gebhart/patrepeval huggingface dataset:
Simulation of Ion Motion at Atmospheric Pressure: Particle Tracing Versus Electrokinetic Flow (2011)

Results obtained with two computational approaches for the simulation of ion motion at elevated pressure are compared with experimentally derived ion current data. The computational approaches used are charged particle tracings with the software package SIMION ver. 8 and finite element based calculations using the software package Comsol Multiphysics ver. 4.0/4.0a. The experimental setup consisted of a tubular corona discharge ion source coupled to a cylindrical measurement chamber held at atmospheric pressure. Generated ions are flown into the chamber at essentially subsonic laminar isothermal conditions. In the simulations, strictly stationary conditions were assumed. The results show very good agreement between the SIMION/SDS model and experimental data. For the Comsol model, only qualitative agreement is observed.
Nitric Oxide-Mediated Regulation of Gamma Interferon-Induced Bacteriostasis: Inhibition and Degradation of Human Indoleamine 2,3-Dioxygenase (2004)

Tryptophan depletion resulting from indoleamine 2,3-dioxygenase (IDO) activity within the kynurenine pathway is one of the most prominent gamma interferon (IFN-gamma)-inducible antimicrobial effector mechanisms in human cells. On the other hand, nitric oxide (NO) produced by the inducible isoform of NO synthase (iNOS) serves a more immunoregulatory role in human cells and thereby interacts with tryptophan depletion in a number of ways. We investigated the effects of NO on IDO gene transcription, protein synthesis, and enzyme activity as well as on IDO-mediated bacteriostasis in the human epithelial cell line RT4. IFN-gamma-stimulated RT4 cells were able to inhibit the growth of Staphylococcus aureus in an IDO-mediated fashion, and this bacteriostatic effect was abolished by endogenously produced NO. These findings were supported by experiments which showed that IDO activity in extracts of IFN-gamma-stimulated cells is inhibited by the chemical NO donors diethylenetriamine diazeniumdiolate, S-nitroso-L-cysteine, and S-nitroso-N-acetyl-D,L-penicillamine. Furthermore, we found that both endogenous and exogenous NO strongly reduced the level of IDO protein content in RT4 cells. This effect was not due to a decrease in IDO gene transcription or mRNA stability. By using inhibitors of proteasomal proteolytic activity, we showed that NO production led to an accelerated degradation of IDO protein in the proteasome. This is the first report, to our knowledge, that demonstrates that the IDO is degraded by the proteasome and that NO has an effect on IDO protein stability.
Innate Lung Defenses and CompromisedPseudomonas aeruginosaClearance in the Malnourished Mouse Model of Respiratory Infections in Cystic Fibrosis (2000)

Cystic fibrosis (CF) is characterized by dysfunction of the digestive and respiratory tracts resulting in generalized malnutrition and chronic respiratory infections. Chronic lung infections with Pseudomonas aeruginosa, intense neutrophil-dominated airway inflammation, and progressive lung disease are the major cause of high morbidity and mortality in CF. Here we investigated the effects of malnutrition in CF on innate lung defenses, susceptibility to P. aeruginosa colonization, and associated inflammation, using aerosol models of acute and chronic infections in normal, malnourished, and transgenic mice. CFTR(m1Unc-/-) knockout mice displayed body weight variations and showed variable pulmonary clearance of P. aeruginosa. This variability was not detected in bitransgenic CFTR(m1Unc-/-)(FABP-hCFTR) mice in which the intestinal defect had been corrected. Diet-induced protein calorie malnutrition in C57BL/6J mice resulted in impaired pulmonary clearance of P. aeruginosa. Tumor necrosis factor alpha (TNF-alpha) and nitrite levels detected upon exposure to P. aeruginosa aerosols were lower in the lungs of the malnourished C57BL/6J mice relative than in lungs of mice fed a normal diet. The role of TNF-alpha and reactive nitrogen intermediates in P. aeruginosa clearance was tested in TNF-alpha and inducible nitric oxide synthase (iNOS) knockout mice. P. aeruginosa clearance was diminished in transgenic TNF-alpha- and iNOS-deficient mice. In contrast to the effects of TNF-alpha and iNOS, gamma interferon knockout mice retained a full capacity to eliminate P. aeruginosa from the lung. Malnutrition also contributed to excessive inflammation in C57BL/6J mice upon chronic challenge with P. aeruginosa. The repeatedly infected malnourished host did not produce interleukin-10, a major anti-inflammatory cytokine absent or diminished in the bronchoalveolar fluids of CF patients. These results are consistent with a model in which defective CFTR in the intestinal tract leads to nutritional deficiency which in turn contributes to compromised innate lung defenses, bacterial colonization, and excessive inflammation in the CF respiratory tract.
Confined placental mosaicism. (1996)

In most pregnancies the chromosomal complement detected in the fetus is also present in the placenta. The detection of an identical chromosomal complement in both the fetus and its placenta has always been expected as both develop from the same zygote. However, in approximately 2% of viable pregnancies studied by chorionic villus sampling (CVS) at 9 to 11 weeks of gestation, the cytogenetic abnormality, most often trisomy, is confined to the placenta. This phenomenon is known as confined placental mosaicism (CPM). It was first described by Kalousek and Dill in term placentas of infants born with unexplained intrauterine growth restriction (IUGR). Contrary to generalised mosaicism, which is characterised by the presence of two or more karyotypically different cell lines within both the fetus and its placenta, CPM represents tissue specific chromosomal mosaicism affecting the placenta only. The diagnosis of CPM is most commonly made when, after the diagnosis of chromosomal mosaicism in a CVS sample, the second prenatal testing (amniotic fluid culture or fetal blood culture analysis) shows a normal diploid karyotype.
A structure‐function approach to optimizing TLR4 ligands for human vaccines (2016)

Adjuvants are combined with vaccine antigens to enhance and modify immune responses, and have historically been primarily crude, undefined entities. Introducing toll-like receptor (TLR) ligands has led to a new generation of adjuvants, with TLR4 ligands being the most extensively used in human vaccines. The TLR4 crystal structures demonstrate extensive contact with their ligands and provide clues as to how they discriminate a broad array of molecules and activate or attenuate innate, as well as adaptive, responses resulting from these interactions. Leveraging this discerning ability, we made subtle chemical alterations to the structure of a synthetic monophosphoryl lipid-A molecule to produce SLA, a designer TLR4 ligand that had a number of desirable adjuvant effects. The SLA molecule stimulated human TLR4 and induced Th1 biasing cytokines and chemokines. On human cells, the activity of SLA plateaued at lower concentrations than the lipid A comparator, and induced cytokine profiles distinct from other known TLR4 agonists, indicating the potential for superior adjuvant performance. SLA was formulated in an oil-in-water emulsion, producing an adjuvant that elicited potent Th1-biased adaptive responses. This was verified using a recombinant <i>Leishmania</i> vaccine antigen, first in mice, then in a clinical study in which the antigen-specific Th1-biased responses observed in mice were recapitulated in humans. These results demonstrated that using structure-based approaches one can predictably design and produce modern adjuvant formulations for safe and effective human vaccines.
Nicotine Medications for Smoking Cessation (1995)

Cigarettes are among the most addicting products known, and the vast majority of people who quit smoking relapse within days.1,2 In the United States, less than 10 percent of the nearly 20 million people who quit smoking for a day remain abstinent one year later.3 Thus, only 2 to 3 percent of smokers become nonsmokers each year.3 Medications that contain nicotine enable health care providers to increase markedly the ability of their patients to achieve and sustain tobacco abstinence. This review summarizes the scientific rationale for nicotine medications, to help clinicians optimize their use.Pathophysiology of Nicotine AddictionClinical . . .
An improved valve-less pump fabricated using deep reactive ion etching (2002)

We present the first valve-less diffuser pump fabricated using the latest technology in deep reactive ion etching (DRIE). The pump is fabricated in a simple micromachining process in a double side polished silicon wafer anodically bonded to a glass wafer. Pump chambers and diffuser elements are etched in the silicon wafer using DRIE while inlet and outlet holes are etched using an anisotropic KOH-etch. The DRIE etch resulted in rectangular diffuser cross-sections. We present results on pumps with different diffuser dimensions in terms of diffuser neck width, length and angle. We reached a maximum pump pressure of 7.6 m H/sub 2/O (74 kPa) and maximum pump flow of 2.3 ml/min for water.
Determinants of bone mass in postmenopausal women (1983)

• Eighty white women, mean age 52 years, within one to six years postmenopausal, were studied to examine the relationship of various factors to bone mass. Forty-four of the women had annual measurements of bone mass, so that the rate of bone loss could be determined. Bone mass was measured by total body neutron activation analysis and photon absorptiometry of the distal radius (total body calcium [TBCa] and bone mineral content [BMC], respectively). Breast-feeding and pregnancy were noted to be associated with higher bone mass; those with lower BMC and/or TBCa tended to have higher serum alkaline phosphatase levels, lower testosterone levels, and more years since the cessation of menses. The rate of bone loss from the radius was greater in those with higher parathyroid hormone levels; those with reduced dietary intake of calcium and lower 25-hydroxyvitamin D levels had a greater rate of loss of TBCa. (<i>Arch Intern Med</i>1983;143:1700-1704)
Ca2+ channel modulating effects of heparin in mammalian cardiac myocytes. (1993)

1. The effect of heparin on L-type Ca2+ channels in rabbit, rat and guinea-pig cardiac myocytes was studied using the whole-cell patch clamp method. 2. Sodium salts of heparin uniformly suppressed the Ca2+ current, ICa, independent of their molecular weight, in the rat and guinea-pig ventricular and rabbit atrial myocytes. The suppression of ICa by heparin was dose dependent and reached its maximum, about 30%, around 10 microM. Heparin did not alter the voltage-dependence or the steady-state inactivation properties of ICa. These effects were specific to heparin as another polysaccharide, dextran, failed to have any effect on ICa. 3. The suppressive effect of heparin was not diminished when [Ca2+]o was increased to 10 mM, or when Ba2+ was the charge carrier through the Ca2+ channel. 4. Spectrophotometric assays showed that heparin-induced changes in [Ca2+]o generally were too small to alter ICa significantly. 5. In myocytes buffered with 0.1 mM EGTA, the suppressive effect of heparin was more prominent on the inactivating than on the maintained component of ICa. 6. When extracellular Na+ was replaced by Cs+, the heparin suppressive effect was accompanied by a 10 mV shift of both the voltage dependence of activation and the steady-state inactivation parameters toward more negative potentials. 7. When both Mg2+ and Na+ were omitted from the bathing solutions, the suppressive effect of heparin was significantly enhanced such that almost 80% of the current was blocked. 8. In Cs(+)-based solutions 10 mM [Mg2+]o suppressed ICa by about 70% and heparin partially relieved this block. Heparin, however, did not counteract the Mg(2+)-induced suppression of ICa in Na(+)-based solution. 9. Extracellularly applied heparin did not alter the isoprenaline-induced enhancement of ICa or interfere with the blocking effect of phorbol esters on ICa. 10. Heparin thus appears to interfere with the permeation of Ca2+ through the channel by a mechanism regulating the Ca(2+)-induced inactivation of the Ca2+ channel. Na+ and Mg2+ appear to alter the kinetics and the magnitude of the suppressive effect of heparin on the Ca2+ channel, suggesting an interaction of these cations with either the Ca2+ or the heparin-binding sites of the channel.
Follicular carcinoma of the thyroid (1991)

Follicular carcinoma deserves a careful preoperative evaluation and multidisciplinary therapy planning. Needle aspiration may be of less value than for other thyroid lesions. If the surgeon is suspicious of a carcinoma, a total lobectomy of the involved side and frozen section may be indicated. Lobectomy with or without isthmusectomy seems to be the minimal treatment for tumors confined to the lobe without nodal metastases. Total thyroidectomy is reserved for patients at high risk by nature of age, large lesions, angioinvasion, capsular invasion, or known metastatic disease where subsequent I-131 therapy is considered likely. I-131 scanning for metastatic disease is indicated in these high-risk patients. I-131 therapy is very valuable for treatment of metastatic disease; and in patients presenting with metastatic disease, total thyroidectomy may be indicated to maximize the therapeutic benefit of the I-131. Judicious planning and care of these patients can result in a 50 to 70% total cure and as high as 85% long-term survival.
Outcome of the First Electron Microscopy Validation Task Force Meeting (2012)

This Meeting Review describes the proceedings and conclusions from the inaugural meeting of the Electron Microscopy Validation Task Force organized by the Unified Data Resource for 3DEM (http://www.emdatabank.org) and held at Rutgers University in New Brunswick, NJ on September 28 and 29, 2010. At the workshop, a group of scientists involved in collecting electron microscopy data, using the data to determine three-dimensional electron microscopy (3DEM) density maps, and building molecular models into the maps explored how to assess maps, models, and other data that are deposited into the Electron Microscopy Data Bank and Protein Data Bank public data archives. The specific recommendations resulting from the workshop aim to increase the impact of 3DEM in biology and medicine.
Efficient dual transcomplementation of adenovirus E1 and E4 regions from a 293-derived cell line expressing a minimal E4 functional unit (1996)

Transgene expression after the administration of recombinant adenovirus with E1 deleted is constantly transient. It is admitted that E1A-substituting activities of cellular or viral origin allow viral antigen synthesis and trigger cytotoxic lymphocyte-mediated clearance of the recipient cells. Our approach to solving this problem relies on the additional deletion of the E4 region from the vector backbone as this region upregulates viral gene expression at both transcriptional and posttranscriptional levels. As a prerequisite to the construction of E1 E4 doubly defective adenoviruses, we investigated the possibility of transcomplementing both functions within a single cell. In particular, the distal ORF6+ORF7 segment from the E4 locus of adenovirus type 5 was cloned under the control of the dexamethasone-inducible mouse mammary tumor virus long terminal repeat. Following transfection into 293 cells, clone IGRP2 was retained and characterized as it can rescue the growth defect of all E1+ E4- adenoviral deletants tested. DNA and RNA analysis experiments verified that the mouse mammary tumor virus promoter drives the expression of the ORF6+ORF7 unit and permits its bona fide alternative splicing, generating ORF6/7 mRNA in addition to the ORF6-expressing primary transcript. Importantly, IGRP2 cells sustain cell confluence for a period longer than that of 293 parental cells and allow the plaque purification of E1- or E4- defective viruses. The dual expression of E1 and E4 regulatory genes within IGRP2 cells is demonstrated by the construction, plaque purification, and helper-free propagation of recombinant lacZ-encoding doubly defective adenoviruses harboring different E4 deletions. In addition, the emergence, if any, of replicative particles during viral propagation in this novel packaging cell line will be drastically impaired as only a limited segment of E4 has been integrated.
In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides (2003)

Locked nucleic acids (LNA) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. The LNA oligonucleotides (LNA PO ODNs) are very stable in vitro and in vivo without the need for a phosphorothiolated backbone. In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides directed against the gene of the large subunit of RNA polymerase II (POLR2A) that are completely synthesized as LNA containing diester backbones. These full LNA oligonucleotides strongly reduce POLR2A protein levels. Full LNA PO ODNs appeared to be very stable compounds when injected into the circulation of mice. Full LNA PO ODNs were continuously administered for 14 days to tumor-bearing nude mice. Tumor growth was inhibited sequence specifically at dosages from 1 mg/kg/day. LNA PO ODNs appeared to be non-toxic at dosages <5 mg/kg/day. Biodistribution studies showed the kidneys to have the highest uptake of LNA PO ODNs and urinary secretion as the major route of clearance. This report shows that LNA PO ODNs are potent genotype-specific drugs that can inhibit tumor growth in vivo.
A common structural motif incorporating a cystine knot and a triple‐stranded β‐sheet in toxic and inhibitory polypeptides (1994)

A common structural motif consisting of a cystine knot and a small triple-stranded beta-sheet has been defined from comparison of the 3-dimensional structures of the polypeptides omega-conotoxin GVIA (Conus geographus), kalata BI (Oldenlandia affinis DC), and CMTI-I (Curcurbita maxima). These 3 polypeptides have diverse biological activities and negligible amino acid sequence identity, but each contains 3 disulfide bonds that give rise to a cystine knot. This knot consists of a ring formed by the first 2 bonds (1-4 and 2-5) and the intervening polypeptide backbone, through which the third disulfide (3-6) passes. The other component of this motif is a triple-stranded, anti-parallel beta-sheet containing a minimum of 10 residues, XXC2, XC5X, XXC6X (where the numbers on the half-cysteine residues refer to their positions in the disulfide pattern). The presence in these polypeptides of both the cysteine knot and antiparallel beta-sheet suggests that both structural features are required for the stability of the motif. This structural motif is also present in other protease inhibitors and a spider toxin. It appears to be one of the smallest stable globular domains found in proteins and is commonly used in toxins and inhibitors that act by blocking the function of larger protein receptors such as ion channels or proteases.
Hohlraum-Driven Mid-Z(SiO2) Double-Shell Implosions on the Omega Laser Facility and Their Scaling to NIF (2009)

High-convergence, hohlraum-driven implosions of double-shell capsules using mid-Z (SiO2) inner shells have been performed on the OMEGA laser facility [T. R. Boehly, Opt. Commun. 133, 495 (1997)]. These experiments provide an essential extension of the results of previous low-Z (CH) double-shell implosions [P. A. Amendt, Phys. Rev. Lett. 94, 065004 (2005)] to materials of higher density and atomic number. Analytic modeling, supported by highly resolved 2D numerical simulations, is used to account for the yield degradation due to interfacial atomic mixing. This extended experimental database from OMEGA enables a validation of the mix model, and provides a means for quantitatively assessing the prospects for high-Z double-shell implosions on the National Ignition Facility [Paisner, Laser Focus World 30, 75 (1994)].
Immunization of ovarian cancer patients with a synthetic Lewisy‐protein conjugate vaccine: A phase 1 trial (2000)

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis y pentasaccharide (Le y )-keyhole limpet hemocyanin (KLH)conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 g of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le y (Le y -ceramide and Le y mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le y -expressing tumor cells. The majority of the patients (16/24) produced anti-Le y antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le y -KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers. Int.
Optimization of drying the semi-dried lamb meat product (jerky) (2019)

Convection drying was used to investigate the drying process of semi-dried lamb. The drying conditions were carried in combination of adding sorbitol and glycerin and salt. The results showed that the most appropriate drying conditions were at temperature of 56oC, drying time of 210 min and wind speed of 0.24 m/s. The addition of sorbitol, glycerin, common salt in product was 4.37%, 1.93%, and 3.4%, respectively which were suitable for maintaining the aw of the product at 0.67 g.
Advances in dataflow programming languages (2004)

Many developments have taken place within dataflow programming languages in the past decade. In particular, there has been a great deal of activity and advancement in the field of dataflow visual programming languages. The motivation for this article is to review the content of these recent developments and how they came about. It is supported by an initial review of dataflow programming in the 1970s and 1980s that led to current topics of research. It then discusses how dataflow programming evolved toward a hybrid von Neumann dataflow formulation, and adopted a more coarse-grained approach. Recent trends toward dataflow visual programming languages are then discussed with reference to key graphical dataflow languages and their development environments. Finally, the article details four key open topics in dataflow programming languages.
Attachment and growth of cultured fibroblast cells on PVA/chitosan-blended hydrogels (1998)

Hydrogels were prepared from poly(vinyl alcohol) and chitosan in various blend ratios. The water contents of the hydrogels were in the range of 65 to 75 wt %. The attachment and growth of fibroblast cells (L-929) on the hydrogels were studied with a cell culture method. On the hydrogels with more than 15 wt % chitosan content, the attached cells were able not only to remain viable but also to proliferate. The relative cell attachment after incubation for 30 h increased with increasing chitosan content in the hydrogels. Cell attachment and growth on the hydrogel with 40 wt % chitosan content exceeded those on collagen, a widely-used mammalian cell culture substrate. The morphology of the cells attached onto the hydrogels with a lower chitosan content was spherical, but in hydrogels with more than 15 wt % chitosan content, the number of spindle-shaped cells increased with increasing chitosan content.