gebhart/patrepeval huggingface dataset:
A prototype chip of multicontext FPGA with DRAM for virtual hardware (2002)

DRAM-type multicontext FPGA has potential for virtual hardware, since it is possible to implement a large number of contexts in a single chip. However, only a few examples have been reported because of the difficulty of the mixed process involving DRAM and logic. Here we try to implement a prototype multicontext FPGA with DRAM for virtual hardware.
Ecological Survey of Wine Yeast Strains by Molecular Methods of Identification (1992)

An ecological study of <i>Saccharomyces cerevisiae</i> strains isolated from the enological fermentative microflora has been conducted in two vineyards (Champagne and Loire Valley) during six consecutive years. The strain identification has been performed by PFE chromosomal patterns or mitochondrial DNA restriction profiles. In both situations a large diversity of molecular patterns has been shown. Some of the strains which were more frequently encountered over the six-year experiment seemed to be widely distributed and representative of one vineyard or one wine production site.
Sequence diversity of V1 and V2 domains of gp120 from human immunodeficiency virus type 1: lack of correlation with viral phenotype (1995)

We analyzed by PCR and direct sequencing 57 viral sequences from 47 individuals infected with human immunodeficiency virus type 1, focussing on the V1 and V2 regions of gp120. There was extensive length polymorphism in the V1 region, which rendered sequence alignment difficult. The V2 hypervariable locus also displayed considerable length variations, whereas flanking regions were relatively conserved. Two-thirds of the amino acid residues in these flanking regions were highly conserved (> 80%), presumably reflecting their critical contribution to V2 structure or function. We also characterized the syncytium-inducing properties of the isolates from which we derived sequence information. There was no correlation between V1 or V2 sequences and the viral phenotype, contrary to a previous report (M. Groenink, R. A. M. Fouchier, S. Broersen, C. H. Baker, M. Koot, A. B. van't Wout, H. G. Huisman, F. Miedema, M. Tersmette, and H. Schuitemaker, Science 260:1513-1516, 1993). The sequence heterogeneity described in this study provides information to suggest that it would be most difficult to exploit the V1 and V2 domains for vaccine development.
A sketch-based interface for detail-preserving mesh editing (2007)

In this paper we present a method for the intuitive editing of surface meshes by means of view-dependent sketching. In most existing shape deformation work, editing is carried out by selecting and moving a handle, usually a set of vertices. Our system lets the user easily determine the handle, either by silhouette selection and cropping, or by sketching directly onto the surface. Subsequently, an edit is carried out by sketching a new, view-dependent handle position or by indirectly influencing differential properties along the sketch. Combined, these editing and handle metaphors greatly simplify otherwise complex shape modeling tasks.
The history and development of the theory and practice of cybercartography (2009)

Abstract This paper describes the development of cybercartography since the introduction of the term in 1997. Although the origins of cybercartography were largely conceptual in nature, the evolution of cybercartography to date has been an iterative process reflecting the creative interplay between theory and practice. A major step forward was made in 2002 when the Geomatics and Cartographic Research Centre at Carleton University received a $2.5 million grant from the Social Sciences and Humanities Research Council of Canada to explore the utility of cybercartography to what was described as the New Economy. By 2006, the interaction between theory and practice had led to considerable advances in cybercartography as a holistic, location-based concept and two new cybercartographic products, the Cybercartographic Atlas of Antarctica and the Cybercartographic Atlas of Canada's Trade with the World, were produced. Between 2006 and 2009, cybercartography was further developed as a result of interaction with indigenous communities, especially in Canada's north and new interactive atlases such as the Kitikmeot Place Names Atlas and the Community Atlas of Arctic Bay were created in cooperation with the communities involved. The Nunaliit Cybercartographic Atlas Framework, built using open source software and open specifications and standards, was developed to facilitate direct input to these atlases. Cybercartography is now entering a new phase in both theory and practice building on a recently completed prototype atlas of Indigenous Perspectives and Knowledge.
TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy (2013)

Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor-the TanCAR, a novel artificial molecule that mediates bispecific activation and targeting of T cells. We demonstrate the feasibility of cumulative integration of structure and docking simulation data using computational tools to interrogate the design and predict the functionality of such a complex bispecific molecule. Our prototype TanCAR induced distinct T cell reactivity against each of two tumor restricted antigens, and produced synergistic enhancement of effector functions when both antigens were simultaneously encountered. Furthermore, the TanCAR preserved the cytolytic ability of T cells upon loss of one of the target molecules and better controlled established experimental tumors by recognition of both targets in an animal disease model. This proof-of-concept approach can be used to increase the specificity of effector cells for malignant versus normal target cells, to offset antigen escape or to allow for targeting the tumor and its microenvironment.Molecular Therapy-Nucleic Acids (2013) 2, e105; doi:10.1038/mtna.2013.32; published online 9 July 2013.
Primary Structural Determinants Essential for Potent Inhibition of cAMP-dependent Protein Kinase by Inhibitory Peptides Corresponding to the Active Portion of the Heat-Stable Inhibitor Protein (1989)

PKI-(5-24)-amide is a 20-residue peptide with the sequence, Thr5-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-A la-Ile-His- Asp24-NH2, that corresponds to the active portion of the heat-stable inhibitor protein of cAMP-dependent protein kinase (Cheng, H.-C., Kemp, B. E., Pearson, R. B., Smith, A. J., Misconi, L., Van Patten, S. M., and Walsh, D. A. (1986) J. Biol. Chem. 261, 989-992). Amino acid residues in PKI-(5-24)-amide responsible for the potent inhibition (Ki = 2.3 nM) of the catalytic subunit of protein kinase were further investigated using deletion and substitution analogs of the synthetic peptide. Residues 5, 23, and 24 were not required for activity since the 17-residue PKI-(6-22)-amide retained full potency. Sequential removal of the first seven amino acids from the NH2 terminus of PKI-(5-24)-amide caused a progressive 50-fold loss of inhibitory potency. In contrast, substitution of either Thr6, Asp9, or Ile11 with alanine, or Ala8 by leucine, in PKI-(5-22)-amide produced less than 3-fold decreases in potency. Of the 2 aromatic residues in PKI-(5-22)-amide, the individual substitution of Phe10 and Tyr7 by alanine caused, respectively, 90- and 5-fold decreases in inhibitory potency, demonstrating important roles for each. This NH2-terminal portion of the peptide is believed to contain a significant portion of alpha-helix. Many recognition or structural determinants are also essential in the COOH-terminal portion of PKI-(5-22)-amide. In addition to the basic subsite provided by the three arginines, several other of the residues are critical for full inhibitory potency. Substitution of Ile22 by glycine in either PKI-(5-22)-amide or PKI-(14-22)-amide lowered the inhibitory potency by 150- and 50-fold, respectively. Separate replacement of Gly17 or Asn20, in either PKI-(5-22)-amide or PKI-(14-22)-amide, caused 7-15-fold decreases in potency. Substitution of both Gly17 and Asn20 together (in PKI-(14-22)-amide) produced a synergistic loss of inhibitory activity. [Leu13,Ile14]PKI-(5-22)-amide, a doubly substituted analog exhibited a 42-fold increase in Ki value. We conclude that Ser13 and/or Gly14, Gly17, Asn20, and Ile22 each contribute important features to the binding of these inhibitory peptides to the protein kinase, either by providing recognition determinants, inducing structure, and/or allowing essential peptide backbone flexibility.(ABSTRACT TRUNCATED AT 400 WORDS)
The reconstruction of 2,631 draft metagenome-assembled genomes from the global oceans (2018)

Microorganisms play a crucial role in mediating global biogeochemical cycles in the marine environment. By reconstructing the genomes of environmental organisms through metagenomics, researchers are able to study the metabolic potential of Bacteria and Archaea that are resistant to isolation in the laboratory. Utilizing the large metagenomic dataset generated from 234 samples collected during the Tara Oceans circumnavigation expedition, we were able to assemble 102 billion paired-end reads into 562 million contigs, which in turn were co-assembled and consolidated in to 7.2 million contigs ≥2 kb in length. Approximately 1 million of these contigs were binned to reconstruct draft genomes. In total, 2,631 draft genomes with an estimated completion of ≥50% were generated (1,491 draft genomes >70% complete; 603 genomes >90% complete). A majority of the draft genomes were manually assigned phylogeny based on sets of concatenated phylogenetic marker genes and/or 16S rRNA gene sequences. The draft genomes are now publically available for the research community at-large.
Monovalent cation effects on intermolecular purine-purine-pyrimidine triple-helix formation (1993)

The binding of a 19-mer guanosine-rich oligodeoxyribonucleotide, TG3TG4TG4TG3T (ODN 1), to a complementary polypurine DNA target was investigated by DNase I footprinting and restriction endonuclease protection assays. Monovalent cations inhibited intermolecular purine-purine-pyrimidine triple-helical DNA formation, with K+ and Rb+ being most effective, followed by NH4+ and Na+. Li+ and Cs+ had little to no effect. Similar results were observed with the G/A-rich oligonucleotide AG3AG4AG4AG3AGCT. Kinetic studies indicated that monovalent cations interfered with oligonucleotide-duplex DNA association but did not significantly promote triplex dissociation. The observed order of monovalent cation inhibition of triplex formation is reminiscent of their effect on tetraplex formation with G/T-rich oligonucleotides. However, using electrophoretic mobility shift assays we found that the oligonucleotide ODN 1 did not appear to form a four-stranded species under conditions promoting tetraplex formation. Taken together, our data suggest that processes other than the self-association of oligonucleotides into tetraplexes might be involved in the inhibitory effect of monovalent cations on purine-pyrimidine-purine triplex formation.
Down-regulation of glucocorticoid receptor mRNA by glucocorticoid hormones and recognition by the receptor of a specific binding sequence within a receptor cDNA clone. (1986)

A cDNA clone for the rat glucocorticoid receptor (GR) was used to study mechanisms of GR mRNA regulation. Treatment of rat hepatoma culture cells with 0.5 microM dexamethasone caused a small, initial increase in the GR mRNA level after 6 hr as well as a 50% to 95% reduction of the GR mRNA level after 24 hr of incubation when studied by RNA blot hybridization. After 72 hr, the initial GR mRNA level was restored. The down-regulation of GR mRNA levels appears to be independent of protein synthesis, since it also was observed in the presence of cycloheximide. However, cycloheximide caused a 4-fold increase in intracellular levels of GR mRNA. Using an immunoprecipitation assay, we could demonstrate that the GR specifically interacts with a GR cDNA clone, which represents a 2.6-kilobase fragment of the 3' nontranslated region of the GR mRNA. Nuclease protection experiments indicate the presence of several internal GR-binding regions in the above fragment.
Extracellular pH Responses in CA1 and the Dentate Gyrus During Electrical Stimulation, Seizure Discharges, and Spreading Depression (2000)

Since neuronal excitability is sensitive to changes in extracellular pH and there is regional diversity in the changes in extracellular pH during neuronal activity, we examined the activity-dependent extracellular pH changes in the CA1 region and the dentate gyrus. In vivo, in the CA1 region, recurrent epileptiform activity induced by stimulus trains, bicuculline, and kainic acid resulted in biphasic pH shifts, consisting of an initial extracellular alkalinization followed by a slower acidification. In vitro, stimulus trains also evoked biphasic pH shifts in the CA1 region. However, in CA1, seizure activity in vitro induced in the absence of synaptic transmission, by perfusing with 0 Ca(2+)/5 mM K(+) medium, was only associated with extracellular acidification. In the dentate gyrus in vivo, seizure activity induced by stimulation to the angular bundle or by injection of either bicuculline or kainic acid was only associated with extracellular acidification. In vitro, stimulus trains evoked only acidification. In the dentate gyrus in vitro, recurrent epileptiform activity induced in the absence of synaptic transmission by perfusion with 0 Ca(2+)/8 mM K(+) medium was associated with extracellular acidification. To test whether glial cell depolarization plays a role in the regulation of the extracellular pH, slices were perfused with 1 mM barium. Barium increased the amplitude of the initial alkalinization in CA1 and caused the appearance of alkalinization in the dentate gyrus. In both CA1 and the dentate gyrus in vitro, spreading depression was associated with biphasic pH shifts. These results demonstrate that activity-dependent extracellular pH shifts differ between CA1 and dentate gyrus both in vivo and in vitro. The differences in pH fluctuations with neuronal activity might be a marker for the basis of the regional differences in seizure susceptibility between CA1 and the dentate gyrus.
Cell‐targeting and cell‐penetrating peptides for delivery of therapeutic and imaging agents (2009)

This review will discuss the basic concepts concerning the use of cell-targeting peptides (CTPs) and cell-penetrating peptides (CPPs) in the context of nanocarrier technology. It deals with the discovery and subsequent evolution of CTPs and CPPs, issues concerning their interactions with cells and their biodistribution in vivo, and their potential advantages and disadvantages as delivery agents. The article also briefly discusses several specific examples of the use of CTPs or CPPs to assist in the delivery of nanoparticles, liposomes, and other nanocarriers.
The Efficacy of Live Attenuated, Cold-Adapted, Trivalent, Intranasal Influenzavirus Vaccine in Children (1998)

A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.
A single receptor encoded by vzg-1 / lp A1 / edg- 2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid (1998)

Extracellular lysophosphatidic acid (LPA) produces diverse cellular responses in many cell types. Recent reports of several molecularly distinct G protein-coupled receptors have raised the possibility that the responses to LPA stimulation could be mediated by the combination of several uni-functional receptors. To address this issue, we analyzed one receptor encoded by ventricular zone gene-1 (vzg-1) (also referred to as lpA1/edg-2) by using heterologous expression in a neuronal and nonneuronal cell line. VZG-1 expression was necessary and sufficient in mediating multiple effects of LPA: [3H]-LPA binding, G protein activation, stress fiber formation, neurite retraction, serum response element activation, and increased DNA synthesis. These results demonstrate that a single receptor, encoded by vzg-1, can activate multiple LPA-dependent responses in cells from distinct tissue lineages.
N-myc Downstream Regulated Gene 1 (NDRG1) Is Fused to ERG in Prostate Cancer (2009)

A step toward the molecular classification of prostate cancer was the discovery of recurrent erythroblast transformation-specific rearrangements, most commonly fusing the androgen-regulated TMPRSS2 promoter to ERG. The TMPRSS2-ERG fusion is observed in around 90% of tumors that overexpress the oncogene ERG. The goal of the current study was to complete the characterization of these ERG-overexpressing prostate cancers. Using fluorescence in situ hybridization and reverse transcription-polymerase chain reaction assays, we screened 101 prostate cancers, identifying 34 cases (34%) with the TMPRSS2-ERG fusion. Seven cases demonstrated ERG rearrangement by fluorescence in situ hybridization without the presence of TMPRSS2-ERG fusion messenger RNA transcripts. Screening for known 5' partners, we determined that three cases harbored the SLC45A3-ERG fusion. To discover novel 5' partners in these ERG-overexpressing and ERG-rearranged cases, we used paired-end RNA sequencing. We first confirmed the utility of this approach by identifying the TMPRSS2-ERG fusion in a known positive prostate cancer case and then discovered a novel fusion involving the androgen-inducible tumor suppressor, NDRG1 (N-myc downstream regulated gene 1), and ERG in two cases. Unlike TMPRSS2-ERG and SCL45A3-ERG fusions, the NDRG1-ERG fusion is predicted to encode a chimeric protein. Like TMPRSS2, SCL45A3 and NDRG1 are inducible not only by androgen but also by estrogen. This study demonstrates that most ERG-overexpressing prostate cancers harbor hormonally regulated TMPRSS2-ERG, SLC45A3-ERG, or NDRG1-ERG fusions. Broader implications of this study support the use of RNA sequencing to discover novel cancer translocations.
Consumer Resistance to Innovations: The Marketing Problem and its solutions (1989)

Considers why customers resist innovations even though they are considered necessary and desirable. Identifies functional barriers such as usage, value, and risk, and psychological barriers such as tradition and image. Concludes that successful innovation lies not in bowing down to consumer resistance, but in understanding the causes and developing a marketing strategy to attack them.
A Mutation in the Interferon-γ –Receptor Gene and Susceptibility to Mycobacterial Infection (1996)

Four children with severe mycobacterial infections had a mutation in the gene for interferon-gamma receptor 1 that leads to the absence of receptors on cell surfaces and a functional defect in the up-regulation of tumor necrosis factor alpha by macrophages in response to interferon-gamma. The interferon-gamma pathway is important in the response to intracellular pathogens such as mycobacteria.
Induction of cellular hsp70 expression by human cytomegalovirus (1990)

Expression of the cellular heat shock protein 70 gene (hsp70) is transiently induced by human cytomegalovirus (HCMV) infection of permissive human diploid fibroblasts. Induction of the cellular heat shock response during critical times of infection had previously been reported to alter the growth of HCMV in vitro. Thus, a potential interaction between heat shock proteins and HCMV expression was indicated. HCMV dramatically increased expression of hsp70 RNA within 8 h of infection. hsp70 RNA remained elevated at 24 and 48 h postinfection and decreased to low levels of 72 h postinfection. Induction of HSP70 protein occurred more slowly; inducible HSP70 protein encoded by this RNA increased within 16 h postinfection and continued to increase throughout infection until 72 h postinfection, when the highest abundance of inducible HSP70 protein was observed. Cells that received both heat (43 degrees C for 70 min) treatment and HCMV infection expressed hsp70 RNA to levels above the sum of levels present in cells given either treatment alone. Furthermore, hsp70 RNA induction occurred earlier and remained elevated longer than in cells infected with HCMV alone or in cells treated with heat alone, respectively. Nevertheless, the pattern of HCMV immediate-early transcript expression at 2, 4, and 6 h postinfection appeared to be unchanged by this prior heat treatment. Our results suggest that heat shock treatment and HCMV infection can act additively in stimulating hsp70 RNA expression. The previously reported stimulation of HCMV growth in vitro following the heat shock response apparently does not result from alterations in the steady-state expression of HCMV immediate-early transcripts.
Androgen-induced production of colony-stimulating factor(CSF) and colony-inhibitory factor(CIF) in the submandibular gland in female mice. (1989)

Both testosterone (T) and 5 alpha-dihydrotestosterone (DHT) significantly increased colony-stimulating factor (CSF) as well as colony-inhibitory factor (CIF) in the submandibular gland (SMG) in female mice. The CIF activity was completely inactivated by heating at 60 degrees C for 15 min, while the CSF activity was stable against the heat treatment. It was found that the CSFs obtained from the androgen-treated female mice and from normal male mice behaved identically in chromatography on hydroxylapatite and Ultro-gel AcA 34 columns. The potency of DHT to increase CSF activity was about 10 times greater than that of T.
Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. (1983)

Docosahexaenoic acid (DCHA), a major polyunsaturated acid component of fish lipid, is not a substrate for prostaglandin synthetase from ram seminal vesicles but is a strong competitive inhibitor (Ki, 0.36 microM) of the conversion by this enzyme of arachidonate (Km, 5.9 microM) to prostaglandins. In contrast, DCHA exhibits little interference to the conversion of arachidonate to metabolites on the leukotriene pathway. DCHA is a very poor substrate for the leukotriene-synthesizing system from RBL-1 cells and no formation of the C22 analog of leukotriene B could be detected from it. The C22 analog of leukotriene C4 was produced by chemical synthesis from DCHA and found to be less than 1/10,000th as active as leukotriene C4 in contracting guinea pig ileum. The DCHA used in this work was obtained in greater than 99.8% purity by a practical process developed for its separation from fish lipid. The cardiovascular protective effects ascribed to dietary intake of fish lipid by certain populations may be due in part to the biological action of DCHA, including the inhibition of prostaglandin biosynthesis.
Differentiation trapping screen in live culture for genes expressed in cardiovascular lineages (2004)

We have developed a gene trap vector that transduces an EGFP-neo fusion gene (Eno) to monitor the expression of trapped genes in living cells and embryos. Upon in vitro differentiation, most gene-trapped embryonic stem (ES) cell clones exhibited detectable green fluorescence in various specialized cell types, which can be followed in the live culture in real time. Populations of ES cell-derived cardiomyocytes, smooth muscle cells, vascular endothelial cells, and hematopoietic cells were readily recognized by their distinctive morphologies coupled with unique activities, allowing efficient screening for clones with trapped genes expressed in cardiovascular lineages. Applying G418 selection in parallel differentiation cultures further increased detection sensitivity and screening throughput by enriching reporter-expressing cells with intensified green fluorescent protein signals. Sequence analyses and chimera studies demonstrated that the expression of trapped genes in vivo closely correlated with the observed lineage specificity in vitro. This provides a strategy to identify and mutate genes expressed in lineages of interest for further functional studies.