gebhart/patrepeval huggingface dataset:
GARP regulates the bioavailability and activation of TGFβ (2012)

Glycoprotein-A repetitions predominant protein (GARP) associates with latent transforming growth factor-β (proTGFβ) on the surface of T regulatory cells and platelets; however, whether GARP functions in latent TGFβ activation and the structural basis of coassociation remain unknown. We find that Cys-192 and Cys-331 of GARP disulfide link to the TGFβ1 prodomain and that GARP with C192A and C331A mutations can also noncovalently associate with proTGFβ1. Noncovalent association is sufficiently strong for GARP to outcompete latent TGFβ-binding protein for binding to proTGFβ1. Association between GARP and proTGFβ1 prevents the secretion of TGFβ1. Integrin α(V)β(6) and to a lesser extent α(V)β(8) are able to activate TGFβ from the GARP-proTGFβ1 complex. Activation requires the RGD motif of latent TGFβ, disulfide linkage between GARP and latent TGFβ, and membrane association of GARP. Our results show that GARP is a latent TGFβ-binding protein that functions in regulating the bioavailability and activation of TGFβ.
Catherine Malabou and the Currency of Hegelianism (2000)

Catherine Malabou is a professor of philosophy at Paris-Nanterre. A collaborator and student of Jacques Derrida, her work shares some of his interest in rigorous protocols of reading, and a willingness to attend to the undercurrents of over-read and “too familiar” texts. But, as she points out, this orientation was shared by Hegel himself. Arguing against Heidegger, Kojève, and other critics of Hegel, the book in which this Introduction appears puts Hegel back on the map of the present.
A nonpeptide agonist of the invertebrate receptor for SchistoFLRFamide (PDVDHVFLRFamide), a member of a subfamily of insect FMRFamide-related peptides. (1995)

We describe a nonpeptide mimetic analog of an invertebrate peptide receptor. Benzethonium chloride (Bztc) is an agonist of the SchistoFLRFamide (PDVDHVFLRFamide) receptors found on locust oviducts. Bztc competitively displaces [125I-labeled Y1]SchistoFLRFamide binding to both high- and low-affinity receptors of membrane preparations. Bztc mimics the physiological effects of SchistoFLRFamide on locust oviduct, by inhibiting myogenic and induced contractions in a dose-dependent manner. Bztc is therefore recognized by the binding and activation regions of the SchistoFLRFamide receptors. This discovery provides a unique opportunity within insects to finally target a peptide receptor for the development of future pest management strategies.
Apparatus for producing uniform solid spheres of hydrogen (1977)

An apparatus has been constructed which produces uniform spheres of solid hydrogen for experiments testing the feasibility of using the solid hydrogen pellets for refueling fusion reactors. Two versions of the apparatus were developed, one which produced 70-μm-diam pellets at the rate of 105/sec and another which produced 210-μm pellets at the rate of 2.6×104/sec. The first step in the pellet production is to liquefy the hydrogen by flowing it through a liquid-helium-cooled heat exchanger. Then, a liquid hydrogen jet is formed by flowing the hydrogen through a nozzle. The jet is broken up into uniform drops by an acoustical excitation. The drops are frozen by evaporation in a pressure less than the triple point pressure of hydrogen. Finally, the drops are injected into vacuum for the experiments.
Uses of biotechnology in modifying plant lipids (1996)

This review discusses fatty acid modification of oilseeds with additional emphasis on production of oxygenated derivatives. In a relatively short period, less than a decade, our understanding of the enzymes involved in plant fatty acid synthesis has increased to the point where we understand how they might be used in oilseed modification. Further, through modern molecular biological techniques, the actual genes for many of these important enzymes have been cloned. Use of genetic transformation systems has allowed us to fundamentally alter the normal biosynthetic pathways in highly specific ways, in manners that would be either difficult or impossible using traditional breeding techniques. Alteration of plant lipid biosynthesis is not restricted to using genes from the plants themselves, but interspecies transfer is possible, either from completely unrelated plant species (often of no commercial value but possessing unusual biochemical properties) or from animals, fungi, and prokaryotic organisms. In this way "designer" plants possessing altered metabolism, tailored to the interests or needs of certain industries, nutritionists, and the consumer can be created.
Phosphorylation of tau protein by purified p34cdc28 and a related protein kinase from neurofilaments. (1992)

It has been suggested that hyperphosphorylation of the tau protein in neurofibrillary tangles may be relevant to the etiology of Alzheimer's disease and that at least one of the hyperphosphorylated sites lies within a consensus sequence for the p34cdc2/cdc28 family of kinases. We describe a new method for large-scale purification of p34cdc28 kinase from Saccharomyces cerevisiae and show that the purified enzyme can phosphorylate bovine and human tau. Phosphorylation was greatly enhanced by the addition of basic and acidic substrate modulators. The effect of the substrate modulators differed both with the structures of the substrates and the modulators. Similar results were obtained with a kinase that could be purified from neurofilaments by p13suc1 affinity chromatography, a hallmark of p34cdc2/cdc28-type kinases. These results are consistent with the hypothesis that a kinase of this type is involved in tau phosphorylation in vivo and open the possibility that hyperphosphorylation in Alzheimer's disease may be controlled by substrate modulators.
Mesothelin Expression in Triple Negative Breast Carcinomas Correlates Significantly with Basal-Like Phenotype, Distant Metastases and Decreased Survival (2014)

Mesothelin is a cell surface associated antigen expressed on mesothelial cells and in some malignant neoplasms. Mesothelin-targeted therapies are in phase I/II clinical trials. The clinicopathologic and prognostic significance of mesothelin expression in triple negative breast carcinomas (TNBC) has not been fully assessed. We evaluated the expression of mesothelin and of basal markers in tissue microarrays of 226 TNBC and 88 non-TNBC and assessed the clinicopathologic features of mesothelin-expressing breast carcinomas. Furthermore, we investigated the impact of mesothelin expression on the disease-free and overall survival of patients with TNBC. We found that mesothelin expression is significantly more frequent in TNBC than in non-TNBC (36% vs 16%, respectively; p = 0.0006), and is significantly correlated with immunoreactivity for basal keratins, but not for EGFR. Mesothelin-positive and mesothelin-negative TNBC were not significantly different by patients' race, tumor size, histologic grade, tumor subtype, lymphovascular invasion and lymph node metastases. Patients with mesothelin-positive TNBC were older than patients with mesothelin-negative TNBC, developed more distant metastases with a shorter interval, and had significantly lower overall and disease-free survival. Based on our results, patients with mesothelin-positive TNBC could benefit from mesothelin-targeted therapies.
Mechanical Strain Promotes Oligodendrocyte Differentiation by Global Changes of Gene Expression (2017)

Differentiation of oligodendrocyte progenitor cells (OPC) to oligodendrocytes and subsequent axon myelination are critical steps in vertebrate central nervous system (CNS) development and regeneration. Growing evidence supports the significance of mechanical factors in oligodendrocyte biology. Here, we explore the effect of mechanical strains within physiological range on OPC proliferation and differentiation, and strain-associated changes in chromatin structure, epigenetics, and gene expression. Sustained tensile strain of 10-15% inhibited OPC proliferation and promoted differentiation into oligodendrocytes. This response to strain required specific interactions of OPCs with extracellular matrix ligands. Applied strain induced changes in nuclear shape, chromatin organization, and resulted in enhanced histone deacetylation, consistent with increased oligodendrocyte differentiation. This response was concurrent with increased mRNA levels of the epigenetic modifier histone deacetylase Hdac11. Inhibition of HDAC proteins eliminated the strain-mediated increase of OPC differentiation, demonstrating a role of HDACs in mechanotransduction of strain to chromatin. RNA sequencing revealed global changes in gene expression associated with strain. Specifically, expression of multiple genes associated with oligodendrocyte differentiation and axon-oligodendrocyte interactions was increased, including cell surface ligands (Ncam, ephrins), cyto- and nucleo-skeleton genes (Fyn, actinins, myosin, nesprin, Sun1), transcription factors (Sox10, Zfp191, Nkx2.2), and myelin genes (Cnp, Plp, Mag). These findings show how mechanical strain can be transmitted to the nucleus to promote oligodendrocyte differentiation, and identify the global landscape of signaling pathways involved in mechanotransduction. These data provide a source of potential new therapeutic avenues to enhance OPC differentiation <i>in vivo</i>.
The effect of conformation on the solution stability of linear vs. cyclic RGD peptides (1999)

The objective of this study was to evaluate the relationship between conformational flexibility and solution stability of a linear RGD peptide (Arg-Gly-Asp-Phe-OH; 1) and a cyclic RGD peptide (cyclo-(1, 6)-Ac-Cys-Arg-Gly-Asp-Phe-Pen-NH2; 2); as a function of pH. Previously, it was found that cyclic peptide 2 was 30-fold more stable than linear peptide 1. Therefore, this study was performed to explain the increase in chemical stability based on the preferred conformation of the peptides. Molecular dynamics simulations and energy minimizations were conducted to evaluate the backbone flexibility of both peptides under simulated pH conditions of 3, 7 and 10 in the presence of water. The reactive sites for degradation for both molecules were also followed during the simulations. The backbone of linear peptide 1 exhibited more flexibility than that of cyclic peptide 2, which was reflected in the rotation about the phi and psi dihedral angles. This was further supported by the low r.m.s. deviations of the backbone atoms for peptide 2 compared with those of peptide 1 that were observed among structures sampled during the molecular dynamics simulations. The presence of a salt bridge between the side chain groups of the Arg and Asp residues was also indicated for the cyclic peptide under simulated conditions of neutral pH. The increase in stability of the cyclic peptide 2 compared with the linear peptide 1, especially at neutral pH, is due to decreased structural flexibility imposed by the ring, as well as salt bridge formation between the side chains of the Arg and Asp residues in cyclic peptide 2. This rigidity would prevent the Asp side chain carboxylic acid from orienting itself in the appropriate position for attack on the peptide backbone.
Scalable HMM based inference engine in large vocabulary continuous speech recognition (2009)

Parallel scalability allows an application to efficiently utilize an increasing number of processing elements. In this paper we explore a design space for application scalability for an inference engine in large vocabulary continuous speech recognition (LVCSR). Our implementation of the inference engine involves a parallel graph traversal through an irregular graph-based knowledge network with millions of states and arcs. The challenge is not only to define a software architecture that exposes sufficient fine-grained application concurrency, but also to efficiently synchronize between an increasing number of concurrent tasks and to effectively utilize the parallelism opportunities in today's highly parallel processors. We propose four application-level implementation alternatives we call ldquoalgorithm stylesrdquo, and construct highly optimized implementations on two parallel platforms: an Intel Core i7 multicore processor and a NVIDIA GTX280 manycore processor. The highest performing algorithm style varies with the implementation platform. On 44 minutes of speech data set, we demonstrate substantial speedups of 3.4times on Core i7 and 10.5times on GTX280 compared to a highly optimized sequential implementation on Core i7 without sacrificing accuracy. The parallel implementations contain less than 2.5% sequential overhead, promising scalability and significant potential for further speedup on future platforms.
Sensitive detection of plastic explosives with self-assembled monolayer-coated microcantilevers (2003)

We report the detection of 10–30 parts-per-trillion levels of pentaerythritol tetranitrate and hexahydro-1,3,5-triazine within 20 s of exposure to a silicon microcantilever with its gold surface modified with a self-assembled monolayer of 4-mercaptobenzoic acid. These measurements correspond to a limit of detection of a few fg.
Deep Recurrent Models with Fast-Forward Connections for Neural Machine Translation (2016)

Neural machine translation (NMT) aims at solving machine translation (MT) problems using neural networks and has exhibited promising results in recent years. However, most of the existing NMT models are shallow and there is still a performance gap between a single NMT model and the best conventional MT system. In this work, we introduce a new type of linear connections, named fast-forward connections, based on deep Long Short-Term Memory (LSTM) networks, and an interleaved bi-directional architecture for stacking the LSTM layers. Fast-forward connections play an essential role in propagating the gradients and building a deep topology of depth 16. On the WMT'14 English-to-French task, we achieve BLEU=37.7 with a single attention model, which outperforms the corresponding single shallow model by 6.2 BLEU points. This is the first time that a single NMT model achieves state-of-the-art performance and outperforms the best conventional model by 0.7 BLEU points. We can still achieve BLEU=36.3 even without using an attention mechanism. After special handling of unknown words and model ensembling, we obtain the best score reported to date on this task with BLEU=40.4. Our models are also validated on the more difficult WMT'14 English-to-German task.
Diazomethyl ketone derivatives of pyrimidine nucleosides (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDiazomethyl ketone derivatives of pyrimidine nucleosidesJohn A. Montgomery and H. Jeanette ThomasCite this: J. Org. Chem. 1981, 46, 3, 594–598Publication Date (Print):January 1, 1981Publication History Published online1 May 2002Published inissue 1 January 1981https://pubs.acs.org/doi/10.1021/jo00316a021https://doi.org/10.1021/jo00316a021research-articleACS PublicationsRequest reuse permissionsArticle Views248Altmetric-Citations21LEARN 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
Migration of Dendritic Cell Subsets and their Precursors (2007)

The ability of dendritic cells (DCs) to initiate and orchestrate immune responses is a consequence of their localization within tissues and their specialized capacity for mobilization. The migration of a given DC subset is typified by a restricted capacity for recirculation, contrasting markedly with T cells. Routes of DC migration into lymph nodes differ notably for distinct DC subsets. Here, we compare the distinct migratory patterns of plasmacytoid DCs (pDCs), CD8alpha(+) DCs, Langerhans cells, and conventional myeloid DCs and discuss how the highly regulated patterns of DC migration in vivo may affect their roles in immunity. Finally, to gain a more molecular appreciation of the specialized migratory properties of DCs, we review the signaling cascades that govern the process of DC migration.
Comparison of the biological actions of TGF beta‐1 and TGF beta‐2: Differential activity in endothelial cells (1988)

Beta transforming growth factor (TGF beta) has multiple in vitro biological effects including stimulation or inhibition of proliferation of specific cell types. A second major form of TGF beta, TGF beta-2, has recently been isolated from porcine platelets, from bovine bone matrix, and from several other sources. The two forms of TGF beta are biologically equipotent with the exception that TGF beta-2 was much less active than TGF beta-1 for inhibition of proliferation of a rat pleuripotent hematopoietic stem cell line. During the purification of beta TGF from bone, we obtained two fraction pools that differed in their ability to inhibit 3H-thymidine incorporation into aortic endothelial cells (AEC). We therefore compared highly purified TGF beta-1 and TGF beta-2 isolated from porcine platelets for inhibition of DNA synthesis in mink lung epithelial cells (MvILu), and in AEC, and for stimulation of 3H-thymidine incorporation in calvarial bone cells (CBC) in 3 experiments. TGF beta-1 and TGF beta-2 inhibited cell proliferation in MvILu with no significant differences in the ED50 (31 +/- 8 pg/ml vs 23 +/- 7). TGF beta-2 was much less potent than TGF beta-1 in inhibiting DNA synthesis in AEC (6310 +/- 985 pg/ml vs 101 +/- 34). The reduced specific activity of TGF beta-2 was also observed in adrenal capillary endothelial cells. Both beta-1 and beta-2 stimulated proliferation of CBC (ED50 26 +/- 2 pg/ml vs 10 +/- 4). We also examined the specificity of the MvILu and AEC inhibition assays. Epidermal growth factor (EGF), platelet derived growth factor (PDGF), acidic and basic fibroblast growth factors (FGF), skeletal growth factor (SGF)/insulin-like growth factor-II (IGF-II), and insulin-like growth factor-I (IGF-I) did not inhibit DNA synthesis in either assay system. However, when the growth factors were added to maximal inhibiting concentrations of TGF beta-1, both acidic and basic FGF significantly reduced TGF beta-1 inhibition in AEC. We conclude that (1) inhibition of DNA synthesis in endothelial cells is relatively specific for TGF beta-1, (2) inhibition of DNA synthesis in MvILu is a sensitive and specific assay for generic TGF beta activity but does not distinguish beta-1 from beta-2, (3) the relative inhibition of DNA synthesis in MvILu and AEC may provide a means to quantitatively estimate TGF beta-1 and TGF beta-2, and (4) both TGF beta-1 and TGF beta-2 are potent mitogens for chicken embryonic calvarial bone cells.
A mouse serum two‐dimensional gel map: Application to profiling burn injury and infection (2004)

With the importance of mouse as a model to study human diseases and the human and rat plasma/serum two-dimensional (2-D) maps being extensively annotated, this study was aimed at constructing a detailed mouse serum 2-D map. Serum proteins from two different inbred strains of mice (BALB/cJ and C57BL/6J) and mice subjected to two different inflammatory stimuli (20% burn injury and lipopolysaccharide (LPS) injection) were separated on overlapping gels covering pH 3-8 and stained with SYPRO Ruby dye. The tryptic peptides from the resolved spots were analyzed by mass spectrometry, leading to the identification of 38 different gene products. With the exception of major urinary proteins found in abundance in male C57BL/6J mice, little strain difference of the mouse serum 2-D was observed. Many proteins detected in the mouse serum 2-D map were not reported in human or rat serum 2-D maps including epidermal growth factor receptor. Three major murine acute-phase proteins (APPs), haptoglobin, serum amyloid A, and serum amyloid P, were highly induced by both inflammatory stimuli. Image analysis shows that the variations of APPs between these two inflammatory models were not uniform although LPS (100 microg/animal) in general was more effective than 20% burn injury in inducing APPs. Serum amyloid A, much more sensitive to endotoxin than burn injury, may represent a sensitive marker to differentiate these two different inflammatory states.
Lipid signalling in pathogenic fungi (2010)

In recent years, the study of lipid signalling networks has significantly increased. Although best studied in mammalian cells, lipid signalling is now appreciated also in microbial cells, particularly in yeasts and moulds. For instance, microbial sphingolipids and their metabolizing enzymes play a key role in the regulation of fungal pathogenicity, especially in Cryptococcus neoformans, through the modulation of different microbial pathways and virulence factors. Another example is the quorum sensing molecule (QSM) farnesol. In fact, this QSM is involved not only in mycelial growth and biofilm formation of Candida albicans, but also in many stress related responses. In moulds, such as Aspergillus fumigatus, QSM and sphingolipids are important for maintaining cell wall integrity and virulence. Finally, fungal cells make oxylipins to increase their virulence attributes and to counteract the host immune defences. In this review, we discuss these aspects in details.
Chloroplast transformation in plants: polyethylene glycol (PEG) treatment of protoplasts is an alternative to biolistic delivery systems (1993)

Nicotiana plumbaginifolia protoplasts were directly transformed by PEG treatment with a cloned 16S rRNA gene isolated from a double antibiotic-resistant Nicotiana tabacum plastid mutant. Putative plastid transformants were selected in cell culture by their spectinomycin resistance and identified by their unselected streptomycin resistance. Alternatively, cell lines were selected in the presence of both antibiotics. The cell line (and its regenerated plants) selected solely for spectinomycin resistance demonstrated an extensive segregation of streptomycin resistance in subsequent tests, while the double-selected line showed stable resistance for both antibiotics. The resistance markers were inherited maternally. In the putative plastid transformants the origin of the resistance mutations was identified by the absence of an AatII site, missing in the donor N. tabacum plastid gene (spectinomycin resistance site) but present in that of wild-type N. plumbaginifolia, and a sequence analysis of the particular nucleotide changes in both resistance sites. Restriction enzyme analysis of total plastid DNA (ptDNA), and the recloning and full sequencing of the fragment introduced, investigated in one of the plastid transformants, showed no DNA rearrangements accompanied with the integration process. Sequence analysis indicated a targeted, homologous integration of the DNA fragment introduced but an unexpectedly complete homology of the parental ptDNA sequences in this region prevented the location of borders. Although the frequency of plastid transformant colonies (2 x 10(-5)) should still be improved, this method for stable chloroplast DNA transformation is comparable with or more efficient than the particle bombardment techniques.