Abstract: This invention provides compounds having the structure: wherein each of R1, R2, R3 and R9 is independently H; straight chain or branched, substituted or unsubstituted C1-C7 alkyl, C2-C7 alkenyl or alkynyl; C3-C7 cycloalkyl or cycloalkenyl; acyl, phenyl, substituted phenyl, or heteroaryl; wherein each dashed line represents a single bond or a double bond with the proviso that if R1 is present, R3 is absent and there is a double bond between N at position 3 and C at position 2 and a single bond between C at position 2 and N at position 1 and if R3 is present, R1 is absent and there is a double bond between N at position 1 and C at position 2 and a single bond between C at position 2 and N at position 3; wherein each of R4, R5 and R6 is independently H, F, Cl, Br, I; straight chain or branched, substituted or unsubstituted C1-C7 alkyl, C2-C7 alkenyl or alkynyl; C3-C7 cycloalkyl or cycloalkenyl; phenyl, substituted phenyl, heteroaryl, —OH, —OR7, —CN, —COR7, —CO2R7,

Abstract: A pharmaceutical composition which comprises the c-kit ligand (KL) purified by applicants or produced by applicants' recombinant methods in combination with other hematopoietic factors and a pharmaceutically acceptable carrier is provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention. This invention provides combination therapies using c-kit ligand (KL) and a purified c-kit ligand (KL) polypeptide, or a soluble fragment thereof and other hematopoietic factors. It also provides methods and compositions for ex-vivo use of KL alone or in combination therapy. A mutated KL antagonist is also described. Such an antagonist may also be a small molecule. Antisense nucleic acids to KL as therapeutics are also described. Lastly, compositions and methods are described that take advantage of the role of KL in germ cells, mast cells and melanocytes.

Abstract: The present invention provides a method of identifying clones encoding for membranal and secreted proteins by deriving probes from membrane-bound polysomes and free-polysomes, and performing a microarray-based comparison of the relative abundance of the different RNA species. Analysis of the results of such comparison and resultant identification of clones encoding for membranal or secreted proteins, provides an efficient tool for identifying targets of drug development. The present invention further provides a method of augmenting a microarray analysis by utilizing RNA extracted from specific subcellular compartments as templates for DNA probes. The method may be used together with conventional differential analysis techniques for improvement of their analysis and gene identification functions.

Abstract: The subject invention provides a method for detecting the presence of human malignant cells in a sample of tumor cells, which comprises contacting the sample with an antibody directed to an epitope present on the &bgr; subunit of human luteinizing hormone or on intact human luteinizing hormone under conditions such that the antibody forms a complex with cells present in the sample if the epitope is present on the surface of the cells, and determining whether the antibody forms such a complex. The subject invention also provides a method for determining whether a tumor present in a human subject is malignant which comprises obtaining a sample of cells from the tumor and detecting the presence of malignant cells in the sample according to the method of the subject invention.

Abstract: This invention provides a non-naturally occurring targeted lipolytic compound comprising a lipolytic agent linked to a targeting agent. In an embodiment, the lipolytic agent is covalently attached to the targeting agent. In an embodiment, the lipolytic agent is a phospholipase and the targeting agent is a viral receptor. This invention further provides for therapeutic uses of the non-naturally occurring targeted lipolytic compound. In an embodiment, the non-naturally occurring targeted lipolytic compound neutralizes virions of the human immunodeficiency virus (HIV).

Abstract: This invention provides a method of diagnosing a predisposition to cancer in a subject comprising: (a) obtaining a nucleic acid sample from the subject; and; (b) determining whether one or more of the subject's Ku70 alleles or regulatory regions to those alleles are deleted or different from the wild type so as to reduce or eliminate the subject's expression of polypeptide having tumor suppressor activity. This invention also provides a method of assessing the severity of cancer in a subject comprising: (a) obtaining a nucleic acid sample from the subject; and (b) determining whether one or more of the subject's Ku70 alleles or regulatory regions to those alleles are deleted or different from the wild type so as to reduce or eliminate the subject's expression of polypeptide having tumor suppressor activity.

Abstract: The present invention relates to a pharmaceutical controlled-release oral drug delivery system comprising as active ingredient at least one &bgr;-lactam antibiotic agent, having a specific absorption site in the small intestine in combination with a polymeric matrix, optionally further containing additional pharmaceutically acceptable constituents, wherein at least 50% of the &bgr;-lactam antibiotic agent are released from the matrix within from about 3 to about 4 hours from oral administration and the reminder of the pharmaceutical agent is released at a controlled rate. The drug delivery system according to the invention optionally further comprises a &bgr;-lactamase inhibitor, preferably in combination with amoxicillin and/or amoxicillin trihydrate as the active ingredient. The polymeric matrix of the pharmaceutical controlled-release oral drug delivery system of the invention my be of hydrophilic and/or hydrophobic nature and the delivery system may further comprise pharmaceutically acceptable additive.

Abstract: This invention is directed to novel aryl sulfonamide and sulfamide compounds which bind selectively to and inhibit the activity of the human Y5 receptor. This invention is also related to uses of these compounds for the treatment of feeding disorders such as obesity, anorexia nervosa, bulimia nervosa, and abnormal conditions such as sexual/reproductive disorders, depression, epileptic seizure, hypertension, cerebral hemorrhage, congestive heart failure or sleep disturbances and for the treatment of any disease in which antagonism of a Y5 receptor may be useful.

Abstract: This invention provides a method for inhibiting thrombosis in a patient whose blood is subjected to extracorporeal blood circulation which comprises contacting the extracorporeal circulating blood with a Factor IXa compound in an amount effective to inhibit thrombosis in the blood of a patient and under conditions such that the Factor IXa compound circulates in the patient. The Factor IXa compound may include an active site-blocked Factor IXa compound or Glu-Gly-Arg chloromethyl ketone-inactivated human factor IXa compound. This invention also provides that the effective amount may be from about 0.1 &mgr;g/ml plasma to about 250 &mgr;g/ml plasma or from about 0.5 &mgr;g/ml plasma to about 25 &mgr;g/ml plasma. The patient may be subjected to extracorporeal blood circulation during transplant surgery or cardiopulmonary bypass surgery.

Abstract: This invention provides an isolated nucleic acid molecule encoding a motor neuron restricted pattern, MNR2, protein. This invention provides an isolated nucleic acid molecule of at least 15 contiguous nucleotides capable of specifically hybridizing with a unique sequence included within the sequence of the nucleic acid molecule encoding a MNR2 protein. This invention provides a purified MNR2 protein, a polyclonal and monoclonal antibody directed to an epitope of an MNR2 protein. This invention provides a method of inducing differentiation somatic motor neurons which comprises expressing MNR2 protein in any neural progenitor cells. This invention provides a transgenic animal which expresses an MNR2 protein. This invention provides a pharmaceutical composition comprising a MNR2 protein and pharmaceutically acceptable carrier.

Abstract: The present invention provides a method of obtaining a composition which comprises determining whether a chemical compound binds to a human 5-HT2 receptor expressed on the surface of a mammalian cell transfected with a vector adapted for expressing the receptor in the cell, and if the compound binds to the receptor, admixing the compound with a carrier. The present invention further provides a method of obtaining a composition which comprises determining whether a chemical compound binds to and activates or binds to and inhibits activation of a human 5-HT2 receptor expressed on the surface of a mammalian cell, wherein the human 5-HT2 receptor is expressed on the surface of a mammalian cell transfected with a vector adapted for expressing the receptor in the cell, and if the compound binds to and activates or binds to and inhibits activation of the receptor, admixing the compound with a carrier.

Abstract: This invention provides a composition comprising an amount of a purified protein selected from a group consisting of bone morphogenetic protein 4, bone morphogenetic protein, bone morphogenetic protein 7, dorsalin-1 and combinations thereof effective to stimulate neural crest cell differentiation and an acceptable carrier. This invention provides different uses of this composition.

Abstract: This invention provides methods of modulating angiogenesis, including promoting or inhibiting angiogenesis, e.g., in connection with treating abnormalities including hemangiomas, hemangiosarcomas, Kaposi's Sarcoma, ischemic disorders, and wounds. These methods involve administration of compounds that are selective agonists or antagonists of Notch4 protein. In addition, this invention provides an isolated nucleic acid molecule encoding a Notch4, an isolated Notch4 protein, vectors comprising an isolated nucleic acid molecule encoding a Notch4 protein, cells comprising such vectors, antibodies directed to Notch4 protein, nucleic acid probes useful for detecting nucleic acids encoding Notch4 protein, and antisense oligonucleotides complementary to any unique sequences of a nucleic acid molecule which encodes Notch4 protein.

Abstract: A torque control type impact wrench includes a first storage section for storing an ideal upper limit of the pulsed torque for screwing a male screw into a female screw, as a first storage value, a second storage section for storing a driving speed at which a driving section drives a torque producing section as a second storage value, and a control section for causing the driving section to drive the torque producing section at the second storage value and stopping the driving section when the pulsed torque exceeds the first storage value, wherein the control section causes the second storage section to store a value, which is larger than the second storage value, as a new second storage value when the pulsed torque does not reach the first storage value within a given time period after the driving section starts.

Abstract: The present invention relates to a dispersible pharmaceutical composition comprising a therapeutically effective amount of L-DOPA ethyl ester, a therapeutically effective amount of a decarboxylase inhibitor, a filler, a disintegrant, and a lubricant. The present invention also provides a method of preparing the pharmaceutical composition described herein.

Abstract: Methods and compounds for the synthesis of heterocycles, including pyrimidine-2,4-diones, are disclosed. Also disclosed are solid supports useful for solid phase synthesis, and methods for making the solid supports.

Abstract: The present invention provides a method of transcriptionally modulating the expression of a gene-of-interest. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell. Additionally, this invention provides a method for determining whether a molecule known to be a modulator of protein biosynthesis is capable of transcriptionally modulating expression of a gene-of-interest.

Abstract: This invention provides a mammalian cell useful for retroviral packaging comprising two plasmids, both of which comprise the 5′ long terminal repeat (LTR) sequence from a helper virus, neither of which comprise a functional &psgr; packaging sequence or a 3′ LTR from the helper virus, one of which comprises the env gene from the helper virus and the other of which comprises the gag and pol genes from the helper virus. This invention also provides a process for preparing a producer cell useful for transferring a foreign gene into a mammalian cell which comprises treating the above-described mammalian cell with a vector plasmid so as to insert the vector plasmid into the cell and thus create the producer cell, the vector plasmid comprising the foreign gene, a functional &psgr; packaging sequence from the helper virus, both the 5′ and 3′ LTRS from the helper virus, and a gene encoding a selectable or identifiable phenotypic trait, and recovering the producer cell so created.

Abstract: The present invention provides for a method for producing a cDNA library enriched for rare cDNAs and reduced in abundant cDNAs which comprises: (a) obtaining a pool of linear double-stranded cDNAs; (b) cloning a first portion of the pool of cDNAs into a first vector to create a first cDNA library; (c) cloning a second portion of the pool of cDNAs into a second vector to create a second cDNA library; (d) producing single-stranded linear cDNA inserts (target cDNA) from the first cDNA library; (e) producing single-stranded circles (target cDNA) from the second cDNA library; (f) producing a pool of abundant linear cDNAs (driver cDNA) from the first and the second DNA libraries; (g) hybridizing the linear cDNA inserts from step (d) or the single-stranded circles from step (e) with an excess amount of the abundant cDNA pool produced from the second cDNA library or the first cDNA library, respectively, from step (f) under hybridization conditions to produce duplexes, and (h) isolating single-stranded linear cDNA ins

Abstract: This invention provides an isolated nucleic acid encoding a mammalian galanin receptor, an isolated galanin receptor protein, vectors comprising isolated nucleic acid encoding a mammalian galanin receptor, cells comprising such vectors, antibodies directed to a mammalian galanin receptor, nucleic acid probes useful for detecting nucleic acid encoding a mammalian galanin receptor, antisense oligonucleotides complementary to unique sequences of nucleic acid encoding a mammalian galanin receptor, nonhuman transgenic animals which express DNA encoding a normal or a mutant mammalian galanin receptor, as well as methods of determining binding of compounds to mammalian galanin receptors.