gebhart/patrepeval huggingface dataset:
Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2 (2003)

The antiangiogenic factor thrombospondin 1 (TSP-1) binds with high affinity to several heparin-binding angiogenic factors, including fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), and hepatocyte growth factor/scatter factor (HGF/SF). The aim of this study was to investigate whether TSP-1 affects FGF-2 association with the extracellular matrix (ECM) and its bioavailability. TSP-1 prevented the binding of free FGF-2 to endothelial cell ECM. It also promoted the mobilization of matrix-bound FGF-2, generating a TSP-1/FGF-2 complex. The region of TSP-1 responsible for these activities was located within the 140-kDa antiangiogenic and FGF-2 binding fragment, whereas the 25-kDa heparin-binding fragment was inactive. Matrix-released FGF-2/TSP-1 complex had a reduced ability to bind to and induce proliferation of endothelial cells. TSP-1 depleted the ECM laid by FGF-2-overproducing tumor cells of its FGF-2-dependent mitogenic activity for endothelial cells. Besides FGF-2, TSP-1 also inhibited VEGF and HGF/SF binding to the ECM and mobilized them from the ECM. Our study shows that TSP-1 acts as a scavenger for matrix-associated angiogenic factors, affecting their location, bioavailability, and function.
A Borrelia-specific monoclonal antibody binds to a flagellar epitope (1986)

In immunofluorescence assays monoclonal antibody H9724 recognized eight species of the spirochetal genus Borrelia but not representatives of the genera Treponema, Leptospira, and Spirochaeta. We examined the reactivity of H9724 against subcellular components of Borrelia hermsii, an agent of relapsing fever, and B. burgdorferi, the cause of Lyme disease. H9724 bound to isolated periplasmic flagella of the two borreliae. In Western blots the antibody reacted with the predominant protein in flagellar preparations from B. hermsii and B. burgdorferi; the apparent molecular weights of these flagellins were 39,000 and 41,000, respectively.
Clinical Evaluation of Anti-Tuberculous Glycolipid Immunoglobulin G Antibody Assay for Rapid Serodiagnosis of Pulmonary Tuberculosis (2001)

Previously we reported the development of a highly sensitive enzyme-linked immunosorbent assay specific for anti-tuberculous glycolipid (anti-TBGL) for the rapid serodiagnosis of tuberculosis. In this study, the usefulness of an anti-TBGL antibody assay kit for rapid serodiagnosis was evaluated in a controlled multicenter study. Antibody titers in sera from 318 patients with active pulmonary tuberculosis (216 positive for Mycobacterium tuberculosis in smear and/or culture tests and 102 smear and culture negative and clinically diagnosed), 58 patients with old tuberculosis, 177 patients with other respiratory diseases, 156 patients with nonrespiratory diseases, and 454 healthy subjects were examined. Sera from 256 younger healthy subjects from among the 454 healthy subjects were examined as a control. When the cutoff point of anti-TBGL antibody titer was determined as 2.0 U/ml, the sensitivity for active tuberculosis patients was 81.1% and the specificity was 95.7%. Sensitivity in patients with smear-negative and culture-negative active pulmonary tuberculosis was 73.5%. Even in patients with noncavitary minimally advanced lesions, the positivity rate (60.0%) and the antibody titer (4.6 +/- 9.4 U/ml) were significantly higher than those in the healthy group. These results indicate that this assay using anti-TBGL antibody is useful for the rapid serodiagnosis of active pulmonary tuberculosis.
METAL ION SELECTIVITY OF MACRORETICULAR CHELATING CATION EXCHANGE RESINS WITH PHOSPHONIC ACID GROUPS ATTACHED TO PHENYL GROUPS OF A STYRENE-DIVINYLBENZENE COPOLYMER MATRIX (2001)

To clarify the metal ion selectivity sequence of the phosphonic acid resin named RSPO, in which the functional groups were introduced into phenyl groups of a macroreticular poly(styrene-co-divinylbenzene) matrix, the distribution of 20 kinds of metal ions from 0.0001 mol/L solution of each metal ion onto RSPO was studied in nitric, hydrochloric, sulfuric, and phosphoric acid media. Distribution ratios of divalent metal ions Ba(II), Ca(II), Cd(II), Co(II), Cu(II), Mg(II), Mn(II), Ni(II), Pb(II), Sr(II), and Zn(II) normally decreased with solutions of increased acidity and were not significantly affected by acid species. The clear effect of acid species was observed in the distribution of Fe(III), Mo(VI), and U(VI); although their distributions from hydrochloric and sulfuric acid media normally decreased with increasing acidity of solutions, the minimum was observed in their distribution from nitric acid media, indicating that they were distributed onto the resin from approximately 6 mol/L nitric acid through the mechanism similar to solvation extraction of their nitrate complexes with organophosphorous compounds. Phosphoric acid markedly depressed the distribution of Fe(III), Mo(VI), and U(VI) but not the distribution of Al(III), Bi(III), Cr(III), Gd(III), La(III), and Lu(III). The overall metal ion selectivity sequence of RSPO is the order of Mo(VI) ≅ Fe(III) ≅ U(VI) > Bi(III) ≅ Lu(III) > Al(III) ≅ Gd(III) > La(III) > Cr(III) > Pb(II) > Mn(II) ≅ Cd(II) ≅ Cu(II) > Ca(II) ≅ Co(II) ≅ Zn(II) ≅ Ba(II) ≅ Sr(II) > Ni(II) ≅ Mg(II). The metal ion selectivity sequence was also illustrated on the basis of uptake of U(VI), Pb(II), Ca(II), Ba(II), Ni(II) from 0.01 mol/L solutions of each metal ion.
Effect of reduced oxygen tension on chondrogenesis and osteogenesis in adipose-derived mesenchymal cells (2005)

Recent studies have demonstrated that adipose-derived mesenchymal cells (AMCs) offer great promise for cell-based therapies because of their ability to differentiate toward bone, cartilage, and fat. Given that cartilage is an avascular tissue and that mesenchymal cells experience hypoxia during prechondrogenic condensation in endochondral ossification, the goal of this study was to understand the influence of oxygen tension on AMC differentiation into bone and cartilage. In vitro chondrogenesis was induced using a three-dimensional micromass culture model supplemented with TGF-beta1. Collagen II production and extracellular matrix proteoglycans were assessed with immunohistochemistry and Alcian blue staining, respectively. Strikingly, micromasses differentiated in reduced oxygen tension (2% O(2)) showed markedly decreased chondrogenesis. Osteogenesis was induced using osteogenic medium supplemented with retinoic acid or vitamin D and was assessed with alkaline phosphatase activity and mineralization. AMCs differentiated in both 21 and 2% O(2) environments. However, osteogenesis was severely diminished in a low-oxygen environment. These data demonstrated that hypoxia strongly inhibits in vitro chondrogenesis and osteogenesis in AMCs.
The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States (2007)

The Cost of Pushing Pills: A New Estimate of Pharmaceutical Promotion Expenditures in the United States
Synthesis of the membrane fusion and hemagglutinin proteins of measles virus, using a novel baculovirus vector containing the beta-galactosidase gene (1990)

An improved baculovirus expression vector was developed to expedite screening and facilitate oligonucleotide-directed mutagenesis. This vector contained twin promoters derived from the P10 and polyhedrin genes of Autographica californica nuclear polyhedrosis virus. The P10 promoter directed the synthesis of beta-galactosidase, whereas the polyhedrin promoter controlled the synthesis of foreign gene products. These two genes recombined with wild-type virus genome to yield recombinants which were polyhedrin negative, produced the foreign gene product, and formed blue plaques when beta-galactosidase indicator was present in the agarose overlay. An origin of replication derived from M13 or f1 bacteriophage was also included in the plasmid to permit the synthesis of single-stranded DNA. This template DNA was used to introduce or delete sequences through the process of site-specific mutagenesis. The measles virus virion possesses a membrane envelope which contains two glycoproteins: the hemagglutinin (H) and membrane fusion (F) proteins. The H polypeptide has receptor-binding and hemagglutinating activity, whereas the F protein mediates virus penetration of the host cell, formation of syncytia, and hemolysis of erythrocytes. Genes for these two glycoproteins were inserted into the NheI cloning site of the modified expression vector described above. The vector and purified wild-type viral DNA were introduced into Sf9 insect cells by calcium phosphate precipitation. A mixture of wild-type and recombinant virus was generated and used to infect Sf9 cells, which were subsequently overlaid with agarose. After 3 days, 0.1 to 1% of the plaques became blue in the presence of beta-galactosidase indicator. At least 70% of these blue viral colonies contained the foreign gene of interest as determined by dot blot analysis. Recombinant virus was separated from contaminating wild-type virus through several rounds of plaque purification. Insect cells were then infected with the purified recombinants, and synthesis of H and F proteins were verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot detection and Coomassie blue staining. Glycosylation of the proteins appeared to be impaired somewhat, and the precursor to the F protein was not completely cleaved by the proteases present in insect host cells. On the other hand, both proteins appeared to be active in hemagglutination, hemolysis, and cell fusion assays. Levels of synthesis were in the order of 50 to 150 mg of protein per 10(8) cells.
Feasibility of a serverless distributed file system deployed on an existing set of desktop PCs (2000)

We consider an architecture for a serverless distributed file system that does not assume mutual trust among the client computers. The system provides security, availability, and reliability by distributing multiple encrypted replicas of each file among the client machines. To assess the feasibility of deploying this system on an existing desktop infrastructure, we measure and analyze a large set of client machines in a commercial environment. In particular, we measure and report results on disk usage and content; file activity; and machine uptimes, lifetimes, and loads. We conclude that the measured desktop infrastructure would passably support our proposed system, providing availability on the order of one unfilled file request per user per thousand days.
Dopamine‐Melanin Colloidal Nanospheres: An Efficient Near‐Infrared Photothermal Therapeutic Agent for In Vivo Cancer Therapy (2012)

A new generation of photothermal therapeutic agents based on biopolymer dopamine-melanin colloidal nanospheres is described. Benefitting from their naturally wide distribution in humans, dopamine-melanin colloidal nanospheres exhibit robust biocompatibility and biodegradability, and provide up to 40% photothermal conversion efficiency. After administration, they can efficiently damage tumors at low power density and short irradiation time without damaging healthy tissues.
Synthesis of 1,4-Diaminocyclitols From l-Serine Methyl Ester (1996)

l-Serine methyl ester hydrochloride was converted to (S)-2-[N-(benzyloxycarbonyl)amino]-3-(tert-butyldimethylsiloxy)propanal (6). Homocoupling of 6 promoted by [V2Cl3(THF)6]2[Zn2Cl6] (1) gave C2-symmetric diol (7). After manipulation of protecting groups and Swern oxidation, 7 was converted to a 1,6-dialdehyde 10. Intramolecular pinacol coupling of 10 with 1 gave a selectively protected 1,4-diamino-2,3,5,6-tetrahydroxycyclohexane, which is the key skeleton of Fortimicin AM and AK.
Evaluation of a Subcutaneous Glucose Sensor out to 3 Months in a Dog Model (1994)

Further development of this type of sensor may provide diabetic patients with a better means of monitoring blood glucose.
Concerted nicking of donor and chromosomal acceptor DNA promotes homology-directed gene targeting in human cells (2011)

The exchange of genetic information between donor and acceptor DNA molecules by homologous recombination (HR) depends on the cleavage of phosphodiester bonds. Although double-stranded and single-stranded DNA breaks (SSBs) have both been invoked as triggers of HR, until very recently the focus has been primarily on the former type of DNA lesions mainly due to the paucity of SSB-based recombination models. Here, to investigate the role of nicked DNA molecules as HR-initiating substrates in human somatic cells, we devised a homology-directed gene targeting system based on exogenous donor and chromosomal target DNA containing recognition sequences for the adeno-associated virus sequence- and strand-specific endonucleases Rep78 and Rep68. We found that HR is greatly fostered if a SSB is not only introduced in the chromosomal acceptor but also in the donor DNA template. Our data are consistent with HR models postulating the occurrence of SSBs or single-stranded gaps in both donor and acceptor molecules during the genetic exchange process. These findings can guide the development of improved HR-based genome editing strategies in which sequence- and strand-specific endonucleolytic cleavage of the chromosomal target site is combined with that of the targeting vector.
Studies on acousto-optical interaction in epitaxial thin film heterostructures (1999)

Thin film epitaxial heterostructures consisting of and /Si have been studied theoretically with interdigital transducer (IDT) electrodes at various locations. The thickness of each individual layer has been optimized for achieving an efficient SAW performance with a high electromechanical coupling coefficient. The structural feasibility and practical implications of various device configurations for an acousto-optical device are discussed. The introduction of a thin non-piezoelectric over-layer onto a piezoelectric film is found to enhance the electromechanical coupling coefficient . In a symmetrical /IDT/ waveguide structure the maximum value of is found to increase from 2.438 to 9.23% for a variation in the thickness of the over-layer in the range 0-0.12. Symmetrical and asymmetrical waveguide structures formed with and thin films in combination have been examined and a symmetrical waveguide structure (/IDT//Si) is found to exhibit a high acousto-optical figure of merit and % for a device operating with the fundamental mode at wavelength m.
RhoA and Rho Kinase-dependent Phosphorylation of Moesin at Thr-558 in Hippocampal Neuronal Cells by Glutamate (2002)

When we were studying phosphorylated proteins in the rat brain after electroconvulsive shock (ECS), we observed the rapid phosphorylation of a 75-kDa protein, which cross-reacted with the anti-phospho-p70 S6 kinase antibody. The phosphorylated protein was purified and identified as moesin, a member of the ezrin/radixin/moesin (ERM) family and a general cross-linker between cortical actin filaments and plasma membranes. The purified moesin from rat brain was phosphorylated at serine and threonine residues. Moesin was rapidly phosphorylated at the threonine 558 residue after ECS in the rat hippocampus, peaked at 1 min, and returned to the basal level by 2 min after ECS. To investigate the mechanism of moesin phosphorylation in neuronal cells, we stimulated a rat hippocampal progenitor cell, H19-7/IGF-IR, with glutamate, and observed the increased phosphorylation of moesin at Thr-558. Glutamate transiently activated RhoA, and constitutively active RhoA increased the basal level phosphorylation of moesin. The inhibition of RhoA and its effector, Rho kinase, abolished increased Thr-558 phosphorylation by glutamate in H19-7/IGF-IR cells, suggesting that the phosphorylation of moesin at Thr-558 in H19-7/IGF-IR cells by glutamate is mediated by RhoA and Rho kinase activation.
Evaluation of alternative approaches for the synthesis of macrocyclic bisindolylmaleimides (2004)

Approaches for the synthesis of macrocyclic bisindolylmaleimides, in which the indole nitrogens are linked with a tether, are described. Two alternative approaches were investigated: macrocyclisation in either the 'southern' (by adding the tether to the bisindolylmaleimide ring system) or the 'northern' district. With two-, three- and four-atom tethers, both of these approaches were unsuccessful for a wide range of attempted macrocyclisation reactions (palladium-catalysed pi-allyl substitution, ring-closing metathesis, McMurry reaction, iodocyclisation, formation of a silylene derivative, substitution of an alpha,omega-disubstituted electrophile). The failure of all of these reactions was ascribed to the strained nature of the target ring system. However, with longer tethers (six to ten atoms), the macrocycles could prepared using either a ring-closing metathesis reaction or by substitution of an alpha,omega-dibromide). Fourteen successful macrocyclisation reactions are described; deprotection gave eleven macrocyclic bisindolylmaleimides in which an imide substituent had been removed.
Encapsulation of Proteins in Transparent Porous Silicate Glasses Prepared by the Sol-Gel Method (1992)

Novel sol-gel synthetic techniques were used to immobilize copper-zinc superoxide dismutase (CuZnSOD), cytochrome c, and myoglobin (Mb) by encapsulation in stable, optically transparent, porous silica glass matrices under mild conditions such that the biomolecules retained their characteristic reactivities and spectroscopic properties. The resulting glasses allowed transport of small molecules into and out of the glasses at reasonable rates but nevertheless retained the protein molecules within their pores. Chemical reactions of the immobilized proteins could be monitored by means of changes in their visible absorption spectra. Silica glasses containing the immobilized proteins were observed to have similar reactivities and spectroscopic properties to those found for the proteins in solution. For example, encapsulated CuZnSOD was demetallated and remetallated, encapsulated ferricytochrome c was reduced and then reoxidized, and encapsulated met Mb was reduced to deoxy Mb and then reacted either with dioxygen to make oxy Mb or with carbon monoxide to make carbonyl Mb.
Regulation of differentiation of vascular smooth muscle cells (1995)

The vascular smooth muscle cell (SMC) in mature animals is a highly specialized cell whose principal function is contraction. The fully differentiated or mature SMC proliferates at an extremely low rate and is a cell almost completely geared for contraction. It expresses a unique repertoire of contractile proteins, ion channels, and signaling molecules that are required for its contractile function and that when taken in aggregate clearly distinguish it from any other cell type. During vasculogenesis, however, the SMC's principal function is proliferation and production of matrix components of the blood vessel wall. Moreover, even in mature animals, the SMC retains remarkable plasticity, such that it can undergo relatively rapid and reversible changes in its phenotype in response to changes in local environmental cues normally required for maintenance of its differentiated state. A key to understanding SMC differentiation is to identify the key environmental signals and factors that induce or maintain the differentiated state of the SMC and to determine the molecular mechanisms that control the coordinate expression of genes encoding for proteins that are necessary for the contractile function of the SMC. The purpose of this review is to summarize our current knowledge of the regulation of SMC differentiation, with a particular emphasis on consideration of how this process is controlled during normal vascular development and how these control processes might be altered in vascular diseases such as atherosclerosis, which are characterized by marked alterations in the differentiated state of the SMC.
Design and Discovery of Small Molecules Targeting Raf-1 Kinase (2002)

Raf kinase, an enzyme which acts downstream in the Ras signaling pathway, is involved in cancerous cell proliferation. Thus, small molecule inhibitors of Raf kinase activity may be important agents for the treatment of cancer. A novel class of Raf-1 inhibitors was discovered, using a combination of medicinal and combinatorial chemistry approaches. This effort culminated in the identification of the clinical candidate BAY 43-9006, currently undergoing Phase I clinical trials. The present review summarizes the medicinal chemistry development of ureas as highly potent inhibitors of Raf-1 kinase. Keywords: diphenyl ureas, bay 43-9006, raf-1 kinase, cancer, ras
Structure and expression of the mutant prealbumin gene associated with familial amyloidotic polyneuropathy. (1986)

We have cloned a chromosomal DNA segment that covers the entire sequence for the mutant prealbumin gene associated with familial amyloidotic polyneuropathy, and determined the sequence of the gene including 581 base-pairs of the 5'-flanking region and 95 base-pairs of the 3'-flanking region, except for the internal portions of the second and third introns. This sequence was aligned with that of the previously determined normal prealbumin gene and both sequences matched perfectly except for a single-base substitution present in the second exon. This substitution is responsible for the transition from valine (GTG) to methionine (ATG) in the mutant prealbumin and creates NsiI and BalI restriction sites in the mutant prealbumin gene. We also analysed prealbumin mRNAs in the livers of a disease-free individual and one with familial amyloidotic polyneuropathy and confirmed that there is no difference in the levels and sizes of the prealbumin mRNAs between the two. As we have demonstrated already that individuals with familial amyloidotic polyneuropathy are heterozygous for the prealbumin gene, carrying one normal and one mutant gene, levels of the two different mRNAs within the liver of an individual with familial amyloidotic polyneuropathy were separately estimated and were demonstrated to be approximately equal.