gebhart/patrepeval huggingface dataset:
Minisequencing: A Specific Tool for DNA Analysis and Diagnostics on Oligonucleotide Arrays (1997)

We describe a method for multiplex detection of mutations in which the solid-phase minisequencing principle is applied to an oligonucleotide array format. The mutations are detected by extending immobilized primers that anneal to their template sequences immediately adjacent to the mutant nucleotide positions with single labeled dideoxynucleoside triphosphates using a DNA polymerase. The arrays were prepared by coupling one primer per mutation to be detected on a small glass area. Genomic fragments spanning nine disease mutations, which were selected as targets for the assay, were amplified in multiplex PCR reactions and used as templates for the minisequencing reactions on the primer array. The genotypes of homozygous and heterozygous genomic DNA samples were unequivocally defined at each analyzed nucleotide position by the highly specific primer extension reaction. In a comparison to hybridization with immobilized allele-specific probes in the same assay format, the power of discrimination between homozygous and heterozygous genotypes was one order of magnitude higher using the minisequencing method. Therefore, single-nucleotide primer extension is a promising principle for future high-throughput mutation detection and genotyping using high density DNA-chip technology.
The Role of Selenium in Chronic Disease (2008)

Selenium functions as a part of proteins known as selenoproteins. Through these selenoproteins, selenium functions as a defensive mechanism for oxidative stress, for the regulation of thyroid hormone activity, and for the redox status of vitamin C and other molecules. In several of its roles, selenium functions as a dietary antioxidant and thus has been studied for its possible role in chronic diseases. This article reviews recent studies regarding selenium status or supplementation in hypertension, cardiovascular disease, cancer, and diabetes mellitus. A few studies regarding aging and mortality are also included. What can be ascertained from this current review is that the maintenance of adequate selenium nutriture and, at minimum, the prevention of a deficiency in selenium would be advisable for all individuals. In addition, the indiscriminant use of selenium supplements should be approached with caution until further randomized, controlled trials monitor the effects of such supplementation, especially on a long-term basis.
Some ribosome-inactivating proteins depurinate ribosomal RNA at multiple sites (1992)

Saporin-S6, a ribosome-inactivating protein (RIP) from Saponaria officinalis released more than 1 mol of adenine/mol of ribosomes from house fly (Musca domestica) larvae and from rat liver. The release of adenine from rat liver ribosomes by several RIPs (plant enzymes with RNA N-glycosidase activity) was examined. Saporins, pokeweed antiviral protein from roots of Phytolacca americana (PAP-R), and trichokirin from Trichosanthes kirilowii seeds depurinated rat liver ribosomes at more than one site. Up to 33 mol of adenine were released from 1 mol of ribosomes. This property is not common to all RIPS.
Base-Free Dehydrogenative Coupling of Enolizable Carbonyl Compounds with Silanes (2012)

A dehydrogenative coupling between enolizable carbonyl compounds and equimolar amounts of triorganosilanes catalyzed by a tethered ruthenium complex with a Ru-S bond is reported. The complex is assumed to fulfill a dual role by activating the Si-H bond to release a silicon electrophile and by abstracting an α-proton from the intermediate silylcarboxonium ion, only liberating dihydrogen as the sole byproduct. Reaction rates are exceedingly high at room temperature with very low loadings of the ruthenium catalyst.
SAR and Mode of Action of Novel Non-Nucleoside Inhibitors of Hepatitis C NS5b RNA Polymerase (2006)

Novel non-nucleoside inhibitors of the HCV RNA polymerase (NS5b) with sub-micromolar biochemical potency have been identified which are selective for the inhibition of HCV NS5b over other polymerases. The structures of the complexes formed between several of these inhibitors and HCV NS5b were determined by X-ray crystallography, and the inhibitors were found to bind in an allosteric binding site separate from the active site. Structure-activity relationships and structural studies have identified the mechanism of action for compounds in this series, several of which possess drug-like properties, as unique, reversible, covalent inhibitors of HCV NS5b.
Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2 (2018)

The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding "up" conformation. In addition, we studied the structures of the SARS-CoV S glycoprotein and its complexes with ACE2 in different in vitro conditions, which may mimic different conformational states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2 complex from some of the prefusion spikes was observed and characterized. We also characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in the postfusion state observed on electron micrographs. Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.
Repression of the Steroidogenic Acute Regulatory Gene by the Multifunctional Transcription Factor Yin Yang 1 (2002)

The transport of cholesterol to the inner mitochondrial membrane by the steroidogenic acute regulatory (StAR) protein is a critical step in steroidogenesis. The current study was designed to examine whether the multifunctional transcription factor Yin Yang 1 (YY1) was able to repress activation of the StAR gene. YY1 bound to three putative YY1-binding sites in the rat StAR promoter. Cotransfection of the StAR promoter linked to a luciferase reporter gene and YY1 in the presence or absence of sterol regulatory element binding protein-1a (SREBP-1a) resulted in transcriptional repression. YY1 was found to colocalize in the nucleus with SREPB-1a. YY1 inhibited SREBP-1a/nuclear factor Y (NF-Y) enhancement of StAR activation and YY1 decreased SREBP-1a binding to a sterol regulatory element in the presence or absence of NF-Y. YY1 also decreased NF-Y binding to a nonconsensus NF-Y-binding motif in the StAR promoter. These studies provide novel information on the mechanisms of YY1-mediated repression of the StAR gene.
p38 Mitogen-Activated Protein Kinase Promotes Cell Survival in Response to DNA Damage but Is Not Required for the G2 DNA Damage Checkpoint in Human Cancer Cells (2010)

p38 mitogen-activated protein kinase (MAPK) is rapidly activated by stresses and is believed to play an important role in the stress response. While Chk1 is known to mediate G(2) DNA damage checkpoint control, p38 was also reported to have an essential function in this checkpoint control. Here, we have investigated further the roles of p38 and Chk1 in the G(2) DNA damage checkpoint in cancer cells. We find that although p38 activation is strongly induced by DNA damage, its activity is not required for the G(2) DNA damage checkpoint. In contrast, Chk1 kinase is responsible for the execution of G(2) DNA damage checkpoint control in p53-deficient cells. The inhibition of p38 activity has no effect on Chk1 activation and gamma-H2AX expression. Global gene expression profiling of cancer cells in response to tumor necrosis factor alpha (TNF-alpha) revealed that p38 plays a strong prosurvival role through the coordinated downregulation of proapoptotic genes and upregulation of prosurvival genes. We show that the inhibition of p38 activity during G(2) DNA damage checkpoint arrest triggers apoptosis in a p53-independent manner with a concurrent decrease in the level of Bcl2 family proteins. Our results suggest that although p38 MAPK is not required for the G(2) DNA damage checkpoint function, it plays an important prosurvival role during the G(2) DNA damage checkpoint response through the upregulation of the Bcl2 family proteins.
Identification of two potential receptor-binding sites for hGM-CSF (2003)

Two receptor-binding sites for hGM-CSF are described. Competitive binding ELISA using four monoclonal antibodies (MAbs) showed different epitope recognitions. The antibody combining sites were mapped using sets of overlapping peptides and hexapeptide libraries prepared by the SPOT synthesis technique. We identified the conformationally dependent epitopes A18E21R23R24F119 and R23E21N17W13 bound by MAb CC5B5 and the nonlinear epitope P118F119W13E14 bound by MAb M1B8. The epitopes recognized by these two MAbs are very closely located on the native protein surface. The peptide L61YKQGKLRGSLTK72 was recognized by MAb M7E10 and the peptide A1PAR4, representing the N-terminal sequence of the protein, was bound by the nonneutralizing MAb CC1H7. Inhibition assays of the GM-CSF biological activity demonstrated that MAb M1B8, CC5B5 and M7E10 bind to domains which are responsible for the interaction of the cytokine with the GM-CSF receptor.
Crystal Chemistry and Luminescence of Ce3+-Doped Lu2CaMg2(Si,Ge)3O12 and Its Use in LED Based Lighting (2006)

In this paper, we describe the formation and luminescence of a new garnet phosphor for light emitting diode (LED) based lighting, Lu2CaMg2(Si,Ge)3O12:Ce3+. The regions for garnet phase formation are initially described with respect to larger rare earth substitution and show reasonable correlation to previous crystal chemistry studies for the garnet parent structure. While the pure silicate phosphor also has apatite second phases, a significant amount of Ce3+ enters the garnet phase, giving Ce3+ luminescence that is significantly redder when compared to typical Al3+ garnet phosphors with quantum efficiencies comparable to commercial Ce3+ garnet phosphors. Potential reasons for the emission red shift and the high quantum efficiency are discussed. Finally, the performance of these new phosphors is tested within LED based lamps. Lamps using these phosphors can reach color temperatures required for general illumination lighting and also have comparable phosphor conversion efficiencies when compared to lamps using typical garnet phosphors.
Super-resolution from a single image (2009)

Methods for super-resolution can be broadly classified into two families of methods: (i) The classical multi-image super-resolution (combining images obtained at subpixel misalignments), and (ii) Example-Based super-resolution (learning correspondence between low and high resolution image patches from a database). In this paper we propose a unified framework for combining these two families of methods. We further show how this combined approach can be applied to obtain super resolution from as little as a single image (with no database or prior examples). Our approach is based on the observation that patches in a natural image tend to redundantly recur many times inside the image, both within the same scale, as well as across different scales. Recurrence of patches within the same image scale (at subpixel misalignments) gives rise to the classical super-resolution, whereas recurrence of patches across different scales of the same image gives rise to example-based super-resolution. Our approach attempts to recover at each pixel its best possible resolution increase based on its patch redundancy within and across scales.
Synthesis of Functionalized Adamantane Derivatives: (3 + 1)-Scaffolds for Applications in Medicinal and Material Chemistry (2013)

Due to its rigid cage structure, adamantane has received considerable interest as a scaffold with a defined tetrahedral geometry. In this paper we describe orthogonally functionalized tetrasub­stituted adamantane derivatives. These compounds may be conjugated to other functional molecules by standard techniques such as amide formation or click chemistry and are thus useful (3 + 1) scaffolds for medicinal and material chemistry.
Yersinia enterocolitica invasin: a primary role in the initiation of infection. (1993)

The ability to invade the intestinal epithelium of mammals is an essential virulence determinant of Yersinia enterocolitica. The chromosomally encoded Y. enterocolitica 8081v invasion gene, inv, was disrupted to assess its role in pathogenesis. The inv mutant (JP273v) was approximately 80-fold less invasive than wild type for cultured epithelial cells. When mice were infected intragastrically, up to 10(7) fewer JP273v were recovered from Peyer's patches early (6-18 hr) after infection compared with wild type. Analysis of the course of infection revealed that the inv mutant had distinct differences relative to wild type in the distribution of visible infectious foci and in tissue colonization; however, the mutant and wild-type strains had similar LD50 values for both orally and intraperitoneally infected mice. The invasion defect of the inv mutant was fully complemented in vitro and in vivo by introduction of the wild-type inv gene in trans. The inv gene product, invasin, appears to play a vital role in promoting entry during the initial stage of infection. During the subsequent establishment of a systemic infection, invasin may be of secondary importance, since the Y. enterocolitica inv mutant was as proficient as wild type at causing a fatal infection in mice. Based on these data, we discuss the role of invasin in a naturally occurring Y. enterocolitica infection.
연구논문 : 청소년 사이버일탈의 특성과 유형에 관한 연구 (2000)

본 연구는 청소년의 컴퓨터활용과 정보화역기능에 의해 야기되는 여러 가지 일탈현상을 `사이버일탈` 즉, `사이버 공간에서의 청소년일탈`로 개념화하고 그것을 유발하는 사이버공간의 특성을 고찰하며 정보사회로의 변화를 주도하는 중심계층으로서 청소년세대의 사이버일탈의 유형과 내용을 알아보는 것을 목적으로 한다. 사이버일탈은 컴퓨터라는 매체의 고유한 특성과 그 매체가 담고 있는 내용물을 포함하는 사이버공간의 특징과 그것을 이용하는 청소년들의 심리적·현실적 상태 등의 몇가지 측면이 복합적으로 작용하는 현상에서 비롯되고 있다. 사이버 공간에서의 청소년일탈과 관련성이 깊은 컴퓨터의 매체적 특성에는 익명성과 비대면성, 시공초월성, 빠른 전파성 등이 지적된다. 자아정체성을 실험하고 탐험하는 청소년시기의 특성, 컴퓨터를 놀이공간과 친근한 인간관계와 소속감 경험의 기회 및 욕구불만의 배출구로 활용하는 청소년의 사이버공간 활용동기 등도 일탈행동과 관련된다. 사이버일탈은 컴퓨터몰입과 인터넷중독의 문제, 사이버범죄 및 부적절한 문제행동 등 3가지로 유형화할 수 있다. 컴퓨터중독은 다른 사람에게 물질적 피해를 입히는 정도는 매우 약하지만 많은 청소년들에게 나타나고 있어 우려된다. 사이버범죄는 해킹, 바이러스 유포, 아이디 도용, 사이버성폭력, 사이버스토킹, 도박 등과 같이 행위에 대한 사회적 반응과 피해가 매우 크며 현실세계의 권위적 처벌이 따른다는 점에서 대표적인 일탈행위로 논의된다. 부적절한 문제행위는 유언비어와 언어폭력, 음란폭력물의 접촉 등과 같이 컴퓨터이용자간의 제재가 따르거나 사회문제화하고 지나친 경우 타인명예훼손과 불건전정보 유포 등으로 처벌이 따른다는 점에서 유의할 필요가 있다.
Reduction of .alpha.,.beta.-acetylenic ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane. High asymmetric induction in aliphatic systems (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of .alpha.,.beta.-acetylenic ketones with B-3-pinanyl-9-borabicyclo[3.3.1]nonane. High asymmetric induction in aliphatic systemsM. Mark Midland, Deborah C. McDowell, Robert L. Hatch, and Alfonso TramontanoCite this: J. Am. Chem. Soc. 1980, 102, 2, 867–869Publication Date (Print):January 1, 1980Publication History Published online1 May 2002Published inissue 1 January 1980https://pubs.acs.org/doi/10.1021/ja00522a083https://doi.org/10.1021/ja00522a083research-articleACS PublicationsRequest reuse permissionsArticle Views1077Altmetric-Citations186LEARN 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
Mechanism of activation of sensory rhodopsin I: evidence for a steric trigger. (1991)

Sensory rhodopsin I (SR-I) and bacteriorhodopsin (BR) from Halobacterium halobium show broad structural and spectroscopic similarities and yet perform distinct functions: photosensory reception and proton pumping, respectively. Probing the photoactive sites of SR-I and BR with 24 retinal analogs reveals differences in the protein environments near the retinal 13-methyl group and near the beta-ionone ring. 13-cis-Retinal does not form a retinylidene pigment with the SR-I apoprotein, although this isomer binds to the BR apoprotein even more rapidly than all-trans-retinal, the functional isomer of both pigments. The activation of both SR-I and BR requires all-trans/13-cis isomerization of retinal;however, a steric interaction between the retinal 13-methyl group and the protein is required for SR-I activation but not for that of BR. These results reveal a key difference between SR-I and BR that is likely to be the initial diverging point in their photoactivation pathways. We propose the 13-methyl group-protein interaction functions as a trigger for SR-I activation--i.e., converts photon absorption by the chromophore into protein conformational changes. A similar steric trigger is essential for activation of mammalian rhodopsin, indicating a common mechanism for receptor activation in archaebacterial and vertebrate retinylidene photosensors.
A biotin‐dependent sodium pump: glutaconyl‐CoA decarboxylase from Acidaminococcus fermentans (1982)

The decarboxylation of glutaconyl-CoA to crotonyl-CoA in the anaerobic bacterium Acidaminococcus fermentans is catalysed by a membrane-bound, biotin-dependent enzyme which requires Na+ for activity. Inverted vesicles from A. fermentans accumulated Na+ only if glutaconyl-CoA was decarboxylated. The Na+ uptake was inhibited by avidin but not by the avidin biotin complex. Detergents and ionophores such as monensin also prevented the Na+ transport. The results indicate that the enzyme is able to convert the free energy of decarboxylation (delta Go' approximately equal to -30 kJ/mol) into a Na+ gradient.
New synthetic reactions. Oxidative decarboxylation (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew synthetic reactions. Oxidative decarboxylationBarry M. Trost and Yoshinao TamaruCite this: J. Am. Chem. Soc. 1975, 97, 12, 3528–3530Publication Date (Print):June 1, 1975Publication History Published online1 May 2002Published inissue 1 June 1975https://pubs.acs.org/doi/10.1021/ja00845a048https://doi.org/10.1021/ja00845a048research-articleACS PublicationsRequest reuse permissionsArticle Views884Altmetric-Citations43LEARN 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
Allosteric Modulation of Muscarinic Acetylcholine Receptors (2007)

Muscarinic acetylcholine receptors (mAChRs) are prototypical Family A G protein coupled-receptors. The five mAChR subtypes are widespread throughout the periphery and the central nervous system and, accordingly, are widely involved in a variety of both physiological and pathophysiological processes. There currently remains an unmet need for better therapeutic agents that can selectively target a given mAChR subtype to the relative exclusion of others. The main reason for the lack of such selective mAChR ligands is the high sequence homology within the acetylcholine-binding site (orthosteric site) across all mAChRs. However, the mAChRs possess at least one, and likely two, extracellular allosteric binding sites that can recognize small molecule allosteric modulators to regulate the binding and function of orthosteric ligands. Extensive studies of prototypical mAChR modulators, such as gallamine and alcuronium, have provided strong pharmacological evidence, and associated structure-activity relationships (SAR), for a "common" allosteric site on all five mAChRs. These studies are also supported by mutagenesis experiments implicating the second extracellular loop and the interface between the third extracellular loop and the top of transmembrane domain 7 as contributing to the common allosteric site. Other studies are also delineating the pharmacology of a second allosteric site, recognized by compounds such as staurosporine. In addition, allosteric agonists, such as McN-A-343, AC-42 and N-desmethylclozapine, have also been identified. Current challenges to the field include the ability to effectively detect and validate allosteric mechanisms, and to quantify allosteric effects on binding affinity and signaling efficacy to inform allosteric modulator SAR.
Ovarian cancer BRCA1 gene therapy: Phase I and II trial differences in immune response and vector stability. (1999)

Gene therapy with viral vectors has shown some promise in nude mice models and in initial Phase I trials of patients with extensive metastatic cancer. A Phase I clinical trial (D. L. Tait et al., Clin. Cancer Res., 3: 1959-1968, 1997) of ovarian cancer patients treated with i.p. retroviral LXSN-BRCA1sv gene therapy reported stable vector, minimal antibody response, and tumor reduction. We initiated a Phase II trial on patients with less extensive disease to evaluate vector pharmacokinetics, immune response, toxicity, and efficacy. Patients received a surgically implanted peritoneal catheter to administer infusions of vector, as well as to retrieve daily samples of peritoneal fluid for analysis. Ovarian cancer patients received four daily i.p. injections of LXSN-BRCA1sv vector therapy for three cycles, 4 weeks apart. Patient peritoneal fluid and plasma were analyzed extensively by PCR, Western blot, complement level (CH50), and chemical and hematological tests. Phase II patients showed no response, no disease stabilization, and little or no vector stability. Because of vector instability and rapid antibody development, which differed dramatically from the Phase I trial data, the trial was terminated after treatment of six patients. Immune system status appears to have played a major role in whether gene therapy was effective. Comparison of Phase I and II patients showed significant differences in tumor burden, immune system status, and response to BRCA1 gene therapy.