gebhart/patrepeval huggingface dataset:
The function of calcium in protein C activation by thrombin and the thrombin-thrombomodulin complex can be distinguished by mutational analysis of protein C derivatives. (1992)

Protein C activation is catalyzed on endothelium by a complex between thrombin and thrombomodulin. Ca2+ stimulates protein C activation in the presence, and inhibits in the absence, of thrombomodulin. Protein C has Asp residues at the P3 and P3' positions relative to the scissile bond at Arg169-Leu. To determine the contribution of these residues to the Ca2+ effect on activation, we have expressed human 4-carboxyglutamic acid (Gla)-domainless protein C and 3 mutants with Asp-->Gly substitutions at P3, P3', and both positions. Ca2+ interaction with the protein C derivatives was monitored by changes in intrinsic fluorescence, and the Ca2+ dependence of activation by thrombin and a complex of thrombin-thrombomodulin with a soluble thrombomodulin derivative (the fourth through sixth epidermal growth factor domains). The affinity for Ca2+ of the mutants was reduced 3-6-fold, which was reflected by a comparable change in the Ca2+ concentration required for the half-maximal rate of activation by the thrombin-thrombomodulin complex. However, Ca2+ no longer effectively inhibited activation of the mutants by thrombin alone. We conclude that 1) the Asp residues play a specific role in the Ca(2+)-dependent inhibition of protein C activation by thrombin; 2) these mutations alter the affinity of Ca2+ for the high affinity binding site; and 3) the Asp residues in the P3 and P3' sites do not contribute in a positive fashion to rapid activation by the thrombin-thrombomodulin complex.
The Physiological Ecology of Cyanidium caldarium (1971)

Summary: The distribution and physiology of Cyanidium caldarium in its natural habitat in acidic hot springs and hot soils have been studied. This eucaryotic alga was the sole photosynthetic organism in habitats with pH less than 5 and temperatures greater than 40°. The upper temperature limit of the alga was 55° to 56° and the optimum temperature for growth was 45°. Temperature strains such as are found in blue-green algae of alkaline thermal habitats were not found for Cyanidium caldarium. In aquatic habitats the lower temperature limit was about 35° to 36°, the organism apparently being unable to compete at temperatures below this with other algae. In soils the alga was found at temperatures as low as 10°, apparently because in terrestrial habitats competition with other algae was less significant. The pH range at which the alga has been found in nature was from 0·05 to 5·0 and growth in culture occurred over this whole range. The optimum pH for growth was between 2 and 3. In nature the alga was found in habitats of widely varying light intensity, up to 7000 ft-candles. The alga became adapted to reduced light intensity by increasing its photopigment concentrations. Photosynthesis in populations adapted to reduced light intensities was inhibited by high light intensities. The alga grew well on glucose in the dark, and the concentration of photosynthetic pigments was reduced. When such bleached cells were transferred to the light in the presence of glucose, pigments were not synthesized and heterotrophic growth continued; when glucose was omitted, pigment synthesis occurred and photosynthetic growth resumed. Glucose did not inhibit pigment synthesis when added to cells growing in the light.
ChemInform Abstract: 1,1′,2,2′‐TETRATHIAFULVALENES. IV. REACTIONS OF CYCLOPROPENE(THI)ONES WITH 1,2‐DITHIOLE COMPOUNDS: THIENO(3,2‐B)THIOPHENES, THIENO(3,2‐B)FURANS, 4H‐FURO(3,2‐B)PYRROLES, 1,2‐DITHIOLE‐3‐(THI)ONES, AND OTHER HETEROCYCLES CONTAINING SULFUR (1982)

Abstract Die Trithione (Ia), (Ib) reagieren mit dem Cyclopropenthion (II) unter S‐Eliminierung zu den Thienothiophenen (III).
Thermal gradient PCR in a continuous-flow microchip (2007)

A new continuous-flow PCR microchip has been developed that operates by cycling a prepared sample within a spatial temperature gradient. This design allows for minimal thermal residence times - a key feature of the protocols used by the fastest commercial PCR equipment. Since thermal gradients are a natural effect of heat dissipation, the appropriate temperature distribution for PCR can be generated by a minimum of one heater held at a steady state temperature. With a thermal gradient of more than 3°C/mm across the width of the chip, each complete PCR cycle requires approximately 2cm of channel length. These glass chips were manufactured using standard glass microfabrication methods as well as the Xurographic rapid prototyping technique. Targets of 110bp and 181bp were amplified from &Fgr;X174 plasmid DNA on these thermal gradient chips as well as on commercial PCR equipment, then subsequently analyzed by gel electrophoresis. Visual inspection of fluorescent images of the stained gels shows that the amplicon size and yield for the systems are comparable.
Identification of Potent Pyrazolo[4,3-h]quinazoline-3-carboxamides as Multi-Cyclin-Dependent Kinase Inhibitors (2010)

Abnormal proliferation mediated by disruption of the mechanisms that keep the cell cycle under control is a hallmark of virtually all cancer cells. Compounds targeting complexes between cyclin-dependent kinases (CDKs) and cyclins (Cy) and inhibiting their activity are regarded as promising antitumor agents to complement the existing therapies. An expansion of pyrazolo[4,3-h]quinazoline chemical class oriented to the development of three points of variability was undertaken leading to a series of compounds able to inhibit CDKs both in vitro and in vivo. Starting from the CDK selective but poorly soluble hit compound 1, we succeeded in obtaining several compounds showing enhanced inhibitory activity both on CDKs and on tumor cells and displaying improved physical properties and pharmacokinetic behavior. Our study led to the identification of compound 59 as a highly potent, orally bioavailable CDK inhibitor that exhibited significant in vivo efficacy on the A2780 ovarian carcinoma xenograft model. The demonstrated mechanisms of action of compound 59 on cancer cell lines and its ability to inhibit tumor growth in vivo render this compound very interesting as potential antineoplastic agent.
Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. (1996)

The efficacy of combination therapy including an oral gelatinase inhibitor (CT1746) and cytotoxic agent was analyzed using the murine Lewis lung carcinoma model. Primary tumors, pulmonary metastases, and sera from tumor-bearing animals had increased gelatinase B activity that was inhibited by CT1746 levels achievable in vivo. The combination of CT1746 and cyclophosphamide (CTX) was significantly more effective than either single agent in delaying local tumor growth (CT1746/CTX, 30.9 +/- 1.7 days; CT1746, 2.6 +/- 0.3 days; CTX, 19.5 +/- 1.1 days; P < .001) and reducing the number and size of pulmonary metastases [CT1746/CTX, 5 +/- 2 (15% metastases > 3 mm); CT1746, 15 +/- 4 (55% > 3 mm); CTX, 11 +/- 3 (63% > 3 mm); no treatment, 24 +/- 5 (62% > 3 mm); P < .001]. These data support the notion of combining matrix metalloproteinase inhibitors and cytotoxic agents to treat certain epithelial malignancies.
Syn-anti conformational analysis of regular and modified nucleosides by 1D 1H NOE difference spectroscopy: a simple graphical method based on conformationally rigid molecules (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSyn-anti conformational analysis of regular and modified nucleosides by 1D 1H NOE difference spectroscopy: a simple graphical method based on conformationally rigid moleculesHelmut Rosemeyer, Gabor Toth, Bozenna Golankiewicz, Zygmunt Kazimierczuk, Werner Bourgeois, Uwe Kretschmer, Heinz Peter Muth, and Frank SeelaCite this: J. Org. Chem. 1990, 55, 22, 5784–5790Publication Date (Print):October 1, 1990Publication History Published online1 May 2002Published inissue 1 October 1990https://pubs.acs.org/doi/10.1021/jo00309a024https://doi.org/10.1021/jo00309a024research-articleACS PublicationsRequest reuse permissionsArticle Views930Altmetric-Citations138LEARN 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
Evolution of Composite Reverse Osmosis Membranes (1985)

ADVERTISEMENT RETURN TO BOOKPREVChapterNEXTEvolution of Composite Reverse Osmosis MembranesJOHN E. CADOTTEJOHN E. CADOTTEFilmTec Corporation, Minneapolis, MN 55435More by JOHN E. CADOTTEDOI: 10.1021/bk-1985-0269.ch012Publication Date (Print):December 12, 1985Publication History Published online23 July 2009Published inprint 12 December 1985Request reuse permissions Copyright © 1985 American Chemical Society. Materials Science of Synthetic MembranesChapter 12pp 273-294ACS Symposium SeriesVol. 269ISBN13: 9780841208872eISBN: 9780841210981Chapter Views362Citations93LEARN ABOUT THESE METRICSChapter 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. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Composites,Membranes,Osmosis,Transition metals Get e-Alerts
RandSys: Thwarting Code Injection Attacks with System Service Interface Randomization (2007)

Code injection attacks are a top threat to today's Internet. With zero-day attacks on the rise, randomization techniques have been introduced to diversify software and operation systems of networked hosts so that attacks that succeed on one host cannot succeed on others. Two most notable system-wide randomization techniques are Instruction Set Randomization (ISR) and Address Space Layout Randomization (ASLR). The former randomizes instruction set for each process, while the latter randomizes the memory address space layout. Both suffer from a number of attacks. In this paper, we advocate and demonstrate that by combining ISR and ASLR effectively, we can offer much more robust protection than each of them individually. However, trivial combination of both schemes is not sufficient. To this end, we make the key observation that system call instructions matter the most to attackers for code injection. Our system, RandSys, uses system call instruction randomization and the general technique of ASLR along with a number of new enhancements to thwart code injection attacks. We have built a prototype for both Linux and Windows platforms. Our experiments show that RandSys can effectively thwart a wide variety of code injection attacks with a small overhead.
Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation (2004)

We explored, by cDNA mini-arrays, gene expression measurements of MVLN, a human breast carcinoma cell line derived from MCF-7, after 4 days of exposure to 17beta-estradiol (E(2)) treatment, in order to extend our understanding of the mechanism of the pharmacological action of estrogens. We focused on 22 genes involved in estrogen metabolism, cell proliferation regulation and cell transformation. The specificity of the E(2) response was reinforced by comparison with 4-hydroxytamoxifen (OH-Tam), ICI 182,780 and E(2)+OH-Tam expression profiles. Real-time quantitative PCR (RTQ-PCR) confirmed the variation of expression of known (TFF1, AREG, IRS1, IGFBP4, PCNA, ERBB2, CTSD, MYC) as well as novel (DLEU2, CCNA2, UGT1A1, ABCC3, ABCC5, TACC1, EFNA1, NOV, CSTA, MMP15, ZNF217) genes. The temporal response of these gene expression regulations was then investigated after 6 and 18 h of E(2) treatment and this allowed the identification of different time-course patterns. Cycloheximide treatment studies indicated first that estrogen affected the transcript levels of ABCC3 and ABCC5 through dissimilar pathways, and secondly that protein synthesis was needed for modulation of the expression of the CCNA2 and TACC1 genes by estrogens. Western blot analysis performed on TFF1, IRS1, IGFBP4, amphiregulin, PCNA, cyclin A2, TACC1 and ABCC5 proteins confirmed the mini-array and RTQ-PCR data, even for genes harboring low variations of mRNA expression. Our findings should enhance the understanding of changes induced by E(2) on the transcriptional program of human E(2)-responsive cells and permit the identification of new potential diagnostic/prognostic tools for the monitoring of estrogen-related disease conditions such as breast cancer.
Acaricide resistance in single and multi-host ticks and strategies for control. (1990)

The majority of reports, concerning resistance in multi-host ticks, continue to be confined to the cyclodiene group and lindane, with sparse references to resistance affecting the organophosphorus acaricides. In contrast, the resistance picture in Boophilus spp., particularly in relation to B. microplus in Australia, continues to degenerate. Recent reports, documenting the emergence of a complex of pyrethroid resistant strains in the latter species, are the cause of considerable current concern, due to the lack of a suitable, commercially available, replacement group. These developments reinforce the need for a close examination of the strategies recommended for the management of acaricide resistance, particularly for Boophilus spp. The choice of options to select, in circumstances following the detection of resistance to an acaricide, is limited to those aimed at preserving the use of the affected chemical, or selection of an effective alternative, either from within the same class, or from a new acaricide group. Success of the former options, including tactics such as increased concentration or eradication of resistant alleles, and the rational choice of alternative acaricides for use in localized areas where necessary, are critically dependent on early detection of a newly emerged resistance mechanism, its localization, and an understanding of its spectrum of effect. Avermectins and acarine growth regulators show promise as potential future tick control agents. However, the dearth of new chemistry in this area stresses the importance of developing optimal strategies to extend the effective life of these and currently available compounds, in areas where they remain effective.(ABSTRACT TRUNCATED AT 250 WORDS)
Molecular Basis Of Surface Antigen Variation In Paramecia (1989)

MOLECULAR BASIS OF SURFACE ANTIGEN VARIATION IN PARAMECIA, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/micro/43/1/annurev.mi.43.100189.000323-1.gif
Ethylene Biosynthesis and its Regulation in Higher Plants (1984)

Crop loss due to soil salinization is an increasing threat to agriculture worldwide. This review provides an overview of cellular and physiological mechanisms in plant responses to salt. We place cellular responses in a time- and tissue-dependent context ...Read More
Instant inkjet circuits (2013)

This paper introduces a low cost, fast and accessible technology to support the rapid prototyping of functional electronic devices. Central to this approach of 'instant inkjet circuits' is the ability to print highly conductive traces and patterns onto flexible substrates such as paper and plastic films cheaply and quickly. In addition to providing an alternative to breadboarding and conventional printed circuits, we demonstrate how this technique readily supports large area sensors and high frequency applications such as antennas. Unlike existing methods for printing conductive patterns, conductivity emerges within a few seconds without the need for special equipment. We demonstrate that this technique is feasible using commodity inkjet printers and commercially available ink, for an initial investment of around US$300. Having presented this exciting new technology, we explain the tools and techniques we have found useful for the first time. Our main research contribution is to characterize the performance of instant inkjet circuits and illustrate a range of possibilities that are enabled by way of several example applications which we have built. We believe that this technology will be of immediate appeal to researchers in the ubiquitous computing domain, since it supports the fabrication of a variety of functional electronic device prototypes.
Independent segregation of two antigenic specificities (VP3 and VP7) involved in neutralization of rotavirus infectivity. (1985)

Antiserum prepared against the M37 strain of rotavirus, recovered from an asymptomatic newborn infant in Venezuela, neutralized two prototype human rotaviruses that define two separate serotypes: serotype 1 (Wa) and serotype 4 (ST3). Thus, the M37 strain is a naturally occurring intertypic rotavirus. Analysis of reassortant viruses produced during coinfection in vitro indicated that the observed dual serotype specificity of M37 resulted from sharing a related outer capsid protein, VP3, with the ST3 virus and another related outer capsid protein, VP7, with the Wa virus. Analysis of single (VP3)-gene-substitution reassortants indicated that VP3 was as potent an immunogen as VP7. In addition, direct evidence was obtained that the serotype specificity of neutralizing antibody elicited by VP3 can differ from the serotype specificity of neutralizing antibody elicited by VP7, indicating the need for a dual system of rotavirus classification in which the neutralization specificity of both VP3 and VP7 outer capsid proteins are identified.
Spectral karyotyping of fresh, non-inseminated oocytes (2002)

The object of this study was to determine the mechanisms producing aneuploidy in female meiosis I by analysing the whole chromosome complement of human non-inseminated and unfertilized fresh oocytes. For this purpose, 131 fresh oocytes were obtained from 16 oocyte donors (24-48 years old). These oocytes were fixed immediately after retrieval and 47 good quality metaphases from 13 donors were analysed by spectral karyotyping to identify all 23 chromosome types. The data was divided into two maternal age groups, 24-34 (n = 31) and > or = 35 years (n = 16). More non-disjunction (13 and 25%), unbalanced predivision (10 and 44%, P < 0.01) and balanced predivision (6 and 62%, P < 0.001) events were found in the older group of oocytes. There was an increase in balanced predivision with decreasing chromosome size (P < 0.001). The present results are the first obtained in fresh oocytes where all chromosomes were specifically identified, and support previous theories that predivision of chromatids is a major factor causing aneuploidy. Previous reports with inseminated, non-fertilized oocytes fixed > or = 24 h after retrieval suffered from artefactual predivision of chromatids triggered by in-vitro ageing of oocytes.
The Arginine-Rich Domains Present in Human Immunodeficiency Virus Type 1 Tat and Rev Function as Direct Importin β-Dependent Nuclear Localization Signals (1999)

Protein nuclear import is generally mediated by basic nuclear localization signals (NLSs) that serve as targets for the importin alpha (Imp alpha) NLS receptor. Imp alpha is in turn bound by importin beta (Imp beta), which targets the resultant protein complex to the nucleus. Here, we report that the arginine-rich NLS sequences present in the human immunodeficiency virus type 1 regulatory proteins Tat and Rev fail to interact with Imp alpha and instead bind directly to Imp beta. Using in vitro nuclear import assays, we demonstrate that Imp alpha is entirely dispensable for Tat and Rev nuclear import. In contrast, Imp beta proved both sufficient and necessary, in that other beta-like import factors, such as transportin, were unable to support Tat or Rev nuclear import. Using in vitro competition assays, it was demonstrated that the target sites on Imp beta for Imp alpha, Tat, and Rev binding either are identical or at least overlap. The interaction of Tat and Rev with Imp beta is also similar to Imp alpha binding in that it is inhibited by RanGTP but not RanGDP, a finding that may in part explain why the interaction of the Rev nuclear RNA export factor with target RNA species is efficient in the cell nucleus yet is released in the cytoplasm. Together, these studies define a novel class of arginine-rich NLS sequences that are direct targets for Imp beta and that therefore function independently of Imp alpha.
Viral infections of the gastrointestinal tract (1993)

Viral infections of the gastrointestinal tract continue to be a major worldwide cause of morbidity and mortality, especially in underdeveloped settings. Rapid improvement in the understanding of viral structure and function, epidemiology, and host immune responses are occurring in conjunction with advances in basic science technologies (monoclonal antibodies, molecular genetic techniques, polymerase chain reaction, and so on). Intestinal adenoviruses, astroviruses, caliciviruses, Norwalk and Norwalk-like viruses, and atypical rotaviruses are all joining Group A rotavirus as well-described human pathogens, although rotavirus continues to be recognized as the leading cause of severe gastroenteritis in children.
Isolation of a Soluble Resistance-Enhancing Factor from Mycobacterium phlei (1966)

Fox, Alfred E. (Warner-Lambert Research Institute, Morris Plains, N.J.), Joachim Anschel, George L. Evans, Raam R. Mohan, and Benjamin S. Schwartz. Isolation of a soluble resistance-enhancing factor from Mycobacterium phlei. J. Bacteriol. 92:285-290. 1966.-Extraction of a crude cell wall preparation from Mycobacterium phlei with 20% urea yielded a fraction which induced a state of enhanced resistance to microbial challenge. The resulting soluble extract, after removal of the urea, represented a 15% yield of solids with the separation of the biologically active component(s) and elimination of toxicity. Single oral or subcutaneous submicrogram doses of this material induced a prolonged state of increased resistance to subsequent challenge with Salmonella enteritidis in mice. This effect appeared as early as 2 hr after oral administration and persisted for at least 30 days. Protection against experimental infection with Staphylococcus aureus was also demonstrated. Resistance to viral challenge with influenza type A was observed after intranasal administration of the M. phlei extract to mice. The isolated material was found to contain carbohydrate, protein, nucleic acids, and lipids. The lipids represented 60% of the total solids, and were all short-chain fatty acids. No toxic effects, including pyrogenicity, could be demonstrated after oral or parenteral administration of this preparation.