gebhart/patrepeval huggingface dataset:
LSD1/KDM1A mutations associated to a newly described form of intellectual disability impair demethylase activity and binding to transcription factors (2016)

Genetic diseases often lead to rare and severe syndromes and the identification of the genetic and protein alterations responsible for the pathogenesis is essential to understand both the physiological and pathological role of the gene product. Recently, de novo variants have been mapped on the gene encoding for the lysine-specific histone demethylase 1 (LSD1)/lysine(K)-specific histone demethylase 1A in three patients characterized by a new genetic disorder. We have analyzed the effects of these pathological mutations on the structure, stability and activity of LSD1 using both in vitro and cellular approaches. The three mutations (Glu403Lys, Asp580Gly and Tyr785His) affect active-site residues and lead to a partial impairment of catalytic activity. They also differentially perturb the ability of LSD1 to engage transcription factors that orchestrate key developmental programs. Moreover, cellular data indicate a decrease in the protein cellular half-life. Taken together, these results demonstrate the relevance of LSD1 in gene regulation and how even moderate alterations in its stability, catalytic activity and binding properties can strongly affect organism development. This depicts a perturbed interplay of catalytic and non-catalytic processes at the origin of the pathology.
[Expression of genes coding for the proteins of intermediate filaments in man]. (1989)

Cellular morphogenesis is a fundamental phenomenon in our understanding of eucaryotic cells. When, where and how these supra molecular structures generate during differentiation to cellular shape? It seems that the cytoskeleton alone is responsible for the formation and maintenance of the cellular shape. The supra molecular organisation of the intermediate filaments is specific for the cell type, the developmental stage and the type of differentiation. The human genes coding for the different subunits of these polymers have now all been isolated, cloned and characterised. The regulation of their expression is now being analysed.
CNS neuronal focal adhesion kinase forms clusters that co‐localize with vinculin (1996)

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase that appears to play a central role in integrin-mediated signal transduction in non-neuronal cells, linking the extracellular matrix to the actin-based cytoskeleton at focal adhesion contacts. Biochemical analysis has revealed the presence of FAK immunoreactivity in cells of neuronal lineage (Zhang et al., 1994) and in the CNS (Burgaya et al. 1995; Grant et al., 1995). In the current work, we have examined the immunodistribution of FAK in nerve cell cultures and tissue sections from the rat CNS. Cultures of B103 CNS neuroblastoma cells and primary cultures of hippocampal neurons both showed abundant FAK immunoreactivity in nerve cell bodies. Immunoreactivity also extended into neurites and growth cones. The most striking feature of FAK distribution was the presence of short, punctate clusters of high FAK concentration. These FAK clusters were maintained in triton-extracted cell ghosts, indicating association with the cytoskeleton. Double-label confocal imaging showed that clusters of FAK coincided with clusters of vinculin, another actin-associated signal transduction molecule implicated in control of growth cone motility. Data from hippocampal sections verified the presence of FAK in adult neurons where it was enriched in somato-dendritic domains and showed a non-uniform distribution. Quantitative FAK immunoprecipitation to compare adult with embryonic brain showed a 7-fold developmental down-regulation of FAK and a 21-fold down-regulation of FAK TyrP. The data suggest that neuronal FAK may participate in signal transduction complexes relevant to neuronal morphogenesis and plasticity. © 1996 Wiley-Liss, Inc.
Reactive oxidant species in asthma (2005)

Since there are considerable discrepancies in erythrocyte or plasma antioxidant enzyme activity in patients with asthma, the problem at this time is attempting to sort out these conflicting results and to find their roles in the pathogenesis of asthma. There is good evidence that antioxidant compounds may have a potential role in the treatment of asthma, especially of asthma exacerbation.
Near-infrared absorbing semitransparent organic solar cells (2011)

We present efficient, semitransparent small molecule organic solar cells. The devices employ an indium tin oxide-free top contact, consisting of thin metal films and an additional organic capping layer for enhanced light in/outcoupling. The solar cell encorporates a bulk heterojunction with the donor material Ph2-benz-bodipy, an infrared absorber. Combination of Ph2-benz-bodipy with C60 as acceptor leads to devices with high open circuit voltages of up to 0.81 V and short circuit current densities of 5-6 mA/cm2, resulting in efficiences of 2.2%-2.5%. At the same time, the devices are highly transparent, with an average transmittance in the visible range (400-750 nm) of up to 47.9%, with peaks at 538 nm of up to 64.2% and an average transmittance in the yellow-green range of up to 61.8%.
Monitoring Thrombin Generation by Electrochemistry: Development of an Amperometric Biosensor Screening Test for Plasma and Whole Blood (2009)

The biosensor system provides a new method for assessing thrombin generation in plasma or whole blood samples as small as 10 microL. The assay is easy to use, thus allowing it to be performed in a point-of-care setting.
Chemical and Electrochemical Oxidative Activation of Arenol Derivatives for Carbon-Carbon Bond Formation (2004)

The oxidative activation of arenes is a powerful and versatile synthetic tactic that enables various functionalization of aromatic rings. Central to this chemistry are oxygenated arenes such as hydroxylated arenes or arenols and their simple alkyl ethers whose electron-releasing functions facilitate the oxidation process. These two classes of arenol derivatives can lead to three different types of oxidized intermediates, each of which expresses its own chemical reactivity that can be exploited for specific bond formation. Free arenols can be subjected to either one- or two-electron oxidation processes to furnish either neutral arenoxy ArO. radicals or arenoxenium ArO+ ions depending on the mode of oxidative activation used. Arenol ethers initially furnish radical cationic ArOR+. species, whose chemistry often expresses the duality of their electronic nature. This review highlights the chemical, biochemical and electrochemical oxidative activation modes that can be used to convert arenol derivatives into either ArO., ArO+ or ArOR+. species and focuses on the structural elaboration of these intermediates in selective carbon-carbon bond-forming reactions. Keywords: Electrochemical, arenoxenium, carbon-carbon, arenol
Macrophages rapidly internalize their tumor necrosis factor receptors in response to bacterial lipopolysaccharide (1989)

The effect of bacterial lipopolysaccharide (LPS) on macrophage receptors for tumor necrosis factor/cachectin (TNF-R) was studied. At equilibrium, iodinated recombinant human TNF alpha (rTNF alpha) bound to 1100 +/- 200 sites/cell on macrophage-like RAW 264.7 cells with a Kd of 1.3 +/- 0.1 x 10(-9) M. Preexposure of RAW 264.7 cells to 10 ng/ml LPS for 1 h at 37 degrees C resulted in complete loss of cell surface TNF alpha binding sites. 50% loss ensued after 1 h with 0.6 ng/ml LPS, or after 15 min with 10 ng/ml LPS. Complete loss of TNF alpha binding sites occurred without change in numbers of complement receptor type 3. No decrease in TNF-R followed preexposure to LPS at 4 degrees C, nor could LPS displace 125I-rTNF alpha from its binding sites. Although TNF-R disappeared from the surface of intact macrophages following exposure to LPS, specific TNF alpha binding sites were unchanged in permeabilized macrophages, indicating that TNF-R were rapidly internalized. Conditioned media from LPS-treated RAW 264.7 cells induced 30% down-regulation of TNF-R on macrophages from LPS-hyporesponsive mice (C3H/HeJ), suggesting that a soluble macrophage product may be responsible for a minor portion of the LPS effect. Additional evidence against endogenous TNF alpha being the major cause of TNF-R internalization was the rapid onset of the effect of LPS on TNF-R compared to the reported onset of TNF alpha production, the relatively high concentrations of exogenous rTNF alpha required to mimic the effect of LPS, and the inability of TNF alpha-neutralizing antibody to block the effect of LPS. LPS-induced down-regulation of TNF-R was complete or nearly complete not only in RAW 264.7 cells, but also in primary macrophages of both human and murine origin, was less marked in human endothelial cells, and was absent in human granulocytes and melanoma cells and mouse L929 cells. Thus, in situ, macrophages and some other host cells may be resistant to the actions of TNF alpha produced during endotoxinemia, because such cells may internalize their TNF-R in response to LPS before TNF alpha is produced.
Detection of Horizontal Gene Transfer by Natural Transformation in Native and Introduced Species of Bacteria in Marine and Synthetic Sediments (1990)

Both naturally occurring marine sediments and artificial sediments were used as supports for natural transformation of marine bacteria. While transformation of Pseudomonas stutzeri ZoBell suspended in artificial seawater was not detected when recipient cells and rifampin resistance DNA were loaded onto sterile sediment columns, transformation could be detected at frequencies 4 to 20 times that of spontaneous resistance when recipient cells and rifampin resistance DNA were loaded onto sterile sediment columns. Treatment of these columns with DNase I reduced transformation frequencies to levels comparable to those of spontaneous-resistance frequencies. Sediments with higher organic contents supported higher frequencies of transformation than did those with lower amounts of organic matter. Transformation was also detected when recipient cells and DNA were loaded on columns prepared from nonsterile sediments, although the frequencies of transformation were lower than when sterile sediments were used. Finally, nonsterilized sediments that were not supplemented with laboratory strains did not support detectable levels of transformation in sediment columns, but when these same sediments were transferred to filters and placed on complex media, transformation was detected at a frequency three times that for spontaneous resistance. This transformation frequency was partially reduced to levels near that for spontaneous resistance by the addition of DNase I to sediment filters. These results indicate that marine sediments facilitate the uptake and expression of exogenous DNA by transformable marine bacteria and that sediments are a more likely niche for natural transformation than the water column in the marine environment.
Stat3 Activation in Murine Colitis Induced by Enterotoxigenic Bacteroides fragilis (2014)

ETBF rapidly induces immune cell pStat3, which is independent of epithelial pStat3. This occurs before ETBF-induced mucosal permeability, suggesting that ETBF, likely through B. fragilis toxin and its action on the colonic epithelial cell, triggers mucosal immune cell Stat3 activation. Peak mucosal Stat3 activation (immune and epithelial cells) occurs subsequently when other colonic bacteria may contribute to the ETBF-initiated immune response due to barrier dysfunction. ETBF induces long-lived, focal colonic Stat3 activation and Th17 immune responses dependent on the ongoing ETBF colonization. Further study is needed to evaluate the early mucosal signaling events, resulting in epithelial Stat3 activation and the sequelae of long-term colonic Stat3 activation.
Prospective Evaluation of Clonal Evolution During Long-Term Follow-Up of Patients With Untreated Early-Stage Chronic Lymphocytic Leukemia (2006)

This clinical trial confirms prospectively that cytogenetic abnormalities detected by FISH can predict overall survival for CLL patients at the time of diagnosis, but also suggests that many patients acquire new abnormalities during the course of their disease. Patients with higher ZAP-70 expression may be more likely to experience such clonal evolution. These findings have important implications for both clinical management and trials of early treatment for patients with high-risk, early-stage CLL.
Reduction of endotoxin-induced vascular permeability by monoclonal antibodies against lipopolysaccharide determinants. (1992)

Endotoxin, a bacterial lipopolysaccharide implicated in the pathogenesis of septic shock, markedly alters vascular permeability following intravenous injection in rabbits. We investigated the ability of murine monoclonal antibodies to confer protection against endotoxin-induced increases in a rabbit model of ocular vascular permeability. Four monoclonal antibodies of differing specificities as well as polymyxin B were compared for their effects on endotoxin from either Escherichia coli or Pseudomonas aeruginosa. Preincubation of endotoxin with antibodies directed against Pseudomonas O side chain or core glycolipid resulted in marked attenuation of vascular permeability due to Pseudomonas endotoxin, but not E. coli endotoxin. Antilipid A antibodies were not significantly effective in neutralizing either endotoxin with in vitro preincubation. Low avidity of the antilipid A antibody, low density of lipid A binding sites, or inaccessibility of the lipid A may have prevented more marked interactions. When administered intravenously prior to endotoxin challenge, none of the antibodies demonstrated the ability to provide specific protection to subsequent endotoxin in this model. They did provide partial nonspecific protection against endotoxins regardless of epitope specificity. When administered prophylactically, polymyxin B, an antibiotic that binds to lipid A, was highly effective in neutralizing the toxic effects of endotoxin. Since antibodies to lipid A reduce mortality in septic shock, the failure to demonstrate efficacy in this study may be due to the marked sensitivity of the rabbit eye to endotoxin. Alternatively, beneficial effects from antiendotoxin antibodies in septic shock may be unrelated to the inhibition of vascular permeability. Some protection from antiendotoxin antibodies may be due to enhancement of nonspecific mechanisms.
Exploring User Defined Gestures for Ear-Based Interactions (2020)

The human ear is highly sensitive and accessible, making it especially suitable for being used as an interface for interacting with smart earpieces or augmented glasses. However, previous works on ear-based input mainly address gesture sensing technology and researcher-designed gestures. This paper aims to bring more understandings of gesture design. Thus, for a user elicitation study, we recruited 28 participants, each of whom designed gestures for 31 smart device-related tasks. This resulted in a total of 868 gestures generated. Upon the basis of these gestures, we compiled a taxonomy and concluded the considerations underlying the participants' designs that also offer insights into their design rationales and preferences. Thereafter, based on these study results, we propose a set of user-defined gestures and share interesting findings. We hope this work can shed some light on not only sensing technologies of ear-based input, but also the interface design of future wearable interfaces.
Breakthroughs for 650-V GaN Power Devices: Stable high-temperature operations and avalanche capability (2015)

Many prior publications have focused on gallium nitride (GaN) dynamic Rdson issues at room temperature, even though GaN power devices have tremendous advantages over silicon (Si) when serving at high temperatures. We show that room-temperature stable dynamic Rdson behavior does not guarantee device reliability, and it is the stable high-temperature dynamic Rdson that determines the ruggedness of the GaN power devices. With our proprietary and innovative designs and optimizations of epitaxial and device structures, we show a completely different dynamic Rdson behavior in contrast to the common trend reported in the literature: a negative dynamic Rdson trend. We demonstrate robust performance and reliability of our new cascode GaN power devices in PFC tests conducted at both room and high temperatures, at high powers, at high-frequency conditions, and in a totem-pole circuit. We speculate on a physical model to explain the observed dynamic Rdson behaviors in terms of trapping, detrapping, and back-gating effects.
The amino acid sequence of pike-whale (lesser-rorqual) pancreatic ribonuclease (1976)

Pancreatic RNAase (ribonuclease) from the pike whale (lesser rorqual, Balaenoptera acutorostrata) was isolated by affinity chromatography. The protein was digested with different proteolytic enzymes. Peptides were isolated by gel filtration, preparative high-voltage paper electrophoresis and paper chromatography. The amino acid sequence of peptides was determined by the dansyl-Edman method. Although we do not have an amino acid composition for the whole protein, all peptide bonds were overlapped by one or more peptides. Residues 85-96 are bridged by a peptide of unstaisfactory composition and the sequence here depends, at least in part, on homology for its confirmation. Another region in which a similar situation obtains is residues 39-40. This pancreatic RNAase differs at 24-33% of the positions from all other mammalian pancreatic RNAases sequenced to date, except for pig RNAase, from which it differs by 19%. This indicates that whale RNAase has evolved independently during the larger part of the evolution of the mammals. Lesser-rorqual pancreatic RNAase is partially glycosidated (30%) at asparagine-76 in an Asn-Ser-Thr sequence (residues 76-78). Pig RNAase also has carbohydrate attached to asparagine-76 and is identical with lesser-rorqual RNAase in residues 76-98. Detailed evidence for the sequence has been deposited as Supplementary Publication SUP 50066 (11 pages) at the British Library Lending Division, Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms ginen in Biochem. J. (1976) 135, 5.
Factored Translation Models (2007)

We present an extension of phrase-based statistical machine translation models that enables the straight-forward integration of additional annotation at the word-level — may it be linguistic markup or automatically generated word classes. In a number of experiments we show that factored translation models lead to better translation performance, both in terms of automatic scores, as well as more grammatical coherence.
Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry (2005)

Daptomycin is a 13 amino acid, cyclic lipopeptide produced by a non-ribosomal peptide synthetase (NRPS) mechanism in Streptomyces roseosporus. A 128 kb region of S. roseosporus DNA was cloned and verified by heterologous expression in Streptomyces lividans to contain the daptomycin biosynthetic gene cluster (dpt). The cloned region was completely sequenced and three genes (dptA, dptBC, dptD) encoding the three subunits of an NRPS were identified. The catalytic domains in the subunits, predicted to couple five, six or two amino acids, respectively, included a novel activation domain and amino-acid-binding pocket for incorporating the unusual amino acid l-kynurenine (Kyn), three types of condensation domains and an extra epimerase domain (E-domain) in the second module. Novel genes (dptE, dptF) whose products likely work in conjunction with a unique condensation domain to acylate the first amino acid, as well as other genes (dptI, dptJ) probably involved in supply of the non-proteinogenic amino acids l-3-methylglutamic acid and Kyn, were located next to the NRPS genes. The unexpected E-domain suggested that daptomycin would have d-Asn, rather than l-Asn, as originally assigned, and this was confirmed by comparing stereospecific synthetic peptides and the natural product both chemically and microbiologically.
Palladium-catalyzed synthesis of arylamines from aryl halides. Mechanistic studies lead to coupling in the absence of tin reagents (1995)

The reaction of aryl halides with secondary amines in the presence of silylamide base and tri-o-tolyphopshine palladium complexes gives arylamine products. This process provides a convenient method for performing these hetero-cross coupling reactions without the necessity for forming tin amides and disposing of tin halides. This reaction follows from a mechanistic analysis of the coupling reaction with tin amides and occurs as a result of the cleavage of palladium aryl halide dimers with secondary amines.
Epidermal growth factor receptor variant III mutations in lung tumorigenesis and sensitivity to tyrosine kinase inhibitors (2006)

The tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva) have shown anti-tumor activity in the treatment of non-small cell lung cancer (NSCLC). Dramatic and durable responses have occurred in NSCLC tumors with mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). In contrast, these inhibitors have shown limited efficacy in glioblastoma, where a distinct EGFR mutation, the variant III (vIII) in-frame deletion of exons 2-7, is commonly found. In this study, we determined that EGFRvIII mutation was present in 5% (3/56) of analyzed human lung squamous cell carcinoma (SCC) but was not present in human lung adenocarcinoma (0/123). We analyzed the role of the EGFRvIII mutation in lung tumorigenesis and its response to tyrosine kinase inhibition. Tissue-specific expression of EGFRvIII in the murine lung led to the development of NSCLC. Most importantly, these lung tumors depend on EGFRvIII expression for maintenance. Treatment with an irreversible EGFR inhibitor, HKI-272, dramatically reduced the size of these EGFRvIII-driven murine tumors in 1 week. Similarly, Ba/F3 cells transformed with the EGFRvIII mutant were relatively resistant to gefitinib and erlotinib in vitro but proved sensitive to HKI-272. These findings suggest a therapeutic strategy for cancers harboring the EGFRvIII mutation.
Polyvinyl Alcohol as an Emulsifying Agent (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyvinyl Alcohol as an Emulsifying AgentG. F. Blehn and M. L. ErnsbergerCite this: Ind. Eng. Chem. 1948, 40, 8, 1449–1453Publication Date (Print):August 1, 1948Publication History Published online1 May 2002Published inissue 1 August 1948https://pubs.acs.org/doi/10.1021/ie50464a024https://doi.org/10.1021/ie50464a024research-articleACS PublicationsRequest reuse permissionsArticle Views1045Altmetric-Citations30LEARN 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 options Get e-Alerts