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Institution

Torrey Pines Institute for Molecular Studies

NonprofitSan Diego, California, United States
About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: T cell & Antigen. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.


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Journal ArticleDOI
TL;DR: The effectiveness of intermediate recombination in evolution strategies is analyzed in light of the typical procedure of initializing trial solutions uniformly about the global optimum of benchmark functions and indicates that this procedure may predispose results in favor of Intermediate recombination.
Abstract: The effectiveness of intermediate recombination in evolution strategies is analyzed in light of the typical procedure of initializing trial solutions uniformly about the global optimum of benchmark functions. Analysis indicates that this procedure may predispose results in favor of intermediate recombination.

52 citations

Journal ArticleDOI
TL;DR: I-Ag7 tetramers containing two such peptides, p79 and p17, are generated that could detect a heterogeneous population of T cells, and a very small number of NOD mouse T cells may represent BDC2.5-like cells.
Abstract: Nonobese diabetic (NOD) mice expressing the BDC2.5 TCR transgene are useful for studying type 1 diabetes. Several peptides have been identified that are highly active in stimulating BDC2.5 T cells. Herein, we describe the use of I-Ag7 tetramers containing two such peptides, p79 and p17, to detect and characterize peptide-specific T cells. The tetramers could stain CD4(+) T cells in the islets and spleens of BDC2.5 transgenic mice. The percentage of CD4(+), tetramer(+) T cells increased in older mice, and it was generally higher in the islets than in the spleens. Our results also showed that tetAg7/p79 could stain a small population of CD4(+) T cells in both islets and spleens of NOD mice. The percentage of CD4(+), tetramer(+) T cells increased in cells that underwent further cell division after being activated by peptides. The avidity of TCRs on purified tetAg7/p79(+) T cells for tetAg7/p79 was slightly lower than that of BDC2.5 T cells. Although tetAg7/p79(+) T cells, like BDC2.5 T cells, secreted a large quantity of IFN-gamma, they were biased toward being IL-10-producing cells. Additionally, <3% of these cells expressed TCR Vbeta4. In vivo adoptive transfer experiments showed that NOD/scid recipient mice cotransferred with tetAg7/p79(+) T cells and NOD spleen cells, like mice transferred with NOD spleen cells only, developed diabetes. Therefore, we have generated Ag-specific tetramers that could detect a heterogeneous population of T cells, and a very small number of NOD mouse T cells may represent BDC2.5-like cells.

52 citations

Journal ArticleDOI
TL;DR: In this article, the authors presented the results of molecular docking simulations with HIV-1 protease for the sb203386 and skf107457 inhibitors by Monte Carlo simulated annealing.
Abstract: We present the results of molecular docking simulations with HIV-1 protease for the sb203386 and skf107457 inhibitors by Monte Carlo simulated annealing. A simplified piecewise linear energy function, the standard AMBER force field, and the AMBER force field with solvation and a soft-core smoothing component are employed in simulations with a single-protein conformation to determine the relationship between docking simulations with a simple energy function and more realistic force fields. The temperature-dependent binding free energy profiles of the inhibitors interacting with a single protein conformation provide a detailed picture of relative thermodynamic stability and a distribution of ligand binding modes in agreement with experimental crystallographic data. Using the simplified piecewise linear energy function, we also performed Monte Carlo docking simulations with an ensemble of protein conformations employing preferential biased sampling of low-energy protein conformations, and the results are analyzed in connection with the free energy profiles. Q 1999 John Wiley & Sons, Inc. Int J Quant Chem 72: 73)84, 1999

51 citations

Journal ArticleDOI
TL;DR: A mutated fatty acid binding protein labeled with the fluorescent molecule acrylodan, whose fluorescence is quenched upon binding bilirubin, is used for quantifying B(f) in plasma and provides accurate plasma sample B( f) concentrations with a single measurement.
Abstract: BACKGROUND: Hyperbilirubinemia in jaundiced neonates is routinely assessed by use of total serum bilirubin. However, the unbound or free form (Bf), not total bilirubin, crosses the blood–brain barrier and can be neurotoxic. Although the peroxidase-mediated oxidation of bilirubin can be used to measure plasma concentrations of Bf, this measurement is relatively complex and the assay is not routinely used. We describe a fluorescence sensor for quantifying Bf in plasma. METHODS: Our method uses a mutated fatty acid binding protein labeled with the fluorescent molecule acrylodan (BL22P1B11), whose fluorescence is quenched upon binding bilirubin. Another configuration (BL22P1B11-Rh) was developed that uses BL22P1B11 together with the fluorophore rhodamine B, which responds by a change in the ratio of its fluorescence. RESULTS: The “Bf probes” were calibrated with aqueous solutions of bilirubin and yielded similar bilirubin dissociation constants [ K d = 16 (1.5) nmol/L]. We used the probes to determine Bf concentrations in equilibrium with human serum albumin (HSA) and in human plasma samples supplemented with bilirubin. We obtained equivalent Bf values in both systems, and the Bf probe results were in agreement with the peroxidase assay. Bf measurements revealed that bilirubin–HSA binding was well described by 2 sites with K d values of 15.4 (1) nmol/L and 748 (14) nmol/L. We measured Bf concentrations in the range expected in jaundiced neonates with a mean CV of approximately 3%. CONCLUSIONS: The BL22P1B11-Rh probe provides accurate plasma sample Bf concentrations with a single measurement, in 1 min with either a handheld Bf meter or a laboratory fluorometer.

51 citations

Journal ArticleDOI
TL;DR: Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorous-Sulfur Incorporation reagents previously disclosed.
Abstract: Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from trans-limonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Π, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both Π enantiomers are available, only one isomer is required-the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.

51 citations


Authors

Showing all 2327 results

NameH-indexPapersCitations
Eric J. Topol1931373151025
John R. Yates1771036129029
George F. Koob171935112521
Ian A. Wilson15897198221
Peter G. Schultz15689389716
Gerald M. Edelman14754569091
Floyd E. Bloom13961672641
Stuart A. Lipton13448871297
Benjamin F. Cravatt13166661932
Chi-Huey Wong129122066349
Klaus Ley12949557964
Nicholas J. Schork12558762131
Michael Andreeff11795954734
Susan L. McElroy11757044992
Peter E. Wright11544455388
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
20235
202210
202153
202060
201950
201842