gebhart/patrepeval huggingface dataset:
Activity of antibodies against Salmonella dublin, Toxoplasma gondii, or Actinobacillus pleuropneumoniae in sera after treatment with electron beam irradiation or binary ethylenimine (1996)

Viral contamination of biological material may constitute a risk when samples are exchanged between countries, and it may be necessary to subject the material to an inactivation treatment. The present study investigated possible adverse effects on antibody activity subsequent to either electron beam irradiation or binary ethylenimine (BEI) treatment. The treatments were performed with sera obtained from pigs or cattle. For each treatment level, the posttreatment activity was plotted against the pretreatment activity, and regression analyses were carried out. The slope of the regression line was used as an estimate for the relative posttreatment activity. For a Toxoplasma gondii indirect enzyme-linked immunosorbent assay (ELISA) and agglutination assay as well as for a Salmonella dublin indirect ELISA, the posttreatment activity was more than 89% of the pretreatment activity when the samples were irradiated in the frozen state (on dry ice) with up to 46. kGy or when they were treated with 5 or 10 mM BEI for up to 48 h. The samples were more sensitive to irradiation in the liquid state. Thus, samples irradiated with 22.6 kGy retained 98% of their activity in the indirect ELISA when they were irradiated in the frozen state on dry ice but only 35% of their activity when they were irradiated in the liquid state at 0 degrees C. The patterns seen in an S. dublin blocking ELISA and an Actinobacillus pleuropneumoniae complement fixation assay differed in that samples with a low level of pretreatment activity were subject to a relatively greater decrease in activity than samples with a high level of pretreatment activity. The complement fixation assay was particularly sensitive to irradiation of serum. It is concluded that serum samples retain sufficient activity by both methods of virus inactivation, especially when used in indirect ELISA or in the T. gondii agglutination assay.
A Gene Controlling Variation in Arabidopsis Glucosinolate Composition Is Part of the Methionine Chain Elongation Pathway (2001)

Arabidopsis and other Brassicaceae produce an enormous diversity of aliphatic glucosinolates, a group of methionine (Met)-derived plant secondary compounds containing a beta-thio-glucose moiety, a sulfonated oxime, and a variable side chain. We fine-scale mapped GSL-ELONG, a locus controlling variation in the side-chain length of aliphatic glucosinolates. Within this locus, a polymorphic gene was identified that determines whether Met is extended predominantly by either one or by two methylene groups to produce aliphatic glucosinolates with either three- or four-carbon side chains. Two allelic mutants deficient in four-carbon side-chain glucosinolates were shown to contain independent missense mutations within this gene. In cell-free enzyme assays, a heterologously expressed cDNA from this locus was capable of condensing 2-oxo-4-methylthiobutanoic acid with acetyl-coenzyme A, the initial reaction in Met chain elongation. The gene methylthioalkylmalate synthase1 (MAM1) is a member of a gene family sharing approximately 60% amino acid sequence similarity with 2-isopropylmalate synthase, an enzyme of leucine biosynthesis that condenses 2-oxo-3-methylbutanoate with acetyl-coenzyme A.
Permanent Left Atrial Tachycardia: Radiofrequency Catheter Ablation Through the Coronary Sinus (2002)

The case of a 13-year-old child with an unusually localized "focal" permanent atrial tachycardia is reported. Electrophysiologic study showed that the earliest atrial activation occurred in the distal coronary sinus and preceded the atrial depolarization recorded along the endocardial side of the lateral part of the mitral annulus. Distal coronary sinus mapping revealed a fragmented, polyphasic atrial electrogram. Radiofrequency current delivery to the site permanently stopped the tachycardia.
The hsp60 Peptide p277 Arrests the Autoimmune Diabetes Induced by the Toxin Streptozotocin (1996)

The development of autoimmune diabetes in the NOD strain of mice (H-2g7) is marked by the presence of T-cells reactive to the p277 peptide of the 6O-kDa heat shock protein (hsp60). We have found that the p277 peptide can be used as a therapeutic vaccine to arrest NOD diabetes. Recently, we found that T-cell autoimmunity to p277 also develops spontaneously in C57BL/KsJ mice (H-2d) during the induction of autoimmune diabetes by a very low dose of the beta-cell toxin streptozotocin (STZ). We now report the inhibition of STZ toxin-induced autoimmune diabetes by p277 peptide therapy. Administration of two doses each of 100 micrograms of peptide p277 in mineral oil given 1 week after toxin induction and 85 days later was most effective. The effect of p277 on STZ toxin-induced diabetes was marked by a shift in p277 autoimmunity from a T-cell proliferative response to the production of anti-p277 antibodies. The anti-p277 antibodies were predominantly of the IgG1 and IgG2b isotypes, known to be regulated by Th2 type cytokines; IgG2a antibody, known to be dependent on interferon (IFN)-gamma, was induced to a much lesser degree. Peptide p277 therapy was specific: treatment of the mice with an immunogenic peptide from the sequence of another antigen, GADp34, failed to prevent the development of diabetes. The GADp34 peptide induced lower titers of specific antibodies, and the antibodies were predominantly of the IgG2a class. Thus, p277 peptide therapy, marked by the induction of Th2-type antibodies, can be effective in toxin-induced autoimmune diabetes.
B-cell epitopes on the hepatitis C virus nucleocapsid protein determined by human monospecific antibodies (1993)

Four monospecific antibodies against the hepatitis C virus nucleocapsid protein, which was expressed by recombinant baculovirus, were obtained by Epstein-Barr virus transformation of B cells from three patients with chronic hepatitis C virus infection. One of these antibodies was IgG and the other three were IgM. Their specificities were characterized initially by enzyme-linked immunosorbent assay and immunoblotting against hepatitis C virus proteins expressed by six recombinant baculoviruses with different hepatitis C virus sequence insertions. These specificities were confirmed, and their epitopes were more precisely determined with a series of overlapping decapeptides made by solid-phase pin technology. Two antibodies (1F4 and 2G6) reacted with the same peptides located near the amino(N)-terminus of nucleocapsid protein (amino acids 33-50). The third antibody (3B5) recognized the peptide consisting of amino acids 133-142, and the fourth antibody (3B9) was mapped to the carboxy(C)-terminus and reacted with a peptide consisting of amino acids 165-174. This epitope has not previously been reported. Two antibodies, 1F4 and 3B9, which are specific to the N-terminus and C-terminus of nucleocapsid protein, respectively, have been stably produced for more than 6 mo and are being subcloned to establish monoclonality. These antibodies should be useful reagents for the study of hepatitis C virus.
Atomic structure and specificity of bacterial periplasmic receptors for active transport and chemotaxis: variation of common themes (1996)

Crystallographic structure refinement at very high resolutions of a dozen periplasmic receptors has revealed that, though they have different sizes (26 to 60 kDa) and little sequence homology, they have high tertiary structure similarity. They consist of two distinct globular domains bisected by a cleft or groove wherein the ligand binds and is buried by a hinge-bending motion between the two domains. Structural analysis also reveals how hydrogen-bonding interactions can be tailored to a wide spectrum of specificity, ranging from the stringent specificity for phosphate and sulphate to the more loose specificity for peptides.
Multipotent Vasculogenic Pericytes From Human Pluripotent Stem Cells Promote Recovery of Murine Ischemic Limb (2011)

Derivation of vasculogenic and multipotent pericytes from hPSC can be used for the development of vasculogenic models using multiple vasculogenic cell types for basic research and drug screening and can contribute to angiogenic regenerative medicine.
Extension of the Replicative Life Span of Human Diploid Fibroblasts by Inhibition of the p33ING1 Candidate Tumor Suppressor (1997)

Previous studies suggest that tumor suppressors may play significant roles in blocking the growth of cells during cellular senescence. We therefore studied the potential involvement of a novel growth inhibitor and candidate tumor suppressor gene called ING1, which we have cloned recently (I. Garkavtsev, A. Kazarov, A. Gudkov, and K. Riabowol, Nat. Genet. 14:415-420, 1996), in the process of cellular senescence. Our results show that the RNA and protein levels of ING1 were 8- to 10-fold higher in senescent cells than in young, proliferation-competent human diploid fibroblasts. Expression of the nuclear p33ING1 protein was regulated during the cell cycle, reaching maximal levels during DNA synthesis. Chronic expression of antisense ING1 RNA reproducibly resulted in extension of the proliferative life span of normal human fibroblasts by approximately seven population doublings.
Computer-aided prototyping for ASIC-based systems (1991)

The use of computer-aided prototyping (CAP) with the RPM Emulation System is described. RPM creates a hardware functional prototype from an ASIC or full-custom chip netlist. It reads the chip netlist and then converts the chip design gates into a prototype design. It then synthesizes the prototype design, obtaining the information it needs to configure the reprogrammable hardware, primarily with partitioning and placement and routing technology. Finally, it physically implements the prototype design by electronically configuring the reprogrammable hardware. RPM includes embedded tools for interactive debugging with access to any internal design node, and a facility for handling quick incremental changes to the design. It is argued that other techniques such as silicon prototyping and manual prototyping are not practical; silicon has a poor debugging ability, and manual prototyping cannot handle large designs. The practical benefits of CAP are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis (2007)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that regulates low density lipoprotein receptor (LDLR) protein levels. The mechanisms of this action, however, remain to be defined. We show here that recombinant human PCSK9 expressed in HEK293 cells was readily secreted into the medium, with the prosegment associated with the C-terminal domain. Secreted PCSK9 mediated cell surface LDLR degradation in a concentration- and time-dependent manner when added to HEK293 cells. Accordingly, cellular LDL uptake was significantly reduced as well. When infused directly into C57B6 mice, purified human PCSK9 substantially reduced hepatic LDLR protein levels and resulted in increased plasma LDL cholesterol. When added to culture medium, fluorescently labeled PCSK9 was endocytosed and displayed endosomal-lysosomal intracellular localization in HepG2 cells, as was demonstrated by colocalization with DiI-LDL. PCSK9 endocytosis was mediated by LDLR as LDLR deficiency (hepatocytes from LDLR null mice), or RNA interference-mediated knockdown of LDLR markedly reduced PCSK9 endocytosis. In addition, RNA interference knockdown of the autosomal recessive hypercholesterolemia (ARH) gene product also significantly reduced PCSK9 endocytosis. Biochemical analysis revealed that the LDLR extracellular domain interacted directly with secreted PCSK9; thus, overexpression of the LDLR extracellular domain was able to attenuate the reduction of cell surface LDLR levels by secreted PCSK9. Together, these results reveal that secreted PCSK9 retains biological activity, is able to bind directly to the LDLR extracellular domain, and undergoes LDLR-ARH-mediated endocytosis, leading to accelerated intracellular degradation of the LDLR.
Identification of a novel member of mouse hsp70 family. Its association with cellular mortal phenotype. (1993)

A novel 66-kDa protein, named p66mot-1, is identified to be associated with cellular mortality by virtue of its presence in cytosolic fractions of serially passaged mouse embryonic fibroblasts (MEF) and the mortal hybrids obtained by the fusion of mortal (MEF) and immortal (MN48-1, derivative of NIH 3T3) cells. Immortal cells lack this protein in their cytosolic fractions. cDNA cloning and homology search placed it in the heat shock protein 70 (hsp70) family. Microinjection of anti-p66 antibody to senescent MEF could transiently stimulate their cell division, which supports the cellular mortality-related function of p66mot-1.
A minimally invasive treatment of severe dental fluorosis. (2007)

This article describes a minimally invasive technique to treat a severe case of enamel fluorosis using microabrasion to eliminate the hypermineralized, white-colored, superficial enamel layer, followed by home bleaching treatment and chairside re-creation of superficial enamel microstructure. The proposed technique may improve the esthetics of fluorotic teeth without requiring other restorative procedures. Microabrasion followed by home bleaching may be an interesting alternative for the restorative treatment of teeth affected by fluorosis.
Small interfering ribonucleic acid design strategies for effective targeting and gene silencing (2011)

The potential and limitations of efficient design predictors obtained from computational algorithms play a crucial role in the development of target-specific siRNAs. Furthermore, the future success of RNA interference therapeutics will depend on their ability to efficiently cross the physiological barriers, selectively target cells-of-interest and finally silence the gene-of-interest without any side effects.
Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine‐induced hyperlocomotion (2006)

Serine proteases in the nervous system have functional roles in neural plasticity. Among them, urokinase-type plasminogen activator (uPA) exerts a variety of functions during development, and is involved in learning and memory. Furthermore, psychostimulants strongly induce uPA expression in the mesolimbic dopaminergic pathway. In this study, doxycycline-regulatable lentiviruses expressing either uPA, a dominant-negative form of uPA, or non-regulatable lentiviruses expressing small interfering RNAs (siRNAs) targeted against uPA have been prepared and injected into the ventral tegmental area (VTA) of rat brains. Over-expression of uPA in the VTA induces doxycycline-dependent expression of its receptor, uPAR, but not its inhibitor, plasminogen activator inhibitor-1 (PAI-1). uPAR expression in the VTA is repressed upon silencing of uPA with lentiviruses expressing siRNAs. In addition, over-expression of uPA in the VTA promotes a 15-fold increase in locomotion activity upon cocaine delivery. Animals expressing the dominant-negative form of uPA did not display such hyperlocomotor activity. These cocaine-induced behavioural changes, associated with uPA expression, could be suppressed in the presence of doxycycline or uPA-specific siRNAs expressing lentiviruses. These data strongly support the major role of urokinase in cocaine-mediated plasticity changes.
Characterization of a Population of Cells in the Bone Marrow that Phenotypically Mimics Hematopoietic Stem Cells: Resting Stem Cells or Mystery Population? (1998)

We have identified a population of cells in murine bone marrow that has many of the phenotypic characteristics attributed to resting hematopoietic stem cells but does not reconstitute irradiated mice. These cells express high levels of Sca-1, H-2K and CD38 and low levels of Thy-1.1, but do not express CD34 nor any of the lineage markers including CD3, CD4, CD5, CD8 NK1.1, I-A, B220, Ig(MGA), CD40, kappa, Mac-1, Gr-1 or Ter119. In addition, this population can be found at normal frequency in nu/nu as well as rag-1-/- mice. These cells incorporate only low levels of Rh123, are resistant to the cytotoxic effects of 5-fluorouracil and, consistent with their resting phenotype, less than 2% of these cells are in the S/G2/M phases of the cell cycle. The only phenotypic characteristic that distinguishes these cells from the lineage- Sca-1+, Thy-1.1low long-term reconstituting hematopoietic stem cell population is their lack of c-kit expression. Here we have explored the possibility that these cells represent a truly resting population of hematopoietic stem cells. We found that the lineage-, Sca-1+, c-kit- cells do not respond to hematopoietic growth factors in vitro, either alone or in combination with stromal layers. Furthermore, these cells do not form in vivo spleen colonies nor do they have the ability to reconstitute irradiated mice. Thus, this population may represent either a population of resting stem cells for which we lack the appropriate activating stimulus, or simply represent a "mystery population" that phenotypically mimics most of the physical properties of resting stem cells. Given the close phenotypic similarity of the c-kit- mystery population cells to the c-kit+ long-term reconstituting stem cells, investigators must be rigorous to exclude their effects from other stem cell assays.
The devil is in the (implementation) details (2012)

Millions of web users today employ their Facebook accounts to sign into more than one million relying party (RP) websites. This web-based single sign-on (SSO) scheme is enabled by OAuth 2.0, a web resource authorization protocol that has been adopted by major service providers. The OAuth 2.0 protocol has proven secure by several formal methods, but whether it is indeed secure in practice remains an open question. We examine the implementations of three major OAuth identity providers (IdP) (Facebook, Microsoft, and Google) and 96 popular RP websites that support the use of Facebook accounts for login. Our results uncover several critical vulnerabilities that allow an attacker to gain unauthorized access to the victim user's profile and social graph, and impersonate the victim on the RP website. Closer examination reveals that these vulnerabilities are caused by a set of design decisions that trade security for implementation simplicity. To improve the security of OAuth 2.0 SSO systems in real-world settings, we suggest simple and practical improvements to the design and implementation of IdPs and RPs that can be adopted gradually by individual sites.
Current and Voltage Measurements in the Gaseous Electronics Conference Rf Reference Cell (1995)

Measurements of the electrical characteristics of discharges in the Gaseous Electronics Conference Radio-Frequency Reference Cell are reviewed here. Topics include: common sources of error in the measurements; comparisons of current and voltage data among GEC cells; the effects of gas impurities, surface conditions and the external circuitry on the reproducibility of the electrical characteristics; and comparisons of current and voltage data with results of other measurements.
New SiGe dielectrics grown at room temperature by low-energy ion beam oxidation and nitridation (1991)

New dielectric materials based on SiGe have been formed at room temperature by direct ion beam oxidation and nitridation. Si0.8Ge0.2 layers were deposited by molecular beam epitaxy on Si(100) and then exposed to a low-energy ion beam of 18O+2 to form oxides and 14N+2 to form nitrides. The ion energies investigated ranged from 100 eV to 1 keV. Thin films of SiGe oxide and SiGe nitride were formed at all energies used as evidenced by in situ x-ray photoelectron spectroscopy analysis. They were found to be insulating by ex situ scanning electron microscopy observations. During the ion beam processing, the Ge content of the alloy layer decreases, due to preferential sputtering of Ge and the Ge compounds. However, as the ion energy is decreased, the concentration of Ge in the alloy remains closer to the original content. The thermal stability of these new SiGe dielectrics was also assessed up to 500 °C.
Foam processing and cellular structure of polypropylene/clay nanocomposites (2002)

Abstract Polypropylene (PP)/clay nanocomposites (PPCNs) were autoclave‐foamed in a batch process. Foaming was performed using supercritical CO 2 at 10 MPa, within the temperature range from 130.6°C to 143.4°C, i.e., below the melting temperature of either PPCNs or maleic anhydride‐modified PP (PP‐MA) matrix without clay. The foamed PP‐MA and PPCN2 (prepared at 130.6°C and containing 2 wt% clay) show closed cell structures with pentagonal and/or hexagonal faces, while foams of PPCN4 and PPCN7.5 (prepared at 143.4°C, 4 and 7.5 wt% clay) had spherical cells. Scanning electron microscopy confirmed that foamed PPCNs had high cell density of 10 7 –10 8 cells/mL, cell sizes in the range of 30–120 μm, cell wall thicknesses of 5–15 μm, and low densities of 0.05–0.3 g/mL. Interestingly, transmission electron microscopic observations of the PPCNs' cell structure showed biaxial flow ‐ induced alignment of clay particles along the cell boundary. In this paper, the correlation between foam structure and rheological properties of the PPCNs is also discussed.
Enantioselective Synthesis of Non‐Natural Aromatic α‐Amino Acids (2004)

We present two complementary methods for the stereoselective synthesis of non-natural alpha-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C(2) or C(3) linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the alpha-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.
Phenelfamycins, a novel complex of elfamycin-type antibiotics. II. Isolation and structure determination. (1988)

A novel complex of elfamycin-type antibiotics has been isolated from submerged fermentation of either Streptomyces violaceoniger AB 999F-80 or Streptomyces violaceoniger AB 1047T-33. Antibiotics were extracted from the fermentation broth with ethyl acetate and from the mycelia with acetone. Purification of individual components was achieved by a combination of solvent partitions, Sephadex LH-20 exclusion, C18 bonded-phase silica gel adsorption, diol partition and liquid-liquid countercurrent chromatographies. Seven closely related components were separated and assigned structures 4, 11, 12, 13, 14, and 16 to phenelfamycins A to F respectively and structure 17 to unphenelfamycin. These structures were elucidated employing a variety of spectroscopic techniques, including extensive use of 1D and 2D NMR spectroscopy.