protocols. For more details about PIM, see: Deering, S., Estrin, D., Farrinaci, D., Jacobson, V., Liu, C., Wei, L., xe2x80x9cProtocol Independent Multicasting (PIM): Protocol Specificationxe2x80x9d, IETF Network Working Group Internet Draft, January, 1995.
Multicasting on the Internet has a unique loss environment. On a particular path the losses occur in bursts, as multicast-enabled routers become congested, rather than the losses having the characteristics associated with white noise. When packets are lost on a particular link in the multicast tree, any downstream receivers lose the same packet.
However, congestion in different parts of network is not correlated since traffic to receivers in other parts of the multicast tree does not necessarily pass through the same congested nodes and therefore does not lose the same bursts of packets. Therefore, path diversity would be a good means for recovering at least some of the missing packets, if there were a way to coordinate such a recovery.
Another problem in IP multicasting is that some Internet Service Providers (ISPs) discriminate against multicast packets and discard them before discarding the packets for other services. Therefore, it would be worthwhile balancing the efficiency of multicast transmissions with the quality of point-to-point transmissions.
These problems have been solved by the Network-Based Service for the Repair of IP Multicast Sessions described in the above referenced, copending U.S. patent application by Maxemchuk, et al. In the Maxemchuk, et al. system, a repair server polls multiple transmit servers to accumulate as many of the packets missing from the multicast session as possible. This improves the quality of audio and video multicasts of live conferences, news broadcasts and similar material from one source to many receivers over the Internet.
The invention disclosed herein is an improvement to the Maxemchuk, et al. system, to provide an automatic invocation of self-monitoring and ranking among several retransmit servers in response to the multicast source""s request to have its multicast session repaired, which is transparent to the end user recipients of the multicast session. The invention disclosed herein also provides for the source""s request to be authorized by a subscription server that causes the source to be billed for the repair service.
The invention is a system and method for the automatic and transparent repair of IP multicast sessions. In one aspect of the invention the method repairs a multicast session in a network, beginning with the step of sending a request message from a source to a subscription server in the network, requesting a repair service for an original multicast session originated by the source. The method continues by sending an enabling signal from the subscription server to a plurality of retransmit servers in the network, to buffer data traffic from the original multicast session, in response to the request. The method continues by buffering a copy of the data traffic at each of the plurality of retransmit servers and monitoring errors in each copy. The method continues by automatically selecting with the plurality of retransmit servers at least one retransmit server from among the plurality, having a minimum of the errors in its respective copy. The method concludes by sending the respective copy as a multicast repair service to a repair server in the network to enable the repair server to provide a repaired multicast session derived from the respective copy.
In another aspect of the invention, the method repairs a multicast session in a network, beginning with the step of sending a request message from a source to a subscription server in the network, requesting a repair service for an original multicast session originated by the source. The method continues by sending an enabling signal from the subscription server to at least one retransmit server and a repair server in the network, to buffer data traffic from the original multicast session, in response to the request. The method continues by buffering a copy of the data traffic at the retransmit server. The method continues by buffering the data traffic in the repair server and monitoring received errors therein. The method continues with the repair server automatically sending a request for the copy in response to the monitoring. The method concludes by sending the copy to the repair server to enable the repair server to automatically provide a repaired multicast session derived from the copy. The subscription server can then cause a billing system to send a bill to the source for the multicast repair service.
The resultant IP multicast sessions are automatically repaired in a manner that is transparent to the end user recipients.

Network-based service for originator-initiated automatic repair of IP multicast sessions


A sample vessel (1, 11) for transferring and analyzing a sample with analyzer instrument, which sample vessel comprises an elongated vessel body (2, 12) for containing the sample and a hinged cap (3, 13) connected in top end area of the vessel body, and the cross-section of the vessel body (2, 12) on a transversal plane in relation to the lengthwise center axis of the vessel body the inner surface of the vessel body is rotationally asymmetrical in relation to the lengthwise center axis, wherein the sample vessel (1, 11) comprises a surface (5, 15) extending upwards from the vessel body, which surface partially surrounds the edge of the cap (3, 13), when the cap is in closed position.

Different kinds of sample vessels, vials and tubes are used for containing samples to be analyzed with analyzer equipment. These samples vessels may contain separate or hinged caps for closing the vessel, and are generally made from plastic or glass. Examples include Thermo Scientific™ Capitol Vial product family.
Other examples of known plastic sample vessels used widely in laboratory work include so-called microcentrifuge tubes, for example from Eppendorf, and various PCR (Polymerase Chain Reaction) reaction tubes.
These kinds of sample vessels are disposable in order to prevent possible sample contamination and other problems related to reusable sample vessels in sample handling and analyzing processes. However, the similarity of these kinds of sample vessels makes them easily mixable, since they are usually identical except for markings identifying the sample, e.g. a hand written or printed label or a barcode requiring machine reading and interpretation, which may cause human derived errors for the analyzing processes.
Known sample vessels also include sample vessels compatible with laboratory automation means and robotic handling. These sample vessels are made of plastic which enhances their durability and flexibility in the automated handling processes. One example of the sample vessels designed for automatic operations is disclosed in publication WO 2012/056116.


An axial spacer for a rotational assembly comprising a body, a rotational assembly attaching member and a centering member. The body comprises an outer ring, an inner ring and a plurality of reinforcing members extending between the inner ring and the outer ring. The reinforcing members each comprise an annular reinforcing rim extending from the outer ring and a connecting beam extending from the annular reinforcing rim to the inner ring. A plurality of web members extend between adjacent reinforcing members and the inner and outer ring, to, in turn, substantially couple adjacent reinforcing members with the inner and outer ring therebetween. The attaching means comprises an opening extending through at least a plurality of the plurality of reinforcing members. The centering member centers the spacer relative to the rotational assembly.

1. Field of the Invention
The present invention relates in general to spacers, and more particularly, to an axial spacer for a rotational assembly, such as, for example, a cooling fan of a vehicle. The invention is not limited to a sole application, but has utility in association with other rotational assemblies and applications.
2. Background Art
The use of spacers is well known in the art. For example, spacers may be utilized on axles and other rotating components to change the axial positioning of an accessory attached thereto. Such spacers comprise extruded members or milled members, which are often formed from metal, or an alloy thereof.
While such spacers have been utilized with success, there have been some drawbacks. For example, spacers are often quite heavy. Thus, they add to the overall rotational load imposed upon the rotating component. This added rotating mass often negates any advantage provided by the axial spacing. Additionally, in other applications, a properly sized spacer is difficult to achieve, and spacers may require special milling or other procedures to achieve a desired dimensional configuration. As such, the use of a conventional spacer may improve the overall operation, but it may remain substantially less than optimized.
Accordingly, it is an object of the invention to provide a spacer which reduces weight and spinning mass, to increase the utility of same, especially, where weight considerations are crucial.
It is another object of the invention to provide for spacers which can be stacked together to achieve a desired thickness.
It is another object of the invention to overcome shortcomings with prior art spacers which suffer from the above-described deficiencies.
These and other objects of the invention will become apparent in light of the specification and claims appended hereto.


A key state detector for a vehicle collects a sequence of battery voltage samples and applies a time-domain to frequency-domain transform (TFT) to the collected samples. The results of the TFT are then applied to an artificial neural network (ANN) to determine if they represent a key-on or key-off state. The ANN is trained based on data collected from the vehicle and is periodically retrained so that the detection of key-on and key-off states conforms to the particular vehicle and tracks the aging of vehicle components.

Many vehicles are equipped with telematics systems that collect data on the operation of the vehicle and control functions of the vehicle in response to a signal from a remote device such as a central monitoring computer or a cellular phone. Examples of data collected include a history of the locations to which the vehicle has traveled and the current status of the vehicle. Examples of functions include locking or unlocking the vehicle doors, or starting the vehicle.
The telematics system of a vehicle may be enabled both when the vehicle is active (i.e. in a key-on state) or when the vehicle is inactive (i.e. in a key-off state). The power used by the telematics system when the vehicle is inactive is desirably much less than when it is active because, in the key-on state, the battery is typically charging while the battery is not charging when the vehicle is inactive, in the key-off state.

Method and apparatus for detecting key-on and key-off states using time-to-frequency transforms


Provided herein is a system and method of a vehicle. The system comprises one or more sensors, processors, maps, and a memory storing instructions that, when executed by the one or more processors, causes the system to perform: monitoring a location of the vehicle while driving; detecting a sign while the vehicle is driving; capturing, frame-by-frame, data of the sign until the sign disappears from a field of view of the sensor; synchronizing each frame of the data with the location of the vehicle; determining a location of the sign based on the frame-by-frame data; in response to determining, at a frame immediately before the sign disappears from the field of view of the sensor, that the vehicle is driving towards the sign, uploading the detected sign and the location of the sign onto the one or more maps; and implementing a driving action based on the sign.

A vehicle, such as an autonomous vehicle (AV), navigates using one or more maps such as a high definition (HD) map. The vehicle may supplement its maps with data from its sensors, which may include other vehicles, pedestrians, objects, and obstacles. Other features may be manually added to the maps. For instance, locations of traffic signs may be manually determined or determined using sensors external to the vehicle. Such a process is time-consuming and inaccurate. For example, some signs may be missed, which may result in unsafe driving behavior. This shortfall is addressed by the present disclosures, which provide recognition and localization of traffic signs on a map so that vehicles can navigate effectively while following the rules of the traffic signs. Additionally, using the features provided in the present disclosures, consumer confidence in reliability of such vehicles may also increase.

System and method for localization of traffic signs


A battery safety unit is disclosed which protects against damage from dangerous acid contained in wet cell automobile batteries. The unit is a molded battery container adapted to anchor a battery securely in a moving automobile while the battery is essentially completely enclosed. The unit has a cover which may be opened or removed simply, but is safely held in place by a plurality of catches and a hinge in ordinary use. Variations in size and shape may be made to accommodate the particular battery being used.

1. Field of the Invention
This invention relates to the field of automotive electrical batteries, and more particularly to the safety and service life thereof.
2. Background of the Prior Art
Every automobile on the road today contains at least one wet cell battery. The battery is an indispensable part of the drive system, providing electrical power for such functions as engine starting, ignition, lights, etc. The heart of the battery is a reservoir of sulfuric acid which chemically reacts with a pair of opposite metallic poles to establish a voltage between them. This voltage is used to run the automobile's electrical devices, such as those mentioned above.
The acid contained in a battery is strong enough to cause serious damage to many parts of the automobile and serious injury to the skin of a person coming in contact with it. This acid can discharge dangerous fumes in cases of overheating due to electrical problems or ambient conditions. Under extreme circumstances a battery can actually explode, spraying its acid in all directions.
If any of these accidents occurs, in addition to damage to the automobile and the people nearby, there will be extensive environmental damage. When liquid or gaseous sulfuric acid is released due to a battery accident it can harm ground water supplies and air quality. The ultimate effect on the health of plants, animals and people may be disastrous. Thus, the effect of a sulfuric acid leak can be widespread, with the damage being multiplied due to the cumulative effect of many such leaks from even a small percentage of the hundreds of millions of cars in operation today.
Some recent automobile batteries have been designed so that they do not require maintenance or the addition of water. These "service free" batteries have been included as manufacturer supplied original equipment on many vehicles. Although batteries of this type are designed to operate without requiring added water, they still have a danger of leakage or explosion.
Another area of concern is the service life of the battery under ordinary and extraordinary conditions. If a battery becomes too cold it will not function properly, because the electrical power output is somewhat reduced. If the battery becomes too hot it will physically deteriorate more quickly than usual and require replacement sooner.
For an automobile battery to perform its function over a long life, it must be accessible for occasional servicing. Such servicing includes checking the amount of acid in the battery and replenishing water (from which the battery forms acid during operation) in the reservoir when low. In case of battery failure it is necessary to have access to the battery to attach auxiliary cables to the terminal posts of the battery to charge the battery or to start the engine. A battery also must be accessible so that it may be removed for replacement with a new battery.
It is therefore an objective of the present invention to provide a unit that will protect both people handling an automotive battery and automotive equipment surrounding a battery from accidental spills of battery acid.
It is another objective of the present invention to provide a battery safety unit that will prevent environmental pollution damage due to battery accidents.
It is a further objective of the present invention to provide a unit that will improve battery life and performance.
It is a still further objective of the present invention to provide a unit that will allow simple and efficient removal, replacement and servicing of an automotive battery.
These and additional objectives of the invention will become apparent to those skilled in the art as the details of the invention are disclosed.


Roughly described, a data processing system comprises a central processing unit and a split network interface functionality, the split network interface functionality comprising: a first sub-unit collocated with the central processing unit and configured to at least partially form a series of network data packets for transmission to a network endpoint by generating data link layer information for each of those packets; and a second sub-unit external to the central processing unit and coupled to the central processing unit via an interconnect, the second sub-unit being configured to physically signal the series of network data packets over a network.

This invention relates to a novel architecture for a network interface device for a data processing system and a method for exchanging network data between the processors of a data processing system, and in particular a blade server. A novel architecture for a PCIe device is also disclosed.
A conventional data processing system comprising one or more processors and a memory is attached to a network by means of a peripheral network interface device. The network interface device allows the data processing system to receive and transmit data over the network. The data processing system and network interface device communicate over a peripheral data bus, such as PCIe.
An Ethernet network interface device includes a controller, which typically forms data packets for transmission over the network, controls the data flows passing through the device and coordinates the transfer of data over the data bus between the data processing system and the network interface device. The physical transfer of data over the network is handled by a so-called "PHY" of the network interface device, which performs the signalling of network data over the network at the physical level of the Ethernet specification.
In a typical data processing system, several data buses may be involved in the transmission or reception of data over the network. Often there are different buses between the processor and memory, local storage devices and peripherals such as the network interface device. Data transfer over each bus has an associated overhead, and, along with the PHY, the various data bus circuits are typically amongst the most expensive components in terms of introduced latency and power requirements during data transmission or reception over a network.
Furthermore, the rate of transmission of data packets over the fabric of the network itself is limited by the network bandwidth, which imposes a maximum data rate between hosts on the network. This can be particularly limiting if the network fabric is used to connect the blades of a blade server.
Conventional network interface devices are provided as peripherals which are connected to a data processing system over a peripheral bus, such as PCIe. The network interface device may be a standalone peripheral card or it may be supported at the motherboard of the data processing system, but the device is accessed by the data processing system over the appropriate bus. This configuration is shown in FIG. 1, in which the CPU 103 of the data processing system 101 accesses the network interface device (NIC) 102 over a PCIe bus 106. The interface between the CPU and the PCIe bus is provided by chipset 105, which also typically provides direct memory access (DMA) to the memory by means of a memory controller. Network interface device 102 comprises a controller 107 and a PHY 108—the controller largely handling data flows at the link layer of the network protocol in use over network 109, and the PHY handling the transmission and reception of network data packets over the network in accordance with the physical layer requirements of the network protocol.
Since the receive and transmit queues for applications executing at processor 103 are located at memory 104, the network interface device must perform reads and writes directly to the memory in order to transmit and receive data over the network. Typically two or three memory accesses are required to effect each transmit operation, and one or two memory accesses are required to effect each receive operation. Often a network interface device will be operable to read and write to the memory by means of direct memory access (DMA), but all such accesses must still be performed over the peripheral data bus. The power consumption of each transmit or receive operation is not insignificant because each access must traverse the serialisation/deserialisation (SERDES) circuitry at the chipset 105 (which provides the interface to the bus for the processor/memory controller) and the SERDES circuitry at the network interface device (which provides the interface to the bus for the NIC). For a high speed network interface device, thousands of transmit and/or receive operations can be performed every second and the total power consumption of such an architecture can become very large. Similarly, the repeated memory accesses over the peripheral data bus introduces a significant latency to the transmit and receive operations performed by the network interface device.
For certain applications, System-on-a-Chip (SoC) devices have been developed which include a processing core and a network interface device, thus placing the network interface device closer to a memory accessible to the processor. For example, the STMicroelectronics STM32W family of SoC devices provides a 32-bit ARM processor and an integrated IEEE 802.15.4 radio. However, integrating a full network interface including a PHY into a processor substantially increases the power required by the processor and hence the amount of heat which must be dealt with at the processor. Furthermore, the signals handled at the PHY introduce a significant amount of additional electrical interference into the processor, making an SoC architecture unsuitable for a high speed CPU.
Improved architectures for allowing the components of a data processing system (such as a CPU and network interface device) to communicate with one another have been proposed, but none provide a low power architecture for a network interface having a low latency data path to host memory. Previous attempts to improve the architecture for internal communications within a data processing system include the IMS T800 Transputer presented in "IMS T800 Architecture", INMOS Technical Note 6, INMOS Ltd, January 1988, which is published at http://www.transputer.net/tn/06/tn06.html. Other such architectures are described in Finn, Gregory G. "An Integration of Network Communication with Workstation Architecture", ACM Computer Communication Review, October 1991, and Hayter, M., McAuley, D., "The Desk Area Network", ACM Transactions on Operating Systems, pp. 14-21, October 1991.
Previously proposed schemes describing Ethernet protocol encapsulation are described in U.S. patent application Ser. Nos. 10/548,121 and 12/105,412.
There is therefore a need for an improved network interface device architecture having lower power requirements and a lower latency data path to host memory.


A hair clipper has a blade block, which includes a fixed blade, a movable blade overlapped with the fixed blade to make sliding contact with the fixed blade, a pressing spring applying a pressing load to maintain a uniform contact pressure between the fixed blade and the movable blade, and a blade base for receiving and retaining the fixed blade and the movable blade and the pressing spring. The blade base has a blade holder retaining the fixed blade and the movable blade and a blade cover attached to the blade holder to cover the fixed blade and the movable blade. Further, the blade holder has a primary retainer member holding end portions of the pressing spring and the blade cover has a secondary retainer member pressing the end portions of the pressing spring in a direction in which the pressing spring is retained by the primary retainer member.

Conventionally, in this kind of hair clipper blade block, a pressing spring which serves to press a movable blade against a fixed blade is normally held in a blade base by fitting bosses provided inside the blade base to boss-holes formed at end portions of the pressing spring and then upsetting or deforming exposed free ends of the boss by cold or hot working. There is also known an alternative method of press fitting a pressing spring to groove portions provided in a blade base (see, e.g., Japanese Patent Laid-open Application No. 10-235036).
In case the pressing spring is fixed by upsetting the bosses as in the prior art, the pressing spring may be retained in a floating state (i.e., the boss holes of the pressing spring may be movable along the axial directions of the bosses) due to processing errors generated by the upsetting process. Further, the reaction force of the pressing spring acts on the deformed bosses all the time. Therefore, if the hair clipper is exposed to elevated temperatures while being circulated in the market or while being used, the deformed bosses may undergo creep deformation and thus the pressing spring may often suffers from floating. This holds true in case of the prior art example in which the pressing spring is press fitted to the groove portions provided in the blade base.
For the reasons noted above, the pressing force of the pressing spring is weak in the prior art hair clipper, which reduces the contact pressure between the fixed blade and the movable blade and thus leaves a gap between the edge portions of the comb-shaped movable and fixed blades. This poses a problem in that the cutting performance of the blade block is impaired and the lifespan of the blade block is reduced depending on the environment in which the hair clipper is used.


A spinning top toy for spinning on a surface includes a shaft part and a body. The shaft part includes a shaft part body and a ground contact part being integrally formed with the shaft part body. The shaft part extends in an axial direction. The body is configured on the shaft part. The ground contact part includes a wheel-shaped body being slidably configured on the shaft part body. The wheel-shaped body is configured to be moved to a first position, and is configured to be moved to a second position. The second position is closer to the surface than the second position in the axial direction. The wheel-shaped body is configured to be in contact with the surface when at the second position.

Conventionally, it is well-known that in order to change rotation characteristics by changing a ground contact area of a rotation shaft, a spinning top toy is rotated at a position by reducing a ground contact surface of a ground contact part or the spinning top toy is revolved by enlarging the ground contact surface (see e.g., Patent Document 1).
In the spinning top toy, a rotary plate is arranged on a body circumferential surface. The rotary plate is rotated in one direction, and the first ground contact part is projected from a lower end of a lower member (the second ground contact part). Accordingly, the ground contact surface becomes small. The rotary plate is rotated in the other direction, and the first ground contact part is retracted to the lower member. The lower end of the lower member which is the second ground contact part is grounded, so that the ground contact surface becomes large.
[Patent Document 1] Japanese Patent No. 5793631

Spinning top toy and spinning top toy set