gebhart/patrepeval huggingface dataset:
Identification of the Anti-angiogenic Site within Vascular Basement Membrane-derived Tumstatin (2001)

Components of vascular basement membrane are involved in regulating angiogenesis. Recently, tumstatin (the NC1 domain of alpha3 chain of type IV collagen) was identified as possessing anti-angiogenic activity. In the present study, the anti-angiogenic activity of tumstatin was localized to the putative 54-132-amino acid Tum-5 domain, and the activity mediated by alpha(v)beta(3) integrin interaction in an RGD-independent manner. The recombinant Tum-5 produced in Escherichia coli and Pichia Pastoris specifically inhibited proliferation and caused apoptosis of endothelial cells with no significant effect on nonendothelial cells. Tum-5 also inhibited tube formation of endothelial cells on Matrigel and induced G1 endothelial cell cycle arrest. Moreover, anti-angiogenic effect of Tum-5 was also examined in vivo using both a Matrigel plug assay in C57BL/6 mice and human prostate cancer (PC-3) xenografts in nude mice. The in vivo results demonstrate that Tum-5 at 1 mg/kg significantly inhibited growth of PC-3 tumors in association with a decrease in CD31 positive vasculature. These in vivo studies also show that, at molar equivalents, human Tum-5 is at least 10-fold more active than human endostatin. In addition, these studies for the first time suggest that through the action of endogenous inhibitors, alpha(v)beta(3) integrin may also function as a negative regulator of angiogenesis. Taken together, these findings demonstrate that Tum-5, a domain derived from tumstatin, is an effective inhibitor of tumor-associated angiogenesis and a promising candidate for the treatment of cancer.
Three Microsomal Omega‐3 Fatty‐acid Desaturase Genes Contribute to Soybean Linolenic Acid Levels (2003)

Three independent genetic loci have been shown to contribute to soybean [ Glycine max (L.) Merrill] seed linolenic acid levels, including the well‐characterized Fan locus. Linolenic acid is the product of omega‐3 fatty‐acid desaturase enzyme activity. The objective of this study was to identify and characterize the family of soybean omega‐3 fatty‐acid desaturase genes and link them to low seed linolenic acid as a tool for the development of molecular markers for low linolenic acid soybean. Using database homology searches and gene cloning, we identified and characterized three soybean microsomal omega‐3 fatty‐acid desaturase genes that contribute to seed linolenic acid levels. Relative expression was characterized by quantitative real‐time RT‐PCR (reverse transcriptase‐polymerase chain reaction). One of the three genes was predominantly expressed in developing seeds. We determined that the low linolenic acid breeding line A5 ( fan fan ) contains two of the genes, but is missing the third sequence. Therefore, the Fan locus can be definitively assigned to one of the three microsomal omega‐3 fatty‐acid desaturase genes present in the soybean genome. Molecular markers for defects in the three genes will enhance soybean programs breeding for low linolenic acid.
Identification and Characterization of a Membrane Permease Involved in Iron-Hydroxamate Transport in Staphylococcus aureus (2000)

Staphylococcus aureus was shown to transport iron complexed to a variety of hydroxamate type siderophores, including ferrichrome, aerobactin, and desferrioxamine. An S. aureus mutant defective in the ability to transport ferric hydroxamate complexes was isolated from a Tn917-LTV1 transposon insertion library after selection on iron-limited media containing aerobactin and streptonigrin. Chromosomal DNA flanking the Tn917-LTV1 insertion was identified by sequencing of chromosomal DNA isolated from the mutant. This information localized the transposon insertion to a gene whose predicted product shares significant similarity with FhuG of Bacillus subtilis. DNA sequence information was then used to clone a larger fragment of DNA surrounding the fhuG gene, and this resulted in the identification of an operon of three genes, fhuCBG, all of which show significant similarities to ferric hydroxamate uptake (fhu) genes in B. subtilis. FhuB and FhuG are highly hydrophobic, suggesting that they are embedded within the cytoplasmic membrane, while FhuC shares significant homology with ATP-binding proteins. Given this, the S. aureus FhuCBG proteins were predicted to be part of a binding protein-dependent transport system for ferric hydroxamates. Exogenous iron levels were shown to regulate ferric hydroxamate uptake in S. aureus. This regulation is attributable to Fur in S. aureus because a strain containing an insertionally inactivated fur gene showed maximal levels of ferric hydroxamate uptake even when the cells were grown under iron-replete conditions. By using the Fur titration assay, it was shown that the Fur box sequences upstream of fhuCBG are recognized by the Escherichia coli Fur protein.
Identification of Proteins Involved in Microglial Endocytosis of α-Synuclein (2007)

Aggregated alpha-synuclein, a protein playing pivotal roles in the pathogenesis of Parkinson disease (PD) and related synucleinopathy, has been shown to activate microglia, the key cells in neuroinflammation. However, the mechanisms by which aggregated alpha-synuclein enters microglia remain uncharacterized. In this study, we first replicated our previous results with a modified protocol that generated aggregated alpha-synuclein more efficiently. Next, using two recently developed proteomic techniques, SILAC (Stable Isotope Labeling of Amino acid in Cell cultures) and PROCEED (PROteome of Cell Exposed Extracellular Domains), we studied the plasma membrane proteins of primary cultured microglia that might be interacting with aggregated alpha-synuclein and mediating its internalization. The results demonstrated that 250 nM alpha-synuclein, aged for 6 h with a magnetic stir bar, was just as potent in activating microglia as the aggregated alpha-synuclein produced by aging without constant agitation for 7 days. The proteomic analysis identified 111 membrane proteins; of these, 46 proteins were altered in relative abundance in the membrane compartment after treatment with aggregated alpha-synuclein for 3 h. Two of these proteins, clathrin and calnexin, were further evaluated with Western blotting, demonstrating good agreement with quantitative proteomics. Finally, immunocytochemical as well as co-immunoprecipitation studies indicated that clathrin was indeed co-localized with internalized alpha-synuclein in microglia. These results suggest for the first time that microglial activation secondary to internalization of aggregated alpha-synuclein likely requires participation of clathrin, which is an essential protein of the polyhedral coat of coated pits and vesicles that play major roles in endocytosis and vesicular trafficking.
Genetic Immunization of Wild-Type and Hepatitis C Virus Transgenic Mice Reveals a Hierarchy of Cellular Immune Response and Tolerance Induction against Hepatitis C Virus Structural Proteins (2001)

To study the effect of genetic immunization on transgenic expression of hepatitis C virus (HCV) proteins, we evaluated the immunological response of HCV transgenic mice to HCV expression plasmids. FVB/n transgenic mice expressing HCV structural proteins (core, E1, and E2) and wild-type (WT) FVB/n mice were immunized intramuscularly with plasmids expressing core (pHCVcore) or core/E1/E2 (pHCVSt). After immunization, HCV-specific humoral and cellular immune response was studied. Both WT and transgenic mice immunized with either HCV construct produced antibodies and exhibited T-cell proliferative responses against core or envelope. In WT mice immunized with pHCVSt, cytotoxic T-lymphocyte (CTL) activities were detected against E2 but not against core or E1, whereas strong CTL activities against core could be detected in WT mice immunized with pHCVcore. In pHCVSt-immunized, transgenic mice, CTL activities against the core or envelope were completely absent, but core-specific CTL activities could be detected in pHCVcore-immunized transgenic mice. A similar pattern of immune responses was also observed in other mouse strains, including a transgenic line expressing human HLA-A2.1 molecules (AAD mice). Despite the presence of a peripheral cellular immunity against HCV, no liver pathology or lymphocytic infiltrate was observed in these transgenic mice. Our study suggests a hierarchy of CTL response against the HCV structural proteins (E2 > core > E1) in vivo when the proteins are expressed as a polyprotein. The HCV transgenic mice can be induced by DNA immunization to generate anti-HCV antibodies and anticore CTLs. However, they are tolerant at the CTL level against the E2 protein despite DNA immunization.
Heterocyclic ambident nucleophiles. IV. The alkylation of metal salts of adenine (1982)

The N3 : N7 : N9 alkylation patterns for reactions of the lithium, sodium, and potassium salts of adenine with various alkylating agents in dimethyl sulfoxide were determined by 1H n.m.r. spectroscopy. Only for the Li+ salt was any significant effect of ionic association noticed. Of the alkylating agents used, only chloromethyl pivalate gave a concentration dependent alkylation pattern. The latter effect was most pronounced with the heterogeneous alkylation conditions of anhydrous Na2CO3/HCONMe2, adenine, and chloromethyl pivalate; here, increasing concentrations changed the main reaction from N7- to N9-alkylation. Solvent effects on the alkylation patterns were also studied. Within the common dipolar aprotic solvent group, (Me2N)3PO, HCONMe2 and Me2SO, effects were small; in protic solvents, particularly formamide, enhanced N3-alkylation was observed.
Speaker normalization on conversational telephone speech (2002)

This paper reports on a simplified system for determining vocal tract normalization. Such normalization has led to significant gains in recognition accuracy by reducing variability among speakers and allowing the pooling of training data and the construction of sharper models. But standard methods for determining the warp scale have been extremely cumbersome, generally requiring multiple recognition passes. We present a new system for warp scale selection which uses a simple generic voiced speech model to rapidly select appropriate frequency scales. The selection is sufficiently streamlined that it can moved completely into the front-end processing. Using this system on a standard test of the Switchboard Corpus, we have achieved relative reductions in word error rates of 12% over unnormalized gender-independent models and 6% over our best unnormalized gender-dependent models.
Repair of O6‐methyl‐guanine residues in DNA takes place by a similar mechanism in extracts from hela cells, human liver, and rat liver (1982)

Extracts from HeLa S3 cells, human liver, and rat liver were found to contain an activity that transfers the methyl group from O6-methyl-guanine residues in DNA to a cysteine residue of an acceptor protein. The molecular weights of the acceptor proteins in HeLA cells and human liver are 24,000 +/- 1,000 and 23,000 +/- 1,000, respectively. Assuming that each acceptor molecule is used only once, the average number of acceptor molecules in HeLa cells was calculated to be about 50,000. The extracts also contained 3-methyl-adenine-DNA glycosylase activity and 7-methyl-guanine-DNA glycosylase activity, although the latter activity was not detected in extracts from human liver in our assay system. Thus, the three major alkylation products resulting from the effect of methylating agents, such as N-methyl-N-nitroso urea, can all be repaired in animal cells. Pretreatment of HeLa cells with N-methyl-N'-nitro-N-nitrosoguanidine (0.1 micrograms/ml) strongly reduced the capacity of HeLa cell extracts to repair O6-methyl-guanine residues, while the activity of three DNA-N-glycosylases was essentially unaltered. This inactivation was not caused by a direct methylation of the enzyme by the carcinogen. The results demonstrate that the mechanism of repair of O6-methyl-guanine residues in DNA is strikingly similar in E coli and animal cells, including humans.
Multiobjective genetic approach for optimal control of photoinduced processes (2007)

We have applied a multiobjective genetic algorithm to the optimization of multiphoton-excited fluorescence. Our study shows the advantages that this approach can offer to experiments based on adaptive shaping of femtosecond pulses. The algorithm outperforms single-objective optimizations, being totally independent from the bias of user defined parameters and giving simultaneous access to a large set of feasible solutions. The global inspection of their ensemble represents a powerful support to unravel the connections between pulse spectral field features and excitation dynamics of the sample.
Learning Object Arrangements in 3D Scenes using Human Context (2012)

We consider the problem of learning object arrangements in a 3D scene. The key idea here is to learn how objects relate to human poses based on their affordances, ease of use and reachability. In contrast to modeling object-object relationships, modeling human-object relationships scales linearly in the number of objects. We design appropriate density functions based on 3D spatial features to capture this. We learn the distribution of human poses in a scene using a variant of the Dirichlet process mixture model that allows sharing of the density function parameters across the same object types. Then we can reason about arrangements of the objects in the room based on these meaningful human poses. In our extensive experiments on 20 different rooms with a total of 47 objects, our algorithm predicted correct placements with an average error of 1.6 meters from ground truth. In arranging five real scenes, it received a score of 4.3/5 compared to 3.7 for the best baseline method.
Predominant HLA-class II bound self-peptides of a hematopoietic progenitor cell line are derived from intracellular proteins (1996)

Human myeloid progenitor cells temporarily express HLA class II molecules during the differentiation pathway to granulocytes and macrophages. The significance of major histocompatibility complex (MHC) class II molecules at this stage of development is unknown. As a first stop of inquiry into their function, we have characterized the profile of major self-peptides bound to the HLA-DR molecules expressed by KG-1 cells, a line that shares many of the phenotypic characteristics of colony-forming unit-granulocyte-macrophage progenitors. Searches of protein data bases showed that all matching peptides bound to the HLA-DR molecules of KG-1 cells corresponded to intracellular, rather than exogenous or transmembrane, precursor proteins. Because the absence of a conventional self-peptide repertoire could be related to altered trafficking of class II molecules, the biosynthesis of HLA-DR and the invariant chain proteins was determined. The MHC class II associated invariant chain protein is synthesized normally in KG-1 cells, but processed fragments of invariant chain, class II-associated invariant chain peptides (CLIPs), occupy the antigen-binding groove of KG-1 class II molecules at a much lower frequency compared with that of mature antigen-presenting cells. Low CLIP occupancy of HLA-DR is a characteristic shared by KG-1 cells, normal CD34+ progenitor cells, and HLA-DR+ breast carcinoma cells. The unusual profile of MHC class II bound peptides and the low level of CLIP bound to HLA-DR suggest that the antigen-processing pathway of KG-1 is different from that characterized in professional antigen-presenting cells and that exogenous antigen-processing may be a developmentally acquired characteristic in the myeloid lineage.
Evidence from the use of monoclonal antibody probes for structural heterogeneity of the growth hormone receptor (1985)

We describe the use of four monoclonal antibodies (MAbs) to the rabbit liver growth hormone (GH) receptor and one raised against purified rat liver GH receptor to characterize liver receptor subtypes which differ in their hormone-binding regions. The anti-(rat liver GH receptor) MAb both inhibited and precipitated rat and rabbit GH receptors, but only one-half of 125I-oGH (ovine GH) binding to liver microsomes could be inhibited by excess antibody. Conversely, only one-half of 125I-anti-(rat GH receptor) MAb binding was inhibited by excess oGH and Scatchard plots for this MAb exhibited two components. Although only 50% of 125I-oGH binding to membranes was inhibited by this MAb, all solubilized receptor could be immunoprecipitated. We postulate two epitopes for the anti-(rat GH receptor) MAb, one located at the hormone-binding site (inhibitory site) and one elsewhere (immunoprecipitating site). A second, rabbit-specific antibody (MAb 7) inhibited 85% of hormone binding but only 30% of 125I-anti-(rat GH receptor) MAb binding to rabbit liver microsomes. A combination of this MAb with the anti-(rat GH receptor) MAb totally inhibited 125I-oGH binding. MAb 7 alone totally inhibited 125I-rat GH binding to rabbit liver microsomes, as it did with 125I-oGH binding to purified receptor. On the basis of these results and others we postulate three types of GH receptor in rabbit liver membranes and ascribe approximate extents of 125I-oGH binding to each. A cytosolic 'GH receptor' which is not poly(ethylene glycol)-precipitable is shown to share five epitopes with 'type 2' microsomal receptors. Purified plasma membrane and endoplasmic reticulum fractions derived from a rabbit liver microsomal preparation have identical antigenic characteristics with respect to the GH-binding region, indicating that the heterogeneity we describe is not related to receptor processing. Of the three types of GH receptor in the plasma membrane of the rabbit (and possibly rat) we postulate that one (type 1) corresponds to the GH receptor involved in stimulating growth and possesses all of the epitopes studied here. A second (type 2) appears to be identical with the cytosolic 'GH receptor' and lacks the epitope for the anti-(rat GH receptor) MAb in the hormone binding site region. A third (type 3) does not possess the epitope for the inhibitory anti-(rabbit GH receptor) MAb, appears not to bind rat GH and is lost during purification. The availability of type-specific MAbs will facilitate assignment of specific functions to liver receptor subtypes which mediate the multiple functions of GH.
Retinal Disease in Mice Lacking Hypoxia-Inducible Transcription Factor-2α (2005)

HIF-2alpha-KO mice exhibit marked retinopathy consistent with complete loss of vision by 1 month of age. Impaired HIF-2alpha signaling in HIF-2alpha-KO mice likely produces functional deficits in cell types in which HIF-2alpha normally is expressed, ultimately resulting in retinopathy. Future studies will address whether the molecular abnormalities described in this study are directly responsible for the retinal disease in HIF-2alpha-KO mice.
Identification of genes differentially expressed in melanoma sublines derived from a single surgical specimen characterised by different sensitivity to cytotoxic T-lymphocyte activity. (2000)

In this study we used differential display technology in an attempt to obtain an insight into the mechanisms underlying escape of tumour cells to the specific cytotoxic T cell response. A primary tumour cell line and autologous tumour infiltrating lymphocytes were raised from a metastatic melanoma sample (ME15). Upon co-culture of tumour infiltrating lymphocytes with irradiated tumour cells, CTL specific for neoplastic cells were generated and cloned. Using a CTL clone, a cytotoxicity resistant tumour subline (ME15R) was immunoselected. We applied a PCR-based differential display technique to amplify DNA sequences differentially expressed in ME15 sublines sensitive (S) or resistant (R) to specific CTL killing. 10 different sequences whose expression was exclusively detectable in ME15S cells were identified. Five of them matched with known expressed sequence tags encoding products of unidentified function. 2 showed high homology with a mitochondrial mRNA and with the gene encoding the S24 ribosomal protein. Most interestingly, genes coding for glutamine synthetase, TGF-beta-3 and PAX3, a well-characterised transcription factor, were only expressed in ME15S cells. The latter gene was found to be transcribed in all healthy tissues tested, but only in a subgroup of established melanoma cell lines. Taken together, our data underline the relevant potential of differential display technology in the molecular analysis of paired tumour lines endowed with different phenotypic characteristics. Cloning of entire open reading frames and transfection studies are warranted to clarify the role of individual differentially displayed genes in the escape of tumour cells from cellular immune response.
Carbon−Heteroatom Bond-Forming Reductive Eliminations of Amines, Ethers, and Sulfides (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon−Heteroatom Bond-Forming Reductive Eliminations of Amines, Ethers, and SulfidesJohn F. HartwigView Author Information Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520-8107 Cite this: Acc. Chem. Res. 1998, 31, 12, 852–860Publication Date (Web):September 4, 1998Publication History Received6 April 1998Published online4 September 1998Published inissue 1 December 1998https://doi.org/10.1021/ar970282gCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views10797Altmetric-Citations1008LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (384 KB) Get e-AlertsSUBJECTS:Amines,Ethers,Ligands,Reductive elimination,Sulfides Get e-Alerts
Vertically integrated silicon-on-insulator waveguides (1991)

A SiO/sub 2/-Si-SiO/sub 2/-Si-SiO/sub 2/-Si structure produced by the separation by implantation of oxygen (SIMOX) process used for dual vertically integrated waveguiding in silicon at lambda =1.3 mu m is discussed. Independent waveguiding is observed when 2- mu m-thick Si cores are separated by 0.36- mu m-thick SiO/sub 2/. Coupled waveguiding is found for an 0.12- mu m intercore oxide thickness.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>