gebhart/patrepeval huggingface dataset:
Measurement, modeling, and analysis of a peer-to-peer file-sharing workload (2003)

Peer-to-peer (P2P) file sharing accounts for an astonishing volume of current Internet traffic. This paper probes deeply into modern P2P file sharing systems and the forces that drive them. By doing so, we seek to increase our understanding of P2P file sharing workloads and their implications for future multimedia workloads. Our research uses a three-tiered approach. First, we analyze a 200-day trace of over 20 terabytes of Kazaa P2P traffic collected at the University of Washington. Second, we develop a model of multimedia workloads that lets us isolate, vary, and explore the impact of key system parameters. Our model, which we parameterize with statistics from our trace, lets us confirm various hypotheses about file-sharing behavior observed in the trace. Third, we explore the potential impact of locality-awareness in Kazaa.Our results reveal dramatic differences between P2P file sharing and Web traffic. For example, we show how the immutability of Kazaa's multimedia objects leads clients to fetch objects at most once; in contrast, a World-Wide Web client may fetch a popular page (e.g., CNN or Google) thousands of times. Moreover, we demonstrate that: (1) this "fetch-at-most-once" behavior causes the Kazaa popularity distribution to deviate substantially from Zipf curves we see for the Web, and (2) this deviation has significant implications for the performance of multimedia file-sharing systems. Unlike the Web, whose workload is driven by document change, we demonstrate that clients' fetch-at-most-once behavior, the creation of new objects, and the addition of new clients to the system are the primary forces that drive multimedia workloads such as Kazaa. We also show that there is substantial untapped locality in the Kazaa workload. Finally, we quantify the potential bandwidth savings that locality-aware P2P file-sharing architectures would achieve.
Molecular analysis of the anaerobic succinate degradation pathway in Clostridium kluyveri (1996)

A region of genomic DNA from Clostridium kluyveri was cloned in Escherichia coli by a screening strategy which was based on heterologous expression of the clostridial 4-hydroxybutyrate dehydrogenase gene. The gene region (6,575 bp) contained several open reading frames which encoded the coenzyme A (CoA)- and NADP+-dependent succinate-semialdehyde dehydrogenase (sucD), the 4-hydroxybutyrate dehydrogenase (4hbD), and a succinyl-CoA;CoA transferase (cat1), as analyzed by heterologous expression in E. coli. An open reading frame encoding a putative membrane protein (orfY) and the 5' region of a gene encoding a sigma 54-homologous sigma factor (sigL) were identified as well. Transcription was investigated by Northern (RNA) blot analysis. Protein sequence comparisons of SucD and 4HbD revealed similarities to the adhE (aad) gene products from E. coli and Clostridium acetobutylicum and to enzymes of the novel class (III) of alcohol dehydrogenases. A comparison of CoA-dependent aldehyde dehydrogenases is presented.
Poly(acrylourethane)-Polyepoxide Semi-interpenetrating Networks Formed by Electron-Beam Curing (1985)

Semi-interpenetrating networks (semi-IPNs) were prepared by electron beam initiated polymerization of difunctional acrylourethane oligomers in the presence of a linear epoxy. Single glass transitions, by differential scanning calorimetric (DSC) and mechanical spectral analyses, were observed for all blend levels, before and after polymerization, indicating a high degree of compatibility. Glass transition temperatures varied smoothly with blend level in the cured semi-IPNs, but marked deviations were noted in the uncured blends. Crystallization of the oligomer by aging the films before curing effected phase separation that could be fixed by electron curing, and optically clear films with two transitions resulted. Stress-strain measurements on the cured films showed a very sharp maximum in toughness around 50 % oligomer. Phase separation forced by precrystallization produced significant toughness increases.
Protection of Renal Epithelial Cells against Oxidative Injury by Endoplasmic Reticulum Stress Preconditioning Is Mediated by ERK1/2 Activation (2003)

We investigated the role of the endoplasmic reticulum (ER) stress response in intracellular Ca2+ regulation, MAPK activation, and cytoprotection in LLC-PK1 renal epithelial cells in an attempt to identify the mechanisms of protection afforded by ER stress. Cells preconditioned with trans-4,5-dihydroxy-1,2-dithiane, tunicamycin, thapsigargin, or A23187 expressed ER stress proteins and were resistant to subsequent H2O2-induced cell injury. In addition, ER stress preconditioning prevented the increase in intracellular Ca2+ concentration that normally follows H2O2 exposure. Stable transfection of cells with antisense RNA targeted against GRP78 (pkASgrp78 cells) prevented GRP78 induction, disabled the ER stress response, sensitized cells to H2O2-induced injury, and prevented the development of tolerance to H2O2 that normally occurs with preconditioning. ERK and JNK were transiently (30-60 min) phosphorylated in response to H2O2. ER stress-preconditioned cells had more ERK and less JNK phosphorylation than control cells in response to H2O2 exposure. Preincubation with a specific inhibitor of JNK activation or adenoviral infection with a construct that encodes constitutively active MEK1, the upstream activator of ERKs, also protected cells against H2O2 toxicity. In contrast, the pkASgrp78 cells had less ERK and more JNK phosphorylation upon H2O2 exposure. Expression of constitutively active ERK also conferred protection on native as well as pkAS-grp78 cells. These results indicate that GRP78 plays an important role in the ER stress response and cytoprotection. ER stress preconditioning attenuates H2O2-induced cell injury in LLC-PK1 cells by preventing an increase in intracellular Ca2+ concentration, potentiating ERK activation, and decreasing JNK activation. Thus, the ER stress response modulates the balance between ERK and JNK signaling pathways to prevent cell death after oxidative injury. Furthermore, ERK activation is an important downstream effector mechanism for cellular protection by ER stress.
Structure and mechanism of Escherichia coli RecA ATPase (2005)

RecA protein catalyses an ATP-dependent DNA strand-exchange reaction that is the central step in the repair of dsDNA breaks by homologous recombination. Although much is known about the structure of RecA protein itself, we do not at present have a detailed picture of how RecA binds to ssDNA and dsDNA substrates, and how these interactions are controlled by the binding and hydrolysis of the ATP cofactor. Recent studies from electron microscopy and X-ray crystallography have revealed important ATP-mediated conformational changes that occur within the protein, providing new insights into how RecA catalyses DNA strand-exchange. A unifying theme is emerging for RecA and related ATPase enzymes in which the binding of ATP at a subunit interface results in large conformational changes that are coupled to interactions with the substrates in such a way as to promote the desired reactions.
Regulation of epithelial and lymphocyte cell adhesion by adenosine deaminase–CD26 interaction (2002)

The extra-enzymic function of cell-surface adenosine deaminase (ADA), an enzyme mainly localized in the cytosol but also found on the cell surface of monocytes, B cells and T cells, has lately been the subject of numerous studies. Cell-surface ADA is able to transduce co-stimulatory signals in T cells via its interaction with CD26, an integral membrane protein that acts as ADA-binding protein. The aim of the present study was to explore whether ADA—CD26 interaction plays a role in the adhesion of lymphocyte cells to human epithelial cells. To meet this aim, different lymphocyte cell lines (Jurkat and CEM T) expressing endogenous, or overexpressing human, CD26 protein were tested in adhesion assays to monolayers of colon adenocarcinoma human epithelial cells, Caco-2, which express high levels of cell-surface ADA. Interestingly, the adhesion of Jurkat and CEM T cells to a monolayer of Caco-2 cells was greatly dependent on CD26. An increase by 50% in the cell-to-cell adhesion was found in cells containing higher levels of CD26. Incubation with an anti-CD26 antibody raised against the ADA-binding site or with exogenous ADA resulted in a significant reduction (50–70%) of T-cell adhesion to monolayers of epithelial cells. The role of ADA—CD26 interaction in the lymphocyte—epithelial cell adhesion appears to be mediated by CD26 molecules that are not interacting with endogenous ADA (ADA-free CD26), since SKW6.4 (B cells) that express more cell-surface ADA showed lower adhesion than T cells. Adhesion stimulated by CD26 and ADA is mediated by T cell lymphocyte function-associated antigen. A role for ADA—CD26 interaction in cell-to-cell adhesion was confirmed further in integrin activation assays. FACS analysis revealed a higher expression of activated integrins on T cell lines in the presence of increasing amounts of exogenous ADA. Taken together, these results suggest that the ADA—CD26 interaction on the cell surface has a role in lymphocyte—epithelial cell adhesion.
Recovery and Detection of Urea Nitrate in Traces* (2007)

Urea nitrate (uronium nitrate, UN) is a powerful improvised explosive, frequently used by terrorists in the Israeli arena. It was also used in the first World Trade Center bombing in New York in February 1993. It is difficult to identify UN in postexplosion debris, because in the presence of water it readily decomposes to its original components, urea and nitric acid. A method for the recovery and detection of urea nitrate in traces is described. The residues are extracted with hot acetone, and the extract chromatographed on chromosorb G-HP. The eluent is analyzed by liquid chromatography mass spectrometry using atmospheric pressure chemical ionization (APCI). By applying this technique, we were able to identify urea nitrate in actual exhibits. It was found that UN can be also formed during the analytical procedure, by certain combinations of urea, nitrate ions, and a source of protons and, hence, the presence of the characteristic adduct ion does not necessarily indicate an "authentic" urea nitrate. Several solutions are suggested to overcome this ambiguity.
A subexponential-time algorithm for computing discrete logarithms overGF(p^2) (1985)

An algorithm for computing discrete logarithms over GF <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(p^{2})</tex> , where <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</tex> is a prime, in subexponential time is described. The algorithm is similar to the Merkle-Adleman algorithm for computing logarithms over GF <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(p)</tex> , but it uses quadratic fields as the appropriate algebraic structure. It also makes use of the idea of a virtual spanning set due to Hellman and Reyneri for computing discrete logarithms over GF <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">(p^{m})</tex> , for <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</tex> growing and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">p</tex> fixed.
Towards MRI-Controlled Ferromagnetic and MC-1 Magnetotactic Bacterial Carriers for Targeted Therapies in Arteriolocapillar Networks Stimulated by Tumoral Angiogenesis (2006)

The delivery of a therapeutic agent through controlled carriers directly to the tumoral lesion can enhance treatment efficacy by reducing dosage while minimizing systemic circulation of toxic compounds through healthy tissues. As such, the induction of a feedback controlled steering force on ferromagnetic carriers from magnetic gradients generated by an upgraded clinical magnetic resonance imaging (MRI) system has been demonstrated by our group. But the gradient strengths required in some sections of the capillary network may be technologically very difficult to achieve for human due mainly to the size and cooling issues of additional gradient coils embedded in the MRI bore. As such, the use of MC-1 magnetotactic bacteria (MTB) pushing microbeads with a therapeutic agent may provide complementary means of propulsion in smaller capillaries. Based on preliminary experimental results, carriers and a new method combining the induction of force in a ferromagnetic material with the thrust provided by MTB for direct targeting to the tumor mass are proposed.
MEK/ERK inhibitor U0126 affects in vitro and in vivo growth of embryonal rhabdomyosarcoma (2009)

We reported previously that the disruption of c-Myc through mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibition blocks the expression of the transformed phenotype in the embryonal rhabdomyosarcoma (ERMS) cell line (RD), thereby inducing myogenic differentiation in vitro. In this article, we investigate whether MEK/ERK inhibition, by the MEK/ERK inhibitor U0126, affects c-Myc protein level and growth of RMS tumor in an in vivo xenograft model. U0126 significantly reduced RMS tumor growth in RD cell line-xenotransplanted mice. Immunobiochemical and immunohistochemical analysis showed (a) phospho-active ERK levels were reduced by U0126 therapy and unaltered in normal tissues, (b) phospho-Myc and c-Myc was reduced commensurate with phospho-ERK inhibition, and (c) reduction in Ki-67 and endothelial (CD31) marker expression. These results indicate that MEK/ERK inhibition affects growth and angiogenic signals in tumor. The RD-M1 cultured xenograft tumor-derived cell line and the ERMS cell line TE671 responded to U0126 by arresting growth, down-regulating c-Myc, and initiating myogenesis. All these results suggest a tight correlation of MEK/ERK inhibition with c-Myc down-regulation and arrest of tumor growth. Thus, MEK inhibitors may be investigated for a signal transduction-based targeting of the c-Myc as a therapeutic strategy in ERMS.
Cells Participating in Immunologic Memory Induced with RNA from the Spleens of Immunized Mice (1984)

Ribonucleic acid (immune RNA, iRNA) extracted from the spleens of mice immunized with heterologous red blood cells induced antigen-specific immunologic memory. The type of cells (T cells, B cells) which participate in immunologic memory induced with iRNA was investigated. Immune RNA-primed T cells cooperated with normal, iRNA-primed or antigen-primed B cells and induced a high IgM response. Immune RNA-primed B cells did not cooperate with normal T cells, but did with iRNA- or antigen-primed T cells. The activities of iRNA-primed T and B cells were antigen-specific.
Sampling and reconstruction with adaptive meshes (2002)

An approach to visual sampling and reconstruction motivated by concepts from numerical grid generation is presented. Adaptive meshes that can nonuniformly sample and reconstruct intensity and range data are presented. These meshes are dynamic models which are assembled by interconnecting nodal masses with adjustable springs. Acting as mobile sampling sites, the nodes observe properties of the input data, such as intensities, depths, gradients, and curvatures. Based on these nodal observations, the springs automatically adjust their stiffnesses so as to distribute the available degrees of freedom of the reconstructed model in accordance with the local complexity of the input data. The adaptive mesh algorithm runs at interactive rates with continuous 3-D display on a graphics workstation It is applied to the adaptive sampling and reconstruction of images and surfaces.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Zinc oxide – analogue of GaN with new perspective possibilities (2004)

Abstract Zinc oxide due to specific electrical, optical and acoustic properties is the important semiconductor material, which has many various applications. There is growing interest in ZnO due to its potential applicability for optoelectronic devices such as light‐emitting diodes, laser diodes and detectors for UV wavelength range. ZnO properties are very close to those of widely recognized semiconductor GaN. The band gap of ZnO (3.37 eV) is close to that of GaN (3.39 eV) but ZnO exciton binding energy (60 meV) is twice larger than that of GaN (28 meV). Optically pumped UV lasing have been demonstrated at room temperature using high textured ZnO films. The excitonic gain close to 300 cm –1 was achieved. ZnO thin films are expected to have higher quantum efficiency in UV semiconductor laser than GaN. The physical properties of ZnO are considered. PEMOCVD technology was used to deposit piezoelectric and highly transparent electroconductive ZnO films. Their properties are discussed. The experiments on polycrystalline ZnO films deposited by RF magnetron sputtering at different partial pressure of oxygen are presented. AFM images were studied in tapping mode for deposited films. The investigated films were dielectric ones and had optical transparency within 65‐85% at thickness in the interval 0.2‐0.6 μm. (© 2004 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Trypsinogen 4 boosts tumor endothelial cells migration through proteolysis of tissue factor pathway inhibitor-2 (2015)

Proteases contribute to cancer in many ways, including tumor vascularization and metastasis, and their pharmacological inhibition is a potential anticancer strategy. We report that human endothelial cells (EC) express the trypsinogen 4 isoform of the serine protease 3 (PRSS3), and lack both PRSS2 and PRSS1. Trypsinogen 4 expression was upregulated by the combined action of VEGF-A, FGF-2 and EGF, angiogenic factors representative of the tumor microenvironment. Suppression of trypsinogen 4 expression by siRNA inhibited the angiogenic milieu-induced migration of EC from cancer specimens (tumor-EC), but did not affect EC from normal tissues. We identified tissue factor pathway inhibitor-2 (TFPI-2), a matrix associated inhibitor of cell motility, as the functional target of trypsinogen 4, which cleaved TFPI-2 and removed it from the matrix put down by tumor-EC. Silencing tumor-EC for trypsinogen 4 accumulated TFPI2 in the matrix. Showing that angiogenic factors stimulate trypsinogen 4 expression, which hydrolyses TFPI-2 favoring a pro-migratory situation, our study suggests a new pathway linking tumor microenvironment signals to endothelial cell migration, which is essential for angiogenesis and blood vessel remodeling. Abolishing trypsinogen 4 functions might be an exploitable strategy as anticancer, particularly anti-vascular, therapy.
5-Nitroindole as an universal base analogue (1994)

4-, 5- and 6-Nitroindole have been investigated and compared with 3-nitropyrrole as universal bases in oligodeoxynucleotides. Of these the 5-nitroindole derivative was found to be superior giving higher duplex stability, and behaving indiscriminately towards each of the four natural bases in duplex melting experiments. 3-Nitropyrrole, whilst not discriminating between the natural bases, was found to lead to considerable destabilisation of the duplexes, particularly when multiple substitutions were made, in contrast to the 5-nitroindole nucleoside.
Identification of Enzyme Inhibitors from Phage-Displayed Combinatorial Peptide Libraries (2001)

In recent years, there have been a growing number of examples of the successful isolation of peptide ligands for enzymes from phage-displayed combinatorial peptide libraries. These peptides typically bind at or near the active site of the enzymes and can inhibit their activity. We review the literature on peptide ligands that have been isolated for enzymes other than proteases as well as present data on peptide ligands we have identified for E. coli dihydrofolate reductase (DHFR) which bind at, or near, the same site as the known inhibitors methotrexate or trimethoprim. Thus, while the peptide ligand isolated from phage-displayed libraries may not resemble the chemical structure of the normal substrate of the enzyme, the peptide can be used as an inhibitor to evaluate the function of the enzyme or for drug discovery efforts (i.e., as a lead compound for peptidomimetic design or as displaceable probe in high-throughput screens of libraries of small molecules).
Effect of CD37 small modular immuno-pharmaceutical (SMIP) on direct apoptosis in chronic lymphocytic leukemia cells via transcriptional up-regulation of the BH3 family member BIM (2009)

3035 Background: CD37 is a tetraspan transmembrane family protein selectively expressed on normal and transformed B-cells. A novel CD37 SMIP was previously demonstrated to mediate superior direct apoptosis and NK-cell mediated killing of chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Methods: Given the superior in vitro apoptosis observed with CD37 SMIP treatment and early clinical activity observed in highly refractory CLL patients, we hypothesized that a unique mechanism of cell killing was utilized by CD37 SMIP . This was pursued in preclinical studies outlined below. Results: Unlike many other agents utilized to treat CLL, death mediated by CD37 SMIP does not depend upon caspase activation. Nonetheless, CD37 SMIP treatment of CLL cells promotes time-dependent induction of mitochondrial membrane depolarization, mitochondrial translocation of Bax, and up-regulation of Bim protein. CD37 SMIP Bim protein induction occurred concomitantly with an increase in BIM mRNA levels. Electrophoretic mobility shift assay using oligonucleotides of the BIM promoter demonstrated increased protein binding activity in nuclear extracts derived from CD37 SMIP treated cells and the physical interaction of FoxO3a transcription factor with the FoxO3a responsive element in the BIM promoter was demonstrated using a “protein pull down” assay and confirmed by chromatin immunoprecipitation assays. Furthermore, CD37 SMIP treatment significantly increased BIM promoter regulated luciferase reporter expression in B-CLL cells. Consistent with a primary role of Bim up-regulation in mitochondrial membrane destabilization and apoptosis, transfection of CLL cells with BIM siRNA resulted in inhibition of CD37 SMIP -induced mitochondrial membrane depolarization and apoptosis. Conclusions: These studies demonstrate CD37 SMIP mediated apoptosis in CLL cells occurs via FoxO3a-dependent transcriptional up-regulation of BIM protein. This distinct mechanism of apoptosis utilized by CD37 SMIP contrasts it with other agents used for CLL treatment. Additionally, it provides a mechanism for the promising clinical activity of TRU-016 (humanized CD37 SMIP ) observed to date in refractory CLL patients. [Table: see text]