gebhart/patrepeval huggingface dataset:
Engineered disulfide bonds as probes of the folding pathway of barnase: Increasing the stability of proteins against the rate of denaturation (1993)

Disulfide bridges have been introduced into barnase to act as probes of folding. One disulfide (between residues 85 and 102) links two loops known to pack together early in the folding pathway. A second disulfide bond (between residues 43 and 80) links two elements of secondary structure known to pack together only after the rate-determining step of folding. The disulfide-bridged proteins are more stable than wild-type by 4.1 and 1.2 kcal mol-1, respectively. The kinetics of unfolding and refolding of the mutant proteins has been measured, and a comparison of the disulfide proteins and their corresponding dithiol forms has been made by use of thermodynamic cycles. These data have been used to construct folding profiles of the disulfide proteins. The disulfide bond engineered into the part of the protein that folds early confers stability upon the intermediate and transition states of folding. The protein with a disulfide bond connecting parts of the protein that fold late is not stabilized until the protein reaches its final folded form. Conversely, in the unfolding pathway, the rate of unfolding of this mutant is lowered considerably. This points to a method of decreasing the rate of denaturation of proteins that are used in medical and biotechnological applications: elements of structure that unfold in or before the rate-determining step of overall unfolding may be stabilized and so slow down the overall unfolding process. The barnase mutant linked between Cys 43 and Cys 80, for example, unfolds 20 times slower than wild-type and 170 times slower than the reduced protein.
On the Role of Discourse Markers for Discriminating Claims and Premises in Argumentative Discourse (2015)

This paper presents a study on the role of discourse markers in argumentative discourse. We annotated a German corpus with arguments according to the common claim-premise model of argumentation and performed various statistical analyses regarding the discriminative nature of discourse markers for claims and premises. Our experiments show that particular semantic groups of discourse markers are indicative of either claims or premises and constitute highly predictive features for discriminating between them.
Graphene-based waveguide integrated dielectric-loaded plasmonic electro-absorption modulators (2013)

Theoretical investigations of graphene-based electro-optic plasmonic modulators with a dielectric ridge were analyzed and the results were presented. The effects of different ridge materials and different spacer dielectric functions were analyzed, showing that a 3 dB modulation with a 65 nm-long waveguide is possible with dielectric-loaded surface plasmon polariton waveguides (DLSPPWs), resulting in an energy per bit only 0.08 fJ/bit. The figure of merit, defined as the ratio between the extinction ratio and the insertion loss, was found to be about 5.2 with a low refractive index ridge and increased to over 17.3 for a high refractive index Si ridge, compared to 3.5 calculated and measured with photonic graphene-based waveguides. Additionally, it was shown that further improvement in terms of the figure of merit is possible with long-range dielectric-loaded surface plasmon polariton waveguides (LR-DLSPPWs), where it was calculated to exceed 72. For such waveguides, a 3 dB modulation was achieved with 10 μm-long waveguides with an energy per bit of 15.8 fJ/bit. The wavelength dependence of the graphene conductivity and, consequently, the attenuation of the waveguide were analyzed for different chemical potentials. It was shown that gate voltage applied across the graphene layers shifts the attenuation curve to shorter wavelengths, with the 3 dB modulation bandwidth exceeding 15 THz for a 12 μm-long DLSPP waveguide.
Exosomal MicroRNAs Derived from Human Amniotic Epithelial Cells Accelerate Wound Healing by Promoting the Proliferation and Migration of Fibroblasts (2018)

Previous work in our laboratory demonstrated that exosomes derived from human amniotic epithelial cells (hAECs) accelerated wound healing by promoting the proliferation and migration of fibroblasts. It is reported that exosomes, which are carriers of the microRNAs (miRNAs) and proteins, play an important role in the regulation of cell-to-cell communication. However, it is still unclear precisely which molecule or which group of molecules carried within hAEC-derived exosomes (hAEC-Exos) mediated wound healing. Here, we explored purified hAEC-Exos together with either proteinase K (PROse) or RNase A on the effect of fibroblasts and cutaneous wound healing. Our experiments demonstrated that hAEC-Exos were positive for exosomal markers CD9, CD63, and CD81. Also, we found that hAEC-Exos could be internalized by fibroblasts and then stimulated cell migration and proliferation. However, the promotive effect of hAEC-Exos was abolished by pretreating hAEC-Exos with RNase A, not PROse. Importantly, <i>in vivo</i> wound healing assay showed that local injection of hAEC-Exos or PROse pretreated hAEC-Exos at skin wounds significantly accelerated wound healing. Our findings revealed an important role of exosomal miRNAs in wound healing.
1982 Spring Meeting (1982)

The 1982 Spring Meeting will be held at The Franklin Plaza Hotel and The Philadelphia Centre Hotel in Philadelphia from May 31 to June 4.
Integrative Genetic Element That Reverses the Usual Target Gene Orientation (2002)

A genetic element integrating site specifically into a prokaryotic gene usually carries a copy of the 3' portion of that gene that restores the active gene even as the original is disrupted. A cryptic element in Mesorhizobium loti instead carries a copy of the 5' end of the tRNA gene into which it integrated. This has implications for the evolution of new integrase-site combinations.
sCLU regulates cisplatin chemosensitivity of lung cancer cells in vivo (2015)

We therefore concluded that the DDP-induced sCLU activation, which involved induction of pAkt and pERK1/2 activation that confer DDP resistance in immunocompromised mice and alteration of this balance, allows sensitization to the antitumor activity of cisplatin chemotherapy.
Human recombinant soluble decay accelerating factor inhibits complement activation in vitro and in vivo (1992)

Complement plays a role in activating the inflammatory response and has been implicated in the pathogenesis of some inflammatory diseases. With a view toward controlling unwanted C activation, we evaluated the C regulator, human decay accelerating factor (DAF). Three forms of recombinant DAF were purified from transfected Chinese hamster ovary cells: glycophosphatidylinositol (GPI)-linked membrane DAF (mDAF) extracted from cell membranes; spontaneously shed soluble DAF (sDAF) derived from mDAF; and a novel secreted protein (seDAF), generated by deletion of the signal for GPI attachment. We show that all three molecules inhibit both the classical and alternative pathways of C activation. The following observations indicate that mDAF extracted from Chinese hamster ovary cells reincorporates into RBC membranes via its GPI anchor: 1) cells that are preincubated with mDAF and then washed remain fully protected from C-mediated hemolysis; 2) incubation with phosphatidylinositol-specific phospholipase C abolishes this protection; and 3) sDAF and seDAF, which lack a GPI anchor, do not associate with cell membranes. mDAF is a more potent inhibitor of C-mediated hemolysis than either sDAF or seDAF, suggesting that incorporation into cell membranes greatly enhances the efficiency with which DAF inhibits C activation on the cell surface. In contrast, C activation in the fluid phase is inhibited by sDAF and seDAF, but not by mDAF, possibly due to interference by serum lipoproteins. A reversed passive Arthus reaction in guinea pigs was used to evaluate the ability of recombinant seDAF to inhibit C activation in vivo. When administered at dermal sites, seDAF reduced the severity of immune complex-mediated inflammatory reactions induced by a reversed passive Arthus reaction, as judged by both gross and histologic examination. These data indicate that seDAF may be useful as an anti-inflammatory therapeutic.
On the Image Sensor Processing for Lane Detection and Control in Vehicle Lane Keeping Systems (2019)

Lane keeping systems for a keeping a vehicle in the desired lane is key to advanced driving assistance system in autonomous vehicles. This paper presents a cost-effective image sensor with efficient processing algorithm for lane detection and lane control applications to autonomous delivery systems. The algorithm includes (1) lane detection by inverse perspective mapping and random sample consensus parabola fitting and (2) lane control by pure pursuit steering controller and classical proportional integral speed controller based on a nonholonomic kinematic model. The image sensor experiments conducted on a 1/10 scale model car maneuvering in a straight⁻curve⁻straight lane validate the better processing performance before, during, and after the turning section over previous work. The image sensor with the processing algorithm achieves the average lane detection error within 5% and maximum cross-track error within 9% in real-time. The development shall pave the way to cost-effective autonomous delivery systems.
The Clinical Pharmacology and Dynamics of Marihuana Cigarette Smoking (1981)

We have studied the dynamics of marihuana smoking, the plasma concentration of delta 9-tetrahydrocannabinol (THC), and the pharmacologic effects produced by the sequential smoking of two 1% marihuana cigarettes at a 2-hour interval. Three males and three females, experienced marihuana smokers, participated in the study. The results indicate that each subject smoked his or her two cigarettes at a similar rate. The THC plasma concentrations produced by the smoking of the second cigarette were slightly lower than those produced by the first cigarette. The levels of the psychologic "high" caused by the two cigarettes were similar. However, the first cigarette accelerated the heart twice as much as the second cigarette. Between males and females there were marked differences in the rate at which the cigarettes were smoked. In particular, males took more puffs, took them more often, and consumed the cigarettes more rapidly than females. The plasma concentrations of THC, the self-reported psychologic effects, and the heart rate acceleration produced by the smoking of the two cigarettes were identical between the sexes.
Cobalt and Cobalt Alloy Castings (2008)

Abstract This article discusses the physical metallurgy of cast cobalt alloys with emphasis on crystallography, compositions, phases and microstructure, and properties. Cobalt alloys are cast by several different foundry methods. The article describes the argon-oxygen decarburization and continuous casting process. It provides information on castability and quality of the casted alloys. The article details postcasting treatment, including heat treatment, hot isostatic pressing, and coatings. It summarizes the applications of cast cobalt alloys.
Unfit for Further Service:Trends in Medical Discharge from the British Army 1861-1998 (2000)

Military service requires individuals who are free from ill-health and who are physically and mentally robust, and throughout history those who have become unfit for service have been discharged on medical grounds. This paper uses published historical records to examine trends in the rate of discharge for six key conditions for the period 1861-1998 and to draw conclusions. In the late 19th and early 20th centuries, communicable diseases such as tuberculosis and syphilis were a major problem together with ill-defined conditions such as "disordered action of the heart". By the mid-20th century, psychiatric and gastrointestinal disorders had become the principal causes of medical discharge, whereas in the late 20th century, the majority of discharges resulted from injuries and musculoskeletal disorders. The pattern of conditions leading to medical discharge from the Army tends to mirror conditions which are prevalent at that time in the civilian population.
Genistein, daidzein, and their .beta.-glycoside conjugates: antitumor isoflavones in soybean foods from American and Asian diets (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGenistein, daidzein, and their .beta.-glycoside conjugates: antitumor isoflavones in soybean foods from American and Asian dietsLori. Coward, Neil C. Barnes, Kenneth D. R. Setchell, and Stephen. BarnesCite this: J. Agric. Food Chem. 1993, 41, 11, 1961–1967Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://doi.org/10.1021/jf00035a027RIGHTS & PERMISSIONSArticle Views2612Altmetric-Citations647LEARN 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 InReddit PDF (889 KB) Get e-Alerts Get e-Alerts
The structural basis of αβ T‐lineage immune recognition: TCR docking topologies, mechanotransduction, and co‐receptor function (2012)

Self versus non-self discrimination is at the core of T-lymphocyte recognition. To this end, αβ T-cell receptors (TCRs) ligate 'foreign' peptides bound to major histocompatibility complex (MHC) class I or class II molecules (pMHC) arrayed on the surface of antigen-presenting cells (APCs). Since the discovery of TCRs approximately 30 years ago, considerable structural and functional data have detailed the molecular basis of their extraordinary ligand specificity and sensitivity in mediating adaptive T-cell immunity. This review focuses on the structural biology of the Fab-like TCRαβ clonotypic heterodimer and its unique features in conjunction with those of the associated CD3εγ and CD3εδ heterodimeric molecules, which, along with CD3ζζ homodimer, comprise the TCR complex in a stoichiometry of 1:1:1:1. The basis of optimized TCRαβ docking geometry on the pMHC linked to TCR mechanotransduction and required for T-cell signaling as well as CD4 and CD8 co-receptor function is detailed. A model of the TCR ectodomain complex including its connecting peptides suggests how force generated during T-cell immune surveillance and at the immunological synapse results in dynamic TCR quaternary change involving its heterodimeric components. Potential insights from the structural biology relevant to immunity and immunosuppression are revealed.
Evaluation of tyrosinase mRNA as a tumor marker in the blood of melanoma patients. (1997)

Using a density gradient method to process the blood samples resulted in a higher detection rate of tyrosinase mRNA than extracting the RNA from the whole blood. However, the relatively low sensitivity in patients with disseminated and progressive disease compared with other reports suggests that tyrosinase mRNA may be of limited value in the management of malignant melanoma.
No association between neutrophil FcγRIIa allelic polymorphism and anti-neutrophil cytoplasmic antibody (ANCA)-positive systemic vasculitis (1999)

ANCA, implicated as having a pathogenic role in systemic vasculitis, can activate tumour necrosis factor-alpha (TNF-alpha)-primed neutrophils by cross-linking surface-expressed ANCA antigens with neutrophil FcgammaRIIa receptors to release reactive oxygen species. The FcgammaRIIa receptor exists as polymorphic variants, R131 and H131, which differ in their ability to ligate human IgG2 and IgG3. Neutrophils homozygous for the FcgammaRIIa-H131 allotype bind more efficiently to IgG3 than the FcgammaRIIa-R131 allotype and are the only human FcgammaR which bind IgG2. Our aim was to determine whether the homozygous FcgammaRIIa-H131 individuals are more susceptible to developing ANCA-associated systemic vasculitis and nephritis due to differential IgG binding and activation. FcgammaRIIa allotype was determined by both allele-specific polymerase chain reaction (PCR) and Southern blotting with allele-specific oligonucleotide probes end-labelled with 32P-gammaATP, after PCR amplification of genomic FcgammaRIIa DNA in 107 Caucasian patients with ANCA+ vasculitis (of whom 89 had renal disease) and 100 ethnically matched controls. Phenotyping of neutrophil FcgammaRIIa alleles was confirmed in some patients by quantitative flow cytometry using murine MoAbs 41H16 and IV.3. Of the patients with ANCA+ systemic vasculitis, 75 had ANCA with specificity for proteinase 3 and 32 with specificity for myeloperoxidase. Overall, no skewing in FcgammaRIIa allotypes was seen in patients compared with controls. No significant increase of the FcgammaRIIa-H131 allotype was found amongst patients irrespective of ANCA specificity, and no association between the FcgammaRIIa allotype and nephritis was found. Our data suggest that the FcgammaRIIa receptor allotype is not a major factor predisposing to the development of ANCA+ systemic vasculitis, or to nephritis.
Clinical review: Vasopressin and terlipressin in septic shock patients. (2004)

Vasopressin (antidiuretic hormone) is emerging as a potentially major advance in the treatment of septic shock. Terlipressin (tricyl-lysine-vasopressin) is the synthetic, long-acting analogue of vasopressin, and has comparable pharmacodynamic but different pharmacokinetic properties. Vasopressin mediates vasoconstriction via V1 receptor activation on vascular smooth muscle. Septic shock first causes a transient early increase in blood vasopressin concentrations; these concentrations subsequently decrease to very low levels as compared with those observed with other causes of hypotension. Infusions of 0.01-0.04 U/min vasopressin in septic shock patients increase plasma vasopressin concentrations. This increase is associated with reduced need for other vasopressors. Vasopressin has been shown to result in greater blood flow diversion from nonvital to vital organ beds compared with adrenaline (epinephrine). Of concern is a constant decrease in cardiac output and oxygen delivery, the consequences of which in terms of development of multiple organ failure are not yet known. Terlipressin (one or two boluses of 1 mg) has similar effects, but this drug has been used in far fewer patients. Large randomized clinical trials should be conducted to establish the utility of these drugs as therapeutic agents in patients with septic shock.
Mechanistic characterization of the MSDH (methylmalonate semialdehyde dehydrogenase) from Bacillus subtilis (2006)

Homotetrameric MSDH (methylmalonate semialdehyde dehydrogenase) from Bacillus subtilis catalyses the NAD-dependent oxidation of MMSA (methylmalonate semialdehyde) and MSA (malonate semialdehyde) into PPCoA (propionyl-CoA) and acetyl-CoA respectively via a two-step mechanism. In the present study, a detailed mechanistic characterization of the MSDH-catalysed reaction has been carried out. The results suggest that NAD binding elicits a structural imprinting of the apoenzyme, which explains the marked lag-phase observed in the activity assay. The enzyme also exhibits a half-of-the-sites reactivity, with two subunits being active per tetramer. This result correlates well with the presence of two populations of catalytic Cys302 in both the apo- and holo-enzymes. Binding of NAD causes a decrease in reactivity of the two Cys302 residues belonging to the two active subunits and a pKapp shift from approx. 8.8 to 8.0. A study of the rate of acylation as a function of pH revealed a decrease in the pKapp of the two active Cys302 residues to approx. 5.5. Taken to-gether, these results support a sequential Cys302 activation process with a pKapp shift from approx. 8.8 in the apo-form to 8.0 in the binary complex and finally to approx. 5.5 in the ternary complex. The rate-limiting step is associated with the b-decarboxylation process which occurs on the thioacylenzyme intermediate after NADH release and before transthioesterification. These data also indicate that bicarbonate, the formation of which is enzyme-catalysed, is the end-product of the reaction.
Relationships among the O-Antigen Gene Clusters of Salmonella enterica Groups B, D1, D2, and D3 (1998)

The O antigen is an important cell wall antigen of gram-negative bacteria, and the genes responsible for its biosynthesis are located in a gene cluster. We have cloned and sequenced the DNA segment unique to the O-antigen gene cluster of Salmonella enterica group D3. This segment includes a novel O-antigen polymerase gene (wzyD3). The polymerase gives alpha(1-->6) linkages but has no detectable sequence similarity to that of group D2, which confers the same linkage. We find the remnant of a D3-like wzy gene in the O-antigen gene clusters of groups D1 and B and suggest that this is the original wzy gene of these O-antigen gene clusters.
αvβ6-Fyn Signaling Promotes Oral Cancer Progression (2003)

We have previously shown that the integrin beta6 is neo-expressed in invasive oral squamous cell carcinoma (SCC) and is correlated with oral tumor progression. However, the mechanism by which the integrin beta6 promotes oral tumor progression is not well understood. The purpose of the present study was to determine whether integrin beta6 signaling activates Fyn and thus promotes oral squamous cell carcinoma progression. We analyzed the integrin beta6 signaling complex and investigated the function of these signaling molecules in oral SCC cells. We found that, upon ligation of the integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it. The activation of Fyn recruited and activated focal adhesion kinase to this complex. This complex was necessary to activate Shc and to couple beta6 signaling to the Raf-ERK/MAPK pathway. This pathway transcriptionally activated the matrix metalloproteinase-3 gene and promoted oral SCC cell proliferation and experimental metastasis in vivo. These findings indicate that integrin beta6 signaling activates Fyn and thus promotes oral cancer progression.
The LOCUS distributed operating system (1983)

LOCUS is a distributed operating system which supports transparent access to data through a network wide filesystem, permits automatic replication of storage, supports transparent distributed process execution, supplies a number of high reliability functions such as nested transactions, and is upward compatible with Unix. Partitioned operation of subnet's and their dynamic merge is also supported. The system has been operational for about two years at UCLA and extensive experience in its use has been obtained. The complete system architecture is outlined in this paper, and that experience is summarized.