Abstract: The present invention provides compositions and methods for binding and/or modulating enzymatic activity of human protein tyrosine phosphatases such as PTP1B. Additionally, the invention provides methods of identifying and using such nucleic acid ligands.

Abstract: A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

Abstract: A chimera protein comprising in the following order: a signal peptide, a proprotein convertase subtilisin/kexin type 9 preproprotein (PCSK9) sequence consisting of amino acid residues at positions 35 to 696 of SEQ ID NO: 38, a transmembrane domain and a cytosolic domain, wherein said cytosolic (CT) domain comprises a sequence able to recycle the protein from the cellular membrane to endosomes.

Abstract: The present invention provides compositions and methods for binding and/or modulating enzymatic activity of human protein tyrosine phosphatases such as PTP1B. Additionally, the invention provides methods of identifying and using such nucleic acid ligands.

Abstract: A mobile trailer for spreading a granular material mixture is disclosed. This trailer comprises at least two containers or bin compartments for containing a respective granular material, a movement-imparting assembly for moving the granular materials and a material mixer and spreader assembly for mixing and spreading the granular materials. Each bin compartment comprises a respective material-exit opening and the material mixer and spreader assembly is positioned near these openings. The movement-imparting assembly comprises a respective movement-imparting device mounted to each bin compartment for moving a respective granular material though a respective opening towards the material mixer and spreader assembly. A controller is linked to the movement-imparting assembly so as to selectively and independently modulate the speed of each movement-imparting device thereby modulating the ratio of each granular material received, mixed and spread by the material mixer and spreader assembly.

Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods of making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.

Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates. Methods making the mice and cell lines derived from the mice are also provided. The present invention also provides methods of identifying inhibitors of the enzymatic activity of PTP-1B as well as inhibitors identified by such methods.

Abstract: The eukaryotic mRNA 5′ cap structure is recognized by eIF4E, which plays an essential role in translational control and cell growth. Members of a family of proteins called eIF4E-binding proteins (4E-BPs) inhibit the activity of eIF4E and consequently repress translation. Following exposure of cells to hormones, cytokines and growth factors, 4E-BPs become hyperphosphorylated and dissociate from eIF4E, to relieve translation inhibition. The phosphorylation events leading to 4E-BP1 dissociation from eIF4E are mediated by the P13-kinase/FRAP/mTOR signaling pathway. The present study addresses the biological importance of 4E-BP1 in vivo by disrupting its gene in the mouse. Homozygous 4E-BP1 deficient mice are healthy and develop normally. However, they show an important decrease in white adipose tissue and blood glucose level, and the males show a decrease in total body weight and an increase in resting metabolic rate.

Abstract: The present invention provides mice that have had their PTP-1B genes disrupted by targeted homologous recombination. The mice have no detectable PTP-1B protein, yet appear to be physiologically normal. However, in the fed state on a normal diet, the mice have half the level of circulating insulin as their wild-type littermates. In glucose and insulin tolerance tests, the mice show an increased insulin sensitivity. When fed a high fat, high carbohydrate diet, the mice show a resistance to weight gain as compared to their wild-type littermates.

Abstract: This invention relates to formulations comprising film-forming components capable of forming per se a physical barrier to pathogens. Thermoreversible gels such as poloxamers are particularly preferred for that use. The film-forming formulations may further comprise microbicides, spermicides or any other drug, which choice is guided by the pathogen, organism or the disease to be inactivated or treated. The formulations are therefore efficient as a physical, and optionally, as a chemical or pharmacological barrier as well as usable as a sustained drug-release system at the locus of administration. A part of the drug may also be entrapped in liposomes or other drug carriers. These formulations are intended for use in the prevention of sexually transmitted diseases, as well as in the treatment of infections, cancer, inflammation or any disease or state which requires a pharmacological treatment. Formulations are applicable to mucosae, skin and eye, for example.

Abstract: An anchoring device for mounting on a boat, particularly a light boat used for sporting purposes. It has a pair of aligned winch drums with cables wound on them into rolls for winding and unwinding in opposite directions; the drums being mounted on a frame for rotation about parallel axes. A manually operable drive is mounted on the frame and on the drums, which drive allows them to be rotated and, in a neutral position, allows them to idle. A manually releasable stop member mounted on the frame cooperates with the drive to stop rotation of the drums so as to prevent the cable from unwinding.