gebhart/patrepeval huggingface dataset:
Antifungal Agents. 9. 3-Aryl-4-[.alpha.-(1H-imidazol-1-yl)arylmethyl]pyrroles: A New Class of Potent Anti-Candida Agents (1995)

A new class of potent antifungal agents, namely, 3-aryl-4-[alpha-(1H-imidazol-1-yl)arylmethyl]-pyrroles, is described. These compounds are related to bifonazole and pyrrolnitrin, two compounds belonging to the class of antimycotic drugs. The synthesis of the title pyrroles has been performed starting from 1,3-diaryl-2-propen-1-ones, which were reacted with tosylmethyl isocyanide to give 3-aroyl-4-arylpyrroles. Reduction of the resulting compounds by lithium aluminum hydride furnished the related alcohols, which were treated with 1,1'-carbonyldimidazole to afford the required imidazole derivatives. Forty-four new pyrroles which incorporate an (arylmethyl)imidazole moiety in the 3-arylpyrrole structure were prepared by the above procedure and tested in vitro against Candida albicans and Candida spp. Among test compounds, 10 were found to be highly active against C. albicans. The most active derivative (27) was twice as potent (MIC90) as bifonazole, and its activity was 4 times greater than those of miconazole and ketoconazole. The other nine compounds showed antifungal activity of the same order of that of bifonazole and were ca. 2 times as active as miconazole and ketoconazole. Derivatives 21 and 27 tested in vivo against C. albicans A170 were shown to be highly effective in rabbit skin candidosis. Pharmacological studies on compounds 27 and other related pyrroles (19, 35, 36, 38, 39, and 49) are in progress to select one of them as a potential candidate for clinical experiments.
Nonregeneration Protocol for Surface Plasmon Resonance:  Study of High-Affinity Interaction with High-Density Biosensors (2006)

Surface plasmon resonance (SPR) has been used in determining kinetics and thermodynamics of biological interaction in the past decades. One difficulty encountered in this technology is the need for a proper regeneration, which means the removal of analytes from the bound complexes to regenerate the activity of the ligands. Regeneration is not always practical since the harsh regeneration reagents may destroy the bioactivity of the ligands. It is even more difficult for complexes with high affinity constants. In this paper, we report a nonregeneration protocol for SPR techniques in which subsequent ligand/analyte interactions can be measured without regeneration; thus ligand biological activity could be retained. Kinetics, binding models, and mathematics of this protocol are discussed in detail using rabbit IgG as the analyte and engineered recombinant antibody A10B single-chain fragment variables (scFv) as the ligand. The affinity constant of rabbit IgG binding with A10B scFv measured by using a nonregeneration protocol was (2.5 +/- 0.2) x 10(7) M(-1), which was comparable with the value determined with a conventional regeneration SPR method ((2.2 +/- 1.5) x 10(7) M(-1)) and quartz crystal microbalance (1.9 x 10(7) M(-1)). A paradigm of streptavidin-biotin binding was analyzed to validate this protocol. The affinity constant for each binding subunit of streptavidin to the immobilized biotin was determined to be (7.3 +/- 0.2) x 10(6) M(-1), which was comparable with the solution-based value of 2 x 10(7) M(-1). The nonregeneration protocol requires a relatively high ligand density on the biosensor surface so that more data points can be obtained before surface saturation. The small size of scFv enables them to be constructed in the biosensors for such purpose.
Stoichiometry and kinetics of the interaction of prostaglandin H synthase with anti-inflammatory agents. (1985)

We have examined the kinetics, stoichiometry, and chemical nature of the interaction of three anti-inflammatory agents (indomethacin, flurbiprofen, and meclofenamic acid) with pure ovine prostaglandin H synthase. The kinetics of the interaction with the synthase for each of the three agents, monitored by the decrease in cyclooxygenase activity, was consistent with the model proposed by Rome and Lands (Rome, L.H., and Lands, W.E.M. (1975) Proc. Natl. Acad. Sci. U.S.A. 72, 4863-4865): a rapid and reversible initial binding, followed by a first-order decay of the synthase-inhibitor complex. A relatively stable form of the cyclooxygenase, which had 4-10% of the initial activity, was the eventual product of this decay process. The dissociation constants evaluated for the initial binding were 1.7 +/- 1.5 microM for indomethacin, 0.2 +/- 0.1 microM for flurbiprofen, and 0.08 +/- 0.06 microM for meclofenamic acid. The values of the first order rate constants for the subsequent decay process were 14.9 +/- 11.3 min-1 for indomethacin, 3.4 +/- 0.7 min-1 for meclofenamic acid, and 16.6 +/- 6.2 min-1 for flurbiprofen. In repeated titrations of the cyclooxygenase with the three agents, 1.3 +/- 0.3 mol of indomethacin, 1.2 +/- 0.1 mol of meclofenamic acid, and 1.2 +/- 0.1 mol of S-(+)-flurbiprofen/mol of synthase dimer were found to result in maximal inhibition of the enzyme. Racemic flurbiprofen required 2.4 +/- 0.3 mol/mol synthase dimer for full effect, and the R-(-)-isomer was not inhibitory. Inhibition of the cyclooxygenase activity by these agents thus appears to result from a stereospecific binding to only one of the subunits of the synthase. Intact indomethacin could be recovered quantitatively after prolonged incubation (in stoichiometric quantities) with the synthase had resulted in maximal inhibition of the cyclooxygenase activity. The time-dependent effect of indomethacin on the cyclooxygenase is thus likely to involve a conformational change in the synthase rather than a covalent interaction.
Heterogeneity in telomere length of human chromosomes (1996)

Vertebrate chromosomes terminate in variable numbers of T2AG3 nucleotide repeats. In order to study telomere repeats at individual chromosomes, we developed novel, quantitative fluorescence in situ hybridization procedures using labeled (C3TA2)3 peptide nucleic acid and digital imaging microscopy. Telomere fluorescence intensity values from metaphase chromosomes of cultured human hematopoietic cells decreased with the replication history of the cells, varied up to six-fold within a metaphase, and were similar between sister chromatid telomeres. Surprisingly, telomere fluorescence intensity values within normal adult bone marrow metaphases did not show a normal distribution, suggesting that a minimum number of repeats at each telomere is required and/or maintained during normal hematopoiesis.
Measurement of dielectric properties of subcutaneous fat with open-ended coaxial sensors (1998)

A three-layer model of stratum corneum, epidermis/dermis and subcutaneous fat has been developed for the capacitance of an open-ended coaxial line in contact with human skin. Applying the model, the electrical properties of subcutaneous fat can be calculated from skin dielectric measurements with three probes of different sizes. The three-layer model is based on a variational formula for the capacitance of the coaxial probe. An accurate approximation for the dielectric constant of the multilayer cutaneous structure is presented for the inverse problem of solving the dielectric constants of various layers. The method was tested at 300 MHz with breast cancer patients who often have radiotherapy-induced late alterations in the structure of subcutaneous fat due to the development of subcutaneous fibrosis. Measurements from 206 sites yielded a good agreement between the dielectric constant of subcutaneous fat and the clinical score for subcutaneous fibrosis.
Two regulatory elements for immunoglobulin kappa light chain gene expression. (1984)

By using internal deletions within a rearranged immunoglobulin kappa light chain gene, the presence of an intron regulatory sequence (enhancer) has been confirmed. Its presence is required for high-level transcription from a plasmid after transfection into myeloma cells. Transfection efficiency was monitored by the activity of a deleted H4 histone gene included in the plasmid. The intron element could be moved upstream of the gene in both orientations, fulfilling the definition of an enhancer. By using 5' deletions, a second regulatory element was located upstream of the "TATA" box, between positions -69 and -104. These two elements both are required for efficient kappa chain gene expression.
Vaccination for hepatitis C virus: closing in on an evasive target (2011)

Hepatitis C virus (HCV) infects more than 170 million people globally and is a leading cause of liver cirrhosis, transplantation and hepatocellular carcinoma. Current gold-standard therapy often fails, has significant side effects in many cases and is expensive. No vaccine is currently available. The fact that a significant proportion of infected people spontaneously control HCV infection in the setting of an appropriate immune response suggests that a vaccine for HCV is a realistic goal. A comparative analysis of infected people with distinct clinical outcomes has enabled the characterization of many important innate and adaptive immune processes associated with viral control. It is clear that a successful HCV vaccine will need to exploit and enhance these natural immune defense mechanisms. New HCV vaccine approaches, including peptide, recombinant protein, DNA and vector-based vaccines, have recently reached Phase I/II human clinical trials. Some of these technologies have generated robust antiviral immunity in healthy volunteers and infected patients. The challenge now is to move forward into larger at-risk or infected populations to truly test efficacy.
Improvement of Escherichia coli production strains by modification of the phosphoenolpyruvate:sugar phosphotransferase system (2005)

The application of metabolic engineering in Escherichia coli has resulted in the generation of strains with the capacity to produce metabolites of commercial interest. Biotechnological processes with these engineered strains frequently employ culture media containing glucose as the carbon and energy source. In E. coli, the phosphoenolpyruvate:sugar phosphotransferase system (PTS) transports glucose when this sugar is present at concentrations like those used in production fermentations. This protein system is involved in phosphoenolpyruvate-dependent sugar transport, therefore, its activity has an important impact on carbon flux distribution in the phosphoenolpyruvate and pyruvate nodes. Furthermore, PTS has a very important role in carbon catabolite repression. The properties of PTS impose metabolic and regulatory constraints that can hinder strain productivity. For this reason, PTS has been a target for modification with the purpose of strain improvement. In this review, PTS characteristics most relevant to strain performance and the different strategies of PTS modification for strain improvement are discussed. Functional replacement of PTS by alternative phosphoenolpyruvate-independent uptake and phosphorylation activities has resulted in significant improvements in product yield from glucose and productivity for several classes of metabolites. In addition, inactivation of PTS components has been applied successfully as a strategy to abolish carbon catabolite repression, resulting in E. coli strains that use more efficiently sugar mixtures, such as those obtained from lignocellulosic hydrolysates.
A Comparative Analysis of the Sequence of the Thymidine Kinase Gene of a Gammaherpesvirus, Herpesvirus Saimiri (1989)

We present the nucleotide sequence of a region from the genome of the A + T-rich gammaherpesvirus, herpesvirus saimiri (HVS), which includes the coding sequences for the viral thymidine kinase (TK) gene. The organization of genes in this region resembles the homologous region of the Epstein-Barr virus (EBV) genome and is very compact, using overlapping coding sequences and with nucleotides shared by initiation and termination codons of neighbouring reading frames. The HVS TK is predicted to contain a 527 residue polypeptide with the first part of the presumptive nucleotide-binding site [(L, I, V)(F, Y)(I, L)(D, E)(G)(X)(X)(G)(L, I, V, M)(G)(K)(T, S)(T, S)] located at residues 212 to 224. This motif is close to the amino terminus of the TK polypeptides of alphaherpesviruses and the polypeptides of the cellular and poxvirus-encoded enzymes. The corresponding reading frame of the human gammaherpesvirus (EBV) also has a long amino-terminal extension but significant amino acid sequence similarities between the HVS and EBV sequences are not observed until the region of the nucleotide-binding site. Comparisons of these homologous carboxy-terminal sequences of the HVS- and EBV-encoded proteins with those from six alphaherpes viruses and proteins encoded by Marek's disease virus (MDV) and the herpesvirus of turkeys (HVT) confirm that the HVS and EBV sequences are products of a distinct lineage. The sequences of alphaherpesvirus enzymes than to those of HVS and EBV. Comparison of these 10 highly divergent TK sequences extends and refines the identification of essential features of this family of herpesvirus enzymes and defines 19 positions at which all sequences have identical residues.
Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide. (2000)

Recent studies have suggested that selective inhibition of mitogenic pathways may improve the antitumor activity of ionizing radiation. The epidermal growth factor receptor (EGFR) is overexpressed and is involved in autocrine growth control in the majority of human carcinomas. Protein kinase A type I (PKAI) plays a key role in neoplastic transformation and is overexpressed in cancer cells in which an EGFR autocrine pathway is activated. We used two specific inhibitors of EGFR and PKAI that are under clinical evaluation in cancer patients: C225, an anti-EGFR chimeric human-mouse monoclonal antibody (MAb); and a mixed-backbone antisense oligonucleotide targeting the PKAI RIalpha subunit (PKAI AS). We tested in human colon cancer (GEO) and ovarian cancer (OVCAR-3) cell lines the antiproliferative activity of MAb C225 and/or PKAI AS in combination with ionizing radiation. In vivo antitumor activity was evaluated in nude mice bearing established GEO xenografts. Dose-dependent inhibition of soft agar growth was observed in both cancer cell lines with ionizing radiation, C225, or PKAI AS oligonucleotide. A cooperative antiproliferative effect was obtained when cancer cells were treated with ionizing radiation followed by MAb C225 or PKAI AS oligonucleotide. This effect was observed at all doses tested in both GEO and OVCAR-3 cancer cell lines. A combination of the three treatments at the lowest doses produced an even greater effect than that observed when two modalities were combined. Treatment of mice bearing established human GEO colon cancer xenografts with radiotherapy (RT), MAb C225, or PKAI AS oligonucleotide produced dose-dependent tumor growth inhibition that was reversible upon treatment cessation. A potentiation of the antitumor activity was observed in all mice treated with RT in combination with MAb C225 or PKAI AS oligonucleotide. Long-term GEO tumor growth regression was obtained following treatment with ionizing radiation in combination with MAb C225 plus PKAI AS oligonucleotide, which produced a significant improvement in survival compared with controls (P < 0.001), the RT-treated group (P < 0.001), or the group treated with MAb C225 plus PKAI AS oligonucleotide (P < 0.001). All mice of the RT + MAb C225 + PKAI AS group were alive 26 weeks after tumor cell injection. Furthermore, 50% of mice in this group were alive and tumor-free after 35 weeks. This study provides a rationale for evaluating in cancer patients the combination of ionizing radiation and selective drugs that block EGFR and PKAI pathways.
Iron(ii)–bis(isonitrile) complexes: novel catalysts in asymmetric transfer hydrogenations of aromatic and heteroaromatic ketones (2010)

Chiral iron(ii)-bis(isonitrile) complexes catalyse the transfer hydrogenation of aromatic ketones with enantioselectivities up to 91% ee, most likely via hydride transfer through imine intermediates, generated by in situ reduction of the isonitrile ligands, whereas iron acts as a Lewis acid to activate the ketone.
Automatic strategies in the Siemens RTL tiled window manager (2003)

The Siemens RTL tiled window manager automatically adjusts the size and position of tiled windows to balance competing demands for screen space. The degree of automation can be set by both the user and control strategies, which range from strictly local to those which can affect all the windows on the screen. These strategies are discussed, the trade-offs involved are indicated and the algorithms used in their implementation are briefly described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An improved approach for robust road marking detection and tracking applied to multi-lane estimation (2013)

In this paper, an original and innovative algorithm for multi-lane detection and estimation is proposed. Based on a three-step process, (1) road primitives extraction, (2) road markings detection and tracking, (3) lanes shape estimation. This algorithm combines several advantages at each processing level and is quite robust to the extraction method and more specifically to the choice of the extraction threshold. The detection step is so efficient, by using robust poly-fitting based on the point intensity of extracted points, that correction step is almost not necessary anymore. This approach has been used in several project in real condition and its performances have been evaluated with the sensor data generated from SiVIC platform. This validation stage has been done with a sequence of 2500 simulated images. Results are very encouraging : more than 95% of marking lines are detected for less than 2% of false alarm, with 3 cm accuracy at a range of 60 m.
One-Pot Reductive Amination of Conjugated Aldehydes and Ketones with Silica Gel and Zinc Borohydride (1998)

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTOne-Pot Reductive Amination of Conjugated Aldehydes and Ketones with Silica Gel and Zinc BorohydrideBrindaban C. Ranu, Adinath Majee, and Arunkanti SarkarView Author Information Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Calcutta - 700 032, India Cite this: J. Org. Chem. 1998, 63, 2, 370–373Publication Date (Web):January 7, 1998Publication History Received19 June 1997Published online7 January 1998Published inissue 1 January 1998https://pubs.acs.org/doi/10.1021/jo971117hhttps://doi.org/10.1021/jo971117hbrief-reportACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views3356Altmetric-Citations107LEARN 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 SUBJECTS:Amines,Anions,Carbonyls,Organic reactions,Zinc Get e-Alerts
Characterization of the O‐antigen gene clusters of Yersinia pseudotuberculosis and the cryptic O‐antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b (2000)

One of the most virulent and feared bacterial pathogens is Yersinia pestis, the aetiologic agent of bubonic plague. Characterization of the O-antigen gene clusters of 21 serotypes of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Y. pestis showed that the plague bacillus is most closely related to and has evolved from Y. pseudotuberculosis serotype O:1b. The nucleotide sequences of both gene clusters (about 20.5 kb each) were determined and compared to identify the differences that caused the silencing of the Y. pestis gene cluster. At the nucleotide sequence level, the loci were 98.9% identical and, of the 17 biosynthetic genes identified from the O:1b gene cluster, five were inactivated in the Y. pestis cluster, four by insertions or deletions of one nucleotide and one by a deletion of 62 nucleotides. Apparently, the expression of the O-antigen is not beneficial for the virulence or to the lifestyle of Y. pestis and, therefore, as one step in the evolution of Y. pestis, the O-antigen gene cluster was inactivated.
Neutralization of Human Extrinsic (Tissue-Type) Plasminogen Activator in Human Plasma: No Evidence for a Specific Inhibitor (1981)

Human extrinsic plasminogen activator (EPA), highly purified from a melanoma cell culture fluid is inactivated in human plasma with a half-life (t 1/2) of 90-105 min. Gel filtration on Ultrogel AcA 34 of mixtures of 125I-labeled EPA and human plasma, incubated at 37 degrees C, revealed the progressive formation of two radioactive components, one with an apparent Mr of 150,000 and one eluting at the void volume. The component with an Mr of 150,000 was identified as consisting at least in part of EPA-alpha 2-antiplasmin complex since: 1) it reacted with antibodies against alpha 2-antiplasmin, but not with antibodies against the other known plasma protease inhibitors, and 2) formation of this component was strongly reduced in plasma specifically depleted in alpha 2-antiplasmin or when the active site of EPA was blocked. The component eluting at the void volume was identified as consisting at least in part of EPA-alpha 2-macroglobulin complex since: 1) it only reacted with antibodies against these two proteins and 2) was not formed in plasma depleted in alpha 2-macroglobulin or when the active site of EPA was blocked. In purified systems alpha 2-antiplasmin inhibited one-chain EPA with a rate constant of 60 M-1s-1 and two-chain EPA with a rate constant of 130 M-1s-1, which corresponds to a t 1/2 in plasma of 180 min or 90 min, respectively. alpha 2-Macroglobulin inhibited one-chain EPA with a rate constant of 15 M-1s-1 and two-chain EPA with a rate constant of 30 M-1s-1, which corresponds to a t 1/2 in plasma of 4 or 2 hrs. All these findings taken together indicate that EPA is slowly neutralized in human plasma primarily by alpha 2-antiplasmin and to a lesser extent by alpha 2-macroglobulin. There appears to be no specific inhibitor in human plasma, which would inactivate EPA either rapidly or to a significant extent.
Superior Laryngeal Nerve Identification and Preservation in Thyroidectomy (2002)

Understanding the 3 anatomic variations of the distal portion of the EBSLN and its relation to the inferior constrictor muscle allows for high rates of identification of this nerve. The EBSLN should be explored during thyroid surgery and identification is possible in most cases. Preservation of the EBSLN maintains optimal function of the larynx.