gebhart/patrepeval huggingface dataset:
Characterization of Polycrystalline Silicon MOS Transistors and Its Film Properties. I (1982)

The characterization of polycrystalline silicon MOS transistors and its film properties are studied, with special emphasis on the relationship between crystalline defects and carrier transport phenomena. An increase in mobility with gate field in polycrystalline silicon MOS transistors and also with doping concentration in polycrystalline silicon films is observed. These phenomena are interpreted as space charge scattering effects caused by a high density of dislocations in the films. U-shaped drain current vs gate voltage curves are observed both in p-channel and n-channel polycrystalline silicon MOS transistors. The anomalous drain current in the accumulation region is interpreted as junction breakdown at the drain edge caused by crystalline imperfections in the films.
Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. (1992)

Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.
Better approaches to finding the needle in a haystack: Optimizing proteome analysis through automation (2000)

Recent evidence has demonstrated a lack of correlation between transcriptional profiles and actual protein levels in cells. Proteome analysis has therefore become indispensable and complementary to genomic analysis for an accurate picture of cellular metabolism. Although proteomics is a relatively young discipline, technology for increasing throughput in proteomic projects is rapidly being developed. The operating paradigm in proteome analysis today is a combination of two-dimensional (2-D) gel electrophoresis (for protein resolution) with mass spectrometry (for protein identification). All the intermediary steps in the procedure including gel staining, image analysis, protein spot excision, digestion and mass spectrometry can be automated to increase efficiency and save time. This report reviews the current state of the proteomics technology and discusses approaches to enhance the sensitivity of 2-D gels with fractionation techniques.
Carbohydrate-deficient glycoprotein syndrome (CDGS)--glycosylation, folding and intracellular transport of newly synthesized glycoproteins. (1995)

Carbohydrate-deficient glycoprotein syndrome (CDGS) is a hereditary glycosylation disorder of unknown origin. In this study we used skin fibroblasts from patients with CDGS to study the glycosylation of three well characterized glycoproteins using gel mobility analysis, endoglycosidase treatments and protein folding studies. We show that glycoprotein transport along the secretory pathway was delayed. Dilation of the rough endoplasmic reticulum indicated a retention phenomenon for selected glycoproteins. However, for all examined glycoproteins cotranslational glycosylation in CDGS fibroblasts was normal.
Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study. (1991)

Sixteen patients with primary breast cancer were studied with a pancarcinoma monoclonal antibody B72.3, an IgG1 molecule directed against tumor-associated glycoprotein (TAG-72) present in several tumors. Five millicuries of 111In was used to label 0.2 mg (six patients), or 2 mg (six patients), or 20 mg using the site-directed bifunctional DTPA method (at carbohydrate moiety). Digital, planar, and SPECT images were obtained at 2, 48, 72 and 96 hr when possible. HAMA levels were obtained before the Mab infusion and at 1, 3, and 6 wk postinfusion. Fourteen of 14 known primary breast lesions were detected by imaging (100% sensitivity). Two fibrocystic lesions were negative. Seven of 14 patients had lymph node metastases by histologic methods, but all were missed by radioimmunoscintigraphy. Tumor uptake of Mab ranged 0.00054%-0.0038% of the ID/g. The tumor-to-normal breast tissue ratio was 4.3 +/- 0.91 (mean +/- s.e.m.). Lymph nodes localization of 111In-B72.3 by tissue analysis was similar for tumor-bearing and normal nodes (0.0039 +/- 0.0023 versus 0.0025 +/- 0.0019). Pharmacokinetics revealed mean plasma half-life of 33.3-41.2 hr for the different doses. There was no statistical difference between any of the pharmacokinetic parameters of different doses. HAMA was positive only in 17% of the patients. The study suggests that this antibody has 100% sensitivity for primary breast cancers, but very poor detection rate of metastatic lesions in axillary lymph nodes; thus making it of questionable value in the initial staging process of this disease.
Improvements in Behaviour and Self-Esteem following Growth Hormone Treatment in Short Prepubertal Children (2011)

On GH treatment, prepubertal short children significantly improved on behavioural, depression, and psychosocial evaluations over a 2-year period of GH treatment. Most change occurred within the first 3 months, which highlights this short period as important not only for growth and metabolic changes but also for behaviour and psychosocial improvements following GH treatment.
Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS, the First Selective Small Molecule Calcitonin Gene-Related Peptide Receptor Antagonist, Following Single Intravenous Administration in Healthy Volunteers (2004)

BIBN 4096 BS ([R-(R*,S*)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.
Systemic inflammation and remote organ injury following trauma require HMGB1 (2007)

High-mobility group box 1 (HMGB1) is a 30-kDa DNA-binding protein that displays proinflammatory cytokine-like properties. HMGB1-dependent inflammatory processes have been demonstrated in models of sterile injury, including ischemia-reperfusion injury and hemorrhagic shock. Here, we tested the hypothesis that the systemic inflammatory response and associated remote organ injury that occur after peripheral tissue injury are highly dependent on HMGB1. Toll-like receptor 4 (TLR4) wild-type (WT) mice subjected to bilateral femur fracture after treatment with neutralizing antibodies to HMGB1 had lower serum IL-6 and IL-10 levels compared with mice treated with nonimmune control IgG. Similarly, compared with injured mice treated with control IgG, anti-HMGB1 antibody-treated mice had lower serum alanine aminotransferase levels and decreased hepatic and gut mucosal NF-kappaB DNA binding. TLR4 mutant (C3H/HeJ) mice subjected to bilateral femur fracture had less systemic inflammation and liver injury than WT controls. Residual trauma-induced systemic inflammation and hepatocellular injury were not ameliorated by treatment with a polyclonal anti-HMGB1 antibody, even though HMGB1 levels were transiently elevated just 1 h after injury in both WT and C3H/HeJ mice. Collectively, these data demonstrate a critical role for a TLR4-HMGB1 pathway in the initiation of systemic inflammation and end-organ injury following isolated peripheral tissue injury.
Mimotope and Anti–Idiotypic Vaccines to Induce an Anti–IgE Response (1999)

We have defined epitopes on human IgE by screening different phage display random peptide libraries with a monoclonal anti-IgE antibody termed BSW17. The selected mimotopes and epitopes within the Cepsilon3 and Cepsilon4 region of IgE induced antibodies that were nonanaphylactogenic and had biological activity similar to BSW17. The chemically synthesized and KLH-coupled IgE epitopes or mimotopes were used to induce an anti-IgE response in rhesus monkeys. The immunized rhesus monkeys were subsequently protected in a PCA test when sensitized with human IgE and triggered with the corresponding allergen. Furthermore, using the same monoclonal anti-IgE antibody, we also generated an anti-idiotypic antibody that showed sequence homology with the IgE epitope in the Cepsilon3 domain. This anti-idiotypic antibody as well as the mimotopes were then used in a mouse model to induce orally an anti-IgE immune response. For this purpose mice were fed by intragastric gavages with bacteriophages displaying the small IgE-homologous structures. Orally immunized mice produced serum anti-IgE antibodies that were inhibited by BSW17 suggesting that it may be possible to induce a systemic anti-IgE response orally.
Exploiting Natural Diversity of AAV for the Design of Vectors with Novel Properties (2011)

Twelve AAV serotypes have been described so far in human and nonhuman primate (NHP) populations while surprisingly high diversity of AAV sequences is detected in tissue biopsies. The analysis of these novel AAV sequences has indicated a rapid evolution of the viral genome both by accumulation of mutations and recombination. This chapter describes how this rich resource of naturally evolved sequences is used to derive gene transfer vectors with a wide array of activities depending on the nature of the cap gene used in the packaging system. AAV2-based recombinant genomes have been packaged in dozens of different capsid types, resulting in a wide array of "pseudotyped vectors" that constitute a rich resource for the development of gene therapy clinical trials. We describe a polymerase chain reaction-based molecular rescue method for novel AAV isolation that uses primers designed to recognize the highly conserved regions in known AAV isolates and generate amplicons across the hypervariable regions of novel AAV genomes present in the analyzed sample.
Reliability of the National Institutes of Health Stroke Scale (1997)

These data extend the previously demonstrated reliability of the NIHSS to non-neurologists and show that both a variety of physician investigators and nurse study coordinators can be rapidly trained to reliably apply the scale in the context of an actual clinical trial.
Nanogaps by direct lithography for high-resolution imaging and electronic characterization of nanostructures (2006)

We report a method for fabricating nanogaps directly with electron beam lithography (EBL). The primary resolution-limit of EBL, electron back-scattering, is reduced dramatically by using a thin-film as a substrate. We show that this resolution enhancement allows one to fabricate metal electrodes with separation from arbitrarily large to under one nanometer. Furthermore, because these nanogaps are on a thin film, they can be imaged with high-resolution transmission electron microscopy (HRTEM). Using these nanogaps we measured the charge transport through several coupled PbSe nanocrystals and correlated the data with detailed structural information obtained by performing HRTEM on the same device.
Mutations in Hepatitis C Virus RNAs Conferring Cell Culture Adaptation (2001)

As an initial approach to studying the molecular replication mechanisms of hepatitis C virus (HCV), a major causative agent of acute and chronic liver disease, we have recently developed selectable self-replicating RNAs. These replicons lacked the region encoding the structural proteins and instead carried the gene encoding the neomycin phosphotransferase. Although the replication levels of these RNAs within selected cells were high, the number of G418-resistant colonies was reproducibly low. In a search for the reason, we performed a detailed analysis of replicating HCV RNAs and identified several adaptive mutations enhancing the efficiency of colony formation by several orders of magnitude. Adaptive mutations were found in nearly every nonstructural protein but not in the 5' or 3' nontranslated regions. The most drastic effect was found with a single-amino-acid substitution in NS5B, increasing the number of colonies approximately 500-fold. This mutation was conserved with RNAs isolated from one cell line, in contrast to other amino acid substitutions enhancing the efficiency of colony formation to a much lesser extent. Interestingly, some combinations of these nonconserved mutations with the highly adaptive one reduced the efficiency of colony formation drastically, suggesting that some adaptive mutations are not compatible.
The Effects of Ventricular Pacing on Left Ventricular Geometry, Function, Myocardial Oxygen Consumption, and Efficiency of Contraction in Conscious Dogs (1998)

The effects of ventricular pacing on left ventricular (LV) dynamic geometry, function, and myocardial oxygen consumption (MVO2) were measured in 12 conscious dogs using sonomicrometry, micromanometry, ultrasonic flow probes, and oximetry catheters during right atrial (A-) and right ventricular (V-) pacing at 150 beats/min. Systolic function was quantified using slopes (MW) and volume-intercepts (VW) of linear relationships between end-diastolic volume (EDV) and stroke work (SW) for data obtained during vena caval occlusion. V-pacing shifted SW-EDV relationships downward (MW decreased from 97 +/- 21 to 81 +/- 21 Kerg/mL) and to the right (VW increased from 14 +/- 11 to 20 +/- 12 mL) in comparison with A-pacing (P < 0.02). These functional changes correlated with altered contractile geometry manifest as early shortening in the septal free wall relative to anterior-posterior dimension (increased minor axis mid-wall eccentricity at end-diastole and begin-ejection). Steady-state LV power output decreased from 802 +/- 213 mW during A-pacing to 514 +/- 170 mW during V-pacing (P < 0.05), while MVO2 remained relatively unchanged during V-pacing (10 +/- 3 mL O2/min vs 11 +/- 3 mL O2/min during A-pacing, P = NS). As a result, overall LV efficiency decreased from 0.24 +/- 0.08 during A-pacing to 0.16 +/- 0.06 during V-pacing (P < 0.05). These data illustrate the impact of V-pacing on dynamic LV geometry and function, including impaired LV work output at all physiological levels of preload. Most importantly, the relationship between LV work output and MVO2 is depressed during V-pacing, emphasizing the interaction between LV mechanics and pump efficiency in intact subjects. As a result, measures taken to restore normal contractile geometry might improve LV efficiency and performance when V-pacing is necessary.
The stability of resting frontal electroencephalographic asymmetry in depression (2003)

Although resting frontal electroencephalographic (EEG) alpha asymmetry has been shown to be a stable measure over time in nonclinical populations, its reliability and stability in clinically depressed individuals has not been fully investigated. The internal consistency and test-retest stability of resting EEG alpha (8-13 Hz) asymmetry were examined in 30 women diagnosed with major depression at 4-week intervals for 8 or 16 weeks. Asymmetry scores generally displayed good internal consistency and exhibited modest stability over the 8- and 16-week assessment intervals. Changes in asymmetry scores over this interval were not significantly related to changes in clinical state. These findings suggest that resting EEG alpha asymmetry can be reliably assessed in clinically depressed populations. Furthermore, intraclass correlation stability estimates suggest that although some traitlike aspects of alpha asymmetry exist in depressed individuals, there is also evidence of changes in asymmetry across assessment occasions that are not closely linked to changes in depressive severity.
New Method for Fast and Accurate Binding‐site Identification and Analysis (2007)

Structure-based drug design seeks to exploit the structure of protein-ligand or protein-protein binding sites, but the site is not always known at the outset. Even when the site is known, the researcher may wish to identify alternative prospective binding sites that may result in different biological effects or new class of compounds. It is also vital in lead optimization to clearly understand the degree to which known binders or docking hits satisfy or violate complementarity to the receptor. SiteMap is a new technique for identifying potential binding sites and for predicting their druggability in lead-discovery applications and for characterizing binding sites and critically assessing prospective ligands in lead-optimization applications. In large-scale validation tests, SiteMap correctly identifies the known binding site in > 96% of the cases, with best results (> 98%) coming for sites that bind ligands tightly. It also accurately distinguishes between sites that bind ligands and sites that don't. In binding-site analysis, SiteMap provides a wealth of quantitative and graphical information that can help guide efforts to modify ligand structure to enhance potency or improve physical properties. These attributes allow SiteMap to nicely complement techniques such as docking and computational lead optimization in structure-base drug design.
Transition Metal Catalyzed Synthesis of Arylamines and Aryl Ethers from Aryl Halides and Triflates: Scope and Mechanism (1998)

Oxidative addition and reductive elimination are the central steps in new palladium-catalyzed chemistry that forms C-N and C-O bonds in arylamines and ethers. In the potential mechanism shown on the right the amine is formed by reductive elimination from a four-coordinate, 16-electron amido aryl complex. The use of a chelating ligand such as 1,1'-bis(diphenylphosphanyl)ferrocene (DPPF) reduces the occurrence of the competing β-hydrogen elimination. X=Br, I; R, R'=alkyl, aryl.
Selective depletion of marrow-T cytotoxic lymphocytes (CD8) in the prevention of graft-versus-host disease after allogeneic bone-marrow transplantation (1988)

Abstract. In vitro depletion of mature pan-T lymphocytes has been widely and successfully used to prevent acute graft-versus-host disease (GVHD) after allogeneic bone-marrow transplantation (BMT). Hpwever, this procedure has been associated with a high incidence of graft failure and leukemic relapse. In this pilot study, we evaluated the efficiency of a selective depletion of human marrow T cytotoxic lymphocytes (CD8), a subset essential to induce GVHD in mice. Eleven patients with hematologic malignancies were included (7 HLA-matched BMT, 4 HLA-mismatched BMT). Marrow treatment with 7 anti-CD8 mAbs and rabbit complement resulted in a marked reduction of CD8 + lymphocytes from 15% (median value; range 7%-31%) to 1% (median value; range <1%-11%). Acute GVHD was not abolished by this procedure despite postgraft immunosuppression. One patient (HLA-mismatched BMT) rejected his graft and had a full autologous recovery. In conclusion, when compared to the data in the literature, CD8 depletion was shown to be less efficient than pan-T-cell depletion in the prevention of GVHD after allogeneic BMT and was still associated with a major complication associated with this procedure, i.e., graft failure.
Automated Spectrophotometric Analyzer for Rapid Single-Point Titration of Seawater Total Alkalinity (2013)

An automated analyzer was developed to achieve fast, precise, and accurate measurements of seawater total alkalinity (AT) based on single-point titration and spectrophotometric pH detection. The single-point titration was carried out in a circulating loop, which allowed the titrant (hydrochloric acid and bromocresol green solution) and a seawater sample to mix at a constant volume ratio. The dissolved CO2 in the sample-titrant mixture was efficiently removed by an inline CO2 remover, which consists of a gas-permeable tubing (Teflon AF2400) submerged in a sodium hydroxide (NaOH) solution. The pH of the mixture was then measured with a custom-made spectrophotometric detection system. The analyzer was calibrated against multiple certified reference materials (CRMs) with different AT values. The analyzer features a sample throughput time of 6.5 min with high precision (±0.33-0.36 μmol kg(-1); n = 48) and accuracy (-0.33 ± 0.99 μmol kg(-1); n = 10). Intercomparison to a traditional open-cell AT titrator showed overall good agreement of 0.88 ± 2.03 μmol kg(-1) (n = 22). The analyzer achieved excellent stability without recalibration over 11 days, during which time 320 measurements were made with a total running time of over 40 h. Because of its small size, low power consumption requirements, and its ability to be automated, the new analyzer can be adapted for underway and in situ measurements.
Low-Temperature Oxidation of Nitrided Iron Surfaces (2003)

The low-temperature (<150 K) oxidation of nitrided iron surfaces exposed to oxygen and water was probed using X-ray photoelectron spectroscopy (XPS), reflection absorption infrared spectroscopy (RAIRS), and mass spectrometry (MS). During exposure of nitrided iron surfaces to oxygen, iron oxynitride (FexNyOz), nitrosonium ions (NO+), as well as nitrite/nitrito- and nitrate-type species were observed. The production of nitrite/nitrito and nitrate species is taken as evidence for the existence of oxygen insertion chemistry into the iron nitride lattice under these low-temperature oxidation conditions. No molecular nitrogen was produced during reactions with oxygen or water in contrast to oxidation studies on other transition metal nitrides. Upon annealing the oxidized overlayer, nitrogen desorbs exclusively as nitric oxide (NO) between 250 and 400 K. In contrast to oxygen, the reactivity of nitrided iron surfaces toward water was limited to the production of adsorbed N−O species.