gebhart/patrepeval huggingface dataset:
Design and Assurance For Reliability (1988)

It is primarily the design of an item which establishes its potential reliability and maintainability. It is a fact of life that the transition from drawings to hardware always results in achieved levels lower than this original design reliability. It is therefore necessary to design to specified levels of reliability and maintainability higher than the field requirements and to follow up with assurance activities aimed at minimising the failures which arise during manufacture and use. Figure 1.1 illustrates the concept of a reliability level fixed by the 'drawings' and a lower field level due to the many failure possibilities arising from manufacture and subsequent use. This chapter outlines the activities and techniques which can be applied in design, to develop equipment to meet the R and M objectives and to minimise failures in manufacture and use.
Monoclonal antibodies as structural probes of surface residues in the regulatory subunit of cAMP-dependent protein kinase II from porcine heart. (1983)

Two murine monoclonal antibodies (H5 and B6) generated against bovine heart type II regulatory subunit of cAMP-dependent protein kinase were shown to cross-react equally well with the homologous subunit from porcine heart. The antibodies demonstrated specificity for only the type II regulatory subunit and showed negligible cross-reactivity with the type I regulatory subunit, the catalytic subunit, and cGMP-dependent protein kinase. Following limited proteolysis of type II regulatory subunit with chymotrypsin, the H5 monoclonal antibody was shown to cross-react with the Mr = 37,000 cAMP-binding domain corresponding to the COOH-terminal region of the polypeptide chain. To more specifically localize the antigenic sites, the porcine type II regulatory subunit was carboxymethylated and cleaved with cyanogen bromide. Both monoclonal antibodies cross-reacted with the NH2-terminal CNBr peptide, and this peptide demonstrated affinities similar to native bovine type II regulatory subunit in competitive displacement radioimmunoassays. Tryptic cleavage of this CNBr fragment destroyed all antigenicity for both monoclonal antibodies, whereas antigenicity was retained following chymotryptic digestion. A single major immunoreactive chymotryptic fragment that cross-reacted with H5 was isolated by gel filtration and reverse phase high performance liquid chromatography. this peptide retained the complete antigenic site and had the following sequence: Asn-Pro-Asp-Glu-Glu-Glu-Glu-Asp-Thr-Asp-Pro-Arg-Val-Ile-His-Pro-Lys-Thr-Asp-Gl n. This antigenic site was localized just beyond the major site of autophosphorylation, approximately a third of the distance from the NH2-terminal end of the polypeptide chain.
The human immunoglobulin loci introduced into mice: V (D) and J gene segment usage similar to that of adult humans (2000)

Variable gene segments of the human immunoglobulin loci are represented in the human peripheral repertoire at different frequencies. XenoMouse strains contain approximately 2 megabases of the human immunoglobulin heavy and kappa light chain loci that functionally recapitulate the human humoral immune system. Analysis of human antibody transcripts from XenoMouse spleens and lymph nodes revealed that V, D and J gene segment utilization from these unimmunized animals were nearly identical to the gene segment utilization reported for humans with extensive antigenic histories.
Expression and regulation of the antimonite, arsenite, and arsenate resistance operon of Staphylococcus xylosus plasmid pSX267 (1992)

The arsenate, arsenite, and antimonite resistance region of the Staphylococcus xylosus plasmid pSX267 was subcloned in Staphylococcus carnosus. The sequenced DNA region revealed three consecutive open reading frames, named arsR, arsB, and arsC. Expression studies in Escherichia coli with the bacteriophage T7 RNA polymerase-promoter system yielded three polypeptides with apparent molecular weights of 8,000, 35,000, and 15,000, which very likely correspond to ArsR, ArsB, and ArsC, respectively. ArsB was distinguished by its overall hydrophobic character, suggesting a membrane association. The arsenate, arsenite, and antimonite resistance was shown to be inducible by all three heavy metal ions. Inactivation of the first gene, arsR, resulted in constitutive expression of resistance. Similar results were obtained with transcriptional fusions of various portions of the ars genes with a lipase reporter gene, indicating a function of ArsR as a negative regulator of a putative promoter in front of arsR. The inactivation of arsR also resulted in reduction of resistance to arsenite and antimonite, while arsenate resistance was unaffected. The three ars genes conferred arsenite resistance in E. coli and arsenite as well as arsenate resistance in Bacillus subtilis.
Selective Intracellular Activation of a Novel Prodrug of the Human Immunodeficiency Virus Reverse Transcriptase Inhibitor Tenofovir Leads to Preferential Distribution and Accumulation in Lymphatic Tissue (2005)

An isopropylalaninyl monoamidate phenyl monoester prodrug of tenofovir (GS 7340) was prepared, and its in vitro antiviral activity, metabolism, and pharmacokinetics in dogs were determined. The 50% effective concentration (EC(50)) of GS 7340 against human immunodeficiency virus type 1 in MT-2 cells was 0.005 microM compared to an EC(50) of 5 microM for the parent drug, tenofovir. The (L)-alaninyl analog (GS 7340) was >1,000-fold more active than the (D)-alaninyl analog. GS 7340 has a half-life of 90 min in human plasma at 37 degrees C and a half-life of 28.3 min in an MT-2 cell extract at 37 degrees C. The antiviral activity (>10 x the EC(50)) and the metabolic stability in MT-2 cell extracts (>35 x) and plasma (>2.5 x) were also sensitive to the stereochemistry at the phosphorus. After a single oral dose of GS 7340 (10 mg-eq/kg tenofovir) to male beagle dogs, the plasma bioavailability of tenofovir compared to an intravenous dose of tenofovir was 17%. The total intracellular concentration of all tenofovir species in isolated peripheral blood mononuclear cells at 24 h was 63 microg-eq/ml compared to 0.2 microg-eq/ml in plasma. A radiolabeled distribution study with dogs resulted in an increased distribution of tenofovir to tissues of lymphatic origin compared to the commercially available prodrug tenofovir DF (Viread).
Differential Antigen Processing by Dendritic Cell Subsets in Vivo (2007)

Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.
A pilot study to investigate the pulmonary effects of digoxin in patients with asthma. (1996)

In this small study digoxin resulted in a decline in spirometry. Further studies in a larger group of patients should be performed to assess this potentially adverse effect of digoxin.
A novel RET gene mutation in a patient with apparently sporadic pheochromocytoma (2015)

Pheochromocytoma (Pheo) is a chromaffin tumor arising from the adrenal medulla. The recent discovery of new germline mutations in RET, SDHA, SDHB, SDHC, SDHD, VHL, NF1, TMEM127, MAX genes, increased the rate of genetic disease from 10% to 28% in patients with apparently sporadic tumor. RET germline mutations cause multiple endocrine neoplasia type 2 syndrome (MEN 2A) characterized by complete penetrance of medullary thyroid cancer (MTC), and lower prevalence of Pheo and hyperparathyroidism. We describe the genetic etiology of an apparently sporadic case of monolateral Pheo in a 42-year-old male patient. A new (not previously reported) MEN 2A-associated germline RET mutation located in exon 11 (Glu632Gly, caused by an A>G point mutation at position 1895 of the RET cDNA) was found in the patient but not in his living first-degree relatives. This observation increases the number of possible germline RET mutations. Genotype-phenotype correlation of this new genetic alteration is unknown, but this rare mutation is probably associated with a low risk for MTC (usually the first tumor diagnosed in MEN 2A syndrome) and with the development of Pheo before the onset of MTC. Since we expect MTC to occur in our patient, strict follow-up is mandatory. Our findings emphasize the relevance of genetic testing in patients with Pheo, especially when the clinical presentation (family history, young age at diagnosis, multiple locations, malignant lesions, and bilateralism) is suggestive.
Moisture‐cured polyurethane/polysiloxane copolymers: Effects of the structure of polyester diol and NCO/OH ratio (2008)

Abstract Moisture‐cured polyurethane is one of the commercially important polymers, which is widely used in sealants, coatings, and reactive hot‐melt adhesives. A series of moisture‐cured polyurethane/polysiloxane (PUSR) copolymers were successfully prepared using a two‐step solution polymerization procedure. Both amine‐terminated polysiloxane (PDMS) and polyester diol were together used as mixed soft segments to react with 4,4′‐diphenlymethane diisocyanate (MDI), and the alkoxysilane was used as end‐capping agents. The effects of structure variation of building blocks such as the polyester diol structure and NCO/OH ratio on the properties and morphology of PUSR copolymers were studied. The tensile properties, dielectric behavior, thermal stability, surface, and water‐repellency properties were investigated. The results showed that the properties and morphology of PUSR copolymers were greatly affected by the variations in molecular architecture. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008
BG-12 (Dimethyl Fumarate) Is Neuroprotective in the Murine Cuprizone/Rapamycin Model of Demyelination and Neurodegeneration (P05.184) (2013)

OBJECTIVE: To characterize neuroprotective effects of dimethyl fumarate on cuprizone/rapamycin-induced demyelination and neurodegeneration.
Human epidermal growth factor receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activityin vitroand in human tumor xenografts (2008)

All four members of the human epidermal growth factor (EGF) receptor (HER) family are implicated in human cancers. Although efficacious in a subset of patients, resistance to single-targeted anti-HER therapy [i.e., cetuximab (Erbitux) and trastuzumab (Herceptin)] is often associated with coexpression of other HER family members. This may be overcome by a HER ligand binding molecule that sequesters multiple EGF-like ligands, preventing ligand-dependent receptor activation. Toward this end, we have combined the HER-1/EGFR and HER-3 ligand binding domains, dimerized with fusion of an Fc fragment of human IgG1. This resulted in a mixture of HER-1/Fc homodimer (HFD100), HER-3/Fc homodimer (HFD300), and HER-1/Fc:HER-3/Fc heterodimer (RB200), also termed Hermodulins. The purified first-generation RB200 bound EGF and neuregulin 1 (NRG1)-beta1 ligands, determined by cross-linking and direct binding studies. The binding affinity for both was approximately 10 nmol/L by dissociation-enhanced lanthanide fluorescence immunoassay using europium (Eu)-labeled ligands. Competition studies with RB200 using Eu-EGF or Eu-NRG1-beta1 revealed that RB200 bound HER-1 ligands, including transforming growth factor-alpha and heparin-binding EGF, and HER-3 ligands NRG1-alpha and NRG1-beta3. RB200 inhibited EGF- and NRG1-beta1-stimulated tyrosine phosphorylation of HER family proteins, proliferation of a diverse range of tumor cells in monolayer cell growth assays, tumor cell proliferation as a single agent and in synergy with tyrosine kinase inhibitors, lysophosphatidic acid-stimulated cell proliferation, and tumor growth in two human tumor xenograft nude mouse models. Taken together, the data reveal that RB200 has the potential to sequester multiple HER ligands and interfere with signaling by HER-1, HER-2, and HER-3.
Synthesis and characterization of zwitterionic silicone sulfobetaine surfactants (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and characterization of zwitterionic silicone sulfobetaine surfactantsSteven A. Snow, William N. Fenton, and Michael J. OwenCite this: Langmuir 1990, 6, 2, 385–391Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February 1990https://pubs.acs.org/doi/10.1021/la00092a017https://doi.org/10.1021/la00092a017research-articleACS PublicationsRequest reuse permissionsArticle Views846Altmetric-Citations54LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Organic solvents strip water off enzymes (1992)

Exchange of enzyme-bound H(2)O with T(2)O in aqueous solution followed by freeze drying provided tritiated water bound to chymotrypsin, subtilisin Carlsberg, and horseradish peroxidase. The desorption of T(2)O from these enzymes suspended in various organic solvents showed that all three enzymes lost enzyme-bound water with peroxidase losing the most T(2)O of the three in solvents of moderate to high polarity. Polar solvent resulted in the highest degree of T(2)O desorption (e.g., methanol desorbed from 56%-62% of the bound T(2)O), while nonpolar solvents resulted in the lowest degree of desorption (e.g., hexane desorbed from 0.4%-2% of the bound T(2)O). Desorption is nearly immediate with most of the desorbable T(2)O being released from the enzymes within the first 5 min. Both solvent dielectric and a measure of the saturated molar solubility of water in a given solvent provide accurate correlations between the properties of the organic solvents and the extent of T(2)O desorption. This investigation shows that water stripping from an enzyme into a nonaqueous medium does occur and can be significant in polar solvents.
Use of Lactose against the Deadly Biological Toxin Ricin (2010)

Developing a technology for detecting and decontaminating biological toxins is needed. Ricin from Ricinus communis is a highly poisonous toxin; it was formerly used for an assassination in London and in postal attacks in the United States. Ricin is readily available from castor beans and could be used as a biological agent. We propose using glycotechnology against the illegal use of ricin. Lactose (a natural ligand of this toxin) was incorporated into polyacrylamide-based glycopolymers at variable sugar densities (18-100%) and evaluated with surface plasmon resonance (SPR) spectroscopy and the real agent, ricin. Glycopolymers (18-65% lactose densities) effectively interfered with the toxin-lactoside adhesion event (>99% efficiency within 20 min). This supported the notion of using the mammary sugar lactose against a deadly biological toxin.
Maize streak virus coat protein binds single- and double-stranded DNA in vitro. (1997)

Maize streak virus (MSV) coat protein (CP) is required for virus movement within the plant. Deletion or mutation of MSV CP does not prevent virus replication in single cells or protoplasts but leads to a loss of infectivity in the inoculated plant. The mechanism by which MSV CP mediates the transfer of MSV DNA from cell to cell and through the vascular bundle is still unknown. Towards understanding the role of MSV CP in virus movement, the interaction of the CP with viral DNA was investigated using the 'south-western' assay. Wild-type and truncated MSV CPs were expressed in E. coli and the expressed CPs were used to investigate interactions with single-stranded (ss) and double-stranded (ds) DNA. The results showed that MSV CP bound ss and ds viral and plasmid DNA in a sequence non-specific manner. The binding domain was mapped to within the 104 N-terminal amino acids of the MSV CP. We propose that the binding of CP to MSV DNA is involved in viral DNA nuclear transport as well as encapsidation and thus may have a role in intra- and inter-cellular movement as well as systemic infection.
Crystallization and Preliminary X-ray Diffraction Studies of a Complex between Interleukin-2 and a Soluble Form of the p55 Component of the High Affinity Interleukin-2 Receptor (1989)

Human recombinant interleukin-2 (IL-2) and a soluble recombinant form of the human p55 (Tac antigen) component of the IL-2 receptor (IL-2R) have been cocrystallized in 1.7-1.8 M ammonium sulfate, in the pH range 7.0-8.2. Variously glycosylated forms of both receptor and ligand can be cocrystallized under those conditions. The best crystals of the putative receptor-ligand complex involve the enzymatically desialylated receptor and unglycosylated IL-2. These crystals belong to the trigonal space group P3(1)2(1) or its enantiomorph, with unit cell dimensions a = b = 91 A and c = 119 A, and diffract to 3.5 A resolution. There is one receptor-ligand complex asymmetric unit, with a Matthews coefficient of 2.7, assuming the presence of one IL-2 molecule-receptor molecule. Interestingly, in addition to IL-2 (Mr = 14,000), the p55 IL-2 receptor (Mr = 44,000) and two fragments of the receptor, of apparent Mr = 35,000 and 25,000, respectively, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the crystals are enriched in a reducible dimeric form of the desialylated receptor (apparent Mr = 90,000), as compared with protein solution from which the crystals grow. The overall amino acid content in the crystals is consistent with a 1:1 ratio of receptor to ligand. A native data set has been collected on a multiwire area detector and the search for suitable heavy atom derivatives is in progress.
Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial (2007)

A randomized double-blind clinical trial was performed to test the safety and efficacy of a low-molecular-weight heparin, tinzaparin (Innohep), for the management of acute painful vasoocclusive crisis characteristic of sickle cell anemia (SCA). We studied 253 patients with acute painful crisis but with no other complications of SCA, randomized to treatment or control groups. In the treatment group, 127 patients received tinzaparin at 175 IU/kg, subcutaneous once daily, along with supportive care including morphine analgesia; in the control group, 126 patients received placebo and the same supportive care. The maximal experimental treatment period was seven days. Analysis revealed a statistically significant reduction in number of days with the severest pain score, overall duration of painful crisis, and duration of hospitalization (p < 0.05 for each comparison of tinzaparin vs. placebo). The decline in pain intensity was sharper for tinzaparin-treated patients, and complications consisted of two minor bleeding events that were reported and treated by cessation of tinzaparin. This investigation demonstrated that tinzaparin, administered at its approved treatment regimen, reduced the severity and duration of acute crisis of SCA.
Production and regulation of interleukin-2 in human lymphoblastic leukemias studied with T-cell monoclonal antibodies (1983)

Human leukemias are illnesses of hemopoietic stem cells that go through processes of self-replication and partial differentiation under the control of as yet largely unknown growth and differentiation factors. IL-2 is a powerful factor controlling proliferation of normal T cells. We report that acute lymphoblastic leukemias of T and non-B, non-T phenotypes produce a growth factor after mitogen stimulation. This factor is able to support the proliferation of human and murine IL-2-dependent cytotoxic cells, has a mol wt of 26,000 daltons by gel filtration, an isoelectric point of 6.6, and its biologic activity is inhibited by an anti IL-2 monoclonal antibody. This factor is, therefore, by all parameters studied very similar to IL-2 produced by normal lymphocytes. A recently developed monoclonal antibody, Pan T2, binds to normal T cells, renders T cells responsive to IL-2, and induces the release of IL-2, which in turn provides the second signal for T-cell proliferation. Mononuclear cells from acute lymphoblastic leukemia do not respond to the addition of this monoclonal antibody unless cocultured with irradiated Daudi cells. Since normal T cells do not require Daudi to produce IL-2 and since Daudi cells do not produce IL-2 under any conditions, we conclude that the cell responsible for IL-2 production in acute lymphatic leukemia is a leukemic T cell with an altered mechanism of IL-2 production at the level of the Pan T2 binding site.
Beamforming Techniques for Multichannel audio Signal Separation (2012)

Beamforming is a signal processing technique. It has been studied in many areas such as radar, sonar, seismology and wireless communications, to name but a few. It can be used for a myriad of purposes, such as detecting the presence of a signal, estimating the direction of arrival, and enhancing a desired signal from its measurements corrupted by noise, competing sources and reverberation. Actually, Beamforming has been adopted by the audio research society, mostly to separate or extract speech for noisy environment. Beamforming techniques basically approach the problem from a spatial point of view. A microphone array is used to form a spatial filter which can extract a signal from a specific direction and reduce the contamination of signals from other directions. In this paper we survey some Beamforming techniques used for multichannel audio signal separation.