gebhart/patrepeval huggingface dataset:
Creation and characterization of 5-fluorodeoxyuridine-resistant Arg50 loop mutants of human thymidylate synthase. (2001)

Thymidylate synthase catalyzes the reductive methylation of dUMP to dTMP and is essential for the synthesis of DNA. Fluoropyrimidines, such as 5-fluorouracil (5-FU), are used extensively in cancer therapy. In the cell, 5-FU is metabolized to 5-fluoro-2'-deoxyuridine 5'-monophosphate, a tight binding covalent inhibitor of thymidylate synthase. Recent studies have identified 5-fluoro-2'-deoxyuridine (5-FdUR) and antifolate-resistant mutants of human thymidylate synthase (TS) that contain single residue substitutions within the highly conserved Arg50-loop, which binds the pyrimidine substrate (Y. Tong et al., J. Biol. Chem. 273: 11611-11618, 1998). We have used random sequence mutagenesis to gain structure-function information about the TS and to create novel drug-resistant mutants for gene therapy. A library of 1.5 million mutants of the Arg50-loop and the nearby residue Tyr 33 was selected to identify mutants of the human enzyme with the ability to complement a thymidylate synthase-deficient Escherichia coli strain and form colonies in the presence of 5-FdUR. E. coli-harboring plasmids that were encoding TS with single, double, and triple amino acid substitutions were identified that survive at dosages of 5-FdUR clearly lethal to E. coli harboring either wild-type thymidylate synthase or constructs encoding previously characterized drug resistant mutants. Four 5-FdUR-resistant mutants were purified to apparent homogeneity. Kinetic studies indicate that these enzymes are highly efficient. Inhibition constants (Ki) for the double mutant K47Q;D48E and the triple mutant D48E;T51S;G52C in the presence of 5-fluoro-2'-deoxyuridine 5'-monophosphate were determined to be 75 to 100 times higher, respectively, than that of the wild-type enzyme. These mutant TSs, or others similarly created and selected, could be used to protect bone marrow cells from the cytotoxic side effects of 5-FU chemotherapy.
Tumor origin detection with tissue-specific miRNA and DNA methylation markers (2017)

Supplementary data are available at Bioinformatics online.
2.5 Ω/□ W/TiN/poly stack gate technology for high density and embedded DRAM technology (2003)

A W/TiN/Poly gate stack has been developed and extensively characterized, and it is applied to a 0.2 /spl mu/m CMOS transistor design for Gigabit and embedded DRAM technology. The gate sheet is less than 2.5 /spl Omega///spl square/ with a 600 /spl Aring//200 /spl Aring//900 /spl Aring/ W/TiN/Poly gate stack at 0.16 /spl mu/m line width. The effective oxide thickness is found to be 3 /spl Aring/ thicker than a comparable poly-only gate. The oxide hard breakdown field can exceed 12 MV/cm and CHC lifetime is greater than 10 years with the W/TiN/Poly gate stack technology. In addition, a drive current of 400 /spl mu/A//spl mu/m for nMOS and 190 /spl mu/A//spl mu/m for pMOS have been achieved at 1 pA//spl mu/m off-current and 1.8 V Vcc with 5 nm gate oxide. This is the highest drive current reported to date for similar technologies.
Preparation and properties of insoluble fibroin films by novel method (2004)

报道一种制备不溶性丝素强白薄膜的新方法.在温和搅拌下,将丝素溶液浓缩至16%,通过调整干燥温度和干燥速率,直接获得不溶于水的丝素薄膜.薄膜结构通过FTIR-ATR和XRD测定,同时对薄膜的机械性能进行研究.结果表明,丝素薄膜在干燥温度高于60℃时,有充足的β折叠结构存在,机械性能良好.当干燥温度为70℃时,材料的拉伸强度和断裂伸长率分别为29.8 MPa和59.6%,远远强于经过甲醇处理的丝素薄膜的机械性能.当干燥温度高于60℃时,材料在水中具有优异的稳定性.由于在丝素薄膜的制备中避免了甲醇的使用并使材料具有更好的机械性能,此方法制备的丝素薄膜更为安全,应用会更广泛.
Sensorimotor gating of the startle reflex: what we said 25 years ago, what has happened since then, and what comes next (2016)

Our 1992 paper, 'The neural substrates of sensorimotor gating of the startle reflex: a review of recent findings and their implications', reviewed a series of (then) new and preliminary findings from cross-species studies of prepulse inhibition of the startle reflex, and commented on their implications. At the time that the report was composed, PubMed listed about 40 citations for studies using the search term 'prepulse inhibition'. In the ensuing 25 years, the field has added about 2700 such reports, reflecting the substantial growth in interest in prepulse inhibition and its utility across a number of different experimental applications. The 30th anniversary of the Journal of Psychopharmacology provides an opportunity to comment briefly on what was described in that 1992 report, how the field has progressed in the subsequent decades, and the paths forward for studies of prepulse inhibition and its use as an operational measure of sensorimotor gating. Among these future paths, we highlight the use of prepulse inhibition as: an endophenotype for genomic studies, and a biomarker for healthy brain circuitry, which may predict sensitivity to psychotherapeutics. Our 1992 report was highly speculative and based on paper-thin empirical data, yet viewed in a certain light, it appears to have contained a basic roadmap for a journey spanning the next 25 years of prepulse inhibition research… and 'what a long, strange trip it's been'.
Characterization of Rigor Mortis Development in Four Broiler Muscles (1991)

Three experiments were conducted to characterize the development of rigor mortis by broiler muscles containing different muscle fiber types. In the first experiment, isotonic shortening was used to detect the development of rigor mortis. Two homogeneous fiber-type muscles were used to model the behavior of red, aerobic, and white anaerobic muscle fibers and two heterogeneous fiber-type muscles were used to evaluate the contribution of these fiber types within a muscle. Rigor mortis development in predominantly red, aerobic muscles was significantly more rapid (P<.05) than that in predominantly white, anaerobic muscle. Commercial chilling procedures slowed (P<.10) rigor mortis development only in red, aerobic muscles. In the second and third experiments the same four test muscles were removed from broilers at .33, .67, 1, 2, 3, 4, 6, and 8 h post-mortem and analyzed for R value and for glycogen and lactic acid. The aerobic muscles showed no change in any biochemical parameters tested after 2 h post-mortem. The anaerobic muscles showed continued metabolic activity beyond 2 h post-mortem and the Pectoralis superficialis exhibited substantial R value and lactic acid increases up to 8 h post-mortem. The rigor mortis development times from the isotonic shortening experiment did not coincide with changes in the monitored biochemical parameters. These results led to the conclusions that rigor mortis development in broiler muscles was more rapid in red fibers than in white fibers, was slowed by chilling only in red fibers, and could not be accurately predicted from biochemical changes.
Gram-positive bacterial resistance: future treatment options. (2003)

Gram-positive infections are a major burden on patients and healthcare systems globally, and the need to treat these infections correctly in an empirical manner has become paramount. Further complicating this changing etiology is the emergence of resistant strains which are no longer predictably susceptible to standard first-line antimicrobials such as oxacillin or vancomycin. Thus, new agents such as linezolid have been developed to alleviate the 'guesswork' of initial empirical prescribing in infections where Gram-positive pathogens may be present. Future agents also being developed for multiresistant Gram-positive infections include evernimicin antibiotics, daptomycin, oritavancin, glycylcyclines and novel broad-spectrum cephalosporins; however, these are still in the development phase.
Production of Mannitol by Fermentation (2003)

Mannitol, a naturally occurring polyol or sugar alcohol, is widely used in the food, pharmaceutical, medicine, and chemical industries. The production of mannitol by fermentation has become attractive because of the problems associated with its production chemically. A number of heterofermentative lactic acid bacteria, yeasts, and filamentous fungi are known to produce mannitol. In this article, research dealing with mannitol production by fermentation using lactic acid bacteria, yeast, and fungi is presented. Several heterofermentative lactic acid bacteria are excellent producers of mannitol using fructose as an electron acceptor. Recent progress in the production of mannitol by fermentation and using enzyme technology as well as downstream processing of mannitol are described. The problems and prospects for mannitol production by fermentation and enzymatic means and future directions of research are highlighted.
The costimulatory role of TIM molecules (2009)

The T-cell immunoglobulin domain and mucin domain (TIM) family, including TIM-1, TIM-2, TIM-3, and TIM-4, is a relatively newly described group of molecules with a conserved structure and important immunological functions, including T-cell activation, induction of T-cell apoptosis and T-cell tolerance, and the clearance of apoptotic cells. TIM-1 costimulates T-cell activation and enhances cytokine production. In humans, TIM-1 also serves as a susceptibility gene for allergy and asthma. TIM-3, expressed on T cells and dendritic cells, regulates T-cell apoptosis and immune tolerance. By contrast, TIM-4, which is expressed primarily on antigen-presenting cells and which is a receptor for phosphatidylserine, regulates T-cell activation and tolerance, in part by mediating the uptake and engulfment of apoptotic cells. The TIM molecules thus have surprisingly broad activities affecting multiple aspects of immunology.
DEMOIR: a hybrid architecture for expertise modeling and recommender systems (2002)

Although employees' expertise has long been regarded as an important asset in organizations at least on a par with capital, goods and documented information, it is only recently that automated systems to enhance the visibility and traceability of employees with particular expertise started to receive research attention. In this paper, we introduce a systematic classification of alternative architectures for a core functionality of expert finding systems, namely expertise modeling. We also analyze the advantages and disadvantages of each approach and present our hybrid solution. We discuss how this solution addresses the requirements of (I) distributed and heterogeneous organizational and personal expertise data sources and, (2) centralized access to extracted expertise information.
Oscillation annealing and driver/tire load torque estimation in Electric Power Steering Systems (2011)

International audience
An authentication model for multilevel security domains (2004)

A large network is composed of many autonomous security domains. Based on the definition of security domain, a lattice model of security domains is described. Subsequently, a model of multilevel security domains combined with the multilevel security is derived. Another important concept tied up with multilevel security domains is authentication. According to the trust relationships between different security domains, an authentication architecture and two authentication protocols suitable for multilevel security domains are proposed in this paper. At last, the authentication protocol is formally analyzed with the aid of the BAN logic.
Epigenetic Cross-Talk between DNA Methylation and Histone Modifications in Human Cancers (2009)

DNA methylation, histone modifications, and the chromatin structure are profoundly altered in human cancers. The silencing of cancer-related genes by these epigenetic regulators is recognized as a key mechanism in tumor formation. Recent findings revealed that DNA methylation and histone modifications appear to be linked to each other. However, it is not clearly understood how the formation of histone modifications may affect DNA methylation and which genes are relevantly involved with tumor formation. The presence of histone modifications does not always link to DNA methylation in human cancers, which suggests that another factor is required to connect these two epigenetic mechanisms. In this review, examples of studies that demonstrated the relationship between histone modifications and DNA methylation in human cancers are presented and the potential implications of these epigenetic mechanisms in human neoplasia are discussed.
Why executives fail abroad (1972)

Abstract Three areas of problem‐origin cause an executive to fail abroad –these are discussed as well as the ramifications of such a failure on the executive, his company, and his country.
<i>Archaeoglobus fulgidus</i> couples CO oxidation to sulfate reduction and acetogenesis with transient formate accumulation (2007)

The genome sequence of Archaeoglobus fulgidus VC16 encodes three CO dehydrogenase genes. Here we explore the capacity of A. fulgidus to use CO as growth substrate. Archaeoglobus fulgidus VC16 was successfully adapted to growth medium that contained sulfate and CO. In the presence of CO and sulfate the culture OD(660) increased to 0.41 and sulfide, carbon dioxide, acetate and formate were formed. Accumulation of formate was transient. Similar results, except that no sulfide was formed, were obtained when sulfate was omitted. Hydrogen was never detected. Under the conditions tested, the observed concentrations of acetate (18 mM) and formate (8.2 mM) were highest in cultures without sulfate. Proton NMR spectroscopy indicated that CO2, and not CO, is the precursor of formate and the methyl group of acetate. Methylviologen-dependent formate dehydrogenase activity (1.4 micromol formate oxidized min(-1) mg(-1)) was detected in cell-free extracts and expected to have a role in formate reuptake. It is speculated that formate formation proceeds through hydrolysis of formyl-methanofuran or formyl-tetrahydromethanopterin. This study demonstrates that A. fulgidus can grow chemolithoautotrophically with CO as acetogen, and is not strictly dependent on the presence of sulfate, thiosulfate or other sulfur compounds as electron acceptor.
Women in mind (2004)

Dear Editor I was more than a little surprised to see the news item under ‘Women in Mind’ section of your journal (MHP 7, 4, 5) quoting Ray Rowden.
Carbohydrate ingestion can completely suppress endogenous glucose production during exercise (1999)

The purposes of this study were 1) to investigate the effect of carbohydrate (CHO) ingestion on endogenous glucose production (EGP) during prolonged exercise, 2) to study whether glucose appearance in the circulation could be a limiting factor for exogenous CHO oxidation, and 3) to investigate whether large CHO feedings can reduce muscle glycogen oxidation during exercise. Six well-trained subjects exercised three times for 120 min at 50% maximum workload while ingesting water (FAST), a 4% glucose solution (LO-Glc), or a 22% glucose solution (HI-Glc). A primed continuous intravenous [6, 6-2H2]glucose infusion was given, and the ingested glucose was enriched with [U-13C]glucose. Glucose ingestion significantly elevated CHO oxidation as well as the rates of appearance (Ra) and disappearance. Ra glucose equaled Ra of glucose in gut (Ra gut) during HI-Glc, whereas EGP was completely suppressed. During LO-Glc, EGP was partially suppressed, whereas Ra gut provided most of the total glucose Ra. We conclude that 1) high rates of CHO ingestion can completely block EGP, 2) Ra gut may be a limiting factor for exogenous CHO oxidation, and 3) muscle glycogen oxidation was not reduced by large glucose feedings.
Intestinal Digestion and Absorption of Cholesterol and Lecithin in the Human (1969)

Cholesterol and lecithin absorption in man was studied by intestinal intubation. β-3H-sitosterol lipid-soluble marker. Cholesterol absorption was limited and progressed over the length of the small intestine; most extensive in the upper part. Lecithin was hydrolyzed to L-α-lysolecithin and free fatty acids, which were absorbed in parallel in the upper small intestine. 3.5–6.5 g lecithin and 0.2–0.4 g cholesterol were delivered via the bile during passage of a test meal. Phospholipids partitioned in a glyceride bile salt mixture in favour of the bile salt micellar phase.
Toxin–antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci (2006)

Vancomycin-resistant enterococci (VRE) are common hospital pathogens that are resistant to most major classes of antibiotics. The incidence of VRE is increasing rapidly, to the point where over one-quarter of enterococcal infections in intensive care units are now resistant to vancomycin. The exact mechanism by which VRE maintains its plasmid-encoded resistance genes is ill-defined, and novel targets for the treatment of VRE are lacking. In an effort to identify novel protein targets for the treatment of VRE infections, we probed the plasmids obtained from 75 VRE isolates for the presence of toxin-antitoxin (TA) gene systems. Remarkably, genes for one particular TA pair, the mazEF system (originally identified on the Escherichia coli chromosome), were present on plasmids from 75/75 (100%) of the isolates. Furthermore, mazEF was on the same plasmid as vanA in the vast majority of cases (>90%). Plasmid stability tests and RT-PCR raise the possibility that this plasmid-encoded mazEF is indeed functional in enterococci. Given this ubiquity of mazEF in VRE and the deleterious activity of the MazF toxin, disruption of mazEF with pharmacological agents is an attractive strategy for tailored antimicrobial therapy.
An improved StatCom model for power flow analysis (2002)

The StatCom is traditionally modeled for power flow analysis as a PV or PQ bus depending on its primary application. The active power is either set to zero (neglecting the StatCom losses) or calculated iteratively. The StatCom voltage and reactive power compensation are usually related through the magnetics of the StatCom. This traditional power flow model of the StatCom neglects the impact of the high-frequency effects and the switching characteristics of the power electronics on the active power losses and the reactive power injection (absorption). In this paper, the authors propose a new StatCom model appropriate for power flow analysis derived directly from the dynamic model of the StatCom. The proposed model can therefore account for the high-frequency effects and power electronic losses, and more accurately predict the active and reactive power outputs of the StatCom.
Estrogen suppresses stromal cell-dependent lymphopoiesis in culture (1995)

Numbers of pre-B cells change dramatically and reciprocally in response to estrogen levels in mice, suggesting that normal lymphopoiesis may be under hormonal control. However, little is known of the mechanisms involved in this process. We found that estrogen receptor mRNA was detectable by RT-PCR in lymphocyte supporting stromal cells as well as B lymphocyte precursors. Unlike glucocorticoids, estrogen did not induce apoptosis in isolated B lineage lymphocytes or interfere with their responsiveness to IL-7 in semisolid agar. Estrogen did inhibit clonal expansion of B cell precursors in a limiting dilution-type assay when the lymphocytes were cultured on a stromal cell clone. In other experiments, B cell precursors at particular stages of differentiation were isolated by cell sorting and cocultured with stromal cells for 4 days. This revealed that some subsets were more sensitive to an estrogen-containing environment than others. Although numbers of recovered cells were greatly reduced, the remaining lymphocytes had undergone relatively normal differentiation. The surviving population was enriched in cells that had acquired cytoplasmic mu chains, BP-1 Ag, and clonability with IL-7. Hormone-mediated inhibition occurred in serum and phenol-red free medium, and in cultures replete with IL-7. Direct contact between stromal cells and lymphocytes was not required. Furthermore, suppression resulted when stromal cells alone were treated with the hormone. These findings indicate that estrogen may regulate B lymphopoiesis via its influence on the microenvironment and that estrogen-induced stromal cell genes merit further study.
Plasticity of TRPC expression in arterial smooth muscle: correlation with store-operated Ca<sup>2+</sup> entry (2004)

Loss of the smooth muscle contractile phenotype is critical in atherosclerosis and in restenosis after angioplasty, but its early signals are incompletely understood. In this study, we have explored the role of transient receptor potential canonical (TRPC) proteins, which have been suggested to mediate store-operated Ca2+ entry (SOCE). Contractility of rat cerebral arteries in organ culture is preserved for several days, whereas SOCE is increased. In correlation with this increase is that nifedipine-insensitive whole cell current, activated by depletion of intracellular Ca2+ stores, was increased by 50% in cells isolated from arteries cultured for 3 days. TRPC1 and TRPC6 mRNA were more than fivefold increased in cells isolated after organ culture, whereas TRPC3 was decreased. Immunofluorescent staining and/or Western blotting of arteries and isolated cells showed upregulation of TRPC1 and TRPC6 proteins during organ culture. In intact arteries, TRPC4 expression correlated with the amount of endothelium present. Ca2+ addition after store depletion caused a contraction in cultured, but not in freshly dissected, arteries. A polyclonal TRPC1 antibody directed against an extracellular epitope inhibited this contraction by approximately 50%. To investigate the basis of the TRPC upregulation and assess its possible clinical significance, segments of human internal mammary artery were organ cultured for 24 h and then exposed to balloon dilatation in vitro, followed by further culturing for up to 48 h. After dilatation, TRPC1 and TRPC6 mRNA were progressively increased compared with undilated control segments. The results of this study indicate that vascular injury enhances plasticity in TRPC expression, that TRPC expression correlates with cellular Ca2+ handling, and that TRPC1 is a subunit of upregulated store-operated Ca2+ channels.
A new process for electrocoagulation (2000)

For water providers needing to make the most of scarce resources, a new electrocoagulation system treats contaminated supplies effectively and economically. An innovative electrocoagulation process has been shown to be effective in treating raw water sources for the production of potable water. The process is a boon to water reuse because it has the capability to remove heavy metals from contaminated water streams and to treat leachates from mining and landfill sites. Study results showed bacteria (i.e., E. coli ) were typically reduced by a factor of log 4.17 to concentrations below the detection limit. Molybdenum was reduced from 9.95 to 0.006 mg/L in leachate at a mining site, and iron was reduced from 130 to 0.015 mg/L in leachate from a landfill site. In the new process, coaxial electrodes permit continuous flow at rates up to 225,000 L/min (5.944 × 10 4 gpm) and above. The technology has no moving parts and operates at a fraction of the cost of other water treatment systems. Because the flocculent produced is chemically inert and does not leach back contaminants, it is readily disposable. In addition to describing the electrocoagulation process, the author discusses the critical role water electrolysis intermediate radicals play in removing bacteria.