gebhart/patrepeval huggingface dataset:
Divergent effects of intravenous GSH and cysteine on renal and hepatic GSH (1992)

There is a growing interest in the therapeutic use of sulfhydryls. To assess the effect of glutathione (GSH) and cysteine on the cellular thiol status, thiols were administered intravenously to rats in doses ranging from 1.67 to 8.35 mmol/kg with and without pretreatment with 4 mmol/kg buthionine-[S,R]-sulfoximine (BSO), an inhibitor of GSH synthesis. One hour after administration of 1.67 mmol/kg GSH, the concentration of GSH rose from 5.2 +/- 1.0 to 8.4 +/- 0.9 mumol/g and from 2.5 +/- 0.5 to 3.7 +/- 0.7 mumol/g in liver and kidneys, respectively. After 8.35 mmol/kg, hepatic GSH did not increase further, but renal GSH rose to 6.7 +/- 1.8 mumol/g. Infusion of cysteine increased hepatic GSH to the same extent as intravenous GSH, but renal GSH did not increase after 1.67 mmol/kg and even significantly decreased to 0.6 +/- 0.2 mumol/g after 8.35 mmol/kg. In the presence of BSO, GSH resulted in a significant increase in renal but not hepatic GSH, suggesting that the kidneys take up intact GSH and indicating that the increment in hepatic GSH was due to de novo synthesis. The present data show that hepatic GSH can be markedly increased in vivo by increasing the supply of cysteine. Measurements of hepatic cysteine indicate that up to a concentration of approximately 0.5 mumol/g cysteine is a key determinant of hepatic GSH, such that the physiological steady-state concentration of GSH in the liver appears to be mainly determined by the availability of cysteine. At higher concentrations GSH does not increase further, possibly due to feedback inhibition of GSH synthesis or increased efflux.(ABSTRACT TRUNCATED AT 250 WORDS)
D‐amino acid residues in peptides and proteins (2003)

We have investigated the D-amino acid residues present in Protein Data Bank (PDB) entries, categorizing them into "real" D-residues and artifacts. In polypeptide chains of more than 20 residues, only a single instance of a "real" D-residue, other than those deliberately designed or engineered, was found. This example was the result of a slow chemical epimerization process. Another 12 designed D-residues were found in these longer polypeptide chains. Smaller peptides of 20 or fewer residues contained 479 "real" D-residues, the majority in various gramicidin, actinomycin, or cyclosporin structures. We found 148 PDB entries with "real" D-residues and a further 186, in which all apparent D-residues are artifacts. Investigating the (phi, psi) preferences of the "real" D-residues, we found that the region around (-60 degrees, -45 degrees ) was almost completely unoccupied, even though it is not formally disallowed. We link the low propensity to occupy this region with the alpha-helix destabilizing properties of D-residues.
Research on a novel inverter based on DC/DC converter topology (2004)

The conventional inverters have the shortcomings of straightway conduction in transistors and the difficulty of realizing soft switching. A novel inverter based on the DC/DC converter topology is presented and studied in this paper. The inverter is comprised of a combined buck/boost DC/DC converter and a bridge circuit. The front stage converter is controlled to output a variable DC voltage and the bridge circuit is to convert the DC voltage to an AC output. The energy feedback technology and one-circle-control scheme are used to improve the dynamic characteristics of the DC converter. The power devices of the inverter bridge can conduct soft switching. The operation principle and the circuit topology of this inverter are analysed. Simulations and experiments are conducted to demonstrate the performance of the proposed inverter.
Effect of Addition of Citric Acid and Casein Phosphopeptide-Amorphous Calcium Phosphate to a Sugar-Free Chewing Gum on Enamel Remineralization in situ (2007)

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) has been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to investigate the effects of CPP-ACP in a fruit-flavoured sugar-free chewing gum containing citric acid on enamel remineralization, and acid resistance of the remineralized enamel, using an in situ remineralization model. The study utilized a double-blind, randomized, crossover design with three treatments: (i) sugar-free gum (2 pellets) containing 20 mg citric acid and 18.8 mg CPP-ACP, (ii) sugar-free gum containing 20 mg citric acid alone, (iii) sugar-free gum not containing CPP-ACP or citric acid. Ten subjects were instructed to wear removable palatal appliances, with 4 half-slab insets of human enamel containing demineralized subsurface lesions and to chew gum (2 pellets) for 20 min 4 times per day for 14 days. At the completion of each treatment the enamel half-slabs were removed and half of the remineralized lesion treated with demineralization buffer for 16 h in vitro. The enamel slabs (remineralized, acid-challenged and control) were then embedded, sectioned and subjected to microradiography to determine the level of remineralization. Chewing with gum containing citric acid and CPP-ACP resulted in significantly higher remineralization (13.0 +/- 2.2%) than chewing with either gum containing no CPP-ACP or citric acid (9.4 +/- 1.2%) or gum containing citric acid alone (2.6 +/- 1.3%). The acid challenge of the remineralized lesions showed that the level of mineral after acid challenge was significantly greater for the lesions exposed to the gum containing CPP-ACP.
New Short Signature Scheme with Weil Pairing (2014)

Short signature is an essential component in cryptography. Short digital signatures are needed in environments where a human is asked to manually key in the signature.. In this paper we propose a new short signature scheme with weil pairing. Also we analyze security and efficiency of our scheme. Security of our scheme is based on expressing the torsion point of curve into linear combination of its basis points; it is more complicated than solving ECDLP(Elliptic Curve Discrete Logarithm Problem). We claim that our new short signature scheme is more secure and efficient than the existing scheme of SedatAkleylek et al. based on bilinear pairing.
Increase Output Energy and Operation Frequency of a Triboelectric Nanogenerator by Two Grounded Electrodes Approach (2014)

Triboelectric nanogenerator (TENG) generally operates using two‐electrodes to form a closed outer circuit loop without directly contacting ground. Here, a newly designed TENG, the two electrodes of which are grounded for doubling the energy output and the operation frequency, is introduced. The TENG operates in two modes: two‐channel mode in which the two electrodes are simultaneously connected to the ground, and single‐channel mode in which the two electrodes are alternately connected to the ground through a self‐triggered vibrating switch. Both modes doubles the total charges to be transported compared to the traditional ungrounded TENG. For the single‐channel TENG, about 30 current peaks with an output frequency of 50 Hz are generated in a single cycle at a motion triggering frequency of 2 Hz. The output energy at a load lower than 10 MΩ of the single‐channel TENG is enhanced, and the enhancing ratio is more than 100 at a load of 100 kΩ. The two electrodes grounded TENG provides a new strategy for effective use of the energy harvested from our living environment.
Dissecting the functional program of Escherichia coli promoters: the combined mode of action of Lac repressor and AraC activator (2001)

The mode of action of regulated promoters is largely determined by kinetic parameters which govern the interaction between promoters and proteins involved in induction and repression of transcription. To gain insight into the interplay between positively and negatively acting transcriptional regulators, in this case AraC and LacR, we have generated a panel of promoter sequences derived from P(lac), the promoter of the Escherichia coli lac operon. The function of these promoters is limited at different steps and to various extents within the pathway of RNA polymerase (RNAP)/promoter interaction. Moreover, in all promoters the cAMP receptor protein binding site was replaced by the binding motif of AraC to prevent pleiotropic effects in vivo upon activation. Analyzing the activation of these promoters by AraC in vivo under conditions of repression by LacR and derepression yielded a three step model of transcription initiation which reveals mechanisms of AraC and LacR action. Our data show three distinct rate limiting steps at which AraC can exert its function. In general, the activator accelerates the formation of the first stable complex between RNAP and promoter. At most promoter sequences, however, its main impact is on the conversion of the closed to the open complex. However, AraC is also capable of eliminating limitations at steps following open complex formation.
Primary Prevention of Acute Coronary Events With Lovastatin in Men and Women With Average Cholesterol Levels (1998)

Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.
T cell anergy (1994)

T cell clonal anergy is a proposed mechanism of immunologic self tolerance in which T cells become functionally inactivated after previous stimulation. MHC class II-restricted antigen presentation by different cell types has been speculated to have a role in determining activation vs. anergy in responding T cells. Human T cells express MHC class II after activation and have been shown to present high concentrations of degraded peptide antigen to autologous T cells resulting in clonal anergy. In contrast to low antigen dose T cell clonal anergy, which occurs in the absence of costimulation, T cell anergy induced by human T cell presentation of antigen results in both primary proliferation and secondary unresponsiveness to high-dose antigenic stimulation. Although clonal anergy was previously thought to prevent autoreactive T cells from ever responding to self antigen presented without costimulation, we postulate that T cell presentation of antigen represents a "fail-safe" mechanism of immunologic self tolerance that would anergize clonally expanded autoreactive T cells when they are surrounded by a high extracellular concentration of degraded self antigen.
Site-specific covalent modification of monoclonal antibodies: in vitro and in vivo evaluations. (1986)

A strategy for covalent modification of monoclonal antibodies utilizing the oxidized oligosaccharide moieties on the molecule was evaluated and compared to more conventional methods. As judged by quantitative in vitro measurements, a monoclonal antibody conjugate prepared via the oligosaccharides retained the homogeneous antigen binding property and affinity of the unmodified antibody. In contrast, conjugates of the same antibody, modified to the same degree on either lysines or aspartic and glutamic acid side chains, were heterogeneous in their antigen binding and had lowered affinity. In vivo biodistribution and nuclear-imaging experiments were also performed with a second monoclonal antibody and a tumor xenograft model. Antibodies modified on the oligosaccharides with either a peptide labeled with iodine-125 or a diethylenetriaminepentaacetic acid chelate with indium-111 localize into target tumors more efficiently than the same antibody radiolabeled on either tyrosines or lysines. These in vivo results, when compared to those reported in the literature for conventionally modified antibodies, suggest that oligosaccharide modification of monoclonal antibodies is a preferred method of preparing conjugates.
Sigma factors fromE. coli, B. subtilis, phage SP01, and phage T4 are homologous proteins (1986)

We show, using dot matrix comparisons and statistical analysis of sequence alignments, that seven sequenced sigma factors, E. coli sigma-70 and sigma-32, B. subtilis sigma-43 and sigma-29, phage SP01 gene products 28 and 34, and phage T4 gene product 55, comprise a homologous family of proteins. Sigma-70, sigma-32, and sigma-43 each have two copies of a sequence similar to the helix-turn-helix DNA binding motif seen in CRP, and lambda repressor and cro proteins. B. subtilis sigma-29, SP01 gp28, and SP01 gp34 have at least one copy similar to this sequence. We propose that a second sequence, conserved in all seven proteins is the core RNA polymerase binding site. A third region, present only in sigma-70 and sigma-43, may also be involved in interaction with core. Available mutational evidence supports our model for sigma factor structure.
Crystal Structure of a Neutralizing Human IgG Against HIV-1: A Template for Vaccine Design (2001)

We present the crystal structure at 2.7 angstrom resolution of the human antibody IgG1 b12. Antibody b12 recognizes the CD4-binding site of human immunodeficiency virus-1 (HIV-1) gp120 and is one of only two known antibodies against gp120 capable of broad and potent neutralization of primary HIV-1 isolates. A key feature of the antibody-combining site is the protruding, finger-like long CDR H3 that can penetrate the recessed CD4-binding site of gp120. A docking model of b12 and gp120 reveals severe structural constraints that explain the extraordinary challenge in eliciting effective neutralizing antibodies similar to b12. The structure, together with mutagenesis studies, provides a rationale for the extensive cross-reactivity of b12 and a valuable framework for the design of HIV-1 vaccines capable of eliciting b12-like activity.
HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development (2011)

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.
Glycale in der organischen Synthese: die Entwicklung umfassender Strategien zum Aufbau von Oligosacchariden und Glycokonjugaten mit biologischer Bedeutung (1996)

Abstract Der vorliegende Aufsatz ist ein persönlicher Überblick über die Forschungsaktivitäten einer einzelnen Arbeitsgruppe zum Aufbau von Oligosacchariden und Glycokonjugaten. Diese Forschung begann vor zwanzig Jahren mit der Untersuchung von Diels‐Alder‐Reaktionen mit komplexen Dienen. Durch Ausweitung auf aldehydartige Heterodienophil‐Äquivalente wurde ein Zugang zu nichtnatürlichen Glycalen gefunden (LACDAC‐Reaktion). Diese Entdeckung war der Auslöser für eine umfassende Untersuchung über die Verwendung von Glycalen zur Synthese von Oligosacchariden und anderen Glycokonjugaten. Die Nutzung von Glycalen als Glycosyldonoren und als Glycosylacceptoren führte zur Strategie der Verknüpfung von Glycalen, deren Anwendbarkeit durch die Entwicklung von mehreren neuen Glycosylierungsverfahren verbessert wurde. Es zeigte sich, daß auf Glycalen basierende Reaktionen gut als Festphasensynthesen durchgeführt werden können. Ferner ist das Prinzip des Glycalzusammenbaus – sowohl in Lösung als auch am festen Träger – dazu verwendet worden, einen relativ kurzen und effizienten Zugang zu einer Vielzahl von biologisch interessanten und möglicherweise wertvollen Verbindungen zu eröffnen. Einige dieser Synthesen, besonders solche auf dem Gebiet der Tumor‐Antigene, haben zu neuartigen Verbindungen geführt, die sich derzeit in einem fortgeschrittenen Stadium vorklinischer Untersuchung befinden. Dieser Aufsatz gibt einen ausführlichen Überblick über die chemischen Aspekte dieser Projekte.
Extensions of packet communication technology to a hand held personal terminal (1971)

Electronic communications technology has developed historically almost completely within what might be called the circuit switching domain. Not until the last decade has the other basic mode of communication, packet switching, become competitive. Thus, as a technology, packet communication has only begun to be explored. Circuit switching can be defined in the broad sense as the technique of establishing a complete path between two parties for as long as they wish to communicate, whereas packet switching is where the communication is broken up into small messages or packets, attaching to each packet of information its source and destination and sending each of these packets off independently and asynchronously to find its way to the destination. In circuit switching all conflicts and allocations of resources must be made before the circuit can be established thereby permitting the traffic to flow with no conflicts. In packet switching there is no dedication of resources and conflict resolution occurs during the actual flow perhaps resulting in somewhat uneven delays being encountered by the traffic. Clearly, without the speed and capability of modern computers, circuit switching represented a cheaper and more effective way to handle communications. For radio frequency assignment and telephone exchanges the resource allocation decisions could be made infrequently enough that manual techniques were originally sufficient. Also, since voice was the main information being communicated, the traffic statistics were sufficiently compatible with this approach to make it quite economic for the period. Packet switching of a kind, the telegram, persisted throughout this period but due to the high cost of switching and the limited demand for fast message traffic never attracted much attention.
Recognition tunneling (2010)

Single molecules in a tunnel junction can now be interrogated reliably using chemically functionalized electrodes. Monitoring stochastic bonding fluctuations between a ligand bound to one electrode and its target bound to a second electrode ('tethered molecule-pair' configuration) gives insight into the nature of the intermolecular bonding at a single molecule-pair level, and defines the requirements for reproducible tunneling data. Simulations show that there is an instability in the tunnel gap at large currents, and this results in a multiplicity of contacts with a corresponding spread in the measured currents. At small currents (i.e. large gaps) the gap is stable, and functionalizing a pair of electrodes with recognition reagents (the 'free-analyte' configuration) can generate a distinct tunneling signal when an analyte molecule is trapped in the gap. This opens up a new interface between chemistry and electronics with immediate implications for rapid sequencing of single DNA molecules.
Stromal Processing Peptidase Binds Transit Peptides and Initiates Their Atp-Dependent Turnover in Chloroplasts (1999)

A stromal processing peptidase (SPP) cleaves a broad range of precursors targeted to the chloroplast, yielding proteins for numerous biosynthetic pathways in different compartments. SPP contains a signature zinc-binding motif, His-X-X-Glu-His, that places it in a metallopeptidase family which includes the mitochondrial processing peptidase. Here, we have investigated the mechanism of cleavage by SPP, a late, yet key event in the import pathway. Recombinant SPP removed the transit peptide from a variety of precursors in a single endoproteolytic step. Whereas the mature protein was immediately released, the transit peptide remained bound to SPP. SPP converted the transit peptide to a subfragment form that it no longer recognized. We conclude that SPP contains a specific binding site for the transit peptide and additional proteolysis by SPP triggers its release. A stable interaction between SPP and an intact transit peptide was directly demonstrated using a newly developed binding assay. Unlike recombinant SPP, a chloroplast extract rapidly degraded both the transit peptide and subfragment. A new degradative activity, distinguishable from SPP, was identified that is ATP- and metal-dependent. Our results indicate a regulated sequence of events as SPP functions during precursor import, and demonstrate a previously unrecognized ATP-requirement for transit peptide turnover.
LFA-1-deficient mice show normal CTL responses to virus but fail to reject immunogenic tumor. (1996)

The leukocyte integrin LFA-1 (CD11a/CD18) plays an important role in lymphocyte recirculation and homotypic interactions. Leukocytes from mice lacking CD11a displayed defects in in vitro homotypic aggregation, in proliferation in mixed lymphocyte reactions, and in response to mitogen. Mutant mice mounted normal cytotoxic T cell (CTL) responses against systemic LCMV and VSV infections and showed normal ex vivo CTL function. However, LFA-1-deficient mice did not reject immunogenic tumors grafted into footpads and did not demonstrate priming response against tumor-specific antigen. Thus CD11a deficiency causes a selective defect in induction of peripheral immune responses whereas responses to systemic infection are normal.
Chronic Granulomatous Disease of Childhood: Clinical, Pathological, Biochemical, Molecular, and Genetic Aspects of the Disease (1990)

The pathobiology of chronic granulomatous disease (CGD) of childhood, a heterogeneous phenotypic disorder characterized by chronic and recurrent infection, has become more completely understood over the past three decades. Blood neutrophils, monocytes, and eosinophils lack a respiratory burst required for effective killing of catalase positive bacteria by reduced by-products of oxygen. The disease is transmitted in at least two genetic forms: X-linked and autosomal recessive. In the X-linked form, a gene coding for a beta subunit protein required for cytochrome b presence on the plasma membrane of phagocytic cells is not expressed. The protein appears to be a constituent of the cytochrome b complex that requires an additional alpha subunit for complete expression. Cytochrome b is likely a component of leukocyte oxidase, which catalyzes the respiratory burst. The autosomal recessive form of the disorder appears to be controlled by a set of genes coding for soluble cofactors essential for oxidase expression. One or more of these cofactors have recently been shown to be deficient in several patients with autosomal recessive CGD. Optional therapy for CGD patients is presently not available. Long-term use of antibiotics may be helpful. The cloned product interferon gamma has been reported to improve superoxide generation, bactericidal activity, and immunoreactive cytochrome b in some CGD neutrophils and monocytes, both in vitro and in vivo. Currently a prospective clinical evaluation of the efficacy of interferon gamma is in progress. Molecular studies of expression and function of the X-CGD gene in phagocytic cells are in progress as well.