Abstract: Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R1)(R2)—O—C(O)-wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar—C(R1)(R2)—O—C(O)— via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar—C(R1)(R2)—O—C(O)— via a nitrogen atom.

Abstract: Described are general means and methods of diagnosing and treating the phenotypic spectrum as well as the overlapping clinical characteristics with several forms of inherited abnormal expression and/or function of the hPXR gene. In particular, polynucleotides of molecular variant hPXR gene which, for example, are associated with insufficient metabolization and/or sensitivity of drugs, and vectors comprising such polynucleotides are provided. Furthermore, host cells comprising such polynucleotides or vectors and their use for the production of variant hPXR proteins are described. In addition, variant hPXR proteins and antibodies specifically recognizing such proteins as well as transgenic non-human animals comprising the above-described polynucleotide or vectors are provided. Described are also methods for identifying and obtaining inhibitors for therapy of disorders related to the malfunction of the hPXR gene as well as methods of diagnosing the status of such disorders.

Abstract: A garment belt including an extendible insert. The insert may flex or stretch while the belt is being worn so that the belt adapts to variations in a wearer's waist size and shape.

Abstract: The present application discloses a class of antibiotic compounds containing an oxazolidinone ring. These compounds have useful activity against Gram-positive pathogens including MRSA and MRCNS and, in particular, against various strains exhibiting resistance to vancomycin and against E. faecium strains resistant to both aminoglycosides and clinically used &bgr;-lactams. The compounds also possess a favorable toxicological profile. This invention further relates to processes for their preparation, to intermediates useful in their preparation, to their use as therapeutic agents and to pharmaceutical compositions containing them.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. in vitro assays for discovering agents which effect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative and hyperproliferative disorders are provided.

Abstract: Compounds of formula (I) as defined herein, or a pharmaceutically acceptable salt, or an in-vivo-hydrolysable ester thereof, are useful as antibacterial agents. Processes for their manufacture and pharmaceutical compositions containing them are described.

Abstract: The present invention makes available methods and reagents for modulating proliferation or differentiation in a cell or tissue comprising contacting the cell with a hedgehog agonist, such as the compounds depicted in FIGS. 32 and 33. In certain embodiments, the methods and reagents may be employed to correct or inhibit an aberrant or unwanted growth state, e.g., by antagonizing a normal ptc pathway or agonizing smoothened or hedgehog activity.

Abstract: Simple microneedle devices for delivery of drugs across or into biological tissue are provided, which permit drug delivery at clinically relevant rates across or into skin or other tissue barriers, with minimal or no damage, pain, or irritation to the tissue. The devices include a substrate to which a plurality of hollow microneedles are attached or integrated, and at least one reservoir, containing the drug, selectably in communication with the microneedles, wherein the volume or amount of drug to be delivered can be selectively altered. The reservoir can be formed of a deformable, preferably elastic, material. The device typically includes a means, such as a plunger, for compressing the reservoir to drive the drug from the reservoir through the microneedles. In one embodiment, the reservoir is a syringe or pump connected to the substrate.

Abstract: A new class of electronic systems, wherein microelectronic semiconductor integrated circuit devices are integrated on a common substrate with molecular electronic devices.

Abstract: The invention concerns a compound of the formula (I): wherein, for example: T is of the formula (IA), (IB), or (IC); R1 is of the formula —NHC(═O)Rb wherein Rb is (1-4C)alkyl; R2 and R3 are hydrogen or fluoro; >A—B— is >C═CH— (but not when T is (IA)) or >CH—CH2—; wherein when T is of the formula (IA) or (IB); R6 is, for example, (1-4C)alkyl; R5 is hydrogen, R10CO—, R10SO2— or R10CS— wherein R10 is, for example, optionally substituted phenyl, or (1-10C)alkyl, or when T is of the formula (IA), (IB); or (IC): R5 and R6 are linked to give a 5- or 6-membered ring which is fused to the ring shown in (IA), (IB), or (IC) so as to give an optionally substituted bicyclic ring; and pharmaceutically acceptable salts thereof, processes for their preparation, pharmaceutical compositions containing them, and their use as antibacterial agents.

Abstract: A method for detecting allelic imbalance (AI) in sample nucleic acid, which method comprises providing multiple copies of a target nucleic acid region present in the sample, the target nucleic acid region comprising a marker of heterozygosity, separating the multiple copies into individual strands then allowing the individual strands to reanneal under conditions which permit the formation of homoduplexes and heteroduplexes, removing any heteroduplexes so formed, subjecting the remaining homoduplexes to the above steps of separation, reannealing and heteroduplex removal one or more times so that any difference in the initial ratio of allelic variants is amplified, and detecting the presence or absence of AI by reference to any difference in allele ratio so detected.

Abstract: Systems and methods including a wireless communications device that consists of a collection of one or more processing elements, optionally forming a computer cluster, that together carry out the functions necessary to exchange information over a plurality of wireless communications links, wherein the communication links may employ different communication protocols, respectively. The systems and methods combine two techniques: the use of multiple flexible processing elements, and a design in which each of the elements can carry out any part of the processing performed by the device, including without limitation the physical, MAC, link, network, transport, and presentation layer processing.

Abstract: Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis.

Abstract: The present invention concerns the discovery that proteins encoded by a family of vertebrate genes, termed here hedgehog-related genes, comprise morphogenic signals produced by tissue patterning centers, and are involved in the formation of ordered spatial arrangements of differentiated tissues in vertebrates. The present invention makes available compositions and methods that can be utilized, for example to generate and/or maintain an array of different vetebrate tissue both in vitro and in vivo.

Abstract: The present invention relates to the development of a positive selection vector based on insertional reconstruction of a reporter gene or of a regulatory gene controlling the expression of a reporter gene. The cloning vector carries a reporter gene or a regulatory gene with a mutation rendering the reporter or the regulatory gene protein functionally inactive. A primer carrying a nucleic acid sequence that corrects the mutation is used during PCR amplification of a targeted nucleic acid sequence, and the amplified DNA fragment is then ligated to the said vector thus reconstructing the wild-type reporter or regulatory gene.

Abstract: The present invention describes a methodology for generating high fidelity PCR products, and also cloning of such high fidelity PCR products in a suitable vector. Generation of polymerase-induced mutant fraction of target sequences during PCR amplification is linearly proportional to the number of doublings of the target sequences. Thus the high fidelity PCR products are generated by minimizing the number of doublings of the target nucleic acid sequences during PCR amplification. Minimization of number of doublings of the target sequences is achieved by reducing the number of cycles of PCR amplification of the target sequences. The high fidelity PCR products thus obtained are then cloned into a suitable vector. As an example, a 960 bp target sequence from E. coli DNA was PCR-amplified only for 3 cycles, and it was then directly cloned into a positive selection cloning vector pRGR2Ap.