gebhart/patrepeval huggingface dataset:
Molecular Characterization of a Putative Arabidopsis thaliana Copper Transporter and Its Yeast Homologue (1995)

At the molecular level, little is known about the transport of copper across plant membranes. We have isolated an Arabidopsis thaliana cDNA by complementation of a mutant (ctr1-3) of Saccharomyces cerevisiae defective in high affinity copper uptake. This cDNA codes for a highly hydrophobic protein (COPT1) of 169 amino acid residues and with three putative transmembrane domains. Most noteworthy, the first 44 residues display significant homology to the methionine- and histidine-rich copper binding domain of three bacterial copper binding proteins, among these a copper transporting ATPase. Mutant yeast cells expressing COPT1 exhibit nearly wild type behavior with regard to growth on a nonfermentable carbon source and resistance to copper and iron starvation. Expression of COPT1 is also associated with an increased sensitivity to copper toxicity. Additionally, COPT1 shows significant homology to an open reading frame of 189 amino acid residues on yeast chromosome VIII. This gene (CTR2) may encode an additional yeast metal transporter able to mediate the uptake of copper. A mutation in CTR2 displays a higher level of resistance to toxic copper concentrations. Overexpression of CTR2 provides increased resistance to copper starvation and is also associated with an increased sensitivity to copper toxicity. The amino acid sequence of CTR2, like Arabidopsis COPT1, contains three potential transmembrane domains. Taken together, the data suggest that a plant metal transporter, which is most likely involved in the transport of copper, has been identified.
A method for the generation of combinatorial antibody libraries using pIX phage display (2002)

For more than a decade, phage displayed combinatorial antibody libraries have been used to generate and select a wide variety of antibodies. We previously reported that the phage coat proteins pVII and pIX could be used to display the heterodimeric structure of the antibody Fv region. Herein, aspects of this technology were invoked and extended to construct a large, human single-chain Fv (scFv) library of 4.5 x 10(9) members displayed on pIX of filamentous bacteriophage. Furthermore, the diversity, quality, and utility of the library were demonstrated by the selection of scFv clones against six different protein antigens. Notably, more than 90% of the selected clones showed positive binding for their respective antigens after as few as three rounds of panning. Analyzed scFvs were also found to be of high affinity. For example, kinetic analysis (BIAcore) revealed that scFvs against staphylococcal enterotoxin B and cholera toxin B subunit had a nanomolar and subnanomolar dissociation constant, respectively, affording affinities comparable to, or exceeding that, of mAbs obtained from immunization. High specificity was also attained, not only between very distinct proteins, but also in the case of the Ricinus communis ("ricin") agglutinins (RCA(60) and RCA(120)), despite >80% sequence homology between the two. The results suggested that the performance of pIX-display libraries can potentially exceed that of the pIII-display format and make it ideally suited for panning a wide variety of target antigens.
Structure and function of plasminogen/plasmin system (2014)

The main physiological function of plasmin is a blood clot fibrinolysis and restore normal blood flow. To date, however, it became apparent that in addition to thrombolysis plasminogen/plasmin system plays an important physiological and pathological role in the degradation of extracellular matrix, embryogenesis, cell migration, tissue remodeling, wound healing, angiogenesis, inflammation and tumor cells migration. This review focuses on the structural features of plasminogen, the regulation of its activation by physiological plasminogen activators, inhibitors of plasmin and plasminogen activators, the role of the plasminogen binding to fibrin, cellular receptors and extracellular ligands in performing various functions by formed plasmin.
Production and characterization of monoclonal antibodies specific for different epitopes of human tenascin (1993)

We have obtained and characterized 11 monoclonal antibodies (mAbs) specific for different domains of human tenascin (TN). Five of these mAbs reacted with epitopes contained in the TN area that undergoes alternative splicing and are thus able to recognize specific TN isoforms. These mAbs are a useful tool to study the expression and distribution of TN and its different isoforms in normal and pathological tissues.
Biosynthesis of Branched-chain Fatty Acid inBacilli: FabD (malonyl-CoA:ACP transacylase) Is Not Essential forIn VitroBiosynthesis of Branched-chain Fatty Acids (2003)

It was found that the partially purified beta-ketoacyl-ACP synthase of Bacillus insolitus did not require the addition of FabD (malonyl-CoA:ACP transacylase, MAT) for the activity assay. This study therefore examined the necessity of FabD protein for in vitro branched-chain fatty acid (BCFA) biosynthesis by crude fatty acid synthetases (FAS) of Bacilli. To discover the involvement of FabD in the BCFA biosynthesis, the protein was removed from the crude FAS by immunoprecipitation. The His-tag fusion protein FabD of Bacillus subtilis was expressed in Escherichia coli and used for the preparation of antibody. The rabbit antibody raised against the expressed fusion protein specifically recognized the FabD in the crude FAS of B. subtilis. Evaluation of the efficacy of the immunoprecipitation showed that a trace of FabD protein was present in the antibody-treated crude FAS. However, this complete removal of FabD from the crude FAS did not abolish its BCFA biosynthesis, but only reduced the level to 50-60% of the control level for acyl-CoA primer and to 80% for alpha-keto-beta-methylvalerate primer. Furthermore, the FabD concentration did not necessarily correlate with the MAT specific activity in the enzyme fractions, suggesting the presence of another enzyme source of MAT activity. This study, therefore, suggests that FabD is not the sole enzyme source of MAT for in vitro BCFA biosynthesis, and implies the existence of a functional connection between fatty acid biosynthesis and another metabolic pathway.
Nuclear congression and membrane fusion: two distinct events in the yeast karyogamy pathway. (1994)

Karyogamy is the process where haploid nuclei fuse to form a diploid nucleus during yeast mating. We devised a novel genetic screen that identified five new karyogamy (KAR) genes and three new cell fusion (FUS) genes. The kar mutants fell into two classes that represent distinct events in the yeast karyogamy pathway. Class I mutations blocked congression of the nuclei due to cytoplasmic microtubule defects. In Class II mutants, nuclear congression proceeded and the membranes of apposed nuclei were closely aligned but unfused. In vitro, Class II mutant membranes were defective in a homotypic ER/nuclear membrane fusion assay. We propose that Class II mutants define components of a novel membrane fusion complex which functions during vegetative growth and is recruited for karyogamy.
Activation of type I cyclic AMP-dependent protein kinases with defective cyclic AMP-binding sites. (1987)

Two S49 mouse lymphoma cell variants hemizygous for expression of mutant regulatory (R) subunits of type I cyclic AMP-dependent protein kinase were used to investigate functional consequences of lesions in the putative cAMP-binding sites of R subunit. Kinase activation properties of wild-type and mutant enzymes were compared using cAMP and six site-selective analogs of cAMP. Kinases from both mutant sublines were relatively resistant to cyclic nucleotide-dependent activation, but they were fully activable by at least some effectors. Relative resistances of the mutant kinases varied from about 5-fold for analogs selective for their nonmutated sites to as much as 700-fold for analogs selective for their mutated sites; resistance to cAMP was intermediate. Apparent affinities of wild-type and mutant R subunits for [3H]cAMP were not appreciably different, but competition experiments with site-selective analogs of cAMP suggested that binding of cAMP to mutant R subunits was primarily to their nonmutated sites. Analyses of cooperativity in cyclic nucleotide-dependent activation of mutant kinases, synergism between site I- and site II-selective analogs in activating the mutant enzymes, and dissociation of bound cAMP from mutant R subunits provided additional evidence that the mutations in these strains selectively inactivated single classes of cAMP-binding sites: phenomena attributable in wild-type enzyme to intrachain interactions between sites I and II were always absent or severely diminished in experiments with the mutant enzymes. These results confirm that R subunit sequences implicated in cAMP binding by homology with other cyclic nucleotide-binding proteins actually correspond to functional cAMP-binding sites. Furthermore, occupation of either cAMP-binding site I or II is apparently sufficient for activation of cAMP-dependent protein kinase. The presence of four functional cAMP-binding sites in wild-type kinase enhances the cooperativity and sensitivity of cAMP-mediated activation.
Low intensity vagal nerve stimulation lowers human thermal pain thresholds (2000)

The effect of vagal nerve stimulation (VNS) on thermal pain sensation was studied in eight subjects who had vagal nerve stimulators surgically implanted for purposes of seizure control. Prior to their involvement in the study, all subjects had the intensity of their VNS (30 Hz, 0.5 ms, 1.0-2.75 mA) adjusted upwards until achieving their desired clinical effect of reduced seizures. Thermal pain thresholds were determined using a Medoc TSA-2001 with a thermode applied to the skin of the forearm. During VNS at settings 100% of those used clinically to control their seizures, subjects showed a statistically significant decrease in their thermal pain threshold of 1.1+/-0.4 degrees C. Acute effects of graded VNS on thermal pain thresholds were determined in seven of the subjects after cessation of chronic VNS. Two thermal threshold measurements were obtained while the subject received sham stimulation (0 mA intensity), during tactile control stimulation and during 30 s of VNS at intensities approximately 33, 66 and 100% of the settings utilized to control their seizures. Tactile control stimulation was provided by electrical stimulation of the skin of the ankle with the intensity adjusted by the patient to match the intensity of any sensations felt in the neck during VNS. Subjects were not aware of the settings employed. Their stimulator was adjusted with each trial and an ascending/descending ordering of intensity was utilized with an inter-trial interval of 2 min. Thermal pain thresholds were significantly decreased in relation to tactile control stimulation at all intensities of VNS tested with the greatest effect occurring at the 66% level. Subjects were also monitored non-invasively and hemodynamic responses to VNS were determined. No significant alterations in hemodynamic variables were observed. The findings of this human study are consistent with experiments in non-human animals which demonstrate a pro-nociceptive effect of low intensity VNS.
Association of the 2-micron DNA plasmid with yeast folded chromosomes. (1980)

The 2-micron DNA plasmid cosedimented in sucrose gradients with the folded chromosome on centrifugation of lysates from logarithmically growing yeast cells. It banded with both the slow-sedimenting g1 form derived from prereplicative cells and the fast-sedimenting g2 form from postreplicative cells. When cells were induced to withdraw from the cell cycle by nitrogen starvation, the folded chromosome was converted to the g0 form, which sedimented more slowly than the g1 form, and only 1/10th the amount of 2-micron DNA cosedimented with this g0 form as compared to the logarithmic-phase forms, g1 and g2. Expression of the temperature-sensitive cell division cycle (cdc) 28 mutation, which defines the "start" of the cell cycle, resulted in a rapid alteration in the folded chromosome sedimentation pattern, and less than 20% of the 2-micron DNA cosedimented with the folded chromosome. These results raise the possibility that association of the 2-micron DNA plasmid with structures in the cell corresponding to the folded chromosome is subject to cell division cycle control.
Use of the laser for welding cracks on the dental enamel. (1987)

An all line argon laser beam of initial power 2W (4000W/cm2-800 J/cm2, after focusing), was used to weld enamel cracks on extracted human teeth. The welding, observed with the naked eye, caused a small heightening in the welded area which was whiter in color than the rest of the enamel. Examinations were performed on the outer surface of the welding with an inverted metallurgical microscope and using a microdurometer. Sections were then made and studied, on the one hand with a light microscope, and on the other using microradiographical methods. The welding was seen to reach across half the enamel thickness. The possibilities for therapeutic applications of this work are discussed.
A functional soluble extracellular region of the platelet-derived growth factor (PDGF) beta-receptor antagonizes PDGF-stimulated responses. (1991)

The platelet-derived growth factor beta-receptor (PDGFr) is a 180-kDa transmembrane glycoprotein which binds BB-PDGF with high affinity. We have expressed the extracellular region of the receptor in Chinese hamster ovary cells using an expression vector that carries a dihydrofolate reductase gene as an amplifiable marker. Upon amplification of the receptor cDNA sequences by methotrexate a 110-kDa soluble form of the receptor extracellular region (XR) was secreted at 12 mg/liter. The soluble XR protein fully retained the high affinity specific binding of the intact PDGFr for BB-PDGF (apparent dissociation constant, 0.4 nM). In the presence of ligand the soluble XR protein formed complexes that migrated on sodium dodecyl sulfate gels at the size expected for dimers of the protein. When added to fibroblast cultures the soluble XR protein blocked the ability of BB-PDGF to stimulate DNA synthesis but did not alter the mitogenic effect of AA-PDGF. The XR fragment also inhibited the binding of BB-PDGF to PDGFr and the activation of PDGFr tyrosine kinase by BB-PDGF. Thus, the soluble extracellular region protein of the PDGFr binds BB-PDGF with high affinity and functions as a specific antagonist of BB-PDGF actions.
Response of dairy calves to vaccinia viruses that express foreign genes (1986)

Repeated intradermal inoculations of calves with wild-type vaccinia virus and recombinant vaccinia viruses expressing human hepatitis B virus surface antigen and herpes simplex virus, type 1, glycoprotein D produced characteristic pox lesions at each site of injection. In some instances, calves were inoculated as many as five times at intervals from 4 to 7 weeks. The lesions invariably were more severe after the second inoculation. Subsequent inoculations produced a less severe area of redness, swelling, necrosis, and scab formation. No other signs of illness, such as an elevation in temperature, were noted in the calves. Vaccinia virus was isolated in low titers from scabs taken at various times after inoculation. No lesions were formed at the sites injected with tissue culture fluid and cellular debris at the same time that virus inoculations were made. Calf contact controls remained normal through the 8-week exposure in isolation units with calves inoculated twice with vaccinia virus. No neutralizing antibody to vaccinia virus was detected in the contact controls. In contrast, the virus-inoculated calves developed neutralizing antibody to vaccinia virus and to herpes simplex virus glycoprotein D in serum. In all cattle, a second inoculation significantly enhanced the neutralizing antibody response within 1 week, suggesting that an anamnestic response had occurred. No antibody to hepatitis B virus surface antigen was elicited in calves after repeated inoculations with vaccinia recombinants that express hepatitis B virus surface antigen and are known to elicit in rabbits antibodies reactive with hepatitis B virus surface antigen.
The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas (2008)

These results suggest that the functional loss of RB1 is common in basal-like tumours, which may play a key role in dictating their aggressive biology and unique therapeutic responses.
Evidence for synergistic interactions between ras, myc and a mutant form of p53 in cellular transformation and tumor dissemination. (1992)

Mouse 10T1/2 cells were transfected with combinations of T24 H-ras, human c-myc and the proline 193 mutant form of p53. The three-gene ras/myc/p53 combination was significantly more efficient than single genes or double gene combinations in inducing transformed foci in vitro. An analysis of cell lines isolated after transfections with ras, ras/myc, ras/p53 and ras/myc/p53 indicated that the last combination contained significantly higher levels of ras protein than the other combinations, produced tumors in syngeneic mice with a shorter latency period, and exhibited an increased ability to form lung tumors in an in vivo experimental metastasis assay. Synergistic interactions between ras, myc and mutant p53 genes were observed in focus formation and metastasis assays, suggesting that the action of the three oncogenes in malignant transformation occurs along separate but interactive pathways. These results support a working model of oncogene cooperativity in which alterations in myc and p53 permit elevated expression of ras, which is important in a mechanism affecting both cellular transformation in vitro and tumor dissemination in vivo.
Design And Operation of the Pioneer Venus Orbiter Ultraviolet Spectrometer (1980)

The University of Colorado's Ultraviolet Spectrometer instrument carried on the Pioneer Venus Orbiter spacecraft is a 125 mm f/5 Ebert-Fastie design with a 250-mm Cassegrainian telescope. The instrument has extensive logic to control the grating motor drive and to adapt the basic spectrometer to the constraints and opportunities of the mission. Success has been achieved in reconciling the confficting requirements of spectroscopic, limb profile, and imaging observations. A description of the instrument operating techniques is given together with representative results of all three types.
Effects of DksA and ClpP protease on sigma S production and virulence in Salmonella typhimurium (1999)

Salmonella typhimurium responds to a variety of environmental stresses by accumulating the alternative sigma factor sigmaS. The repertoire of sigmaS -dependent genes that are subsequently expressed confers tolerance to a variety of potentially lethal conditions including low pH and stationary phase. The mechanism(s) responsible for triggering sigmaS accumulation are of considerable interest, because they help to ensure survival of the organism during encounters with suboptimal environments. Two genes associated with regulating sigmaS levels in S. typhimurium have been identified. The first is clpP, encoding the protease known to be responsible for degrading sigmaS in Escherichia coli. The second is dksA, encoding a protein of unknown function not previously associated with regulating sigmaS levels. As predicted, clpP mutants accumulated large amounts of sigmaS even in log phase. However, dksA mutants failed to accumulate sigmaS in stationary phase and exhibited lower accumulation during acid shock in log phase. DksA appears to be required for the optimal translation of rpoS based upon dksA mutant effects on rpoS transcriptional and translational lacZ fusions. The region of rpoS mRNA between codons 8 and 73 is required to see the effects of dksA mutations. This distinguishes the role of DksA from that of HF-I (hfq ) in rpoS translation, as the HF-I target area occurs well upstream of the rpoS start codon. DksA appears to be involved in the expression of several genes in addition to rpoS based on two-dimensional SDS-PAGE analysis of whole-cell proteins. As a result of their effects on gene expression, mutations in clpP and dksA decreased the virulence of S. typhimurium in mice, consistent with a role for sigmaS in pathogenesis.
Evaluation of the Low Frame Error Rate Performance of LDPC Codes Using Importance Sampling (2007)

We present an importance sampling method for the evaluation of the low frame error rate (FER) performance of LDPC codes under iterative decoding. It relies on a combinatorial characterization of absorbing sets, which are the dominant cause of decoder failure in the low FER region. The biased density in the importance sampling scheme is a mean-shifted version of the original Gaussian density, which is suitably centered between a codeword and a dominant absorbing set. This choice of biased density yields an unbiased estimator for the FER with a variance lower by several orders of magnitude than the standard Monte Carlo estimator. Using this importance sampling scheme in software, we obtain good agreement with the experimental results obtained from a fast hardware emulator of the decoder.
Nuclear Magnetic Resonance Spectroscopy for the Study of B-Cell Epitopes (1996)

High-resolution nuclear magnetic resonance (NMR) spectroscopy is a structural technique that is finding increasing use in the study of antibody-antigen interactions. In this review we describe how the dynamic structural parameters obtained from NMR spectroscopy can further our understanding of B-cell epitopes and their function. Specific applications of NMR spectroscopy to examine the residues on peptides and proteins that contact the antibody combining site are also described. These include "footprinting" techniques using H-D exchange-COSY NMR spectroscopy, which are particularly useful for epitope mapping of protein antigens. For smaller systems, such as Fab-or Fv-peptide complexes, nuclear magnetization transfer difference NMR spectroscopy, transferred nuclear Overhauser effect spectroscopy, double-quantum-filtered NOE spectroscopy, and isotope editing techniques have been applied. The interpretation and limitations of the data obtained from these procedures and anticipated improvements in these applications in the future are discussed.
Direct Sub-Angstrom Imaging of a Crystal Lattice (2004)

Despite the use of electrons with wavelengths of just a few picometers, spatial resolution in a transmission electron microscope (TEM) has been limited by spherical aberration to typically around 0.15 nanometer. Individual atomic columns in a crystalline lattice can therefore only be imaged for a few low-order orientations, limiting the range of defects that can be imaged at atomic resolution. The recent development of spherical aberration correctors for transmission electron microscopy allows this limit to be overcome. We present direct images from an aberration-corrected scanning TEM that resolve a lattice in which the atomic columns are separated by less than 0.1 nanometer.
American Economic Association (2008)

Following its foundation, the American Economic Association (AEA) cultivated a unique professional visibility, struggling to establish its professional credentials and to demonstrate the usefulness of economists’ ostensible skills. While celebrating the virtues of ‘free markets’, the AEA was itself shaped by government and collective action. In the latter half of the 20th century, the AEA promoted a ‘New Economics’ focused on macroeconomic intervention and regulation. However, these developments fostered a new generation of specialists with different views of public purpose, the appropriate role of government, and how professional economists could participate in the formulation and implementation of public policy.