gebhart/patrepeval huggingface dataset:
IFRA: Post-silicon bug localization in processors (2009)

IFRA overcomes challenges associated with an expensive step in post-silicon validation of processors - pinpointing the bug location and the instruction sequence that exposes the bug from a system failure. On-chip recorders collect instruction footprints (information about flows of instructions, and what the instructions did as they passed through various design blocks) during the normal operation of the processor in a post-silicon system validation setup. Upon system failure, the recorded information is scanned out and analyzed off-line for bug localization. Special self-consistency-based program analysis techniques, together with the test program binary of the application executed during post-silicon validation, are used. Major benefits of using IFRA over traditional techniques for post-silicon bug localization are: 1. It does not require full system-level reproduction of bugs, and, 2. It does not require full system-level simulation. Simulation results on a complex super-scalar processor demonstrate that IFRA is effective in accurately localizing electrical bugs with very little impact on overall chip area.
Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders? (2018)

Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in "distant" pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.
Amplification of JC virus DNA from brain and cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy (1991)

We have established an assay to detect JC viral DNA in brain tissue and CSF of patients with progressive multifocal leukoencephalopathy (PML) and amplified a 106-base pair segment of the gene encoding JC viral large T antigen by polymerase chain reaction (PCR) from the brains of eight patients with PML and from one of six CSF samples. Brain and CSF of patients without PML did not yield JC virus-specific DNA amplification products. Southern analysis documented that the sequences of the 106-base pair PCR product and JC viral DNA are identical. This assay can be used in the diagnosis of PML and to investigate the biology of JC virus.
Adalimumab in clinical practice. Outcome in 70 rheumatoid arthritis patients, including comparison of patients with and without previous anti-TNF exposure (2005)

Our clinical experience confirms that adalimumab is effective and safe in the treatment of RA. It also shows adalimumab is effective in patients with previous biological failures, particularly patients with secondary failure to infliximab.
URBAN PUBLIC TRANSPORTATION IN SEOUL: SYSTEM, OPERATION, USE BY PEOPLE (2000)

Subways and buses are among the most important elements of the public transit system in Seoul, Korea. This paper describes details of these subway and bus systems. However, community bus lines are not dealt with in detail because the firms operating them do not produce statistical data on their operations. Data represented in this research is from 1996 and 1997. The first section discusses system and route information. Next, a section on operations discusses organization, operation characteristics, and facilities. The last section discusses usage including mode shares, ridership trends, and user characteristics.
Expression of L‐type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in liver tumor lesions of rat models (2001)

LAT1 was related to tumor growth. We think that LAT1 can possibly enhance its ability to promote tumor growth in cooperation with 4F2hc.
Small Molecule Disruption of Quorum Sensing Cross-Regulation in Pseudomonas aeruginosa Causes Major and Unexpected Alterations to Virulence Phenotypes (2015)

The opportunistic pathogen Pseudomonas aeruginosa uses three interwoven quorum-sensing (QS) circuits-Las, Rhl, and Pqs-to regulate the global expression of myriad virulence-associated genes. Interception of these signaling networks with small molecules represents an emerging strategy for the development of anti-infective agents against this bacterium. In the current study, we applied a chemical approach to investigate how the Las-Rhl-Pqs QS hierarchy coordinates key virulence phenotypes in wild-type P. aeruginosa. We screened a focused library of synthetic, non-native N-acyl l-homoserine lactones and identified compounds that can drastically alter production of two important virulence factors: pyocyanin and rhamnolipid. We demonstrate that these molecules act by targeting RhlR in P. aeruginosa, a QS receptor that has seen far less scrutiny to date relative to other circuitry. Unexpectedly, modulation of RhlR activity by a single compound induces inverse regulation of pyocyanin and rhamnolipid, a result that was not predicted using genetic approaches to interrogate QS in P. aeruginosa. Further, we show that certain RhlR agonists strongly repress Pqs signaling, revealing disruption of Rhl-Pqs cross-regulation as a novel mechanism for QS inhibition. These compounds significantly expand the known repertoire of chemical probes available to study RhlR in P. aeruginosa. Moreover, our results suggest that designing chemical agents to disrupt Rhl-Pqs crosstalk could be an effective antivirulence strategy to fight this common pathogen.
Physical Interaction between Specific E2 and Hect E3 Enzymes Determines Functional Cooperativity (1997)

The cellular protein E6AP functions as an E3 ubiquitin protein ligase in the E6-dependent ubiquitination of p53. E6AP is a member of a family of functionally related E3 proteins that share a conserved carboxyl-terminal region called the Hect domain. Although several different E2 ubiquitin-conjugating enzymes have been shown to function with E6AP in the E6-dependent ubiquitination of p53 in vitro, the E2s that cooperate with E6AP in the ubiquitination of its normal substrates are presently unknown. Moreover, the basis of functional cooperativity between specific E2 and Hect E3 proteins has not yet been determined. Here we report the cloning of a new human E2, designated UbcH8, that was identified in a two-hybrid screen through specific interaction with E6AP. We demonstrate that UbcH7, an E2 closely related to UbcH8, can also bind to E6AP. The region of E6AP involved in complex formation with UbcH8 and UbcH7 was mapped to its Hect domain. Furthermore, we show that UbcH5 and UbcH6, two highly homologous E2s that were deficient for interaction with E6AP, could associate efficiently with another Hect-E3 protein, RSP5. Finally, only the E6AP-interacting E2s could function in conjunction with E6AP in the ubiquitination of an E6 independent substrate of E6AP, whereas the noninteracting E2s could not. Taken together, these studies demonstrate for the first time complex formation between specific human E2s and the Hect domain family of E3 proteins and suggest that selective physical interaction between E2 and E3 enzymes forms the basis of specificity for functionally distinct E2:E3 combinations.
Accumulation of RNA homologous to human papillomavirus type 16 open reading frames in genital precancers (1988)

The accumulation of human papillomavirus type 16 (HPV-16)-specific RNAs in tissue sections from biopsies of patients with genital precancers was studied by in situ hybridization with single-stranded 35S-labeled RNA. These analyses revealed that the most abundant early-region RNAs were derived from the E4 and E5 open reading frames (ORFs). RNAs homologous to the E6/E7 ORFs were also detected, whereas RNAs homologous to the intervening E1 ORF were not. This suggests that the E4 and E5 mRNAs are derived by splicing to the upstream E6/E7 ORFs, consistent with studies of HPV-11 in condylomata (L. T. Chow et al., Cancer Cells (Cold Spring Harbor) 5:55-72, 1987). Abundant RNAs homologous to the 5' portion of L1 were also detected. These RNAs were localized to the apical strata of the epithelium. HPV-16 RNAs accumulated in discrete regions of these lesions, and when present were most abundant in the upper cell layers of the precancerous epithelium. RNAs homologous to early ORFs were also detected in some germinal cells within the basal layer of the epithelium.
Atomic force microscopy and friction force microscopy of chemically modified surfaces (1994)

We describe the study of a chemically modified quartz surface by atomic force microscopy and friction force microscopy. The chemically modified surface was covered with hydrocarbon (HC) and fluorocarbon (FC) in different parts. The region selective surface chemical modification with two different silanization reagents was successfully accomplished by the following procedure: exposed quartz surfaces of a quartz plate covered with microlithographically prepared patterns of chromium film were first modified with one of the silanization reagents, then the patterns of chromium film were etched, and finally, newly exposed quartz surfaces were modified with the other silanization reagent. The chemical modification with such etching allowed patterning with a submicrometer scale. Since the location of the surfaces covered with two different chemical species was known in the chemically modified surfaces, assignment of the measured frictions to the individual surfaces was definite. The relative values of the difference in friction between HC and FC regions were roughly 1:4.
<title>Content-based retrieval of music and audio</title> (1997)

Though many systems exist for content-based retrieval of images, little work has been done on the audio portion of the multimedia stream. This paper presents a system to retrieve audio documents y acoustic similarity. The similarity measure is based on statistics derived from a supervised vector quantizer, rather than matching simple pitch or spectral characteristics. The system is thus able to learn distinguishing audio features while ignoring unimportant variation. Both theoretical and experimental results are presented, including quantitative measures of retrieval performance. Retrieval was tested on a corpus of simple sounds as well as a corpus of musical excerpts. The system is purely data-driven and does not depend on particular audio characteristics. Given a suitable parameterization, this method may thus be applicable to image retrieval as well.
DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study (2012)

Among high-risk pregnancies, sequencing circulating cell-free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies.
Thermal behavior of core-shell and three-shell layered clusters: Melting ofCu1Au54andCu12Au43 (2006)

The meltinglike transition of the ${\mathrm{Cu}}_{1}{\mathrm{Au}}_{54}$ and ${\mathrm{Cu}}_{12}{\mathrm{Au}}_{43}$ clusters is investigated by canonical Monte Carlo simulations, based on the second-moment approximation of the tight-binding potentials. The structures of both the ${\mathrm{Cu}}_{1}{\mathrm{Au}}_{54}$ and ${\mathrm{Cu}}_{12}{\mathrm{Au}}_{43}$ clusters, shown to be icosahedral, are obtained from the so-called semi-grand-canonical ensemble Monte Carlo simulation at $100\phantom{\rule{0.3em}{0ex}}\mathrm{K}$. A core-shell structure is found in ${\mathrm{Cu}}_{1}{\mathrm{Au}}_{54}$, with a single Cu atom in the center and 54 Au atoms on the surface and in interior shells of the cluster. On the other hand, ${\mathrm{Cu}}_{12}{\mathrm{Au}}_{43}$ possesses a three-shell onionlike structure, with a single Au atom located in the center, 12 Cu atoms in the middle shell, and 42 Au atoms occupying the surface shell of the cluster. Melting characteristics are observed by the changes in the caloric curve, heat capacity, root-mean-square bond-length fluctuation, and deformation parameter. It is found that doping of ${\mathrm{Au}}_{55}$ with a single Cu atom can sharply raise the melting point of the cluster. In addition, the three-shell onionlike structure can be transformed into the core-shell structure at the higher temperatures after melting. It is also found that surface segregation of Au atoms in ${\mathrm{Cu}}_{1}{\mathrm{Au}}_{54}$ and ${\mathrm{Cu}}_{12}{\mathrm{Au}}_{43}$ occurs in the liquid phase. In addition, the simulation results show that the melting point increases with the concentration of Cu in the 55-atom Cu-Au bimetallic cluster.
CXCR2 Inhibition – a novel approach to treating CoronAry heart DiseAse (CICADA): study protocol for a randomised controlled trial (2017)

EudraCT, 2016-000775-24 . Registered on 22 July 2016. International Standard Randomised Controlled Trial Number, ISRCTN48328178 . Registered on 25 February 2016.
Brand differences of free-base nicotine delivery in cigarette smoke: the view of the tobacco industry documents (2006)

The recent availability of internal tobacco industry documents provides significant insight into industry knowledge and manipulation of tobacco smoke delivery. One critical area of research is the role of smoke chemistry in determining the absorption and effects of smoke constituents, especially harm producing or pharmacologically active compounds. Independent scientific research has suggested that the nicotine dosing characteristics, hence the addiction potential of cigarettes, may be determined in part by the amount of free-base nicotine in cigarette smoke and its effects on the location, route, and speed of absorption in the body and on the sensory perception effects of the inhaled smoke. Tobacco industry documents describe the use of a number of methods internally for measuring free-base nicotine delivery. These include the common use of cigarette "smoke pH" as a means to estimate the fraction of free-base nicotine in the particulate matter (PM) in cigarette smoke, as well as efforts to measure free-base nicotine directly. Although these methods do not provide accurate absolute measures of free-base nicotine in smoke, consistencies observed in the findings across the various manufacturers indicate: (1) real relative differences in the acid/base chemistry of the smoke from different brands of cigarettes; (2) a connection between differences in free-base levels and brand-dependent differences in sensory perception and smoke "impact"; and (3) levels of free-base nicotine that are greater than have typically been publicly discussed by the industry. Furthermore, the results of these methods are generally consistent with those of a recent study from the Centers for Disease Control and Prevention which directly measured the free-base fraction of nicotine across a range of cigarette types. Consideration of the likely fundamental importance of free-base nicotine levels in cigarette smoke, together with the efforts discussed in the tobacco industry documents to measure such levels, indicates that the public health community would benefit from additional research to assess directly the delivery of free-base nicotine in cigarette smoke across brands. This may be especially useful for those products ("light", "ultralight", "reduced carcinogen", etc) that have been promoted, either explicitly or implicitly, as "harm reducing".
Individual adenovirus E1B proteins induce transformation independently but by additive pathways (1991)

The specific contributions of human adenovirus type 5 early region 1B (E1B) proteins were examined using mutants which synthesize these products individually. In cooperation with E1A, transformation of primary baby rat kidney cells was achieved with either the 176R protein or 496R protein alone, albeit at an efficiency considerably less than that observed when both were present. These results indicate that transformation mediated by either E1B product can proceed independently, but that the processes involved are additive.
Review: Death Domain Receptors and Their Role in Cell Demise (1998)

Apoptotic signals are transduced by five death domain-containing receptors--TNFR1, Fas, DR3, DR4, and DR5--by binding to their ligands. The intracellular portion of all these receptors contains a region, approximately 80 amino acids long, referred to as the "death domain" (DD). On activation by its ligand, the DD recruits various proteins that mediate cell death. These proteins, in turn, recruit other proteins via their DDs or death effector domains (DED). The actual destruction of the cell, however, is accomplished by serial activation of a family of proteases referred to as caspases. Cell death is, in part, regulated by transmembrane decoy receptors that contain either none of or only part of the DD. This article briefly reviews what is known about the receptors and other proteins involved in apoptosis. In addition, because numerous proteins that mediate apoptosis have been discovered independently and simultaneously and thus are known by many different names, a comprehensive cross-referenced list of these proteins is provided.
135. The preparation of benziminazoles from α-benzamido-acids and peptides (1956)

R. Crawford and J. T. Edward, J. Chem. Soc., 1956, 673 DOI: 10.1039/JR9560000673
Genomic disorders: A window into human gene and genome evolution (2010)

Gene duplications alter the genetic constitution of organisms and can be a driving force of molecular evolution in humans and the great apes. In this context, the study of genomic disorders has uncovered the essential role played by the genomic architecture, especially low copy repeats (LCRs) or segmental duplications (SDs). In fact, regardless of the mechanism, LCRs can mediate or stimulate rearrangements, inciting genomic instability and generating dynamic and unstable regions prone to rapid molecular evolution. In humans, copy-number variation (CNV) has been implicated in common traits such as neuropathy, hypertension, color blindness, infertility, and behavioral traits including autism and schizophrenia, as well as disease susceptibility to HIV, lupus nephritis, and psoriasis among many other clinical phenotypes. The same mechanisms implicated in the origin of genomic disorders may also play a role in the emergence of segmental duplications and the evolution of new genes by means of genomic and gene duplication and triplication, exon shuffling, exon accretion, and fusion/fission events.
In Vivo Methods for Screening and Preclinical Testing (2004)

The classic question in the field of drug discovery is: Which tumor model is a satisfactory predictor for cancer in humans? The classic answer is: None of them!
Characterization of the Extracellular Polymeric Substances Produced by Escherichia coli Using Infrared Spectroscopic, Proteomic, and Aggregation Studies (2008)

The aim of this study was twofold: first, to characterize the free extracellular polymeric substances (EPS) and bound EPS produced by Escherichia coli during different growth phases in different media, and then to investigate the role of the free EPS in promoting aggregation. EPS was extracted from a population of E. coli MG1655 cells grown in different media composition (Luria-Bertani (LB) and Luria-Bertani with the addition of 0.5 w/v% glucose at the beginning of the growth phase (LBG)) and at different growth phases (6 and 24 h). The extracted EPS was characterized using Fourier transform infrared spectroscopy and further identified using one-dimensional gel-based electrophoresis and tandem mass spectrometry. E. coli MG1655 was found to produce significantly lower amounts of bound EPS compared to free EPS under all conditions. The protein content of free EPS increased as the cells progressed from the exponential to stationary phase when grown in LB or LBG, while the carbohydrate content only increased across the growth phases for cells grown in LBG. FTIR revealed a variation in the different functional groups such as amines, carboxyl, and phosphoryl groups for free EPS extracted at the different growth conditions. Over 500 proteins were identified in the free EPS, with 40 proteins common in all growth conditions. Proteins with functionality related to amino acid and carbohydrate metabolism, as well as cell wall and membrane biogenesis were among the highest proteins identified in the free EPS extracted from E. coli MG1655 under all growth and media conditions. The role of bound and free EPS was investigated using a standardized aggregation assay. Bound EPS did not contribute to aggregation of E. coli MG1655. The readdition of free EPS to E. coli MG1655 resulted in aggregation of the cells in all growth conditions. Free EPS extracted from the 24 h E. coli MG1655 cultures grown in LB had the greatest effect on aggregation of cells grow in LBG, with a 30% increase in aggregation observed.
Gα encoding gene family of the malaria vector mosquito Anopheles gambiae: Expression analysis and immunolocalization of AGαq and AGαo in female antennae (2006)

To initiate a comprehensive investigation of chemosensory signal transduction downstream of odorant receptors, we identified and characterized the complete set of genes that encode G-protein alpha subunits in the genome of the malaria vector mosquito An. gambiae. Data are provided on the tissue-specific expression patterns of 10 corresponding aga-transcripts in adult mosquitoes and pre-imago developmental stages. Specific immunoreactivity in chemosensory hairs of female antennae provides evidence in support of the participation of a subset of AGalphaq isoforms in olfactory signal transduction in this mosquito. In contrast, AGalphao is localized along the flagellar axon bundle but is absent from chemosensory sensilla, which suggests that this G-protein alpha subunit does not participate in olfactory signal transduction.
Effect of P/E Cycling on Drain Disturb in Flash EEPROMs Under CHE and CHISEL Operation (2004)

Drain disturb is studied in NOR flash EEPROM cells under CHE and CHISEL programming operation, before and after repeated program/erase (P/E) cycling. Drain disturb is shown to originate from band-to-band tunneling under CHISEL operation, unlike under CHE operation where it originates from source-drain leakage. Under identical initial programming time, CHISEL operation always shows slightly lower program/disturb (P/D) margin before cycling but similar P/D margin after repetitive P/E cycling when compared to CHE operation. The degradation of gate coupling coefficient that affects source/drain leakage and the increase in trap-assisted band-to-band tunneling seems to explain well the behavior of CHE and CHISEL drain disturb after cycling.