The present invention relates to modified Fc regions of antibodies, and uses thereof, such as in antibodies that contain an Fc region of the present invention.

Considerable information has been published and is known about monoclonal antibodies and their utility in research, diagnosis, and in the treatment of multiple diseases, including cancer. Over a dozen monoclonal antibodies have government regulatory approval for therapeutic use in patients.
Antibodies with different properties (improved affinity, avidity and pharmacokinetics, for example) and structures, including fully human antibodies, chimeric antibodies with both human and non-human elements, Fab antibodies, and other antibody structures, have been constructed in the laboratory using molecular biology techniques, such as cloning, phage display, transgenic mice and mutagenesis. Goals of therapeutic antibody improvement include overcoming host anti-antibody responses and extending half-life of therapeutic antibodies, and there is a continuing need for improved antibodies.
The present invention pertains to modified Fc regions of antibodies, and uses thereof, such as in antibodies that contain a Fc region (e.g., in a full-length IgG antibody including full-length IgG1, IgG2, IgG3 or IgG4, a chimeric antibody, or a humanized antibody), or in a fusion protein that contains a Fc region, or a part of a Fc region (referred to as an "immunoglobulin (Ig) fusion protein", "Fc fusion protein", or "Fc fusion polypeptide"), of the present invention. Modified Fc regions of antibodies have been described in the art, including in U.S. Patent Application Number US2006/104989). The modified Fc regions of the present invention have a single amino acid substitution (also referred to as a Fc variant herein) at positions disclosed herein relative to the sequence of a corresponding unmodified (wild-type or parent) Fc region, and have one or more properties that differ from a corresponding unmodified Fc region as well as from other modified Fc regions that have been described in the art, such as increased binding to one or more Fc receptors and/or modified binding under different pH conditions. The modified Fc regions of the preset invention can be incorporated into any antibody or Fc fusion polypeptide using standard molecular biology techniques, and all such modified antibodies and Fc fusion polypeptides are intended to be encompassed by the invention. Fc refers to the last two constant region Ig domains of IgA, IgD, and IgG, and the last three constant region Ig domains of IgE and IgM, and the flexible hinge N-terminal to these domains. For IgA and IgM, Fc may include the J chain. Fc is bound by receptors, FcRs, which are present on certain cells. As the affinity of the interaction between Fc and certain FcRs present on particular cells correlates with targeted cytotoxicity, and clinical efficacy in humans correlates with the allotype of high or low affinity polymorphic forms of certain FcRs, an antibody or fusion polypeptide with a Fc region optimized for binding to one or more FcRs may result in more effective destruction of cancer cells.
In certain embodiments, the modified Fc regions of the present invention impart improved properties to a polypeptide or a complex which includes a polypeptide into which the Fc region is incorporated, e.g., a complex such as a full-length antibody, chimeric antibody or humanized antibody which includes an Ig heavy chain having an modified Fc region, such as increased or modified binding to one or more FcRs, and/or increased or modified antibody dependent cellular cytotoxicity (ADCC), as compared to a corresponding polypeptide or complex, such as an antibody, incorporating a corresponding unmodified (a wild-type or parent) Fc region, or a different modified Fc region. Thus, a corresponding polypeptide or antibody that lacks one or more of the Fc region modifications disclosed herein and differs in FcR binding as compared to a polypeptide or antibody incorporating a Fc region of the invention, may have a native (wild-type) Fc region sequence or may have a Fc region sequence with amino acid sequence modifications (such as additions, deletions and/or substitutions) other than those disclosed herein that result in increased or modified binding to at least one FcR. In some embodiments of the invention, modified Fc regions of the invention impart increased or decreased half life to a molecule.
In one embodiment of the invention, an modified Fc region of the invention contains one of the substitutions described herein. In other embodiments, an modified Fc region of the invention contains two, three, four, five or more substitutions described herein in combination, which may additively or synergistically enhance the properties of the modified Fc regions of the invention. In another embodiment, the invention includes a polypeptide having an modified Fc region of the invention, i.e., it is an Fc fusion polypeptide that contains one of the substitutions described herein. In one embodiment, the non-Fc region of the fusion polypeptide includes a target binding molecule. In other embodiments, the invention includes a polypeptide having an modified Fc region of the invention that contains two, three, four, five, six, ten, twelve, or more substitutions described herein in combination. In one embodiment, the invention includes an antibody or antigen-binding antibody fragment having an modified Fc region of the invention that contains one of the substitutions described herein. In other embodiments, the invention includes an antibody or antigen-binding antibody fragment having an modified Fc region of the invention that contains two, three, four, five, six, ten, twelve or more substitutions described herein in combination.
In another embodiment, the invention includes a polypeptide, e.g., one in a complex of polypeptides such as an antibody or an Fc fusion polypeptide, or a conjugate which includes a Fc region conjugated to another molecule (a Fc fusion conjugate), having an modified Fc region of the invention that contains one of the substitutions described herein. In other embodiments, the invention includes a polypeptide, e.g., one in a complex of polypeptides such as an antibody or a Fc fusion polypeptide, or a conjugate which includes a Fc region conjugated to another molecule, having an modified Fc region of the invention that contains two, three, four, five or more substitutions described herein in combination, as well as one or more other substitutions, which other substitutions may impart properties other than those associated with the substituted position(s) and/or substitutions in the modified Fc regions of the invention, or may additively or synergistically enhance the properties of the modified Fc regions of the invention. In some embodiments of the invention, a polypeptide with an modified Fc region of the invention has one or more of the functional properties described herein. For polypeptides with modified Fc regions of the invention that also include a non-FcR target binding molecule domain, which optionally together with other polypeptides may form an antibody, the target binding molecule domain or variable regions of the antibody may specifically bind virtually any target molecule or antigen. Accordingly, in one aspect, the invention pertains to a polypeptide having a Fc region (e.g., an IgG Fc region, such as an IgG1 Fc region) with the following amino acid substitution at the following amino acid residues (positions) in a Fc region: M252I, P257C, P257I, P257T, E258D, E258F, E258G, E258I, E258K, E258L, E258Q, E258S, E258V, E258W, V259E, V259G, V259I, V259R, T260A, T260C, T260F, T260L, T260N, T260S, T260W, S426C, S426N, V427S, V427T, M428F, M428Y, E430I, E430L, E430Q, A431F, A431H, A431P, H433A, H433E, H433R, N434A, N434D, N434F, N434G, N434H, N434I, N434M, N434R, N434V, N434W, N434Y, H435K, or these substitutions at any combination of those positions. For all positions discussed herein, numbering is according to the EU index as in Kabat (Kabat et al., 1991). Those skilled in the art of antibodies will appreciate that this convention consists of non-sequential numbering in specific regions of an Ig sequence, enabling a normalized reference to conserved positions in Ig families. Thus, the positions of any given Ig as defined by the EU index will not necessarily correspond to its sequential sequence.
In addition to the polypeptide, protein or other complex, e.g., a conjugate, incorporating an modified Fc region of the invention described herein, the invention also encompasses polynucleotides and expression vectors encoding an modified Fc region or polypeptides having an modified Fc region, including libraries of those polynucleotides and expression vectors, host cells into which such polynucleotides or expression vectors have been introduced, for instance, so that the host cell produces a polypeptide having the modified Fc region, libraries of host cells, and methods of making, culturing or manipulating the host cells or libraries of host cells. For instance, the invention includes culturing such host cells so that a polypeptide with a modified Fc region is produced, e.g., secreted or otherwise released from the host cell. Pharmaceutical compositions and kits which include a polypeptide, protein or other complex with an modified Fc region of the invention, and/or polynucleotides, expression vectors or host cells encoding polypeptides having such an modified Fc region, are also encompassed. Moreover, use of a polypeptide, protein or conjugate with an modified Fc region of the invention, such as in Fc receptor binding assays or to induce ADCC activity in vitro or in vivo, is also encompassed by the invention. The invention also provides a polypeptide, protein, conjugate, polynucleotide, expression vector, and/or host cell of the invention for use in medical therapy, as well as the use of a polypeptide, protein or other complex, polynucleotide, expression vector, and/or host cell of the invention for the manufacture of a medicament, e.g., useful to induce ADCC activity in vitro or in vivo.
An antibody, as used herein, is a protein having one or more polypeptides encoded by all or part of mammalian Ig genes, including polyclonal or monoclonal antibodies, which specifically binds to one or more Fc receptors (FcRs), and, if one or more variable regions are present, the protein binds to an antigen, which protein is optionally glycosylated. A full-length antibody has a structure corresponding to the natural biological form of an antibody found in nature including variable and constant regions. For example, a full-length antibody may be a tetramer, generally with two identical pairs of two Ig chains, each pair having one light chain and one heavy chain. Each light chain includes immunoglobulin domains VL and CL, and for IgG, each heavy chain includes immunoglobulin domains VH and CH, where CH includes Cγ1, Cγ2, and Cγ3. In humans, Ig genes include kappa (K) and lambda (λ) light chain genetic loci and heavy chain genetic loci, which include constant region genes mu (μ), delta (δ), gamma (γ), sigma (σ), and alpha (α) for the IgM, IgD, IgG, IgE, and IgA isotypes, respectively.
An antibody further, as used herein, unless otherwise specified, includes full-length antibodies and fragments thereof, including naturally occurring antibodies, chimeric antibodies, recombinant antibodies including humanized antibodies, or antibodies subjected to other in vitro alterations, and antigen binding fragments thereof.
A "parent Fc", as used herein, can be a naturally occurring Fc region of an IgA, IgD, IgE, IgG or IgM class of antibody. Alternatively, the source of a parent Fc is a Fc region from a naturally occurring antibody, including IgG1, IgG1, IgG3, IgG4, IgA1, or IgA2. A parent Fc region to be modified may be selected for its FcR binding affinity and/or FcR binding pattern, and an modified Fc region of the invention has at least an enhanced affinity for at least one FcR, but may otherwise have the same pattern of FcR binding, as the parent Fc region.
A parent Fc region is preferably one that interacts with one or more FcRs, including but not limited to FcγRs, FcαRs, FcμRs, FcδRs, FcRn, and viral FcγR. An modified Fc region of the invention derived from such a parent Fc region is one that has an enhanced interaction with one or more FcRs and enhanced ADCC, relative to the parent Fc region. ADCC generally requires the Fc region to be combined with a binding domain (e.g., an antibody variable domain). Methods to detect FcR binding and ADCC are known to the art.
FcRs are defined by their specificity for immunoglobulin isotypes and are well known in the art.
An Fc containing fusion includes a polypeptide where a Fc region with favorable FcR binding, and optionally favorable pharmacokinetics, is linked to one or more molecules. The linkage may be synthetic in nature, e.g., via chemical conjugation, or via recombinant expression, i.e., a fusion polypeptide is formed. Thus, the molecule linked to a Fc region may be a molecule useful to isolate or purify the Fc region, e.g., a tag such as a Flag-tag, Strep-tag, glutathione S transferase, maltose binding protein (MBP) or a His-tag, or other heterologous polypeptide, e.g., a ligand for a receptor, an extracellular domain of a receptor, or a variable region of a heavy Ig chain, and/or another molecule.
Once a vector encoding an modified Fc region of the invention or Fc region containing polypeptide such as an Ig heavy chain with an modified Fc region or other Fc fusion polypeptide, the vector may be introduced into a host cell, optionally along with other vectors, e.g., a vector encoding an Ig light chain, or into a host cell modified to express another polypeptide such as an Ig light chain, or into an in vitro transcription/transcription reaction, so as to express the encoded polypeptide. The modified Fc region, Ig heavy chain and Ig light chain may also be expressed in the same vector and introduced into a host cell. For some expression systems, host cells may be cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying desired sequences. A resulting polypeptide with an modified Fc region is optionally isolated, e.g., from host cell supernatants, and screened for one or more activities.
In one embodiment, the Fc region may be one that is anchored to the surface of a cell, such as a host cell, e.g., via fusion with a transmembrane domain.
Suitable host cells for expressing the polynucleotide in the vectors are the prokaryotic, yeast, or higher eukaryotic cells. Suitable prokaryotes for this purpose include eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia, e.g., E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B. subtilis, Pseudomonas such as P. aeruginosa, and Streptomyces. Eukaryotic microbes such as filamentous fungi or yeast are also suitable cloning or expression hosts for polypeptide variant-encoding vectors. Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces hosts such as, e.g., K. lactis, K. fragilis, K. bulgaricus, K. wickeramii, K. waltii, K. drosophilarum, K. thermotolerans, and K. marxianus; Pichia pastoris, Candida, Trichoderma reesia, Schwanniomyces such as Schwanniomyces occidentalis; and filamentous fungi such as Neurospora, Penicillium, Tolypocladium, and Aspergillus hosts may be employed. Suitable host cells for the expression of glycosylated polypeptides are derived from multicellular organisms. Examples of invertebrate cells for expression of glycosylated polypeptide include plant and insect cells. Examples of eukaryotic cell generation, screening and production hosts include 3T3 mouse fibroblast cells, BHK21 Syrian hamster fibroblast cells, MDCK, dog epithelial cells, Hela human epithelial cells, PtK1 rat kangaroo epithelial cells, SP2/0 mouse plasma cells, and NSO mouse mouse plasma cells, HEK 293 human embryonic kidney cells, COS monkey kidney cells, CHO, CHO-S Chinese hamster ovary cells, R1 mouse embryonic cells, E14.1 mouse embryonic cells, H1 human embryonic cells, H9 human embryonic cells, PER C.6, and human embryonic cells. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts such as Spodoptera frugiperda, Aedes aegypti, Aedes albopictus, Drosophila melanogaster, and Bombyx mori may be used. For instance, viral vectors maybe used to introduce a polynucleotide of the invention, particularly for transfection of Spodoptera frugiperda cells. Plant cell cultures of cotton, corn, potato, soybean, petunia, tomato, and tobacco can also be utilized as hosts. Examples of useful vertebrate cells include mammalian cells, e.g., human, simian, canine, feline, bovine, equine, caprine, ovine, swine, or rodent, e.g., rabbit, rat, mink or mouse cells, such as CHO cells. Transgenic plants and animals may be employed as expression systems, although glycosylation patterns in those cells may be different from human glycoproteins. In one embodiment, transgenic rodents are employed as expression systems. Bacterial expression may also be employed. Although bacterially expressed proteins lack glycosylation, other alterations may compensate for any reduced activity such as poor stability and solubility, which may result from prokaryotic expression.
Optionally, an Fc region or Fc containing polypeptide is isolated from host cells, e.g., from host cell supernatants, or an in vitro transcription/translation mixture, yielding a composition. An isolated polypeptide in the composition is one which has been isolated from at least one other molecule found in host cells, host cell supernatants or the transcription/translation mixture, e.g., by fractionation on immunoaffinity or ion-exchange columns; ethanol precipitation; reverse phase HPLC; chromatography on silica or on an anion-exchange resin such as DEAE; chromatofocusing; SDS-PAGE; ammonium sulfate precipitation; gel filtration using, for example, Sephadex G-75; or ligand affinity chromatography. For some applications, the isolated polypeptide in the composition is the predominant species present (i.e., on a molar basis it is more abundant than any other individual species in the composition), and preferably comprises at least about 50 percent (on a molar basis), more preferably more than about 85%, about 90%, about 95%, and about 99, of all macromolecular species present. The isolated Fc region or Fc containing polypeptide may be subjected to further in vitro alterations, e.g., treated with enzymes or chemicals such as proteases, molecules such as those which alter glycosylation or ones that are useful to conjugate (couple) the isolated Fc region or Fc region containing polypeptide to another molecule such as a label including but not limited to fluorescent labels (e.g., FITC, rhodamine, lanthanide, phosphors), enzymatic labels (e.g., horseradish peroxidase, /3-galactosidase, luciferase, alkaline phosphatase), chemiluminescent labels, biotinyl groups, avidin groups, or polypeptide epitopes recognized by a secondary reporter (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags), sugars, lipids, fats, paramagnetic molecules or sound wave emitters, metals, or synthetic polymers.
Methods to screen for activities associated with polypeptides or complexes that incorporate a Fc region, including but not limited to FcR binding (see, for example, U.S. Pat. Nos. 6,737,056, 7,217,797, 8,088,376, all incorporated herein by reference), are well known to the art. For instance, to assess ADCC activity of a Fc containing polypeptide, an in vitro and/or in vivo ADCC assay, may be performed using varying effector:target ratios, e.g., PBMC and NK cells or in a animal model, respectively. In one embodiment, Fc containing polypeptides expressed by host cells are screened for enhanced FcR receptor binding affinity or activity in vitro and/or in vivo and/or ADCC activity in vitro and/or in vivo. In one embodiment, the binding of a FcR by a Fc containing polypeptide with an modified Fc region of the present invention is greater than the binding of that receptor by a corresponding polypeptide with an unmodified Fc region. Thus, by introducing amino acid sequence modifications described herein in a wild-type or parent Fc region or a Fc region containing polypeptide, which wild-type or parent Fc region preferably elicits ADCC and optionally is a human Fc region, e.g., a native sequence human Fc region human IgG sequence, a modified Fc region is obtained which binds FcR with better affinity and mediates ADCC in the presence of human effector cells more effectively than the wild-type or parent Fc region or Fc region containing polypeptide. Soluble FcRs such as recombinant soluble human CD 16 and recombinant soluble human CD32 can be contacted with one or more different modified Fc regions in parallel, and modified Fc regions having one or more substitutions that enhance binding to human CD16 but not to human CD32, relative to an unmodified Fc region, are identified. Those substitutions may be combined with other substitutions that enhance binding. A combination of substitutions of the present invention in an Fc region or Fc region containing polypeptide may yield a combinatorially modified Fc region, or a combinatorially modified Fc region containing polypeptide with synergistically enhanced properties.
Other methods to identify polypeptides with modified Fc regions, including antibodies with an modified Fc region, with desirable properties, and thus a corresponding polynucleotide sequence, which method may be employed alone or in combination with methods described above, include using modeling, e.g., 3D-modeling, of modified Fc regions, preferably in the context of the molecule to be screened for activity, e.g., an antibody with the Fc region, to select for Fc regions with particular characteristics. Characteristics that may be screened for by modeling include, but are not limited to, a particular angle near FcR binding sites, hinge architecture, intra- and inter-molecular chain interactions, e.g., substitutions that promote or disrupt hydrophobic interactions or stabilize conformation in a particular region. Thus, a 3D model of a Fc region containing polypeptide having at least one of the substituted positions of the invention in combination with one or more other substitutions may be employed to identify combinations of substitutions to be introduced into a polynucleotide for expression in host cells.
The Fc variants of the present invention, whether or not incorporated into a heterologous polypeptide, e.g., incorporated into a Fc fusion with a ligand for a cell surface receptor, e.g., CTLR-4 ligand or heavy chain of an antibody, or conjugated to a molecule of interest, as well as polynucleotides and host cells encoding those variants, optionally in combination with one or more other agents, e.g., therapeutic or research reagents, are useful in a variety of methods, e.g., in screening methods, prophylactic methods, therapeutic methods, veterinary methods and agricultural methods. The one or more other agents include other Fc region or Fc region containing polypeptides, including those with unmodified Fc regions. In one embodiment, an Fc variant is incorporated into an antibody or other Fc fusion polypeptide and that antibody or Fc fusion polypeptide, optionally in conjunction with one or more other useful compositions, employed to target particular cells. In one embodiment, an Fc variant containing antibody or an antigen-binding fragment thereof targets and optionally kill target cells that bear the target antigen. In another embodiment, a Fc variant containing antibody or an antigen-binding fragment thereof targets and activates cells that bear the target antigen, e.g., thereby increasing expression of another antigen, such as a viral or cellular antigen. In one embodiment, the Fc variants or polypeptides incorporating an Fc variant of the present invention may be used to prevent, inhibit or treat various conditions or diseases, in humans and non-humans, including non-human mammals. For example, an antibody containing an modified Fc region of the invention may be administered to a human or non-human animal which is at risk of, e.g., prone to having a disease, prior to the onset of the disease and so prevent or inhibit one or more symptoms of that disease. A Fc region or Fc region containing polypeptide, or a conjugate thereof, may be administered after clinical manifestation of a disease in a human or non-human animal to inhibit or treat the disease. In one embodiment, a pharmaceutical composition comprising an antibody or Fc fusion polypeptide of the present invention is administered to a human or non-human animal with an autoimmune, immunological, infectious, inflammatory, neurological, or neoplastic disease, e.g., cancer. Fc regions or Fc region containing polypeptides of the invention may be administered alone or in combination with one or more other therapeutic agents, including but not limited to cytotoxic agents, e.g., chemotherapeutic agents, cytokines, growth inhibitory agents, anti-hormonal agents, kinase inhibitors, anti-angiogenic agents, cardioprotectants, or other therapeutic agents, in amounts that are effective for the purpose intended. The skilled medical practitioner can determine empirically the appropriate dose or doses of therapeutic agents including Fc regions or Fc region containing polypeptides of the present invention that are may thus be administered concomitantly with one or more other therapeutic regimens. For example, an antibody or Fc fusion polypeptide of the present invention may be administered to a patient along with chemotherapy or other therapy, e.g., other agents such as an anti-angiogenic agent, a cytokine, radioisotope therapy, or both chemotherapy and other therapies. In one embodiment, the antibody or Fc fusion of the present invention may be administered in conjunction with one or more other antibodies or Fc fusions, which may or may not comprise a Fc variant of the present invention. In one embodiment, a Fc containing polypeptide of the present invention is administered with a chemotherapeutic agent, i.e., a chemical compound useful in the treatment of cancer. A chemotherapeutic or other cytotoxic agent may be administered as a prodrug, i.e., it is in a form of a pharmaceutically active substance that is less cytotoxic to cells compared to the drug and is capable of being converted into the drug.
Pharmaceutical compositions are also contemplated having an Fc region, an Fc fusion polypeptide, antibodies having a Fc region, or conjugates thereof, that are formulated, optionally with one or more other agents. Formulations of antibodies, Fc regions, or Fc region containing polypeptides, or conjugates, of the present invention are prepared for storage by mixing the antibodies, Fc regions, or Fc region containing polypeptides, or conjugates, having the desired degree of purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed., 1980), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as antioxidants; alkyl parabens; low molecular weight (less than about 10 residues) polypeptides; hydrophilic polymers; amino acids; monosaccharides; and other carbohydrates; chelating agents; fillers; binding agents; additives; coloring agents; salt-forming counter-ions; metal complexes; and/or non-ionic surfactants. Other formulations includes lipid or surfactant based formulations, microparticle or nanoparticle based formulations, including sustained release dosage formulations, which are prepared by methods known in the art.
The concentration of the Fc region, antibody or other Fc region containing polypeptide of the present invention in the formulation may vary from about 0.1 to 100 weight %. In a preferred embodiment, the concentration of the Fc region, antibody or Fc fusion polypeptide is in the range of 0.001 to 2.0 M. In order to treat a patient, an effective dose of the Fc region, or antibody or other Fc region containing polypeptide, and conjugates thereof, of the present invention may be administered. By "therapeutically effective dose" herein is meant a dose that produces the effects for which it is administered. Dosages may range from 0.01 to 100 mg/kg of body weight or greater, for example 0.1, 1, 10, or 50 mg/kg of body weight, with 1 to 30 mg/kg being preferred, although other dosages may provide beneficial results. The amount administered is selected to prevent treat a particular condition or disease. Administration of the Fc region, or antibody or other Fc region containing polypeptide, and conjugates thereof, of the present invention maybe continuous or intermittent, depending, for example, upon the recipient's physiological condition, whether the purpose of the administration is therapeutic or prophylactic, and other factors known to skilled practitioners. The administration of the Fc region, or antibody or other Fc region containing polypeptide, and conjugates thereof, of the present invention may be essentially continuous over a preselected period of time or may be in a series of spaced doses. Both local and systemic administration is contemplated.
Administration of the pharmaceutical composition comprising a Fc region, an antibody or other Fc containing polypeptide and conjugates of the present invention, preferably in the form of a sterile aqueous solution, may be done in a variety of ways, including, but not limited to, orally, subcutaneously, intravenously, intranasally, intraotically, transdermally, topically, intraperitoneally, intramuscularly, intrapulmonary, inhalable technology, vaginally, parenterally, rectally, or intraocularly. In some instances, for example for the treatment of wounds, inflammation, etc., the antibody or Fc fusion may be directly applied as a solution or spray.

Modified antibody regions and uses thereof


The present invention provides a transonic blade that concurrently achieves reduction in shock loss at a design point and improvement in stall margin in blades operating in a flow field of transonic speed or higher in an axial-flow rotating machine. A cross-sectional surface at each of spanwise positions of the blade is shifted parallel to a stagger line connecting a leading edge with a trailing edge of the blade. A stacking line is shifted toward an upstream side of working fluid. The stacking line connects together respective gravity center positions of blade cross-sectional surfaces at spanwise positions in a range from a hub cross-sectional surface joined to a rotating shaft or an outer circumferential side casing of a rotating machine to a tip cross-sectional surface lying at a position most remote from the hub cross-sectional surface in a spanwise direction.

In the context of the recent increase in fuel cost, the importance of improved efficiency in axial-flow rotating machines has grown, such as industrial gas turbines and jet engines. One of means of improving efficiency in the axial-flow rotating machine is to reduce a blade loss. The blade loss is roughly classified into a profile loss occurring at a radial cross-sectional surface (airfoil) of a blade and the other losses. Examples of the other losses include a shock loss and a secondary loss. The recent axial-flow rotating machines subjected to a large load per one stage have an increased Mach number of working fluid flowing into a blade. Therefore, the shock loss tends to increase. In other words, a reduction in shock loss largely contributes to an improvement in performance of the rotating machine.
A technology (Water Atomization Cooling, WAC) has recently been studied in which fine droplets are sprayed to an air intake duct located at an inlet of a gas turbine compressor to cool intake air through the evaporation thereof for performance improvement. Incidentally, the technology relating to the WAC is described in e.g. patent document 1. The WAC is executed to lower the inlet temperature of the compressor; therefore, the overall gas turbine tends to increase a pressure ratio. Further, the evaporation resulting from the WAC causes a mixture gas of main flow air and water vapor. Since this mixture gas has lower acoustic velocity than air due to the presence of mixed water vapor, the Mach number increase which is the ratio of flow velocity to acoustic velocity. Thus, it is expected that shock loss at a transonic stage will increase.
Studies to reduce a shock loss have been made in the past. One of them is a study in which the shape of a stacking line is modified, with the stacking line being a line connecting together the gravity center positions of airfoil at respective spanwise positions. As shown in patent document 2, the following blade is proposed as a technology for modifying the shape of the stacking line. The cross-sectional surfaces in a range from a mean cross-sectional surface, which is an intermediate cross-sectional surface between a hub cross-sectional surface and a tip cross-sectional surface, to the hub cross-sectional surface and the tip cross-sectional surface are shifted toward the upstream side to form an S-shaped stacking line. In addition, the amount of shifting of the tip cross-sectional surface is maximized. Patent document 2 teaches that shifting the tip side toward the upstream can reduce various losses caused by shock waves. If the tip side is shifted toward the upstream side, there is a problem as below. A flow is earlier increased in velocity on the tip side to lower static pressure. A flow on the hub side moves toward the tip side to reduce the flow rate, which makes it easy to develop a boundary layer on the hub side. In patent document 2, the amount of downstream shift of the blade cross-sectional surfaces close to the mean cross-sectional surface is reduced, thereby suppressing an increase in loss resulting from the development of the boundary layer on the hub side.


Methods and apparatuses for indicating an interference distribution in frame between base stations are provided. The method comprises: in response to a mismatch between a first frame allocation used by a first base station and a second frame allocation used by a second base station, transmitting, from the first base station to the second base station, a message for indicating an interference distribution in frame, A new information element, i.e., UL ABS (uplink Almost Blank Subframe) is introduced to indicate the uplink ABS information of the interfering base station. A modified DL ABS with a flag is used to indicate the downlink ABS information of the interfering base station, wherein the flag is to indicate that the DL ABS is used to protect UL transmission in the recipient base station.

This section introduces aspects that may help facilitate a better understanding of the invention(s). Accordingly, the statements of this section are to be read in this light and are not to be understood as admissions about what is in the prior art or what is not in the prior art.
The abbreviations and terms appearing in the description and drawings are defined as below.    3GPP Third Generation Partnership Project    ABS Almost Blank Subframe    BS Base Station    DL Downlink    eNB E-UTRAN NodeB, Base Station in E-UTRAN    E-UTRAN Evolved UTRAN    FDD Frequency Division Duplex    IE Information Element    LTE-A Long Term Evolution-Advanced    TDD Time Division Duplex    UE User Equipment    UL Uplink
Wireless communication systems include a network of devices for providing wireless connectivity to wireless-enabled devices including mobile units, smart phones, tablet devices, laptops, desktops, and other types of user equipment. The network access devices include base stations, base station routers, access points, e-node-Bs (eNBs), and the like. The entities within the wireless communication system generally conform to standards and/or protocols that facilitate communication over the air interface. For example, wireless communication systems are currently being developed that operate according to the Long Term Evolution (LTE) standards and/or protocols defined by the Third Generation Partnership Project (3GPP, 3GPP2). The LTE-Advanced standard supports both frequency division duplexing (FDD) and time division duplexing (TDD). Service providers are expected to implement both types of systems depending on the circumstances of the deployment scenario. The advantages to deploying a TDD system include efficient use of the radio spectrum because TDD uses a single frequency resource and does not require the paired set of frequency resources used to implement FDD.
FIG. 1 shows the FDD frame structure and the TDD frame structure defined in LTE system. As shown in FIG. 1, one radio frame has an overall length of 10 ms.
In FDD frame structure, the frame is divided into a total of 10 subframes, each having a length of 1 ms. The uplink (UL) subframes and the downlink (DL) subframes are transmitted on different frequencies fUL and fDL.
In TDD frame structure, the 10 ms frame comprises two half frames, each 5 ms long. Each half frame is further split into five subframes, each 1 ms long. The subframes may be divided into UL transmission subframe, DL transmission subframe, and special subframe. The special subframes consist of three fields: Downlink Pilot Time Slot (DwPTS), Guard Period (GP), and Uplink Pilot Time Slot (UpPTS).
One of the advantages of using LTE TDD is that it is possible to dynamically change the uplink and downlink ratio and characteristics to meet various load conditions. Motivated by TDD spectrum operator desire to better control interference from co-channel deployments and for traffic adaptation, in LTE-A, the use of dynamic reconfiguration of TDD frame allocation is currently being considered for possible standardization in Release 11.
However, interference between neighbour base stations and/or user equipments may arise due to the dynamic reconfiguration of TDD frame allocation in neighbour base stations. For example, base-station-to-base-station (BS-to-BS) interference occurs when one base station transmits a downlink signal to a user equipment in a subframe while a neighbour base station is attempting to receive an uplink signal from other user equipment during the same subframe. For another example, user-equipment-to-user-equipment (UE-to-UE) interference occurs when one or more user equipment are transmitting uplink signals to a base station in a subframe while other user equipments are trying to receive downlink signals from another base station during the same subframe.
Generally speaking, the UE-to-UE or BS-to-BS interference may occur when different uplink and downlink frame allocations are used in neighbour cells, for example, when these neighbour cells are from different operators, or the neighbour cells belong to different network (e.g., one is LTE-FDD, the other is LTE-TDD). The UE-to-UE or BS-to-BS interference may also occur in future systems, e.g., device to device communication system.

Interference indicator for wireless communication systems


Financial data associated with one or more “contributing consumers” is obtained from one or more sources. The financial data obtained from the one or more contributing consumers is then aggregated, analyzed, and/or categorized, according to one or more events causing the changes and one or more criteria/parameters associated with the financial transaction data and/or the contributing consumer. The aggregated and/or categorized data representing the event related changes in the financial data is then stored. A “user consumer” then initiates a request for predictive event cost data associated with one or more specified events and the aggregated and/or categorized data representing the event related changes in the financial data is searched based. Results data representing the changes in the financial data for one or more similarly situated contributing consumers associated the specified event is then obtained and presented to the user consumer.

It is often very important for consumers to determine, as far in advance as possible, what bills they are likely to be responsible for, and any fluctuations that may occur in their finances. This is obviously true for budgeting purposes, but it is also true when contemplating life and/or purchase events, such as a change in marital status, having a child, change of residence, or when considering whether a given product and/or service should be purchased and/or what features of a given product and/or service are most important.
A consumer whose personal and financial situation has been relatively static generally knows what bills to expect, and what fluctuations are likely to occur in their finances, if any. Consequently, these static consumers are less likely to be caught off guard by hidden costs and/or changes in their finances. However, the reality for many consumers is that they will experience numerous life and/or financial events, some of which are beyond the control of the consumer. Consequently, for many consumers, when they do experience, expect, and/or contemplate, personal and/or financial events, determining what bills/costs are likely to be associated with the event, and/or what the financial impact of the event is likely to be, is an important, if not central, concern. However, making such a determination can be a relatively difficult task, and may not be recognized as an issue until the event takes place, despite the fact that, in most cases, it is better to prepare for the financial consequences of an event as far ahead of the event as possible.
For instance, a given consumer may have recently been informed that they will be having a baby. In this case, particularly if the baby is a first child, the consumer may be very interested in determining the expected costs and/or other financial impact of parenthood. The consumer can probably relatively accurately determine some of the costs associated with the baby, such as, for instance, the hospital costs under the consumer's healthcare plan and perhaps the financial impact of maternity leave. The consumer can probably also fairly accurately determine the cost of food and perhaps clothing for the baby. However, in many cases, there are hidden costs/bills and/or other financial changes associated with a life event like having a child that the consumer may not be able to identify so readily, such as, but not limited to: tax consequences of parenthood; costs of local preschools; cost of life insurance for the parents; daycare costs; diaper costs; expenses associated with keeping a residence warmer for the baby; various protective devices and household upgrades associated with a baby; baby related accessory costs, such as car seats, toys, cribs, play pens, etc. As noted, often these costs are overlooked by parents-to-be, especially first-time parents. Some of the costs/changes in financial situation associated with having a baby may be general in nature while others are area and/or demographically variable.
As another example, a consumer buying, or contemplating buying, a house for the first time may be unaware of numerous bills/costs associated with home ownership either in general, or associated with a given area such as, but not limited to: trash service; property taxes; sewer service; gardener service; and various utilities and maintenance costs and/or how these cost fluctuate according to season and/or from month-to-month.
As another example, a consumer buying, or contemplating buying, a new car may be unaware of numerous bills/costs associated with ownership of the new car, such as: differences in gasoline consumption/cost between the new car and any existing vehicle; differences in maintenance costs between the new car and an existing vehicle; differences in insurance costs between the new car and an existing vehicle; etc. Some of the costs/changes in financial situation associated with buying a new car may also be general in nature while others are area and/or demographically variable.
As a result of the situation described above, currently it can be quite difficult for many consumers to determine the actual total costs and/or financial impact associated with a given life and/or financial event, both in terms of identifying all likely bills, and in terms of anticipating fluctuations in recurring/anticipated bills. Consequently, many consumers are faced with unexpected costs/bills, and many carefully prepared budgets are negated by these unexpected costs/bills. This can cause significant consumer stress and have a direct effect on the consumer's ability to deal with the event, both financially and emotionally.

Method and system for predictive event budgeting based on financial data from similarly situated consumers


A control-flow dataflow graph pipelined loop structure that includes a loop body that processes an input value to generate an output value in successive iterations of the loop body, where the output value is captured by a circulate node coupled to the loop body, a loop valid node coupled to the loop body that determines a final loop iteration, and an output value storage node coupled to the circulate node, where the output value storage node ignores output values generated after the loop valid node determines the final loop iteration has occurred. Also, a control-flow dataflow graph pipelined loop structure that includes a loop body that processes an input value to generate an output value in successive iterations of the loop body, where the output value is captured by a circulate node coupled to the loop body, and a loop driver node coupled to the circulate node, where the loop driver node sets a period for each iteration of the loop body.

1. Field of the Invention
The present invention relates to pipelined loop structures that are produced by reconfigurable hardware compilers. More specifically, the invention relates to compiling pipelined loop structures that have a variable number of loop cycles and variable length clock latency.
2. Relevant Background
As instruction processors continue to increase rapidly in processing power, they are used more often to do computationally intensive calculations that were once exclusively done by supercomputers. However, there are still computationally intensive tasks, including, for example, compute-intensive image processing and hydrodynamic simulations that remain impractical to do on modem instruction processors.
Reconfigurable computing is a technology receiving increased interest in the computing arts. Traditional general purpose computing is characterized by computer code executed serially on one or more general purpose processors. Reconfigurable computing is characterized by programming reconfigurable hardware, such as Field Programmable Gate Arrays (FPGAs) to execute logic routines.
Reconfigurable computing offers significant performance advances in computation-intensive processing. For example, the reconfigurable hardware may be programmed with a logic configuration that has more parallelism and pipelining characteristics than a conventional instruction processor. Also, the reconfigurable hardware may be programmed with a custom logic configuration that is very efficient for executing the tasks assigned by the program. Furthermore, dividing a program's processing requirements between the instruction processor and the reconfigurable hardware may increase the overall processing power of the computer.
Software programs that are written in a high level language like, for example, C or Fortran can be converted into software that is executable in reconfigurable hardware with Multi-Adaptive Processor ("MAP") compilers. Loop structures in the high level language may be converted by the MAP compiler into a form that exploits parallelism and pipelining characteristics of reconfigurable hardware.
Unfortunately, existing MAP compilers only work with a small subset of all loop structures where the loops have a predetermined number of loop iterations before the loop terminates and that have periods of one clock, among other requirements. Thus, there remains a need for compilers that can compile loop structures where the loop does not terminate after a predetermined number of iterations and where the loop has a period greater than one clock.


A connector arrangement comprising an elongate member with electrically conducting areas forming a first connector and a second connector being arranged inside said elongate member ? The second connector is usable independently of the first connector.

Connectors and connector arrangement are commonly used to electrically connect two devices with each other. One type of connectors are audio connectors which are for example used to connect headphones or loudspeakers to audio equipment, for example portable or non-portable audio equipment, cell phones, personal computers, and the like. Commonly used audio connectors include 6.35 mm, 3.5 mm or 2.5 mm audio connectors. The male form of such audio connectors usually comprise a generally elongate member with different areas of the circumferential surface being electrically insulated from each other to provide a plurality of contacts. Conventional arrangements of such contacts are referred to as TS (Tip Sleeve), TRS (Tip Ring Sleeve) or TRRS (Tip Ring Ring Sleeve) connectors, indicated that a tip contact is insulated from a sleeve contact which is generally adjacent to the head, with no, one or two so-called ring contacts in between. For example, a TS connector may be used for mono audio, a TRS connector may be used for stereo audio and a TRRS connector may be used for stereo audio with an additional signal, for example a video signal.
Corresponding female connectors to the above-described male audio connectors may have an elongate hole with contact elements arranged therein corresponding to the positions of the insulated areas mentioned above.
These audio connectors have a basically standardized shape, such that for example headphones manufactured by one manufacturer may be used with portable audio equipment like a MP3 player from another manufacturer.
Besides female audio connectors, many audio devices have further connectors for further purposes, for example an antenna connector, a power connector, a data connector and the like. Such a plurality of connectors sometimes makes it difficult for a user to use the device since each device, cable or the like has to be plugged into the right connector. In case a device like loudspeakers or headphones are provided with additional functions, such a device may have more than one connector, for example to receive audio signals and power from the audio device, which makes connecting the device with the audio device somewhat inconvenient.
Therefore, there is a general need for improved connector arrangements offering more flexibility.

Connector arrangement having multiple independent connectors


The reduction of surface recombination is required for the manufacture of electronic devices made of silicon as well as for the application of various measurements and analytical methods for determining the purity of silicon. According to this invention, a process will be described for applying a laquer layer to the surface of silicon wafers, wherby the surface recombination velocity will be reduced to a value below 100 cm/s.

This invention concerns a process for reducing the surface recombination velocity of silicon wafers.
When manufacturing electronic devices from silicon, a procedure for reducing surface recombination will usually be required for their functioning as well as for the application of various measurements and analytical methods. In particular, this is true for determining bulk recombination lifetime--which is a measure for the purity of silicon with regard to electrically active impurities. However, for the determination of this bulk recombination lifetime a necessary condition is that the smallest dimension of the sample must exceed four times the diffusion length of the free charge carriers. Generally, this requirement is not met by standard silicon wafers as their thickness is usually less than the diffusion length of the charge carriers. Only if the surface recombination velocity becomes sufficiently low, that is below 100 cm/s, will it be possible to measure bulk lifetime on standard silicon wafers with sufficient precision to monitor the purity of silicon wafers before and after technological processes for the device production.
A reduction of the surface recombination velocity in silicon can be achieved by thermally growing a silicon dioxide (SiO.sub.2) layer in an oxidizing atmosphere at temperatures in the range of about 800-1200.degree. C. In the literature, and in common usage, such layers are also frequently designated by the more comprehensive heading "surface passivation". In general, surface passivation also includes the additional aspect of "protection against environmental influences". Due to the excellent mechanical, chemical, and electronic properties of the SiO.sub.2 layer, today this type of layer is used in almost all areas of silicon semiconductor technology.
However, there are some applications where this type of layer cannot be used with satisfactory results. On the one hand, this is the case for devices which cannot withstand the high temperature-time stress occurring during the growth of this layer. Another case is the measurement of bulk lifetime in order to detect heavy metals in Si wafers in the ppb range. Here it is very difficult, or even impossible to quantify how oxidation will influence the heavy metal content of the wafer by additional contamination, or segregation, precipitation, and evaporation. On the one hand, depending on the ratio of contamination levels of wafer and oxidation furnace, contamination from the tube may diffuse into the wafer to be examined. But, on the other hand, it is also possible that contamination will outdiffuse from the wafer and accumulate in the oxide or precipitate homogenously or heterogenously. In all these cases mentioned above, carrier lifetime measured subsequently no longer represents the original impurity level of the wafer. A further problem with thermal oxidation is the poor reproducibility of the density of states at the interface Si--SiO.sub.2, which determines the surface recombination velocity. FIG. 5 illustrates the lifetime distribution of a thermally oxidized wafer, with a low average lifetime of 85.84 .mu.s, which is mainly determined by the recombination at the Si--SiO.sub.2 interface.
To overcome the problem of thermal stress, there is the possibility of using a SiO.sub.2 layer deposited by the CVD (Chemical Vapor Deposition) process or one of its variants--PECVD (Plasma Enhanced CVD) or Photo CVD--instead of the thermally grown oxide layer. Depending on the process used, temperatures from approximately 100.degree. C. to 900.degree. C. are applied. A further advantage of these processes is that even layers such as silicon nitride Si.sub.3 N.sub.4 or silicon oxinitride SiO.sub.x N.sub.y can be deposited.
A serious disadvantage of these known deposited CVD layers is their poor ability to decrease the surface recombination velocity. Therefore they belong to the passivation layers in an extended sense, where the aspect "protection against environmental influences" takes precedence. For device applications, these layers will be used only in connection with a thin thermal SiO.sub.2 layer grown directly onto the silicon surface. For the same reason, and due to the fact that there are equipment specific contamination problems, so far no relevant analytical applications are known.
The analytical application is further complicated by the fact that the diffusion coefficients of the impurity metals of interest in Si are mostly some orders of magnitude higher than those of the doping elements P, B, As, and Sb. Therefore temperature-time stress, which is tolerable even for highly sensitive devices, can cause unpredictable changes in the contamination level, as already mentioned in the context of thermal oxidation.
Furthermore, it is known that hydrogen and halogens (F, Cl, Br, J, and At) present at the Si surface will reduce surface recombination velocity. This can be achieved, for instance, by treating the Si surface with hydrofluoric acid (HF). A serious disadvantage of this method is that the reduction of surface recombination disapears under the influence of atmospheric oxygen within a few minutes after removing the wafer from the liquid. This precludes any device application. A known application in the analytical area is the "Elymat Method" for measuring charge carrier diffusion length in Si wafers. Here, the wafer is placed inside a cuvette containing diluted HF during the measurement. Due to the hazards involved in handling HF, a rather large technical expense is required to reduce risks for the operating personnel.
A method which has become known more recently is to put the Si surfaces, freshly etched with HF, into an alcoholic iodine or bromine solution, as described e.g. by H. Msaad, J. Michel, J. J. Lappe and L. C. Kimmerling in "Electronic Passivation of Silicon Surfaces by Halogens" (to be published in "Journal of the Electrochemical Society" 1994). There, surface recombination velocities of less than 1 cm/s are achieved, which is an excellent value compared to about 100 cm/s achieved by thermal SiO.sub.2. A disadvantage of this method--just as with the previous one--is that the effect remains stable only as long as the wafer remains in the solution. An advantage is the considerably lower hazard potential involved in handling an alcoholic iodine solution, compared to HF. Nevertheless, handling the liquid involves a substantial additional effort.

Process for reducing the surface recombination speed in silicon


Water draining means (a water drain pipe and a water drain valve (54)) is provided that drains water out of a pot. A control device (80) makes the water draining means drain the water inside the pot when one of the following conditions is fulfilled: [1] the retention time counted by a first time counter (101a) has reached a predetermined time; [2] the total time, as counted by a second time counter (101b), that has elapsed after the water started to be fed has reached a predetermined time; [3] the total amount of water, as detected by a fed water amount detector (102), that has been fed into the pot has reached a predetermined amount; [4] the total water feed time, as counted by a third time counter (101c), for which the water has been fed into the pot has reached a predetermined time; and [5] an instruction to drain the water is entered via an operation panel (13). Thus, while the amount of water consumed and the work burden on the user associated with water replenishment are reduced, the water retained inside the steam generating device (pot) is prevented from getting spoilt, and the interior of the steam generating means can be kept sanitary.

There have conventionally been proposed various steam cooking apparatuses that heat-cook an article-to-be-heated placed inside a heating chamber by feeding into it steam generated with a steam generating device (for example, a pot). One such steam cooking apparatus is disclosed in Patent Document 1 listed below. In this steam cooking apparatus, after an article-to-be-heated is steam-cooked with steam generated with a steam generating device, while the heater of the steam generating device is kept de-energized, cooling water is fed into the steam generating device. Thus, after steam-cooking, the steam generating device is quickly cooled, so that the user can readily start after-cooking work (for example, the cleaning of the interior of the apparatus). The water that has been fed into the steam generating device is drained through a drain passage.
On the other hand, in the apparatus disclosed in Patent Document 2 listed below, when an operation member for requesting the stop of operation is operated, all the liquid present inside a steam generating device is drained. Thus, every day, when the operation of the apparatus is stopped, impurities that have been concentrated inside the steam generating device are drained. In this way, without a need for the steam generating device to be provided with a control device such as a concentration meter, the apparatus can continue its day-to-day operation.
Patent Document 1: JP-A-H7-243649
Patent Document 2: JP-A-H11-94203


An apparatus is disclosed for enhancing the sound level of portable devices by providing a sound reflector between the portable device and a case. The sound reflector includes a shield which functions to redirect output from rear facing speakers toward the front. The sound reflector can be extended for redirecting sound or retracted when not in use. A case incorporating a retractable sound reflector is also disclosed.

Portable devices such as mobile phones, tablets, etc. have gained significant popularity in recent years. These devices are used for various functions in addition to conventional voice-based communication. For example, various service providers offer premium features which allow users to watch videos, movies, etc. on the portable devices. There are also various websites which allow users to upload and watch video content from other users.
Portable devices typically include one or more speakers that allow users hear sound without the use of accessories such as headphones. Such speakers are generally placed at different locations on the rear surface of the portable device. For example, a single speaker may be centrally located along an edge of the rear surface, while dual speakers may be located in an opposing manner on the rear surface to simulate stereo sound. Due to the location of these speakers, the amount of sound which reaches the user is reduced based on the distance to a solid reflecting surface. Users often compensate for this reduction by placing a hand or object behind the speaker in order to reflect sound in their direction. This can be a cause of frustration and/or accidents because the portable device is not held in a secure manner.
Based on the foregoing, there is a need to provide a cost effective and simple manner to improve the sound from portable devices.

Apparatus for enhancing sound from portable devices


A method of adding primitives in real time to a model to produce a non-photorealistic rendering (NPR) of a model includes storing attribute data for each one of the primitives. A ring buffer is provided, having at least one stage, for each vertex of the model which is to have a primitive. Within each ring buffer, data is stored representative of a direction of each one of the primitives. Information is retrieved from the ring buffer by using a pointer, wherein the pointer is incremented and iterated over each stage of the ring buffer.

1. Field of the Invention
The present invention relates generally to non-photorealistic rendering (NPR) of images, and, more particularly, to a system, method, and apparatus for creating primitives for a 3-dimensional model in real-time.
2. Description of the Related Art
There are embodiments in the art which add primitives such as motion lines to line drawings. For example, motion lines have been added to cartoon animations to give the appearance of motion or to emphasize a particular object's motion in the animation. In such an embodiment, motion lines are typically employed to make the movement of such objects appear as realistic, or "photo-realistic," as possible.
There are other embodiments in which primitives such as motion lines are automatically added to line drawings. In such embodiments, motion lines are added to static scenes at authoring time and then applied and rendered. The direction and other characteristics of each line, such as visibility and perspective correctness, are calculated at the authoring time from attribute information stored for each object to which motion lines are to be drawn for each frame. Such embodiments use key-frame data, where all of the attribute data for each object to which motion lines are to be drawn is stored within a file or memory separately for each frame. Since this attribute information is processed separately for each frame, such an embodiment consumes much of a system's resources.
An embodiment which relies less on a system's resources is therefore desired, so primitives such as motion lines may quickly be added to a frame. It is desirable to have an embodiment capable of processing a series of successive frames in an animation, for example, in which motion lines are not merely calculated from stored attribute information at authoring time for each frame. An improved embodiment would use, in addition to key-frame data, per-frame data, or data relating to the position and movement of an object in an animation based upon the position of the object in previous frames.
It is also desirable to add primitives such as motion lines not only to a line drawing, but also to a 3-dimensional (3-D) model with polygonal geometry. It is desirable for such a system to use both per-frame data and key-frame data. A system using per frame data calculates motion lines based upon the positions of objects to which they attach in previous frames. Thus, physics can be applied to objects in each frame, and motion can be illustrated by resultant motion lines based upon the positions of objects in a series of frames, unlike previous systems, which calculate positions and other physical properties separately for each frame.
An embodiment is desired in which primitives such as motion lines may be added in real time. Therefore, an embodiment in which speed is optimized is desired.

Method and apparatus for adding real-time primitives


Combined cleanup and heat sink systems work with nuclear reactor coolant loops. Combined systems may join hotter and colder sections of the coolant loops in parallel with any steam generator or other extractor and provide optional heat removal between the same. Combined systems also remove impurities or debris from a fluid coolant without significant heat loss from the coolant. A cooler in the combined system may increase in capacity or be augmented in number to move between purifying cooling and major heat removal from the coolant, potentially as an emergency cooler. The cooler may be joined to the hotter and colder sections through valved flow paths depending on desired functionality. Sections of the coolant loops may be fully above the cooler, which may be above the reactor, to drive flow by gravity and enhance isolation of sections of the coolant loop.

Nuclear reactors with high operating temperatures may use a fluid heat exchange media, such as a liquid metal or molten salt, for coolant. The heat exchange media may transfer heat from a reactor to a heat exchanger and/or turbine for energy extraction and electricity generation as well as act as a heat sink to remove decay heat or other unwanted heat during operation or a shutdown condition. Many reactor designs, including, for example, liquid sodium-cooled fast reactors, such as the PRISM reactor, use multiple loops of heat exchange media to efficiently transfer heat away from a reactor for electrical generation and cooling. One loop may be an intermediate loop that is heated in an intermediate heat exchanger and then passed through a steam generator connected to a turbine and generator. Any fluid heat exchange media, such as liquid lead or sodium, molten salts, etc. may be used for this heat exchange in the intermediate loop.
Intermediate loops using fluid media may benefit from cleanup of the heat exchange media to remove impurities or debris that may accumulate during operation in a nuclear reactor environment. FIG. 1 is an illustration of a related art cleanup system 10 useable with an intermediate loop carrying a fluid heat exchange media. For example, system 10 may be a sodium cleanup loop useable with an intermediate coolant loop of a liquid sodium reactor or molten salt reactor.
As shown in FIG. 1, system 10 includes input 50 and output 67 that may connect to a same leg of an intermediate coolant loop, just far enough apart to prevent backflow or short-circuiting between the two, such as a few feet apart. Input 50 and output 67 may be intake from and returns to an intermediate coolant loop, removing and then re-supplying a relatively small amount of coolant from/to the intermediate loop. Pump 51 may push the fluid coolant through system 10. Regenerative heat exchanger 60 may be used to initially cool an incoming coolant stream 61 with outgoing, cooler coolant that is to be resupplied to the intermediate loop by output 67. The cooled coolant stream 62 may then flow to cooler 70, which may be a series of smaller tubes with fins exposed to an open air fan 71 to convect away further heat. Cooler 70 may lower the temperature of the coolant sufficiently so that impurities, such as oxides, will solidify or precipitate from the fluid coolant.
Purifier 80 may include chemical reactants, catalysts, and/or mechanical filters like cold traps, mesh, or other filter media that removes impurities or debris, including precipitates that come out of solution, following cooler 70. Bypass valves 81 and 82 may permit flow bypass of purifier 80, allowing flow to be raised or lowered slowly, and otherwise controlled, through purifier 80 during startup or shutdown. Colder, filtered coolant then passes back through regenerative heat exchanger 60 through input 66 to reheat the coolant to near operating temperatures before being returned to an intermediate loop via output 67, typically just downstream from inlet 50 in the intermediate loop. In this way, the coolant passed through system 10 for cleanup minimizes heat loss from the intermediate loop.

Coolant cleanup and heat-sinking systems and methods of operating the same


An antenna mount comprising: a building attachment section including an accessible end; and an antenna support section including a free end and a second accessible end. The accessible end and the second accessible are attached to each other by a joint. The free end is designed so that the antenna can be attached to it. The invention is designed so that the free end is vertical and the antenna is situated far away enough from the building so that it will clear the building when rotated 360°.

(1) Field of the Invention
The present invention relates to the field of building construction and more particularly to the field of mounting antennas on buildings.
(2) Description of the Related Art
We are used to seeing radio and TV antennas on buildings throughout the world. We used to see Yagi, log-periodic, loop and similar antennas. With the advent of HDTV and satellite television, we are now seeing dish antennas. They all look fairly ugly and detract from the beauty of the building design. This is particularly true in residential housing areas. In such areas, each individual homeowner is free to select his own TV service provider. If service using an antenna is selected by the homeowner, a technician installs the antenna where he determines the best signal can be received. It may be the roof or a wall. Each service has a preferred antenna design and support structure. Examples are shown on FIGS. 1-6. Eventually, each house in an area has different antennas, sprouting at different locations and angles on each house, which renders the area less beautiful.
What is needed is an identical antenna mounting system for each house in a neighborhood. One way to force uniformity would be for a builder to preinstall a mount on the building.
Development of an antenna mount which can be preinstalled on a building, yet provide sufficient flexibility for the owner's needs represents a great improvement in the field of building construction and satisfies a long felt need of owners and builders.