Abstract: The invention features devices and methods for treatment of pain. The drug delivery device is a drug delivery system adapted for whole implantation in a subject and to provide pain relief by delivery of fentanyl or a fentanyl congener (e.g., sufentanil) over a protracted period of time (e.g., at least 3 days or more than 3 days). The device comprises a housing defining a reservoir that contains a drug formulation, a pump operatively connected to the housing so as to facilitate movement of drug out of the reservoir and out of the device, and a thermal expansion element which defines a flow pathway comprising a thermal expansion channel to accommodate thermal expansion of formulation in the reservoir. The device can further comprise a valve positioned within the flow pathway so as to prevent movement of drug out of the reservoir prior to use.

Abstract: Methods and compositions for screening for transdominant effector peptides and RNA molecules selected inside living cells from randomized pools are provided.

Abstract: Method for screening for an antiviral agent, by determining whether a potential agent interacts with a virus or cellular component which allows or prevents preferential translation of a virus RNA compared to a host RNA under virus infection conditions; and determining whether any interaction of the agent with the component reduces the level of translation of an RNA of the virus.

Abstract: Compositions of the invention include composites comprising a biomaterial having compounds thereon with enhanced cell binding with respect to collagen. These composites are useful for soft and hard tissue repair or reconstruction and for in vitro uses. Suitable compounds with enhanced cell binding include synthetic peptides that mimic the conformation necessary for recognition and docking of collagen binding species (such as cell surface receptors for collagen and fibronectin) and have the amino acid residues -Ile-Ala- folded in a &bgr;-bend.

Abstract: The present invention provides random cDNA expression vector libraries, comprising expression vectors which comprise random cDNAs positioned in sense orientation. Also provided are random cDNA expression vector libraries, comprising expression vectors which comprise random cDNAs positioned in antisense orientation. Methods for producing these libraries through directional cloning of random cDNAs are also provided. Also provided herein are methods of using these libraries to screen for agents capable of modulating cell phenotype in desirable ways.

Abstract: The invention provides a non-invasive assay for the detection of a SLOS affected individual by determining the ratio of at least one of the specific SLOS steroid analytes, dehydro-estriol (8-DHE3) and a dehydro-pregnanetriol (7-DHPT) to their normal steroid counterparts estriol (E3) and pregnanetriol (PT), respectively. 8-DHE3 and 7-DHPT represent metabolites which accumulate in the blood and urine of an individual with SLOS or an individual carrying a SLOS affected fetus. The invention provides for a reliable and reproducible method of screening women for SLOS affected fetuses early on in pregnancy.

Abstract: The present invention features vanilloid receptor polypeptides and vanilloid receptor-related polypeptides, specifically the capsaicin receptor subtypes VR1 and VR2 (VRRP-1), as well as the encoding polynucleotide sequences. In related aspects the invention features expression vectors and host cells comprising such polynucleotides. In other related aspects, the invention features transgenic animals having altered capsaicin receptor expression, due to, for example, the presence of an exogenous wild-type or modified capsaicin receptor-encoding polynucleotide sequence. The present invention also relates to antibodies that bind specifically to a capsaicin receptor polypeptide, and methods for producing these polypeptides. Further, the invention provides methods for using capsaicin receptor, including methods for screening candidate agents for activity as agonists or antagonists of capsaicin receptor activity, as well as assays to determine the amount of a capsaicin receptor-activating agent in a sample.

Abstract: Method for screening for an antiviral agent, by determining whether a potential agent interacts with a virus or cellular component which allows or prevents preferential translation of a virus RNA compared to a host RNA under virus infection conditions; and determining whether any interaction of the agent with the component reduces the level of translation of an RNA of the virus.

Abstract: The identity of the polymorphic nucleotide in a target sequence having at least two known variants can be easily and efficiently detected by hybridizing at least one primer upstream of the biallelic marker and performing extension reactions using the target DNA with the hybridized primer, where a first reaction is conducted in the absence of a deoxyribonucleoside triphosphate or ribonucleoside triphosphate complementary to the first known variant, and a second reaction is conducted in absence of a deoxyribonucleoside triphosphate or ribonucleoside triphosphate complementary to the second known variant. Determining the lengths of the primers and any extension products from both reactions will indicate which variant or variants are present in a DNA sample.

Abstract: Compounds that are effective lipoxygenase inhibitors, and methods and pharmaceutical compositions for inhibiting lipoxygenases and for treatment of lipoxygenase-mediated conditions in humans and other subjects. The compounds, methods and pharmaceutical compositions utilize subersic terpenoids, jaspic terpenoids, igernellic terpenoids, hippospongic terpenoids, halicondric terpenoids, dictyodendric terpenoids, and/or heteronemic terpenoids, and synthetic derivatives or analogs thereof. Exemplary compounds include (−)-subersic acid, (+)-subersin, jaspaquinol, (−)-jaspic acid, igernellin, halisufate 7, and hipposulfate C and D, and derivatives thereof.

Abstract: The present invention is directed to methods of detecting the presence of a bipolar mood disorder susceptibility locus in an individual, comprising analyzing a sample of DNA for the presence of a DNA polymorphism on the short arm of chromosome 18 between the telomere and D18S481, wherein the DNA polymorphism is associated with a form of bipolar mood disorder. The invention for the first time provides strong evidence of a susceptibility gene for bipolar mood disorder that is located in the terminal 5 cM region of the short arm of chromosome 18. The disclosure describes the use of linkage analysis and genetic markers in this 5 cM region to fine map the region and the use of genetic markers to genetically diagnose (genotype) bipolar mood disorder in individuals, to confirm phenotypic diagnoses of bipolar mood disorder, to determine appropriate treatments for patients with particular genotypic subtypes.

Abstract: The invention features and methods and compositions for oxide production on a Copper substrate, e.g., a Copper or Copper alloy substrate, to provide for improved adhesion of Copper substrate to polymeric material, e.g., such as used in manufacture of printed circuit boards. The oxide-producing compositions of the invention, which may be either acidic or ammoniacal, comprise 1) a source of Cu++ (Cupric) ions; 2) a source of a primary electrolyte that is non-interactive with Copper ions; 3) a Cuprous ligand, e.g., a halide ion, preferably chloride, which also serves as a secondary electrolyte; and 4) an optional organic. Acidic oxide-producing compositions comprise a strong acid as the primary electrolyte. The primary electrolyte of ammoniacal oxide-producing compositions is a non-interactive, ammonium salt of acid, which provides a highly soluble Cupric ammonium salt. The secondary electrolyte of the oxide-producing compositions is selected so as to be compatible with the primary electrolyte.

Abstract: The invention features methods of high throughput screening of candidate drug agents and rapid identification of drug targets by examining induction of the stress response in a host cell, e.g., the stress response in wildtype host cells and/or in host cells that differ in target gene product dosage (e.g., host cells that have two copies of a drug target gene product-encoding sequence relative to one copy). In general, induction of the stress response in wildtype host cells indicates that a candidate agent has activity of the drug. Induction of a relatively lower or undetectable stress response in a host cell comprising an alteration in gene product dosage indicates that the host cell is drug-sensitive and is altered in a gene product that plays a role in resistance to the drug.

Abstract: Methods for the production of a mucin-type glycopeptide comprising a transglycosylation using a sugar acceptor such as peptide and a sugar donor as an oligosaccharide with an endo-&agr;-N-acetylgalactosaminidase under a given condition is disclosed. The method provides a new practical way to produce mucin-type glycopeptides in industry and can provide an sufficient amount of the mucin-type glycopeptides in a practical use.

Abstract: The invention relates generally to methods of screening for drugs which bind to and/or regulate cellular proteins involved in drug resistance, particularly resistance of tumor cells to chemotherapeutic agents.

Abstract: The present invention is directed to novel polypeptides, nucleic acids and related molecules which have an effect on or are related to the cell cycle. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided by the present invention are methods for identifying novel compositions which mediate cell cycle bioactivity, and the use of such compositions in diagnosis and treatment of disease.

Abstract: The present invention features methods for recruitment of bone marrow-derived stem cells (e.g., endothelial cell precursors, hematopoietic stem cells) by administration of nicotine or other nicotine receptor agonist. The methods of the invention can be used in, for example, treatment of conditions amenable to treatment by recruitment of bone marrow-derived stem cells (e.g., neutropenia).

Abstract: The present invention is directed to compositions and methods including peptides which have a high affinity for each other and, when linked to a protein, are used to help fold the protein into a compact structure. By virtue of its stability and constraints, this scaffold can prolong the activity of any embedded protein sequences in the presence of cellular and other proteases. The compact structure can have other functional sequences embedded, and is preferable to linear and less constrained peptides for library screening, for creating structurally-biased peptide libraries and for targeting to specific intracellular and extracellular compartments. Compositions of the present invention can be displayed on the surface of viruses, archaebacteria, prokaryotic and eukaryotic cells for library screening, drug screening and display. Methods of the present invention are useful for screening in vivo for intracellular effector proteins modulating signaling pathways and to identify interacting proteins in vitro.

Abstract: The present invention provides methods of determining whether test cells in a sample are cancerous or not and determining if lymphocytes are activated or not. The method measures the test cell's DNA ploidy and the cellular activity of an enzyme such as an esterase, which has altered expression in cancer cells. Esterase activity can be measured using fluorescent compounds such as fluorescein diacetate.

Abstract: The invention features devices and methods for the systemic delivery of fentanyl or a fentanyl congener (e.g., sufentanil) to treat pain. In the present invention, a drug formulation comprising fentanyl or a fentanyl congener is stored within a drug delivery device (e.g., contained in a reservoir or impregnated within a matrix within the controlled drug delivery device). The drug formulation comprises an amount of drug sufficient for treatment and is stable at body temperatures (i.e., no unacceptable degradation) for the entire pre-selected treatment period. The drug delivery devices store the drug formulation safely (e.g., without dose dumping), provide sufficient protection from bodily processes to prevent unacceptable degradation of the formulation, and release the drug formulation in a controlled fashion at a therapeutically effective rate to treat pain.