gebhart/patrepeval huggingface dataset:
Oxidation of dihydropyridine calcium channel blockers and analogs by human liver cytochrome P-450 IIIA4 (1991)

A series of 21 different 4-substituted 2,6-dimethyl-3-(alkoxycarbonyl)-1,4-dihydropyridines was considered with regard to oxidation to pyridine derivatives by human liver microsomal cytochrome P-450 (P-450). Antibodies raised against P-450 IIIA4 inhibited the microsomal oxidation of nifedipine and felodipine to the same extent, as did cimetidine and the mechanism-based inactivator gestodene. Gestodene was approximately 10(3) times more effective an inhibitor than cimetidine, on a molar basis. When rates of oxidation of the 1,4-dihydropyridines were compared to each other in different human liver microsomal preparations, all were highly correlated with each other with the exceptions of a derivative devoid of a substituent at the 4-position and an N1-CH3 derivative. A P-450 IIIA4 cDNA clone was expressed in yeast and the partially purified protein was used in reconstituted systems containing NADPH-cytochrome P-450 reductase and cytochrome b5. This system catalyzed the oxidation of all of the 1,4-dihydropyridines except the two for which poor correlation was seen in the liver microsomes. Principal component analysis supported the view that most of these reactions were catalyzed by the same enzyme in the yeast P-450 IIIA4 preparation and in the different human liver microsomal preparations, or by a closely related enzyme showing nearly identical properties of catalytic specificity and regulation. The results indicate that the enzyme P-450 IIIA4 is probably the major human catalyst involved in the formal dehydrogenation of most but not all 1,4-dihydropyridine drugs.
Glioma-derived exosomes drive the differentiation of neural stem cells to astrocytes (2020)

Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, colony stimulating factor and interleukin 6 of the STAT3 family and Hes family bHLH transcription factor 1 also increased by 2.3, 10, 4.7 and 2.9 fold, respectively. We further examined the effects of these exosomes on rat fetal neural stem cell (rNSC) differentiation using the secreted exosomes from U87 glioma cells or exosomes from U87 cells that were stimulated with interleukin 1β (IL-1β). The rNSCs, extracted from rat brains at embryonic day 14 (E14), underwent a culture protocol that normally leads to predominant (~90%) differentiation to ODCs. However, in the presence of the exosomes from untreated or IL-1β-treated U87 cells, significantly more cells differentiated into astrocytes, especially in the presence of exosomes obtained from the IL-1β-challenged glioma cells. Moreover, glioma-derived exosomes appeared to inhibit rNSC differentiation into ODCs or astrocytes as indicated by a significantly increased population of unlabeled cells. A portion of the resulting astrocytes co-expressed both CD133 and glial fibrillary acidic protein (GFAP) suggesting that exosomes from U87 cells could promote astrocytic differentiation of NSCs with features expected from a transformed cell. Our data clearly demonstrated that exosomes secreted by human glioma cells provide a strong driving force for rat neural stem cells to differentiate into astrocytes, uncovering potential pathways and therapeutic targets that might control this aggressive tumor type.
Regulation of Hypoxia-Inducible mRNAs by the von Hippel-Lindau Tumor Suppressor Protein Requires Binding to Complexes Containing Elongins B/C and Cul2 (1998)

The von Hippel-Lindau tumor suppressor protein (pVHL) binds to elongins B and C and posttranscriptionally regulates the accumulation of hypoxia-inducible mRNAs under normoxic (21% O2) conditions. Here we report that pVHL binds, via elongin C, to the human homolog of the Caenorhabditis elegans Cul2 protein. Coimmunoprecipitation and chromatographic copurification data suggest that pVHL-Cul2 complexes exist in native cells. pVHL mutants that were unable to bind to complexes containing elongin C and Cul2 were likewise unable to inhibit the accumulation of hypoxia-inducible mRNAs. A model for the regulation of hypoxia-inducible mRNAs by pVHL is presented based on the apparent similarity of elongin C and Cul2 to Skp1 and Cdc53, respectively. These latter proteins form complexes that target specific proteins for ubiquitin-dependent proteolysis.
Intrinsically disordered sequences enable modulation of protein phase separation through distributed tyrosine motifs (2017)

Liquid-liquid phase separation (LLPS) is thought to contribute to the establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules. To understand how folded domains and IDRs can cooperate to modulate LLPS, we generated a series of engineered proteins. These were based on fusions of an IDR derived from the RNA granule protein FUS (fused in sarcoma) to a multivalent poly-Src homology 3 (SH3) domain protein that phase-separates when mixed with a poly-proline-rich-motif (polyPRM) ligand. We found that the wild-type IDR promotes LLPS of the polySH3-polyPRM system, decreasing the phase separation threshold concentration by 8-fold. Systematic mutation of tyrosine residues in Gly/Ser-Tyr-Gly/Ser motifs of the IDR reduced this effect, depending on the number but not on the position of these substitutions. Mutating all tyrosines to non-aromatic residues or phosphorylating the IDR raised the phase separation threshold above that of the unmodified polySH3-polyPRM pair. These results show that low-complexity IDRs can modulate LLPS both positively and negatively, depending on the degree of aromaticity and phosphorylation status. Our findings provide plausible mechanisms by which these sequences could alter RNA granule properties on evolutionary and cellular timescales.
Ramucirumab (IMC-1121B): A Novel Attack on Angiogenesis (2010)

Angiogenesis is a critical hallmark of malignancy, and attempts to inhibit this process have characterized the age of biologic anticancer therapies for solid tumors. VEGF receptor-2 is the premier receptor responsible for many of the cancer-driven VEGF-induced spectrum of biologic changes, including modification of blood vessel structure and function, proliferation and migration. Unlike all clinically approved angiogenesis inhibitors, the fully human monoclonal antibody ramucirumab (IMC-1121B) specifically and potently inhibits VEGF receptor-2. Phase I clinical trials have shown safety across a wide range of ramucirumab doses with impressive, albeit early, evidence of both stable disease and partial responses in a variety of tumor types. In this article, we review the current data on ramucirumab and make comparisons with commercially available antiangiogenic agents.
Quantitative research on tight oil microscopic state of Chang 7 Member of Triassic Yanchang Formation in Ordos Basin, NW China (2015)

With nuclear magnetic resonance (NMR) and micrometer-nanometer CT Scanning technology, quantitative research was carried out of the micro-existing state of tight oil in the Chang7 Member of the Triassic Yanchang Formation in the Ordos Basin. The total reserves of the tight oil in the reservoirs were determined using NMR technology. The initial oil saturation was measured as 63.99%. The 2-D slice images of the tight oil reservoirs were obtained using CT Scanning technology, and the 3-D images were acquired after digital synthesis processing. Accordingly, the existence states of the tight oil in the reservoirs are divided into six types, namely thin film form, cluster form, throat form, emulsion form, particle form and isolation form. It is found by quantitative calculation of the contents of tight oil in different existence states of tight oil that the emulsion form and thin film form are the main existence states, which account for 70% of the total amount of the tight oil in the reservoirs, followed by the cluster and particle forms. The contents of isolation form and throat form tight oil are low. The contents of tight oil in various existence states are related to initial water saturation, clay mineral content and pores structure of the reservoirs.
Switched parasitic elements for antenna diversity (1999)

Switched parasitic elements provide a useful implementation of antenna pattern diversity. The basic principle is presented with some examples of wire antennas computed using the method of moments. The modeled diversity gain available from selection combining of uncorrelated signals is used to quantify the expected improvement relative to nondiversity antennas. The advantage of the switched parasitic concept is that it is a relatively simple system, which can give the adaptive antenna performance of many branch selection or switched diversity.
Nickel(0)-catalyzed alternating copolymerization of carbon dioxide with diynes to poly(2-pyrones) (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNickel(0)-catalyzed alternating copolymerization of carbon dioxide with diynes to poly(2-pyrones)Tetsuo Tsuda, Kenichi Maruta, and Yukio KitaikeCite this: J. Am. Chem. Soc. 1992, 114, 4, 1498–1499Publication Date (Print):February 1, 1992Publication History Published online1 May 2002Published inissue 1 February 1992https://pubs.acs.org/doi/10.1021/ja00030a065https://doi.org/10.1021/ja00030a065research-articleACS PublicationsRequest reuse permissionsArticle Views358Altmetric-Citations52LEARN 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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Synergistic Re-Activation of Epigenetically Silenced Genes by Combinatorial Inhibition of DNMTs and LSD1 in Cancer Cells (2013)

Epigenetic gene silencing, mediated by aberrant promoter DNA hypermethylation and repressive histone modifications, is a hallmark of cancer. Although heritable, the dynamic nature and potential reversibility through pharmacological interventions make such aberrations attractive targets. Since cancers contain multiple epigenetic abnormalities, combining therapies that target different defects could potentially enhance their individual efficacies. 5-Aza-2'-deoxycytidine (5-Aza-CdR), FDA-approved drug for the treatment of myelodysplastic syndrome, can inhibit DNA methyltransferases (DNMTs) upon incorporation into the DNA of dividing cells, resulting in global demethylation. More recently, the first histone demethylase, lysine specific demethylase 1 (LSD1), which demethylates both histone and non-histone substrates, has become a new target for epigenetic therapy. Using, clorgyline, an LSD1 inhibitor (LSD1i) to treat cancer cell lines, we show that clorgyline employs two mechanisms of action depending on the cell type: it can either induce global DNA demethylation or inhibit LSD1-driven H3K4me2 and H3K4me1 demethylation to establish an active chromatin configuration. We also investigate the therapeutic efficacy of combining 5-Aza-CdR with clorgyline and determine that this combinatorial treatment has synergistic effects on reactivating aberrantly silenced genes by enriching H3K4me2 and H3K4me1. Many of the reactivated genes are categorized as cancer testis antigens or belong to the interferon-signaling pathway, suggesting potential implications for immunotherapy. Together, our results demonstrate that combinatorial treatment consisting of a DNMT inhibitor (DNMTi) and an LSD1i have enhanced therapeutic values and could improve the efficacy of epigenetic therapy.
Models for metal binding sites in zinc enzymes. Syntheses of tris[4(5)-imidazolyl]carbinol (4-TIC), tris(2-imidazolyl)carbinol (2-TIC), and related ligands, and studies on metal complex binding constants and spectra (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModels for metal binding sites in zinc enzymes. Syntheses of tris[4(5)-imidazolyl]carbinol (4-TIC), tris(2-imidazolyl)carbinol (2-TIC), and related ligands, and studies on metal complex binding constants and spectraChaucer C. Tang, Dariush Davalian, Paul Huang, and Ronald BreslowCite this: J. Am. Chem. Soc. 1978, 100, 12, 3918–3922Publication Date (Print):June 1, 1978Publication History Published online1 May 2002Published inissue 1 June 1978https://pubs.acs.org/doi/10.1021/ja00480a043https://doi.org/10.1021/ja00480a043research-articleACS PublicationsRequest reuse permissionsArticle Views1098Altmetric-Citations98LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Graft chimeras and somatic hybrids for new cultivars (1995)

Abstract Three techniques were evaluated as methods for plant improvement: protoplast fusion in vitro for somatic hybrids, protoplast co‐culture in vitro for chimeras, and graft manipulation in planta for periclinal chimeras. Methods were developed initially for herbaceous, solanaceous species and then evaluated on two species of woody Actinidia . Protoplasts from tomato (2 n = 24) and Bü (a Solanum hybrid obtained by fusing nightshade and dihaploid potato protoplasts, 2 n = 96) were fused at laboratories located at Kiel, Germany, and Levin, New Zealand. Identical methods were used at each laboratory, and plants were regenerated from the hybrid callus. At Kiel, only 1.6% of the regenerants were symmetric fusions that contained 120 chromo somes. One chimeric plant remained genomically stable during 3 years of in vitro growth and a further year in the glasshouse. At Levin, 83% of regenerants were asymmetric fusions with additional nightshade or Bii genomes. Some regenerants, however, contained a single nightshade genome. Protoplasts from Actinidia were fused using the methods detailed for the solanaceous plants, but regeneration of plants was not achieved. Chimeric plants were obtained by co‐culturing Bü and tomato plants. At Kiel, 2.1% of the regenerants were chimeric. Co‐cultures of protoplasts between Actinidia arguta and A. deliciosa , at Levin, did not produce regenerative callus. Periclinal chimeras were sought from in planta grafts between tomato and nightshade. Two chimeric shoots were obtained. On the basis of epidermal hair type, pollen compatibility, seed and fruit set, one chimera had the histogenic LI layer of nightshade over LII and LIII histogenic layers of tomato (NTT), and the other had two layers of nightshade over one layer of tomato (NNT). Chimera NTT was more stable than NNT, but both produced axillary shoots with characteristics of the other chimera. Periclinal chimeras were also sought from graft unions in planta and in vitro between A. arguta and A. deliciosa . From in planta grafts, all adventitious shoots were A. arguta . From in vitro grafts, 75% of the shoots that regenerated were A. deliciosa and none was chimeric. Each of these techniques has the potential to produce new plants. However, the probability of success was low and therefore a large number of regenerants would be required from which to select the desired plants.
Assessment of cancer and virus antigens for cross-reactivity in human tissues (2016)

Our method is implemented as a Java program, with curated datasets stored in a MySQL database. It predicts all naturally possible self-antigens for a given sequence of a therapeutic antigen (or epitope) and after filtering for predicted immunogenicity outputs results as an index and profile of CR to the self-antigens in 22 human tissues. The program is implemented as part of the iCrossR webserver, which is publicly available at http://webclu.bio.wzw.tum.de/icrossr/ CONTACT: d.frishman@wzw.tum.deSupplementary information: Supplementary data are available at Bioinformatics online.
Structure of a furo[3,2-b]pyrrole derivative (1988)

C 9 H 9 NO 3 cristallise dans P2 1 /n avec affinement jusqu'a 0,048. Les deux heterocycles ont une structure quasiment plane. Les molecules sont reliees par liaison hydrogene
Bi-directional high-voltage DC-DC-converter for advanced railway locomotives (2010)

Increase of power demands of DC electric locomotives requires increasing catenaries voltage (which presently is 3 kV, 1.5 kV and 0.75 kV, respectively) 4, 6, 8, 10 times and more. At the traction substation, the rectifier will be adapted. The existing traction contact network (catenaries) is kept for direct current, and the novel N-cell dc/dc bidirectional converter without transformer will be located on the electric locomotive. Each cell voltage is defined by the locomotive power train DC input level, thus balancing of capacitor voltages is not required. Simulation results of the proposed 6-cell converter have confirmed the validity of predicted properties of the converter. Realization of a 10 kW model unit has been already started. The proposed converter added with four alternating current valves and the reversible rectifier, allows implementing of the galvanic separation of the load by using the output transformer operating at raised frequency.
MALDI-TOF Mass Spectrometry-Based SNP Genotyping (2003)

Since the invention of dideoxy DNA sequencing (1), the genomes of a number of organisms have been either partially or completely sequenced, including two draft sequences of the human genome (2,3). This offers new opportunities to investigate genetic diversity within and between species. Based on this, an expanding quantity of genetic markers has found widespread use in academic, clinical, and commercial areas.
Elicitation of Broadly Neutralizing Influenza Antibodies in Animals with Previous Influenza Exposure (2012)

The immune system responds to influenza infection by producing neutralizing antibodies to the viral surface protein, hemagglutinin (HA), which regularly changes its antigenic structure. Antibodies that target the highly conserved stem region of HA neutralize diverse influenza viruses and can be elicited through vaccination in animals and humans. Efforts to develop universal influenza vaccines have focused on strategies to elicit such antibodies; however, the concern has been raised that previous influenza immunity may abrogate the induction of such broadly protective antibodies. We show here that prime-boost immunization can induce broadly neutralizing antibody responses in influenza-immune mice and ferrets that were previously infected or vaccinated. HA stem-directed antibodies were elicited in mice primed with a DNA vaccine and boosted with inactivated vaccine from H1N1 A/New Caledonia/20/1999 (1999 NC) HA regardless of preexposure. Similarly, gene-based vaccination with replication-defective adenovirus 28 (rAd28) and 5 (rAd5) vectors encoding 1999 NC HA elicited stem-directed neutralizing antibodies and conferred protection against unmatched 1934 and 2007 H1N1 virus challenge in influenza-immune ferrets. Indeed, previous exposure to certain strains could enhance immunogenicity: The strongest HA stem-directed immune response was observed in ferrets previously infected with a divergent 1934 H1N1 virus. These findings suggest that broadly neutralizing antibodies against the conserved stem region of HA can be elicited through vaccination despite previous influenza exposure, which supports the feasibility of developing stem-directed universal influenza vaccines for humans.
Double immunocytochemical labeling of cell and tissue samples with monoclonal anti-bromodeoxyuridine. (1989)

We describe a new monoclonal antibody (designated Bu20a) against bromodeoxyuridine (BrdU). This antibody was selected by screening against human tissues using the APAAP technique, and shows no crossreactivity with normal nuclei. It stains BrdU incorporated into the nuclei of a wide range of cell types, including human tonsil lymphoid cells, normal mouse tissues, and human tumors growing in nude mice. A double-labeling technique is described using this antibody in which cell smears or tissue sections are first labeled by an immunoperoxidase procedure for a cellular antigen (e.g., mouse or human histocompatibility class II antigen, T-lymphocyte antigen, keratin) and BrdU is then detected by indirect immunofluorescence. This procedure, which was applied to a variety of human and animal cells and tissues, is of wide potential value in analyzing the phenotype of S-phase cells and in co-localizing antigen expression and BrdU incorporation in tissue sections.
Technologies towards broadband ISDN (1990)

It is argued that it is vital to form a sound strategy for developing broadband integrated services digital network (BISDN) technology and services and deploying them in the field, so that smooth migration from the existing network is accelerated. Three major steps in this context are to expand fiber networks into the subscriber loop area to provide broadband capabilities everywhere, to construct a universal digital network that facilitates smooth evolution from the existing network to the broadband network of the future through deployment of (SDH) synchronous digital hierarchy transmission systems, and to integrate both services and network components through introduction of asynchronous transfer mode (ATM) technologies. Development efforts now being carried out at Fujitsu and Fujitsu Laboratories along this line are described, and the impact on network construction and service offerings is indicated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>