gebhart/patrepeval huggingface dataset:
Electromigration early failure void nucleation and growth phenomena in Cu and Cu(Mn) interconnects (2013)

Electromigration early failure void nucleation and growth phenomena were studied using large-scale, statistical analysis methods. A total of about 496,000 interconnects were tested over a wide current density and temperature range (j = 3.4 to 41.2 mA/μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , T = 200 to 350°C) to analyze the detailed behavior of the current density exponent n and the activation energy E <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">a</sub> . The results for the critical V1M1 downstream interface indicate a reduction from n = 1.55±0.10 to n = 1.15±0.15 when lowering the temperature towards 200°C for Cu-based interconnects. This suggests that the electromigration downstream early failure mechanism is shifting from a mix of nucleation-controlled (n = 2) and growth-controlled (n = 1) to a fully growth-controlled mode, assisted by the increased thermal stress at lower temperatures (especially at use conditions). For Cu(Mn)-based interconnects, a drop from n = 2.00±0.07 to n = 1.64±0.2 was found, indicating additional effects of a superimposed incubation time. Furthermore, at lower current densities, the E <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">a</sub> value seems to drop for both Cu and Cu(Mn) interconnects by a slight, but significant amount of 0.1 - 0.2eV. Implications for extrapolations of accelerated test data to use conditions are discussed. Furthermore, the scaling behavior of the early failure population at the NSD=-3 level (F~0.1%) was analyzed, spanning 90, 65, 45, 40 and 28 nm technology nodes.
Pathway Analysis for Drug Repositioning Based on Public Database Mining (2014)

Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public databases including the MMDB, PubChem BioAssay, GEO DataSets, and the BioSystems databases. Entrez E-Utilities were applied, and in-house Ruby scripts were developed for data retrieval and pathway analysis to identify and evaluate relevant pathways common to the retrieved drug targets. Pathways pertinent to clinical uses or MOAs were obtained for most drugs. Interestingly, some drugs identified pathways responsible for other diseases than their current therapeutic uses, and these pathways were verified retrospectively by in vitro tests, in vivo tests, or clinical trials. The pathway enrichment analysis based on drug target information from public databases could provide a novel approach for elucidating drug MOAs and repositioning, therefore benefiting the discovery of new therapeutic treatments for diseases.
Levels of Tumor Necrosis Factor α/Cachectin (TNFα) in Sera from Patients with Sickle Cell Disease (1993)

Serum levels of tumor necrosis factor alpha/cachectin (TNF alpha) were studied in a group of adult patients with sickle cell disease (SCD), which include 31 patients with homozygous SS hemoglobinopathy and 10 patients bearing double heterozygous SC hemoglobinopathy and in their matched normal controls. All patients tested did not show any form of crisis for at least 4 weeks prior to the extraction of the sample. The amount of TNF alpha in serum was quantitated by means of an immunoenzymatic assay with a lower limit of detection of 25 pg/ml. The percentage of sera with detectable levels of TNF alpha was significantly increased in SCD patients as compared with the normal controls. Mean TNF alpha values in individuals with detectable levels of the cytokine were also significantly higher in the whole group of SCD patients and in patients bearing either SS or SC hemoglobinopathies than in the control group. An inverse correlation was observed between the percentages of Hb F and the levels of TNF alpha found in the sera from the patients.
The use of magnetic fields to improve photon dose distributions for radiation therapy-a possible approach to "poor man's proton" beam properties (2002)

Several researchers have proposed the use of magnetic fields to modify the dose distributions for electron beams over the past 50 years. However, the potential use of magnetic fields to improve the dose distributions produced by X-ray beams has been largely ignored due to the conventional paradigm that magnetic fields are not expected to affect the behavior of uncharged radiations like X-rays and neutrons. This assumption is not necessarily valid. The authors have studied the effect of intense locally applied transverse magnetic fields on X-ray dose distributions for various beam energies, field sizes, and magnetic field strengths using Monte Carlo simulation. Significant dose enhancement is found close to the proximal magnetic field gradient region due to the prevention of secondary electrons from traveling downstream; whereas significant dose reduction is observed close to the distal gradient due to the need for re-establishment of the secondary electronic build-up region. The degree of dose enhancement and reduction along the central axis of the beam can be up to 100% and 60% respectively under idealized conditions. The isodose distributions for realistic magnetic fields also show lateral shifts of the electron dose deposition patterns. The authors' preliminary data show that a transversely applied magnetic field is capable of producing controllable and almost proton-like dose peaks in addition to dose dips in X-ray beams. This magnetic field induced dose modulation has the potential under certain circumstances of increasing the dose to the target volume and reducing the dose to the adjacent normal tissues in photon radiation therapy.
Homodimerization Restores Biological Activity to an Inactive Erythropoietin Mutant (1998)

Erythropoietin (Epo) is believed to transduce a signal by bringing two Epo receptors into close proximity, enabling cross-phosphorylation. We compared monomeric Epos with homodimers in which two Epo monomers are linked by polyglycine. Monomeric Epo mutant R103A is unable to support Epo-dependent cell growth or trigger Janus kinase 2 and STAT5 activation, even at concentrations greater than 7,000 times that sufficient for wild-type Epo activity. In contrast, R103A homodimer induces proliferation and transduces signal at concentrations similar to that of wild-type Epo monomer and homodimer. These experiments show that two discrete domains on Epo are required for receptor binding and activation. Our results also suggest that the EpoR can be dimerized by different forms and sizes of molecules, as long as two recognition motifs are provided in the same molecule. Design of other dimeric molecules may enhance our understanding of cytokine specificity and signal transduction.
Differential activity and potential mechanism of action of pralatrexate (PDX) methotrexate, and pemetrexed (Alimta) in human cancer models in vivo and in vitro (2007)

A135 This pilot study investigated the mechanism of action of PDX and its differences from other antifolates, and compared the in vivo activity of 3 antifolates against 2 NSCLC models. In vitro studies included evaluation of reduced folate carrier (RFC) expression by reverse transcription polymerase chain reaction (RT PCR) in MV522 and H460 xenograft models. We also compared the short-term uptake (assessment of RFC-1 transporter) and folylpolyglutamate synthase (FPGS) activity (polyglutamylation) using radiolabeled PDX, MTX (both at 5 µM) and Alimta (20 µM) in H460 cells in vitro. Inhibition of DHFR by the 3 antifolates was quantified in a cell-free assay against human recombinant DHFR. We compared in vivo activity of PDX and MTX (both at 1 mg/kg and 2 mg/kg), and Alimta (150 mg/kg) in the MV522 and H460 xenografts. Endpoints included mean tumor growth inhibition or regression. We further evaluated activity and/or expression of certain folate-dependent enzymes: DHFR, TS, and FPGS using kinetic assays and immunostaining in tumor tissue.  RFC expression in MV522 and H460 cells was below the limit of detection for the assay. In H460 cells, the total uptake of radiolabeled drugs measured at 15 and 60 minutes was similar at both times (MTX), decreased over time (Alimta), or increased over time (PDX). A significantly smaller fraction of radiolabeled MTX entered the cells in comparison with PDX or Alimta. Radiolabeled species (conceivably polyglutamylated PDX) had a bell-shaped distribution of different Rf values than the drug alone. It appeared in a time-dependent manner in lysates from PDX-treated cells with much less polyglutamylation seen in MTX or Alimta-treated cells, suggesting greater polyglutamylation of PDX than either MTX or Alimta. Apparent Ki values for DHFR inhibition in a cell-free assay were 6.25 nM, 12 nM, and >200 nM for PDX, MTX, and Alimta, respectively. In vivo, PDX dose-dependently inhibited tumor growth in H460 and MV522 xenografts with greater PDX activity seen in the more rapidly growing H460 model. The activity of MTX and Alimta was also model-dependent. PDX was more effective than MTX or Alimta in each tumor xenograft model. PDX, Alimta and MTX exerted qualitative differences in regulation of TS enzymatic activity and protein expression, and DHFR protein content in H460 and MV522 tumor xenografts. Unlike Alimta and MTX, PDX downregulated most of these endpoints.  These results suggest that PDX has mechanistically different activity from MTX and Alimta. Some of the observed differences include enhanced uptake of PDX into the cell and subsequent greater intracellular polyglutamylation and intracellular accumulation that translate into greater tumor growth inhibition by PDX than either MTX or Alimta in NSCLC xenograft models in vivo.  Supported by Allos Therapeutics, Inc.
β-Catenin Status Predicts a Favorable Outcome in Childhood Medulloblastoma: The United Kingdom Children's Cancer Study Group Brain Tumour Committee (2005)

Nuclear accumulation of beta-catenin appears to be a marker of favorable outcome in medulloblastoma, and should be investigated further in large group-wide trials.
Speeding up program execution using reconfigurable hardware and a hardware function library (2002)

This paper describes a co-design environment which follows a new approach for speeding up compute intensive applications. The environment consists of three major components. First, a target architecture consisting of a uniprocessor host and a board with dynamically reconfigurable FPGAs and memory modules; second, a library of functions pre-synthesized for hardware or software implementation; and third, a tool which takes as input an application described in C and partitions it into hardware and software parts at functional granularity using information obtained by profiling the application. An important feature of the partitioning tool is a new efficient heuristic specifically suited for the architecture with reconfigurable hardware.
The updated ionospheric delay model to improve the performance of GPS single‐frequency receivers (2000)

A regional updating technique is suggested for the global ionospheric delay model ( Klobuchar's [1987] model). The updating procedure uses series of values of the ionospheric delay (ID) which are reconstructed from distance measurements at two Global Positioning System working frequencies. We consider the situation where Klobuchar's model is updated from measurements from a single ground‐based reference station. We exemplify the use of a regional updating of the ID model under undisturbed ionospheric conditions, as well as under solar eclipse and magnetic storm conditions. In all cases presented, using the proposed technique the standard deviation between predicted and measured ID values was reduced by a factor of 1.2–2.8 as compared with Klobuchar's original model used under the same conditions. A tentative estimate is made of the variation in the ionospheric rms error in determining the user's location (UPL) through the use of the regional updating technique. For the examples considered in this study, on applying the regional updating of Klobuchar's model, the ionospheric rms error in determining the UPL was found to be lower by a factor of 1.3–2.6 than that obtained by using the same model without updating.
Inside the Windows 95 file system (1997)

From IFSMgr to the Internet Where Do Filenames Go? Pathways to the File System File System API Mapping The New MS-DOS File System Dispatching File System Requests Monitoring File Activity Anatomy of a File System Driver VFAT: The Virtual FAT File System Driver Virtual Memory, the Paging File, and Pagers VCACHE: Caches Big and Small A Survey of IFSMgr Services VREDIR: The Microsoft Networks Client Looking Ahead. Appendices: MultiMon - Setup, Usage, and Extensions MultiMon - Monitor Reference IFSMgr Data Structures IFS Development Aids.
A Novel Approach to 2,2‐Disubstituted 1,2‐Dihydro‐4‐phenylquinolines (1994)

Abstract The reaction of 2‐(1‐phenylvinyl)aniline and 4‐chloro‐2‐(1‐phenylvinyl)aniline with acetophenone derivatives, 1‐(naphthalen‐1‐yl)ethanone and 1‐(furan‐2‐yl)ethanone in toluene at 110–115° with toluene‐4‐sulfonic acid as a catalyst leads in good‐to‐excellent yields to the 2,2‐disubstituted 1,2‐dihydro‐4‐phenyl‐quinolines 1–18 ( Scheme 1, Table ). The structure of the new racemic 1,2‐dihydroquinolines 1–18 is determined by NMR spectroscopy. A reaction mechanism proceeding via a 6π‐electrocyclic rearrangement of 2‐(1‐phenylvinyl)anils 19 as the key step is proposed for the formation of these compounds ( Scheme 1 ). The scope and limitations of the novel methods are discussed ( Scheme 2 ).
<i>Candida albicans</i>dimorphism as a therapeutic target (2011)

The ability to switch between yeast and hyphal growth forms (dimorphism) is one of the most discussed and best investigated virulence attributes of the human pathogenic fungus Candida albicans. Both morphological forms seem to be important for virulence and have distinct functions during the different stages of disease development, including adhesion, invasion, damage, dissemination, immune evasion and host response. In this review, we will provide an overview of the known and potential roles of C. albicans dimorphism and will discuss the potential benefit of drugs that can inhibit the morphological transition.
Identification of surface proteins mediating adherence of CD11/CD18-deficient lymphoblastoid cells to cultured human endothelium. (1990)

Patients with the severe form of leukocyte adhesion deficiency syndrome do not express the CD11/CD18 adhesion complex on any of their leukocytes. Nevertheless, their lymphocytes, unlike their phagocytes, emigrate to extravascular sites of inflammation, demonstrating that surface proteins other than CD11/CD18 can mediate lymphocyte adherence to endothelium. Using a B-lymphoblastoid cell line (B-LCL) established from a CD11/CD18-deficient patient and cultured human umbilical vein endothelial cells (HEC), we investigated the CD11/CD18-independent mechanism(s) of lymphocyte adherence to endothelium. Monoclonal antibodies directed to the alpha 4 polypeptide (CD49d) and the beta 1 polypeptide (CD29) of the lymphocyte VLA-4 integrin receptor (CD49d/CD29), and to vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cell significantly inhibited the adherence of the CD11/CD18-deficient B-LCL to untreated HEC and to HEC treated with recombinant human tumor necrosis factor-alpha. We suggest that the interaction of the lymphocyte receptor VLA-4 with the endothelial ligand VCAM-1 induced by cytokines at sites of inflammation or immune reaction represents a CD11/CD18-independent pathway of lymphocyte emigration.
Sulfidation kinetics of industrial steels in a refinery crude oil at 300 °C: reactivity at the nanometer scale (2010)

Abstract High temperature sulfidic corrosion has caused safety and reliability issues in refinery units for decades. The objective of the work was to investigate the kinetics of sulfidation under refinery conditions and to characterize, at the nanometer scale, the sulfide layers formed on different steels. The experiments were performed in an autoclave filled with a refinery high‐sulfur crude oil at 300 °C on XC18 carbon steel (Fe–0.18%C), P5 alloy steel (Fe–5% Cr–0.5%Mo) and 304L stainless steel (Fe–18% Cr–8%Ni). The duration of the test ranged from a few hours to a few days. The combination of X‐ray diffraction and transmission electronic microscopy showed the presence of pyrrhotite (Fe 1− x S) on XC18, P5 and 304L samples. For all alloys, the S 2p core level decomposition (X‐ray photoelectron spectroscopy) proved the presence of five sulfur species on the surface: sulfide (main species), disulfide, elemental sulfur, sulfite and sulfate. On 304L, the presence of chromium oxide and nickel sulfide was revealed by XPS, whereas chromium sulfide was hardly detected. The macroscopic kinetics of sulfidation was followed by mass loss. The results showed that a parabolic law can fit the kinetics of sulfidation of XC18 and P5 steels. The kinetics of sulfidation of the adherent sulfide layer formed on 304L steel, determined from XPS measurements, follows a logarithmic law. Copyright © 2010 John Wiley & Sons, Ltd.
Polymicrobial Interactions: Impact on Pathogenesis and Human Disease (2012)

Microorganisms coexist in a complex milieu of bacteria, fungi, archaea, and viruses on or within the human body, often as multifaceted polymicrobial biofilm communities at mucosal sites and on abiotic surfaces. Only recently have we begun to appreciate the complicated biofilm phenotype during infection; moreover, even less is known about the interactions that occur between microorganisms during polymicrobial growth and their implications in human disease. Therefore, this review focuses on polymicrobial biofilm-mediated infections and examines the contribution of bacterial-bacterial, bacterial-fungal, and bacterial-viral interactions during human infection and potential strategies for protection against such diseases.
Complexing of chromium(III) and aluminum(III) cations with phosphorus-containing cellulose-based fibrous sorbent (2009)

Sorption of Al3+ and Cr3+ cations from sulfuric acid solutions with a cellulose phosphate-based fibrous sorbent was examined.
Critical micelle concentrations of gangliosides (1979)

The micellar properties of mixed, bovine gangliosides and purified galactosyl-N-acetylacetylgalactosaminyl (N-acetylneuraminyl) galactosylglucosylceramide were studied by gel filtration, equilibrium dialysis, and band and boundary centrifugation in sucrose gradients. The dissociation of micelles is very slow (days) in water and required us to approach equilibrium by association of monomers rather than by the dissociation of micelles. The gangliosides were therefore first converted into very low molecular weight aggregates (1-3 molecules) by dissolving them in Me2SO. Galactosyl-N-acetylgalactosaminyl(N-acetylneuraminyl)galactosylglucosylceramide was then diluted into aqueous sucrose gradients and sedimented by the boundary centrifugation technique. This gave a sedimenting micelle and a nonsedimenting monomer concentration of (1-2) x 10-10 M (or less) which corresponds to the critical micelle concentration value. The mixed gangliosides revealed two micellar sizes (i.e., 10 and 4.5 S), the slower sedimenting species being formed from the larger one with time (days). The critical micelle concentration of the mixed gangliosides was found to be approximately 10-8 M by a gel filtration, equilibrium dialysis, and band centrifugation.
Monoclonal antibody 7H6 reacts with a novel tight junction-associated protein distinct from ZO-1, cingulin and ZO-2. (1993)

The tight junction is an essential element of the intercellular junctional complex; yet its protein composition is not fully understood. At present, only three proteins, ZO-1 (Stevenson, B. R., J. D. Siliciano, M. S. Mooseker, and D. A. Goodenough. 1986. J. Cell Biol. 103:755-766), cingulin (Citi, S., H. Sabanay, R. Jakes, B. Geiger, and J. Kendrick-Jones. 1988. Nature (Lond.). 333:272-275) and ZO-2 (Gumbiner, B., T. Lowenkopf, and D. Apatira. 1991. Proc. Natl. Acad. Sci. USA. 88:3460-3464) are known to be associated with the tight junction. We have generated a monoclonal antibody (7H6) against a bile canaliculus-rich membrane fraction prepared from rat liver. This 7H6 antigen was preferentially localized by immunofluorescence at the junctional complex regions of hepatocytes and other epithelia, and 7H6-affiliated gold particles were shown electron microscopically to localize at the periphery of tight junctions. Immunoblot analysis of a bile canaliculus-rich fraction of rat liver using 7H6, anti-ZO-1 antibody (R26.4C), and anti-cingulin antibody revealed that 7H6 reacted selectively with a 155-kD protein, whereas R26.4C reacted only with a 225-kD protein. Anti-cingulin antibody reacted solely with 140 and 108-kD proteins, indicating that the protein recognized by 7H6 is immunologically different from ZO-1 and cingulin. Immunoprecipitation of detergent extracts obtained from metabolically labeled MDCK cells with R26.4C coprecipitated a 160-kD protein, which corresponds to ZO-2, with ZO-1. However, 7H6 did not react with the 160-kD protein. These results strongly suggest that the 7H6 antibody recognizes a novel tight junction-associated protein different from ZO-1, cingulin and ZO-2.
Deficiency of the Leukotriene B4 Receptor, BLT-1, Protects against Systemic Insulin Resistance in Diet-Induced Obesity (2011)

Chronic inflammation is an underlying factor linking obesity with insulin resistance. Diet-induced obesity promotes an increase in circulating levels of inflammatory monocytes and their infiltration into expanding adipose tissue. Nevertheless, the endogenous pathways that trigger and sustain chronic low-grade inflammation in obesity are incompletely understood. In this study, we report that a high-fat diet selectively increases the circulating levels of CD11b(+) monocytes in wild-type mice that express leukotriene B(4) receptor, BLT-1, and that this increase is abolished in BLT-1-null mice. The accumulation of classically activated (M1) adipose tissue macrophages (ATMs) and the expression of proinflammatory cytokines and chemokines (i.e., IL-6 and Ccl2) was largely blunted in adipose tissue of obese BLT-1(-/-) mice, whereas the ratio of alternatively activated (M2) ATMs to M1 ATMs was increased. Obese BLT-1(-/-) mice were protected from systemic glucose and insulin intolerance and this was associated with a decrease in inflammation in adipose tissue and liver and a decrease in hepatic triglyceride accumulation. Deletion of BLT-1 prevented high fat-induced loss of insulin signaling in liver and skeletal muscle. These observations elucidate a novel role of chemoattractant receptor, BLT-1, in promoting monocyte trafficking to adipose tissue and promoting chronic inflammation in obesity and could lead to the identification of new therapeutic targets for treating insulin resistance in obesity.
Efficiency of dislocation density reduction during heteroepitaxial growth of diamond for detector applications (2013)

The development of dislocation density and micro-strain in heteroepitaxial diamond films on iridium was measured over more than two decades of thickness up to d ≈ 1 mm. Simple mathematical scaling laws were derived for the decrease of dislocation density with increasing film thickness and for its correlation with micro-strain. The Raman line width as a measure of micro-strain showed a huge decrease to 1.86 cm−1, close to the value of perfect single crystals. The charge collection properties of particle detectors built from this material yield efficiencies higher than 90% in the hole-drift mode, approaching the performance of homoepitaxial films.