gebhart/patrepeval huggingface dataset:
A Novel Sphingosine-dependent Protein Kinase (SDK1) Specifically Phosphorylates Certain Isoforms of 14-3-3 Protein (1998)

Protein kinases activated by sphingosine or N,N'-dimethylsphingosine, but not by other lipids, have been detected and are termed sphingosine-dependent protein kinases (SDKs). These SDKs were previously shown to phosphorylate endogenous 14-3-3 proteins (Megidish, T., White, T., Takio, K., Titani, K., Igarashi, Y., and Hakomori, S. (1995) Biochem. Biophys. Res. Commun. 216, 739-747). We have now partially purified one SDK, termed SDK1, from cytosol of mouse Balb/c 3T3(A31) fibroblasts. SDK1 is a serine kinase with molecular mass 50-60 kDa that is strongly activated by N, N'-dimethylsphingosine and sphingosine, but not by ceramide, sphingosine 1-phosphate, or other sphingo-, phospho-, or glycerolipids tested. Its activity is inhibited by the protein kinase C activator phosphatidylserine. Activity of SDK1 is clearly distinct from other types of serine kinases tested, including casein kinase II, the alpha and zeta isoforms of protein kinase C, extracellular signal-regulated mitogene-activated protein kinase 1 (Erk-1), Erk-2, and Raf-1. SDK1 specifically phosphorylates certain isoforms of 14-3-3 (eta, beta, zeta) but not others (sigma, tau). The phosphorylation site was identified as Ser* in the sequence Arg-Arg-Ser-Ser*-Trp-Arg in 14-3-3 beta. The sigma and tau isoforms of 14-3-3 lack serine at this position, potentially explaining their lack of phosphorylation by SDK1. Interestingly, the phosphorylation site is located on the dimer interface of 14-3-3. Phosphorylation of this site by SDK1 was studied in 14-3-3 mutants. Mutation of a lysine residue, located 9 amino acids N-terminal to the phosphorylation site, abolished 14-3-3 phosphorylation. Furthermore, co-immunoprecipitation experiments demonstrate an association between an SDK and 14-3-3 in situ. Exogenous N, N'-dimethylsphingosine stimulates 14-3-3 phosphorylation in Balb/c 3T3 fibroblasts, suggesting that SDK1 may phosphorylate 14-3-3 in situ. These data support a biological role of SDK1 activation and consequent phosphorylation of specific 14-3-3 isoforms that regulate signal transduction. In view of the three-dimensional structure of 14-3-3, it is likely that phosphorylation by SDK1 would alter dimerization of 14-3-3, and/or induce conformational changes that alter 14-3-3 association with other kinases involved in signal transduction.
Cloning of an alternate form of vascular cell adhesion molecule-1 (VCAM1). (1991)

Vascular cell adhesion molecule-1 (VCAM1) of the Ig superfamily is induced by the inflammatory cytokines interleukin-1 and tumor necrosis factor on human umbilical vein endothelial cells (HUVECs). It binds to mononuclear leukocytes via the integrin VLA-4. We have cloned and expressed a cDNA encoding a new form of human VCAM1 containing an additional Ig homologous domain inserted between the third and fourth domains of the original six-domain protein. Characterization of mRNA from HUVECs from three individuals at various time points after induction by tumor necrosis factor indicates that both the long and short VCAM1 mRNAs are made by all three individuals, with the long form predominating quantitatively. Immunoprecipitation of VCAM1 protein from cos7 cells transfected with each cDNA and from cultured endothelial cells followed by deglycosylation suggests that the long form is the major form found on endothelium. The two forms may result from alternate splicing of a precursor mRNA. Both forms support adhesion of VLA-4-expressing cell lines.
Interaction of Glycogen Synthase Kinase 3β with the DF3/MUC1 Carcinoma-Associated Antigen and β-Catenin (1998)

The DF3/MUC1 mucin-like glycoprotein is highly overexpressed in human carcinomas. Recent studies have demonstrated that the cytoplasmic domain of MUC1 interacts with beta-catenin. Here we show that MUC1 associates with glycogen synthase kinase 3beta (GSK3beta). GSK3beta binds directly to an STDRSPYE site in MUC1 and phosphorylates the serine adjacent to proline. Phosphorylation of MUC1 by GSK3beta decreases binding of MUC1 to beta-catenin in vitro and in vivo. GSK3beta-mediated phosphorylation of MUC1 had no apparent effect on beta-catenin levels or the transcriptional coactivation function of beta-catenin. The results, however, demonstrate that MUC1 expression decreases binding of beta-catenin to the E-cadherin cell adhesion molecule. Negative regulation of the beta-catenin-MUC1 interaction by GSK3beta is associated with restoration of the complex between beta-catenin and E-cadherin. These findings indicate that GSK3beta decreases the interaction of MUC1 with beta-catenin and that overexpression of MUC1 in the absence of GSK3beta activity inhibits formation of the E-cadherin-beta-catenin complex.
Abundance-Ratio-Based Semiquantitative Analysis of Site-Specific N-Linked Glycopeptides Present in the Plasma of Hepatocellular Carcinoma Patients (2014)

Aberrant structures of site-specific N-linked glycans are closely associated with the tumorigenesis of hepatocellular carcinoma (HCC), one of the most common fatal cancers worldwide. Vitronectin (VTN) is considered a candidate glycobiomarker of HCC. In this study, we describe a reliable and simple quantification strategy based on abundance ratios of site-specific N-linked glycopeptides of VTN to screen for potential biomarkers. A total of 14 unique N-linked glycans corresponding to 27 unique N-linked glycopeptides were characterized at three N-linked sites (Asn-86, -169, and -242) present in VTN. These glycans could be good candidate markers for HCC. Among these glycans, the abundance ratio of two representative glycoforms (fucosyl vs non-fucosyl) was significantly increased in HCC plasma relative to normal plasma. This strategy was also successfully applied to another potential HCC biomarker, haptoglobin. Furthermore, we demonstrate that our approach employing tandem mass tag (TMT) and target N-linked glycopeptides of VTN is a useful tool for quantifying specific glycans in HCC plasma relative to normal plasma. Our strategy represents a simple and potentially useful screening platform for the discovery of cancer-specific glycobiomarkers.
Activation of STING requires palmitoylation at the Golgi (2016)

Stimulator of interferon genes (STING) is essential for the type I interferon response against DNA pathogens. In response to the presence of DNA and/or cyclic dinucleotides, STING translocates from the endoplasmic reticulum to perinuclear compartments. However, the role of this subcellular translocation remains poorly defined. Here we show that palmitoylation of STING at the Golgi is essential for activation of STING. Treatment with palmitoylation inhibitor 2-bromopalmitate (2-BP) suppresses palmitoylation of STING and abolishes the type I interferon response. Mutation of two membrane-proximal Cys residues (Cys88/91) suppresses palmitoylation, and this STING mutant cannot induce STING-dependent host defense genes. STING variants that constitutively induce the type I interferon response were found in patients with autoimmune diseases. The response elicited by these STING variants is effectively inhibited by 2-BP or an introduction of Cys88/91Ser mutation. Our results may lead to new treatments for cytosolic DNA-triggered autoinflammatory diseases.
Sample-oriented task-driven visualizations (2014)

We often use datasets that reflect samples, but many visualization tools treat data as full populations. Uncertain visualizations are good at representing data distributions emerging from samples, but are more limited in allowing users to carry out decision tasks. This is because tasks that are simple on a traditional chart (e.g. "compare two bars") become a complex probabilistic task on a chart with uncertainty. We present guidelines for creating visual annotations for solving tasks with uncertainty, and an implementation that addresses five core tasks on a bar chart. A preliminary user study shows promising results: that users have a justified confidence in their answers with our system.
Mother-to-Infant Transmission of Intestinal Bifidobacterial Strains Has an Impact on the Early Development of Vaginally Delivered Infant's Microbiota (2013)

Among infants born vaginally, several Bifidobacterium strains transmit from the mother and colonize the infant's intestine shortly after birth. Our data suggest that the mother's intestine is an important source for the vaginal delivered infant's intestinal microbiota.
Characterization of the Gastrointestinal Microbiota in Health and Inflammatory Bowel Disease (2011)

The enteric bacterial flora play a key role in maintaining health. Inflammatory bowel disease is associated with quantitative and qualitative alterations in the microbiota. Early characterization of the microbiota involved culture-dependent techniques. The advent of metagenomic techniques, however, allows for structural and functional characterization using culture-independent methods. Changes in diversity, together with quantitative alterations in specific bacterial species, have been identified. The functional significance of these changes, and their pathogenic role, remain to be elucidated.
Totally Synthetic Routes to the Higher Monosaccharides (1987)

Abstract The evolution of a strategy to synthesize the title compounds is described. Three principal developments allowed realization of this goal: (1) the attainment of high margins of diastereofacial selectivity and regioselectivity in the construction of pyranoid systems via the Lewis acid‐catalyzed cyclocondensation reaction of activated dienes and aldehydes; (2) the exploitation of stereoselective reactions for functionalization of the pyranoid matrix; and (3) the discovery of stereoselective reactions for extending the chiral biases of pyranoid systems to newly emerging stereogenic centers on side chains. The coordination of these components in the synthesis of target systems of high biological interest is described.
Increased polymerase fidelity of the 3TC-resistant variants of HIV-1 reverse transcriptase (1997)

Human immunodeficiency virus type 1 (HIV-1) variants with resistance mutations in the reverse transcriptase (RT) gene appear during drug therapy with the nucleoside analogue 2',3'-dideoxy-3'-thiacytidine (3TC). These 3TC-resistant RT variants have a single point mutation that changes the 184Met residue into either Val or Ile. Both codon 184 variants are frequently observed in 3TC-treated patients and can also be selected in cell culture infections. We demonstrated previously that the 184Ile and 184Val RT enzymes exhibit a processivity defect in in vitro assays, with 184Ile being the least processive enzyme [Met(wt) >Val >Ile]. In this study, we measured the polymerase fidelity of the wild-type (184Met) and 3TC-resistant RT enzymes (184Ile and 184Val) on DNA and RNA templates. Both virion- extracted and Escherichia coli -expressed recombinant RT enzymes were used to measure the nucleotide misinsertion and mispair extension efficiencies. The 3TC-resistant enzymes were more accurate than the wild-type RT protein in both type of assays. The order of accuracy observed for the codon 184 variants [Ile >Val >Met(wt)] may suggest an inverse correlation between the fidelity and processivity properties of these enzymes.
The Single-Cavity Multiple-Device Oscillator (1971)

The output power from 12 IMPATT diodes has been combined in a single-cavity multiple-device oscillator. The oscillator is free from the well-known moding problem of multiple-device oscillators. The objective of this paper is to present the oscillator-circuit theory, which clearly indicates why this particular circuit configuration can give a stable operation free from moding problems. To handle the formidable equations necessary for the analysis, the eigenfunction approach is extensively used. The condition for stable operation, the noise performance, and the locking behavior of the oscillator are all discussed. The noise performance is similar and the locking behavior identical to those of single-device oscillators.
GLYCOGEN SYNTHASE KINASE 3β INHIBITION REDUCES THE DEVELOPMENT OF NONSEPTIC SHOCK INDUCED BY ZYMOSAN IN MICE (2006)

Glycogen synthase kinase 3 has recently been identified as a ubiquitous serine-threonine protein kinase that participates in a multitude of cellular processes and plays an important role in the pathophysiology of a number of diseases. In the present study, we have investigated the effects of 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), a glycogen synthase kinase 3beta inhibitor, on the development of nonseptic shock caused by zymosan (dose, 500 mg/kg i.p. suspension in saline) in mice. Organ failure and systemic inflammation in mice was assessed 18 h after administration of zymosan and/or TDZD-8; another group of mice was monitored for 12 days (for clinical score and mortality). Treatment of mice with TDZD-8 (dose, 10 mg/kg i.p., 1 and 6 h after zymosan administration) attenuated the peritoneal exudation and the migration of polymorphonuclear cells caused by zymosan. TDZD-8 also attenuated the lung, liver, and pancreatic injury, the renal dysfunction caused by zymosan, and the increase in myeloperoxidase activity caused by zymosan in the lung and in the intestine. Immunohistochemical analysis for inducible nitric oxide synthase, nitrotyrosine, poly(ADP-ribose), CD30, CD30 ligand, and Fas ligand revealed positive staining in lung and intestinal tissues obtained from zymosan-injected mice. The degree of staining for inducible nitric oxide synthase, nitrotyrosine, poly(ADP-ribose), CD30, CD30 ligand, and Fas ligand were markedly reduced in tissue sections obtained from zymosan-injected mice that had received TDZD-8. This study provides the first evidence that TDZD-8 attenuates the degree of zymosan-induced, nonseptic shock in mice.
Role of Active Drug Transporters in Refractory Multiple Myeloma (2009)

Drug resistance is a major drawback for cancer chemotherapy protocols and previous studies have demonstrated the overexpression of the P-glycoprotein (P-gp) as mechanism by which myeloma cells develop multidrug resistance (MDR). However, other molecules may apparently promote MDR in multiple myeloma (MM). They include both lung resistance-related protein (LRP) and p53 activation. The inhibition of P-gp in MM patients treated with melphalan (PAM) has been associated to increased toxicity, whereas defective apoptosis due to down-modulation of the NF-kB is a feature of MDR+ myeloma cells. On the contrary, clinical trials with proteasome inhibitors have been successfully carried out to overcome MDR despite their toxicity profile. Recently, sigma receptors (sigmaR)(S), namely sigmaR(1) and sigmaR(2), have been found to be overexpressed in breast cancer cells. In addition, their levels correlate with both P-gp upregulation and MDR development. By contrast, selective inhibitors of sigmaR(S) as PB28, disrupt the P-gp signals and restore the apoptosis machinery in malignant cells. We have reviewed the major pathogenetic events promoting MDR in MM and focused on the sigmaR(S) as potential mechanism driving this function. We demonstrate that MDR+ myeloma cells overexpress the sigmaR(2) and that the treatment with PB28 induces P-gp down-modulation through the activation of the caspases enrolled in both extrinsic and intrinsic apoptotic pathways. Thus, sigmaR(2) inhibitors may be tentatively proposed for the treatment of PAM-resistant MM patients.
Thermodynamic analysis of monoclonal antibody binding to duplex DNA (1997)

A technique based on fluorescence polarization (anisotropy) was used to measure the binding of antibodies to DNA under a variety of conditions. Fluorescein-labeled duplexes of 20 bp in length were employed as the standard because they are stable even at low ionic strength yet sufficiently short so that both arms of an IgG cannot bind to the same duplex. IgG Jel 274 binds duplexes in preference to single-stranded DNA; in 80 mM NaCl Kobs for (dG)20.(dC)20 is 4.1x10(7) M-1 compared with 6.4x10(5) M-1 for d(A5C10A5). There is little sequence specificity, but the interaction is very dependent on ionic strength. From plots of log Kobs against log[Na+] it was deduced that five or six ion pairs are involved in complex formation. At low ionic strength,Kobs is independent of temperature and complex formation is entropy driven with DeltaH degrees obs and DeltaC degrees p,obs both zero. In contrast, in 80 mM NaCl DeltaC degrees p,obs is -630 and -580 cal mol-1K-1 for [d(TG)]10.[d(CA)]10 and (dG)20.(dC)20 respectively. IgG Jel 241 also binds more tightly to duplexes than single-stranded DNA, but sequence preferences were apparent. The values for Kobs to [d(AT)]20 and [d(GC)]20 are 2.7x10(8) and 1.3x10(8) M-1 respectively compared with 5.7x10(6) M-1 for both (dA)20. (dT)20 and (dG)20.(dC)20. As with Jel 274, the binding of Jel 241 is very dependent on ionic strength and four or five ionic bonds are involved in complex formation with all the duplex DNAs which were tested. DeltaC degrees p,obs for Jel 241 binding to [d(AT)]20 was negative (-87 cal mol-1K-1) in 80 mM NaCl but was zero at high ionic strength (130 mM NaCl). Therefore, for duplex-specific DNA binding antibodies DeltaC degrees p,obs is dependent on [Na+] and a large negative value does not correlate with sequence-specific interactions.
Antigenic structure of the central conserved region of protein G of bovine respiratory syncytial virus (1997)

Epitopes were resolved at the amino acid level for nine monoclonal antibodies (MAbs) directed against the central conserved region of protein G of bovine respiratory syncytial virus (BRSV-G). Peptide binding studies showed which amino acids in the epitope contributed to antibody binding. The details of the epitopes were compared with the high-resolution structure of a synthetic peptide corresponding to the central conserved region of BRSV-G, and this indicated which face of the central conserved region is the antigenic structure. The major linear epitope of the central conserved region of BRSV-G is located at the tip of the loop, overlapping a relatively flat surface formed by a double disulfide-bonded cystine noose. At least one, but possibly two sulfur atoms of a disulfide bridge that line the conserved pocket at the center of the flat surface, is a major contributor to antibody binding. Some of the residue positions in the epitope have mutated during the evolution of RSV-G, which suggests that the virus escaped antibody recognition with these mutations. Mutations that occur at positions 177 and 180 may have only a local effect on the antigenic surface, without influencing the structure of the backbone, whereas mutations at positions 183 and 184 will probably have major structural consequences. The study explains the antigenic, structural, and functional importance of each residue in the cystine noose which provides information for peptide vaccine design. Additionally, analysis of the epitopes demonstrated that two point mutations at positions 180 and 205 define the preliminary classification of BRSV subgroups.
Tire Pressure Monitoring System and Wireless Passive Surface Acoustic Wave Sensor (2014)

The TPMS can not only save fuel and protect the tire, but also make the driver more safety. Tire safety is attracting the driver's attention, the United States had developed laws to enforce the TPMS installation in the car and the deadline is in 2008. In this paper, the basic structure and the implement method of TPMS are introduced. The active sensors are already used in most of the TPMS applications. The SAW theory and some wireless passive SAW pressure and temperature sensors which suit for the TPMS application are illustrated, because the passive sensor is becoming the focus in the TPMS research field. Passive SAW sensor is the good choice for TPMS, according to its wireless, passive, zero age rate, small size etc. The wireless passive SAW TPMS is one of the most important research direction. In this paper, some kinds of passive SAW sensor are introduced, which are used in TPMS.
Interaction of fibronectin with collagen fibrils (1981)

The interaction of fibronectin with native collagen during collagen fibril formation was investigated. Fibronectin prepared from serum, or from the cell surface, bound to the forming collagen fibrils while less fibronectin bound to preformed fibers. Denatured collagen competed with native collagen in binding fibronectin. Fibronectin delayed the precipitation of collagen fibrils but did not alter the total amount of fibrils formed. Fibronectin which was heated to 30 degrees C for 30 min did not promote cell adhesion but still bound to native collagen and delayed fiber formation. The collagen-binding fragment of fibronectin produced by digestion either with chymotrypsin or with neutrophil elastase had a similar effect in delaying fibril formation, but the cell-binding fragment was not active. These studies indicate that fibronectin can bind to aggregating collagen fibers probably at the same site shown previously to bind to denatured collagen. Since fibronectin inhibits the rate of collagen fibrillogenesis, it may regulate the size of collagen fibers.
Development and Evaluation of an Ultrasonic Ground Water Seepage Meter (2001)

Submarine ground water discharge can influence significantly the near-shore transport and flux of chemicals into the oceans. Quantification of the sources and rates of such discharge requires a ground water seepage meter that provides continuous measurements at high resolution over an extended period of time. An ultrasonic flowmeter has been adapted for such measurements in the submarine environment. Connected to a steel collection funnel, the meter houses two piezoelectric transducers mounted at opposite ends of a cylindrical flow tube. By monitoring the perturbations of fluid flow on the propagation of sound waves inside the flow tube, the ultrasonic meter can measure both forward and reverse fluid flows in real time. Laboratory and field calibrations show that the ultrasonic meter can resolve ground water discharges on the order of 0.1 microm/sec, and it is sufficiently robust for deployment in the field for several days. Data from West Neck Bay, Shelter Island, New York, elucidate the temporal and spatial heterogeneity of submarine ground water discharge and its interplay with tidal loading. A negative correlation between the discharge and tidal elevation was generally observed. A methodology was also developed whereby data for the sound velocity as a function of temperature can be used to infer the salinity and source of the submarine discharge. Independent measurements of electrical conductance were performed to validate this methodology.
11. Cellular response to cancer chemopreventive agents: contribution of the antioxidant responsive element to the adaptive response to oxidative and chemical stress (1999)

Cancer chemopreventive agents can act by inhibiting either the acquisition of mutations or the neoplastic processes that occur subsequent to mutagenesis. Compounds that reduce the rate at which mutations arise, referred to as blocking agents, exert their effects largely through their ability to induce the expression of antioxidant and detoxification proteins. This is achieved by the transcriptional activation of a small number of genes that are co-regulated through the presence of an antioxidant responsive element (ARE) in their promoters. Blocking agents can cause gene induction by producing oxidative and/or chemical stress within the cell and, as the inducible proteins act to ameliorate the metabolic insult, the process represents a form of adaptive response. The transcription factors which mediate this response through the ARE are members of the basic leucine zipper superfamily. The mechanism whereby cells sense and respond to the chemical signal(s) generated by chemopreventive blocking agents is discussed.