gebhart/patrepeval huggingface dataset:
Rapid and efficient synthesis of nucleoside 5'-0-(1-thiotriphosphates), 5'-triphosphates and 2',3'-cyclophosphorothioates using 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRapid and efficient synthesis of nucleoside 5'-0-(1-thiotriphosphates), 5'-triphosphates and 2',3'-cyclophosphorothioates using 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-oneJanos Ludwig and Fritz EcksteinCite this: J. Org. Chem. 1989, 54, 3, 631–635Publication Date (Print):February 1, 1989Publication History Published online1 May 2002Published inissue 1 February 1989https://pubs.acs.org/doi/10.1021/jo00264a024https://doi.org/10.1021/jo00264a024research-articleACS PublicationsRequest reuse permissionsArticle Views3866Altmetric-Citations319LEARN 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
Expression of human soluble tissue factor in yeast and enzymatic properties of its complex with factor VIIa. (1992)

The extracellular domain of human tissue factor (TF, amino acids 1-217) was expressed in Saccharomyces cerevisiae, using the inducible yeast acid phosphatase promoter and the yeast invertase signal sequence to direct its secretion into the culture broth. Two active soluble forms sTF alpha (high molecular weight form) and sTF beta (low molecular weight form) were purified, the yield being approximately 10 and 1 mg/liter of culture supernatant, respectively. sTF alpha had an apparent molecular mass of 150 kDa on SDS-polyacrylamide gel electrophoresis and contained more than 200 residues of mannose/mol of protein. sTF beta had an apparent molecular mass of 37 kDa and contained 22 residues of mannose/mol of protein. N-Glycosidase F treatments of both rTFs reduced the apparent molecular mass to 35 kDa. The amino-terminal sequences and amino acid compositions of sTF alpha and sTF beta were consistent with those deduced from the cDNA sequence, thereby indicating that the difference in molecular mass is caused by heterogeneity of oligosaccharide structures. Of these recombinant TFs, sTF beta enhanced factor VIIa-amidolytic activity 40-fold toward the chromogenic substrate and 147-fold toward the fluorogenic substrate, affecting mainly the kcat value. The enhancement was comparable with that of TF purified from human placenta. The TF-mediated enhancement of factor VIIa-amidolytic activity was inhibited by heparin-activated antithrombin III, forming a high molecular weight complex. As treatment of sTF beta with denaturants such as guanidine hydrochloride or urea led to a biphasic loss of the activity, the extracellular domain of TF probably consists of two discrete domains. This expression system provides a significant amount of the extracellular domain of TF so that studies of interactions with factor VII are feasible.
VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research (2016)

Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict performs amplicon aware variant calling for polymerase chain reaction (PCR)-based targeted sequencing often used in diagnostic settings, and is able to detect PCR artifacts. Finally, VarDict also detects differences in somatic and loss of heterozygosity variants between paired samples. VarDict reprocessing of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than previously published variant calls. We believe VarDict will greatly facilitate application of NGS in clinical cancer research.
Melanoma-specific CD4+ T cells recognize nonmutated HLA-DR-restricted tyrosinase epitopes. (1996)

Tyrosinase was the first melanoma-associated antigen shown to be recognized by CD4+ T cells. In this study, we have identified two HLA-DRB1*0401-restricted peptides recognized by these T cells: Ty 56-70 and Ty 448-462. As with many of the MHC class I-restricted melanoma epitopes, both are nonmutated self peptides that have intermediate and weak MHC binding affinities, respectively. Mutated and truncated versions of these peptides were used to define their MHC binding anchor residues. Anchor residues were then modified to derive peptides with increased MHC binding affinities and T cell stimulatory properties. Ty 56-70 and Ty 448-462 enhance the list of immunogenic HLA-A2-, A24-, and B44-restricted tyrosinase peptides already described. Thus, tyrosinase provides a model for anti-melanoma vaccines in which a single molecule can generate multivalent immunization incorporating both CD4+ and CD8+ T cell responses.
The Mercury System: Embedding Computation into Disk Drives (2004)

Having inexpensive data storage has enabled the amassing of vast amounts of information. At present, these data sets far exceed the capacity of modern processors, so searching them has become a serious challenge. In a recent invited talk at the High Performance Embedded Computing Workshop, John Reynders of Celera Genomics commented that, "The size of the databases we deal with is no longer measured in terabytes, but in exabytes." The Mercury system is a prototype data search engine that can be embedded within the disk drive itself. We focus on the specific problems associated with searches of unstructured, unindexed data. Three specific applications include approximate matching of text (important for text searches of specific interest to homeland security where the original alphabet is different than the Latin alphabet and transliteration is involved), genomics and proteomics searches (important biological applications), and image searches (also of significant interest for homeland security).
Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa (2002)

Persistent expression of Mcm2, Mcm5, and Ki-67 proteins in luminal compartments of dysplastic oesophageal squamous epithelium and dysplastic Barrett's mucosa may be diagnostic markers and imply disruption of cell cycle control and differentiation in these dysplastic epithelia.
Angiopoietin-1 inhibits toll-like receptor 4 signalling in cultured endothelial cells: role of miR-146b-5p (2015)

Ang-1 disrupts TLR4 signalling, resulting in inhibition of LPS-induced inflammatory responses in endothelial cells. This inhibition occurs through selective targeting of IRAK1 and TRAF6 proteins by miR-146b-5p.
Neutrophil Elastase: Mediator of Extracellular Matrix Destruction and Accumulation (2006)

Of the myriad proteolytic enzymes implicated in the development of lung disease, neutrophil elastase has undoubtedly some of the most versatile effects. Although its key physiologic role is in innate host defense, it can also participate in tissue remodeling and possesses secretagogue actions that are now recognized as important to local inflammatory responses. Although unopposed neutrophil elastase activity has been implicated in the development of emphysema for several decades, only relatively recently has a pathogenetic function been ascribed to this serine proteinase in situations where excessive extracellular matrix deposition occurs. The use of genetically manipulated animal models is starting to uncover the potential ways in which its actions might influence fibrotic lung repair. Emerging evidence suggests that the engagement of cellular pathways with more direct effects on fibrogenic mediator generation and collagen synthesis appears to underpin the actions of neutrophil elastase in promoting lung matrix accumulation.
DNA Vaccination with the Hantaan Virus M Gene Protects Hamsters against Three of Four HFRS Hantaviruses and Elicits a High-Titer Neutralizing Antibody Response in Rhesus Monkeys (2001)

Four hantaviruses-Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus-are known to cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. HTNV causes the most severe form of HFRS (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. Previously, we demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene elicited neutralizing antibodies and protected hamsters against infection with SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters with the HTNV M gene conferred sterile protection against infection with HTNV, SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M gene elicited high levels of neutralizing antibodies. These are the first immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a neutralizing antibody response is considered a surrogate marker for protective immunity in humans, our protection data in hamsters combined with the immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines could protect humans against the most severe forms of HFRS.
Diffusion tensor imaging using single‐shot SENSE‐EPI (2002)

SENSitivity Encoding (SENSE) greatly enhances the quality of diffusion-weighted echo-planar imaging (EPI) by reducing blurring and off-resonance artifacts. Such improvement would also be desirable for diffusion tensor imaging (DTI), but measures derived from the diffusion tensor can be extremely sensitive to any kind of image distortion. Whether DTI is feasible in combination with SENSE has not yet been explored, and is the focus of this study. Using a SENSE-reduction factor of 2, DTI scans in eight healthy volunteers were carried out with regular- and high-resolution acquisition matrices. To further improve the stability of the SENSE reconstruction, a new coil-sensitivity estimation technique based on variational calculus and the principles of matrix regularization was applied. With SENSE, maps of the trace of the diffusion tensor and of fractional anisotropy (FA) had improved spatial resolution and less geometric distortion. Overall, the geometric distortions were substantially removed and a significant resolution enhancement was achieved with almost the same scan time as regular EPI. DTI was even possible without the use of quadrature body coil (QBC) reference scans. Geometry-factor-related noise enhancement was only discernible in maps generated with higher-resolution matrices. Error boundaries for residual fluctuations in SENSE reconstructions are discussed. Our results suggest that SENSE can be combined with DTI and may present an important adjunct for future neuroimaging applications of this technique.
Mild Regioselective Monobromination of Activated Aromatics and Heteroaromatics withN-Bromosuccinimide in Tetrabutylammonium Bromide (2005)

Highly regioselective nuclear bromination of activated aromatic and heteroaromatic compounds has been accomplished using N-bromosuccinimide in tetrabutylammonium bromide. Predominant para-selective monobromination of activated aromatics such as phenols and anilines, rate acceleration of bromination for moderately activated and less reactive substrates on addition of acidic montmorillonite K-10 clay, with or without microwave assistance, are the notable features of this protocol.
APPOSITION AND DRAINAGE OF LARGE SKIN FLAPS BY SUCTION (1957)

Summary The use of suction for drainage and apposition of skin flaps to underlying tissues, already described for use after radical mastectomy, has been applied to other areas where skin flaps and dead space remain after operations, notably in the neck, groin, and in amputation wounds. The advantages of the method are stated, points of technique in general and for special areas are detailed, and results mentioned.
Ionizing Radiation Predisposes Nonmalignant Human Mammary Epithelial Cells to Undergo Transforming Growth Factor β–Induced Epithelial to Mesenchymal Transition (2007)

Transforming growth factor beta1 (TGFbeta) is a tumor suppressor during the initial stage of tumorigenesis, but it can switch to a tumor promoter during neoplastic progression. Ionizing radiation (IR), both a carcinogen and a therapeutic agent, induces TGFbeta activation in vivo. We now show that IR sensitizes human mammary epithelial cells (HMEC) to undergo TGFbeta-mediated epithelial to mesenchymal transition (EMT). Nonmalignant HMEC (MCF10A, HMT3522 S1, and 184v) were irradiated with 2 Gy shortly after attachment in monolayer culture or treated with a low concentration of TGFbeta (0.4 ng/mL) or double treated. All double-treated (IR + TGFbeta) HMEC underwent a morphologic shift from cuboidal to spindle shaped. This phenotype was accompanied by a decreased expression of epithelial markers E-cadherin, beta-catenin, and ZO-1, remodeling of the actin cytoskeleton, and increased expression of mesenchymal markers N-cadherin, fibronectin, and vimentin. Furthermore, double treatment increased cell motility, promoted invasion, and disrupted acinar morphogenesis of cells subsequently plated in Matrigel. Neither radiation nor TGFbeta alone elicited EMT, although IR increased chronic TGFbeta signaling and activity. Gene expression profiling revealed that double-treated cells exhibit a specific 10-gene signature associated with Erk/mitogen-activated protein kinase (MAPK) signaling. We hypothesized that IR-induced MAPK activation primes nonmalignant HMEC to undergo TGFbeta-mediated EMT. Consistent with this, Erk phosphorylation was transiently induced by irradiation and persisted in irradiated cells treated with TGFbeta, and treatment with U0126, a MAP/Erk kinase (MEK) inhibitor, blocked the EMT phenotype. Together, these data show that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to neoplastic progression.
Genotype and phenotype resistance: an overview. (2000)

Drug resistance is a major factor contributing to the failure of antiretroviral therapy. The rapid turnover of the human immunodeficiency virus type 1 (HIV-1) and the error-prone reverse transcriptase both contribute to the extensive emergence of resistant variants. The understanding of resistance and cross-resistance patterns is essential for the appropriate selection of treatment regimens for HIV-infected individuals. Although genotypic and phenotypic assays of drug resistance are not currently recommended for routine use, preliminary data has emphasized the role of resistance testing in guiding the choice of initial antiretroviral therapy, in explaining reasons for failure, and in selecting subsequent therapy for patients failing their current regimen. This article reviews the advantages and disadvantages of currently available resistance assays, as well as mechanisms and patterns of resistance and cross-resistance.
A Monoclonal Antibody against Wnt-1 Induces Apoptosis in Human Cancer Cells (2004)

Aberrant activation of the Wingless-type (Wnt)/beta-catenin signaling pathway is associated with a variety of human cancers. Little is known regarding the role that Wnt ligands play in human carcinogenesis. To test whether a Wnt-1 signal is a survival factor in human cancer cells and thus may serve as a potential cancer therapeutic target, we investigated the effect of inhibition of Wnt-1 signaling in a variety of human cancer cell lines, including non small cell lung cancer, breast cancer, mesothelioma, and sarcoma. Both monoclonal antibody and RNA interference (RNAi) were used to inhibit Wnt-1 signaling. We found that incubation of a monoclonal anti-Wnt-1 antibody induced apoptosis and caused downstream protein changes in cancer cells overexpressing Wnt-1. In contrast, apoptosis was not detected in cells lacking or having minimal Wnt-1 expression after the antibody incubation. RNAi targeting of Wnt-1 in cancer cells overexpressing Wnt-1 demonstrated similar downstream protein changes and induction of apoptosis. The antibody also suppressed tumor growth in vivo. Our results indicate that both monoclonal anti-Wnt-1 antibody and Wnt-1 siRNA inhibit Wnt-1 signaling and can induce apoptosis in human cancer cells. These findings hold promise as a novel therapeutic strategy for cancer.
Synthesis and surface properties of chemodegradable anionic surfactants: Diastereomeric (2‐n‐alkyl‐1,3‐dioxan‐5‐yl) sulfates with monovalent counter‐ions (2000)

Abstract Sodium, potassium and ammonium cis ‐ and trans ‐(2‐ n ‐alkyl‐1,3‐dioxan‐5‐yl) sulfates 6–8 (alkyl: n ‐C 9 H 19 , 6a–8a , and n ‐C 11 H 23 , 6b–8b ) were synthesized in a reaction of aliphatic aldehydes 1a,b with glycerol 2 followed by separation in high yields of individual geometric isomers of cis ‐and trans ‐2‐ n ‐alkyl‐5‐hydroxy‐1,3‐dioxanes, cis ‐ 3a,b and trans ‐ 3a,b , followed by sulfation with sulfur trioxide‐pyridine complex, and finally neutralization with NaOH, KOH, and NH 4 OH, respectively. Physical data of the compounds and some surface properties of 2‐ n ‐nonyl derivatives, such as critical micelle concentration (CMC), effectiveness of aqueous surface tension reduction (Π CMC ), surface excess concentration Γ CMC , and the surface area demand per molecule (A CMC ), were determined. It was shown that the surface activity of these compounds is influenced both by their geometric structure and by the monovalent counter‐ion.
Applications of MALDI Mass Spectrometry in Clinical Chemistry (2015)

MALDI-TOF MS has already transformed the practice of clinical microbiology and this review illustrates how and why it is now set to play an increasingly important role in in vitro diagnostics in particular, and clinical chemistry in general.
Genetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activation (2011)

Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive neurodegenerative disease characterized by axonal dystrophy, abnormal iron deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, which encodes group VI Ca 2+ -independent phospholipase A 2 (iPLA 2 or iPLA 2 b). Here we show that genetic ablation of PLA2G6 in mice (iPLA 2 b -/-) leads to the development of cerebellar atrophy by the age of 13 months. Atrophied cerebella exhibited significant loss of Purkinje cells, as well as reactive astrogliosis, the activation of microglial cells, and the pronounced upregulation of the pro-inflammatory cytokines tumor necrosis factor-a (TNF-a) and interleukin-1b (IL-1b). Moreover, glial cell activation and the elevation in TNF-a and IL-1b expression occurred before apparent cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests that iPLA 2 b -/-mice are a valuable model for cerebellar atrophy in INAD and that early antiinflammatory therapy may help slow the progression of cerebellar atrophy in this deadly neurodegenerative disease.
Composition and density of microflora in the subungual space of the hand (1988)

There were significant quantitative differences in the composition and density of microflora in different areas of the hands of 26 adult volunteers. The subungual spaces had an average log10 CFU of 5.39, compared with a range from 2.55 to 3.53 for other hand sites. In quantitative cultures from five subungual spaces in 26 subjects, coagulase-negative staphylococci were the dominant organisms, with Staphylococcus epidermidis, S. haemolyticus and S. hominis being the most frequently isolated species. Other bacteria recovered from subungual spaces included gram-negative bacilli in 42.3% of subjects, with Pseudomonas species composing 31.3% of this group, and coryneforms in 42.3% of subjects, with multiply resistant JK group coryneforms making up 12.5%. Yeasts were isolated from 69.0% of subjects sampled, with 51.3% of the yeasts identified as Candida parapsilosis. The subungual coagulase-negative staphylococci were susceptible to most antibiotics, with resistance to penicillin, ampicillin, and erythromycin detected in 23 to 38% of isolates.
Synthesis of Spiro[4.5]decan-1-ones: A Formal Synthesis of Acoradienes and Related Sesquiterpenes via Rhodium-catalyzed Claisen Rearrangement/Hydroacylation (1996)

A novel procedure for the synthesis of spiro[4.5]decan-1-ones starting from commercially available substances is described. The key-step is a one-pot combination of Claisen rearrangement of allyl vinyl ethers followed by an intramolecular hydroacylation1 catalysed by RhCl(cod)(dppe).2 The intermediate pent-4-enals generated by the initial [3.3] sigmatropic rearrangement exhibit substitution patterns which have previously been described as unsuitable for the rhodium catalysed intramolecular hydroacylation.3,4 This procedure allows the synthesis of ketone 2, a key intermediate in the total synthesis of acoradienes and acorones.5
Chemistry: The Molecular Nature of Matter and Change (1995)

Keys to the study of chemistry the components of the matter stoichiometry - mole-mass relationships in chemical systems the major classes of chemical reactions gases and the kinetic-molecular theory thermochemistry - energy flow and chemical change quantum theory and atomic structure electron configuration and chemical periodicity models of chemical bonding molecular shape and theories aof covalent bonding intermolecualr forces - liquids, solids, and changes of state the properties of mixtures - solutions and colloids periodic patterns in the main-group elements - bonding, structure, and reactivity organic compound and the atomic properties of carbon kinetics - rates and mechanisms of chemical reactions equilibrium - the extent of chemical reactions acid-base equilibria in aqueous systems ionic equilibria in aqueous systems thermodynamics - entropy, free energy, and the direction of chemical reactions electrochemistry - chemical change and electrical work nuclear reactions and their applications the transition elements and their coordination compounds the elements in nature and industry. Appendices: math review reference tables answers to selected problems glossary credits index.
8Gb 3D DDR3 DRAM using through-silicon-via technology (2009)

DRAMs in modules are preferably arranged in multiple ranks to increase system band-width. However, this limits the input/output (I/O) speed since increased channel loading causes degradation in signal integrity. To overcome the I/O speed limit, several buffered module solutions have been proposed, where data pins are buffered by additional chips. However, this increases power consumption and latency significantly. We present a 3D DRAM with TSVs that overcomes the limits of conventional module approaches. Important architectural aspects, and key 3D technologies such as inter-rank seamless read scheme, TSV check and repair scheme, and a power-noise reduction method are presented.