Abstract: Provided are a controller and a machine learning device that perform machine learning to optimize the servo gain of a machine inside a facility in accordance with action conditions, action environments, and a priority factor of the machine. The control system observes machine information on a machine as state, acquires information on machining by a machine as determination data, calculates a reward based on the determination data and reward conditions, performs the machine learning of the adjustment of the servo gain of the machine, determines an action of adjustment of the servo gain of the machine based on the state data and a machine learning result of the adjustment of the servo gain of the machine, and changes the servo gain of the machine, based on the action of adjustment of the determined servo gain.

Abstract: Rabbit G alpha 16 polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing rabbit G alpha 16 polypeptides and polynucleotides in screening of antagonists or agonists of cells co-expressing a G-protein coupled receptor and rabbit G alpha 16.

Abstract: The present invention provides inter alia, isolated “sculpin-type intracellular AFPs” from shorthorn sculpin and their corresponding nucleic acids. The sculpin-type intracellular AFPs are alanine-rich polypeptides that are synthesized in the peripheral tissues such as the skin and gills of fish. These skin-type AFPs are encoded by a distinct set of AFP genes that lack a signal peptide, which is indicative of their intracellular location. The polypeptides are used to make cells cold resistant and to improve the palatability of cold foods and liquids. Cold resistant eukaryotes and prokaryotes, including plants, animals and bacteria are made using the sculpin-type intracellular antifreeze polypeptides and nucleic acids. Moreover, the present invention provides methods for preserving cells, tissues and organs ex vivo using the AFPs described herein.

Abstract: The present invention relates to lung cells having a novel phenotype, morphology, and immunoprotectant properties. The invention further relates to cell lines derived from such cells and methods for producing such cells, both in vivo and in vitro. The invention additionally relates to expression products of such cells and cell lines. The present invention also relates to the application methods that temporarily ameliorate CFTR deficiency to in utero therapy, with the surprising result that amelioration then extends beyond birth and beyond the duration of the temporary in utero effect to become long-lasting amelioration.

Abstract: Transgenic mice having a phenotype characterized by the substantial depletion of a mature lymphocytic cell type otherwise naturally occurring in the species from which the transgenic mouse is derived. The phenotype is conferred in the transgenic mouse by a transgene contained in at least the precursor stem cell of the lymphocytic cell type which is depleted. The transgene comprises a DNA sequence encoding a lymphatic polypeptide variant which inhibits maturation of the lymphocytic cell type.

Abstract: The present invention relates to transgenic models of heart failure and, more particularly, to transgenic animals and methods for testing the usefulness of chemical compounds in treating or preventing heart failure. A transgenic mouse was developed wherein Gs&agr; is selectively overexpressed approximately three-fold in the heart. Although steady state adenylyl cyclase activities are not altered, both the percent of agonist high affinity &bgr;-adrenergic receptors as well as the rate of catalyst activation are increased. In addition, physiological and pathological studies revealed that chronically-facilitated sympathetic stimulation causes adverse cardiac effects.

Abstract: Methods to manipulate animals such as pigs, and the animals and tissues thereby derived, to reduce their immunogenicity following implantation into humans, are described. These methods are based on the discovery that certain carbohydrate structures on pig tissues, which require expression of the gene encoding the &agr; 1→3 galactosyl transferase enzyme, are targets for natural preformed antibodies of humans and elicit further antibody production in humans, while other carbohydrate structures do not or do so in a reduced amount. In the preferred embodiment, animals are produced by homologous recombination of the gene encoding &agr; 1→3 galactosyl transferase in embryonic stem cells or by microinjection into embryos of sequences eliminating or decreasing expression of &agr; 1→3 galactosyl transferase. In alternative embodiments, animals are produced having reduced amounts of &agr; 1→3 galactosyl epitopes or epitopes which are masked by sialylation or fucosylation.

Abstract: Myeloproliferative leukemia receptor (mpl) ligands, such as thrombopoietin, act on a primitive subpopulation of human stem cells having the characteristics of self-renewal and ability to give rise to all hematopoietic cell lineages. Thrombopoietin supports both megakaryocytic differentiation and primitive progenitor cell expansion of CD34+ and CD34+ sub-populations (CD34+Lin−, CD34+Thy-1+Lin−, and CD34+Lin− Rh123lo). Thrombopoietin also stimulated quiescent human stem cells to begin cycling. Thus, mpl ligands are useful for expanding primitive stem cells for restoration of hematopoietic capabilities and for providing modified human stem cells for gene therapy applications.

Abstract: A transgenic mouse, containing an oncogene or a tumor suppressor gene operably linked to a urothelium-specific promoter in its germ cells and somatic cells serves as an animal model system for human bladder cancer.

Abstract: The invention provides assays for the identification of modulators of Site-1 protease. Further provided by the invention are expression constructs and the transgenic cells useful for the development of such assays for Site-1 specific protease. The cells allow the implementation of in vitro assays for potential modulators of Site-specific proteases. Still further provided by the invention are in vitro assays employing Site-1 protease which has been isolated from cells.

Abstract: Chimeric proteins and DNA encoding chimeric proteins are provided, where the chimeric proteins are characterized by an extracellular domain capable of binding to a ligand in a non-MHC restricted manner, a transmembrane domain and a cytoplasmic domain capable of activating a signaling pathway. The extracellular domain and cytoplasmic domain are not naturally found together. Binding of ligand to the extracellular domain results in transduction of a signal and activation of a signaling pathway in the cell, whereby the cell may be induced to carry out various functions relating to the signalling pathway. A wide variety of extracellular domains may be employed as receptors, where such domains may be naturally occurring or synthetic. The chimeric DNA may be used to modify lymphocytes as well as hematopoietic stem cells as precursors to a number of important cell types.

Abstract: The present invention provides an effective approach to achieve the tightly modulated production of L-DOPA and/or dopamine at a preselected target location in the brain of a mammal by combining gene therapy approaches to supply a key enzyme in the synthesis of L-DOPA, and novel drug delivery modalities to administer a uniform level of a modulator of the activity of such key enzyme. The fine-tuned administration of the modulator establishes continuously uniform levels of modulator which in turn allow the effective modulation of L-DOPA and/or dopamine levels at a preselected target location in the brain of the mammal.

Abstract: A composition for in vivo transfection of non-human mammalian male germ cells comprises a nucleic acid or transgene, and a gene delivery system, and optionally a protective internalizing agent, such as an endosomal lytic agent, a virus or a viral component, which is internalized by cells along with the transgene and which enhances gene transfer through the cytoplasm to the nucleus of the male germ cell. A pharmaceutical preparation and a transfer kit utilize the composition. A method for introducing a polynucleotide into non-human mammalian male germ cells comprises the administration of the composition to a non-human mammalian. A method for isolating or selecting transfected cells utilizes a reporter gene, and a method for administering transfected male germ cells utilizes male germ cells which have been transfected in vitro.

Abstract: The present invention provides methods for inhibiting the growth of selected tumors utilizing recombinant viral vectors. Briefly, within one aspect of the present invention, a method for inhibiting the growth of a selected tumor is provided comprising the step of directly administering to a warm-blooded animal a vector construct which directs the expression of at least one anti-tumor agent, such that the growth of said tumor is inhibited. Representative examples of anti-tumor agents include immune activators and tumor proliferation inhibitors.

Abstract: This invention relates to transgenic non-human animals comprising a disrupted endothelial nitric oxide synthase gene. These animals exhibit abnormal wound-healing properties and hypertension. This invention also relates to methods of using the transgenic animals to screen for compounds having a potential therapeutic utility for vascular endothelial disorders, such as hypertension, cerebral ischemia or stroke, atherosclerosis and wound-healing activities. Moreover, this invention also relates to methods of treating a patient suffering from hypertension and wound-healing abnormalities with the compounds identified using the transgenic animals, and methods of making the transgenic animals. A method of treating a wound using nitroglycerin is also provided.

Abstract: A method for screening candidate antimicrobial compounds is described that utilizes a human vaginal xenograft engrafted in a non-human host. The method may be performed by using pathogen inoculated human vaginal xenografts in order to screen a wide range of candidate antimicrobials administered topically or systemically.

Abstract: This invention provides novel materials and methods involving the heterologous expression of transcription factors which are useful for effecting transcription of target genes in genetically engineered cells or organisms containing them. Target gene constructs and other materials useful for practicing the invention are also disclosed.

Abstract: Provided is a method of stimulating a class I-restricted immune response to a protein of interest or antigenic portion thereof in a host, as well as a protein delivery vehicle for use in the method. A nucleic acid molecule encoding the protein of interest or antigenic portion thereof is introduced into an avirulent Salmonella spp., such that the resulting Salmonella encodes a chimeric protein comprising the protein of interest or antigenic portion thereof and an injectable protein which is a target of a type III secretion system or an injectable portion thereof. This resulting Salmonella can be introduced into a host, in which the Salmonella will inject the chimeric protein into the cytosol of the cells of the host. The injection of the chimeric protein results in the stimulation of a class I-restricted immune response to the protein of interest or antigenic portion thereof in the host.

Abstract: Provided is a genetic identification and characterization of a gene which encodes an essential yeast mitotic spindle protein. The protein functions in anaphase spindle elongation. The invention also provides an identification of a protein which interacts with this mitotic spindle protein. The proteins identified and characterized by the present invention are useful as development candidates for cancer chemotherapeutic agents, anti-fungal compounds, and other anti-mitotic agents.

Abstract: A method of producing a non-human mammalian model of chronic cerebral inflammation is disclosed. The method comprises introducing into the mammal's brain a polynucleotide that does not encode amyloid precursor protein (APP). Applicants have discovered that APP expression is not necessary to mimic the symptoms of human neurodegenerative diseases. The mammalian models mimic in an in vivo system some of the physical manifestations of diseases of the central nervous system, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and encephalopathies. The models are useful in screening putative prophylactic and therapeutic compositions for addressing symptoms of chronic cerebral inflammation.