gebhart/patrepeval huggingface dataset:
Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinity (1999)

Nitric oxide (NO) inhalation has been reported to increase the oxygen affinity of sickle cell erythrocytes. Also, proposed allosteric mechanisms for hemoglobin, based on S-nitrosation of beta-chain cysteine 93, raise the possibility of altering the pathophysiology of sickle cell disease by inhibiting polymerization or by increasing NO delivery to the tissue. We studied the effects of a 2-hour treatment, using varying concentrations of inhaled NO. Oxygen affinity, as measured by P(50), did not respond to inhaled NO, either in controls or in individuals with sickle cell disease. At baseline, the arterial and venous levels of nitrosylated hemoglobin were not significantly different, but NO inhalation led to a dose-dependent increase in mean nitrosylated hemoglobin, and at the highest dosage, a significant arterial-venous difference emerged. The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion.
Synomones of two sympatric species deter attack by the pine engraver, Ipspini (Coleoptera: Scolytidae) (1992)

The capture of pine engravers, Ipspini (Say), in ipdienol-baited, multiple-funnel traps in British Columbia was significantly reduced when devices releasing ipsenol or verbenone were placed in the traps. These results suggest that ipsenol and verbenone are synomones released by Ipslatidens (LeC.) and the mountain pine beetle, Dendroctonusponderosae Hopk., respectively. When verbenone and ipsenol were released together from five stations 2 m apart on felled trees, at 50 and 1.5 mg per day per tree, respectively, there was a 66.7% reduction in the number of logs attacked and a 98.8% reduction in attack density. The same treatment caused a 74.1% reduction in attack density on standing trees surrounded by a 4 × 4 grid of 16 release devices at 5- m centres. The antiaggregant composition of verbenone plus ipsenol has considerable operational potential for use in precommercial thinnings and in areas where standing pines are of high value; e.g., in rural subdivisions, shelterbelts, and recreational forests.
Hyperhydration: tolerance and cardiovascular effects during uncompensable exercise-heat stress (1998)

This study examined the efficacy of glycerol and water hyperhydration (1 h before exercise) on tolerance and cardiovascular strain during uncompensable exercise-heat stress. The approach was to determine whether 1-h preexercise hyperhydration (29.1 ml H 2 O/kg lean body mass with or without 1.2 g/kg lean body mass of glycerol) provided a physiological advantage over euhydration. Eight heat-acclimated men completed three trials (control euhydration before exercise, and glycerol and water hyperhydrations) consisting of treadmill exercise-heat stress (ratio of evaporative heat loss required to maximal capacity of climate = 416). During exercise (∼55% maximal O 2 uptake), there was no difference between glycerol and water hyperhydration methods for increasing ( P &lt; 0.05) total body water. Glycerol hyperhydration endurance time (33.8 ± 3.0 min) was longer ( P &lt; 0.05) than for control (29.5 ± 3.5 min), but was not different ( P &gt; 0.05) from that of water hyperhydration (31.3 ± 3.1 min). Hyperhydration did not alter ( P &gt; 0.05) core temperature, whole body sweating rate, cardiac output, blood pressure, total peripheral resistance, or core temperature tolerance. Exhaustion from heat strain occurred at similar core and skin temperatures and heart rates in each trial. Symptoms at exhaustion included syncope and ataxia, fatigue, dyspnea, and muscle cramps ( n = 11, 10, 2, and 1 cases, respectively). We conclude that 1-h preexercise glycerol hyperhydration provides no meaningful physiological advantage over water hyperhydration and that hyperhydration per se only provides the advantage (over euhydration) of delaying hypohydration during uncompensble exercise-heat stress.
Hidden Formaldehyde in E-Cigarette Aerosols (2015)

This letter reports a chemical analysis of vapor from electronic cigarettes that shows high levels of formaldehyde, a known carcinogen. The authors project that the associated incremental lifetime risk of cancer could be higher than that from long-term smoking.
Chiral synthesis via organoboranes. 18. Selective reductions. 43. Diisopinocampheylchloroborane as an excellent chiral reducing reagent for the synthesis of halo alcohols of high enantiomeric purity. A highly enantioselective synthesis of both optical isomers of Tomoxetine, Fluoxetine, and Nisoxetine (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChiral synthesis via organoboranes. 18. Selective reductions. 43. Diisopinocampheylchloroborane as an excellent chiral reducing reagent for the synthesis of halo alcohols of high enantiomeric purity. A highly enantioselective synthesis of both optical isomers of Tomoxetine, Fluoxetine, and NisoxetineMorris Srebnik, P. V. Ramachandran, and Herbert C. BrownCite this: J. Org. Chem. 1988, 53, 13, 2916–2920Publication Date (Print):June 1, 1988Publication History Published online1 May 2002Published inissue 1 June 1988https://pubs.acs.org/doi/10.1021/jo00248a005https://doi.org/10.1021/jo00248a005research-articleACS PublicationsRequest reuse permissionsArticle Views1822Altmetric-Citations108LEARN 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
Facile 3D direct manipulation (1993)

Anexpenmental 3D interface is described, including rendering acceleration hardware, a 3D mouse, and 3D interaction techniques. A 3D cursor, controlled by the augmented mouse, allows direct manipulation of 3D objects. Objects are selected by placing the tip of the cursor inside. Objects can be moved in 3D, or simultaneously moved and rotated using a technique called "tail-dragging."
Detection of methicillin resistance in Staphylococcus aureus isolates using two-step triplex PCR and conventional methods. (2007)

A two-step triplex PCR assay targeting the mecA, femA, and nuc genes was developed for the detection of methicillin resistance genes harbored by some Staphylococcus aureus isolates and for the simultaneous identification of such isolates at the species level. The triplex PCR revealed the presence of the femA and nuc genes in all the S. aureus isolates examined (n=105). Forty-four clinical isolates were mecA positive and no foodborne isolates were mecA positive. The PCR results had a 98 or 99% correlation with the results of PBP2a latex agglutination tests or oxacillin susceptibility tests, respectively.
Selective growth response to IL‐3 of a human leukaemic cell line with megakaryoblastic features (1988)

A new human leukaemic cell line (M-O7) with the phenotypic characteristics of CFU-mega is described. Its cells are positive for T200 leucocyte common antigen (LCA) and negative with MAbs recognizing T and B cells and mature myelomonocytic antigens. In contrast, they react with MAbs recognizing antigenic determinants common to multi-lineage (CD13, CD33, CD34) and to bipotent erythromegakaryoblastic (CD36, H25) haemopoietic precursors, and with MAbs specific for platelet glycoproteins (CD41w, CD42w). A small proportion (10%) of the cells were large and multinucleated, and on electron-microscopy examination showed peripheral splitting of platelet-like cytoplasm particles. When transferred to a serum-free Iscove modified Dulbecco's medium supplemented with human insulin and transferrin, M-O7 cells stop proliferating. Of the haemopoietic growth factors tested for their ability to restore the proliferative activity of this quiescent population, only rH IL-3 proved effective. Moreover, it also increased the cloning efficiency in methylcellulose more than any other CSFs. The M-O7 cell line may provide a valuable tool for the biological assay of IL-3, and a model for biochemical studies of the megakaryocytic lineage.
Dengue virus NS1 triggers endothelial permeability and vascular leak that is prevented by NS1 vaccination (2015)

The four dengue virus serotypes (DENV1 to DENV4) are mosquito-borne flaviviruses that cause up to ~100 million cases of dengue annually worldwide. Severe disease is thought to result from immunopathogenic processes involving serotype cross-reactive antibodies and T cells that together induce vasoactive cytokines, causing vascular leakage that leads to shock. However, no viral proteins have been directly implicated in triggering endothelial permeability, which results in vascular leakage. DENV nonstructural protein 1 (NS1) is secreted and circulates in patients' blood during acute infection; high levels of NS1 are associated with severe disease. We show that inoculation of mice with DENV NS1 alone induces both vascular leakage and production of key inflammatory cytokines. Furthermore, simultaneous administration of NS1 with a sublethal dose of DENV2 results in a lethal vascular leak syndrome. We also demonstrate that NS1 from DENV1, DENV2, DENV3, and DENV4 triggers endothelial barrier dysfunction, causing increased permeability of human endothelial cell monolayers in vitro. These pathogenic effects of physiologically relevant amounts of NS1 in vivo and in vitro were blocked by NS1-immune polyclonal mouse serum or monoclonal antibodies to NS1, and immunization of mice with NS1 from DENV1 to DENV4 protected against lethal DENV2 challenge. These findings add an important and previously overlooked component to the causes of dengue vascular leak, identify a new potential target for dengue therapeutics, and support inclusion of NS1 in dengue vaccines.
Strong Time Dependence of the 76-Gene Prognostic Signature for Node-Negative Breast Cancer Patients in the TRANSBIG Multicenter Independent Validation Series (2007)

This independent validation confirmed the performance of the 76-gene signature and adds to the growing evidence that gene expression signatures are of clinical relevance, especially for identifying patients at high risk of early distant metastases.
Double‐blind randomized controlled clinical trial of the interleukin‐6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate (2006)

These results indicate that targeted blockade of IL-6 signaling is a highly efficacious and promising means of decreasing disease activity in RA.
Dominant negative mutator mutations in the mutL gene of Escherichia coli (1996)

The mutL gene product is part of the dam-directed mismatch repair system of Escherichia coli but has no known enzymatic function. It forms a complex on heteroduplex DNA with the mismatch recognition MutS protein and with MutH, which has latent endonuclease activity. An N-terminal hexahistidine-tagged MutL was constructed which was active in vivo. As a first stop to determine the functional domains of MutL, we have isolated 72 hydroxylamine-induced plasmid-borne mutations which impart a dominant-negative phenotype to the wild-type strain for increased spontaneous mutagenesis. None of the mutations complement a mutL deletion mutant, indicating that the mutant proteins by themselves are inactive. All the dominant mutations but one could be complemented by the wild-type mutL at about the same gene dosage. DNA sequencing indicated that the mutations affected 22 amino acid residues located between positions 16 and 549 of the 615 amino acid protein. In the N-terminal half of the protein, 12 out of 15 amino acid replacements occur at positions conserved in various eukaryotic MutL homologs. All but one of the sequence changes affecting the C-terminal end of the protein are nonsense mutations.
Assessment of the extent of oxidative stress induced by intravenous ferumoxytol, ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model (2011)

Intravenous (i.v.) iron is associated with a risk of oxidative stress. The effects of ferumoxytol, a recently approved i.v. iron preparation, were compared with those of ferric carboxymaltose, low molecular weight iron dextran and iron sucrose in the liver, kidneys and heart of normal rats. In contrast to iron sucrose and ferric carboxymaltose, low molecular weight iron dextran and ferumoxytol caused renal and hepatic damage as demonstrated by proteinuria and increased liver enzyme levels. Higher levels of oxidative stress in these tissues were also indicated, by significantly higher levels of malondialdehyde, significantly increased antioxidant enzyme activities, and a significant reduction in the reduced to oxidized glutathione ratio. Inflammatory markers were also significantly higher with ferumoxytol and low molecular weight iron dextran rats than iron sucrose and ferric carboxymaltose. Polarographic analysis suggested that ferumoxytol contains a component with a more positive reduction potential, which may facilitate iron-catalyzed formation of reactive oxygen species and thus be responsible for the observed effects. Only low molecular weight iron dextran induced oxidative stress and inflammation in the heart.
Involvement of the Molecular Chaperone Ydj1 in the Ubiquitin-Dependent Degradation of Short-Lived and Abnormal Proteins in Saccharomyces cerevisiae (1996)

In Escherichia coli and mitochondria, the molecular chaperone DnaJ is required not only for protein folding but also for selective degradation of certain abnormal polypeptides. Here we demonstrate that in the yeast cytosol, the homologous chaperone Ydj1 is also required for ubiquitin-dependent degradation of certain abnormal proteins. The temperature-sensitive ydj1-151 mutant showed a large defect in the overall breakdown of short-lived cell proteins and abnormal polypeptides containing amino acid analogs, especially at 38 degrees C. By contrast, the degradation of long-lived cell proteins, which is independent of ubiquitin, was not altered nor was cell growth affected. The inactivation of Ydj1 markedly reduced the rapid, ubiquitin-dependent breakdown of certain beta-galactosidase (beta-gal) fusion polypeptides. Although degradation of N-end rule substrates (arginine-beta-gal and leucine-beta-gal) and the B-type cyclin Clb5-beta-gal occurred normally, degradation of the abnormal polypeptide ubiquitin-proline-beta-gal (Ub-P-beta-gal) and that of the short-lived normal protein Gcn4 were inhibited. As a consequence of reduced degradation of Ub-P-beta-gal, the beta-gal activity was four to five times higher in temperature-sensitive ydj1-151 mutant cells than in wild-type cells; thus, the folding and assembly of this enzyme do not require Ydj1 function. In wild-type cells, but not in ydj1-151 mutant cells, this chaperone is associated with the short-lived substrate Ub-P-beta-gal and not with stable beta-gal constructs. Furthermore, in the ydj1-151 mutant, the ubiquitination of Ub-P-beta-gal was blocked and the total level of ubiquitinated protein in the cell was reduced. Thus, Ydj1 is essential for the ubiquitin-dependent degradation of certain proteins. This chaperone may facilitate the recognition of unfolded proteins or serve as a cofactor for certain ubiquitin-ligating enzymes.
Electromechanical response in liquid crystal gels and networks (2003)

The uniqueness of liquid crystals (LCs) lies in the large anisotropies in their properties, which can be utilized to generate high electromechanical responses. In a properly oriented liquid crystal polymer system, an external electric field can induce re-orientation of the mesogenic units possessing a dielectric anisotropy, which, when coupled with the shape anisotrophy of the mesogenic units, can in turn produce large mechanical strain. Anisotropic liquid crystal gels, which can be obtained by <i>in situ</i> photopolymerization of the reactive LC molecules in the presence of non-reactive LC molecules in an oriented state, are an example of such liquid crystal polymer systems. It has been shown that a homeotropically aligned liquid crystal gel in its nematic phase exhibits high electrically induced strain (&gt;2%) with an elastic modulus of 100MPa and a high electromechanical conversion efficiency (75%) under an electric field of 25 MV/m. These anisotropic LC polymeric materials could provide a technologically compatible system for such applications as artificial muscles and as micro-electromechanical devices.
Attenuation of Allergic Contact Dermatitis Through the Endocannabinoid System (2007)

Allergic contact dermatitis affects about 5% of men and 11% of women in industrialized countries and is one of the leading causes for occupational diseases. In an animal model for cutaneous contact hypersensitivity, we show that mice lacking both known cannabinoid receptors display exacerbated allergic inflammation. In contrast, fatty acid amide hydrolase-deficient mice, which have increased levels of the endocannabinoid anandamide, displayed reduced allergic responses in the skin. Cannabinoid receptor antagonists exacerbated allergic inflammation, whereas receptor agonists attenuated inflammation. These results demonstrate a protective role of the endocannabinoid system in contact allergy in the skin and suggest a target for therapeutic intervention.
Xenoantigens and xenoantibodies (1998)

Major efforts are being directed towards determining and modifying the glycosylated epitopes on pig vascular endothelial cells, against which human natural antibodies are directed. Genetic engineering techniques are being used in an effort to knock out or replace the major alpha galactosyl (alpha Gal) epitopes in mice, but to-date these have been only modestly successful in prolonging functional survival of such modified organs. Competitive glycosylation involving insertion of the gene for alpha 1,2 fucosyltransferase results in reduction of alpha Gal expression but also of presentation of hitherto cryptic antigens against which natural human antibodies are directed or could develop. The introduction of the gene for N-acetylglucosaminyltransferase III has been demonstrated to significantly reduce alpha Gal expression, and the intracellular expression of single chain Fv antibodies against alpha 1,3 galactosyltransferase also represses this enzyme activity. Several other carbohydrate antigens have been identified that could act as targets for human natural antibodies, and these include Gal alpha 1-3Le(x), Hanganutziu-Deicher, Tn, and Forssman antigens. The alternative approach, namely, the depletion of the recipient's natural antibodies, is proving difficult, but techniques for inducing B cell tolerance are being explored. The induction of a state of mixed hematopoietic chimerism in alpha Gal knockout mice has resulted in tolerance to the alpha Gal antigen. Tolerance to the SLA antigens of miniature swine is also being attempted in baboons by the transfer of SLA Class II genes into baboon bone marrow cells. It is hoped that one or a combination of these approaches may overcome the problem created by the presence of pig antigens against which humans have xenoreactive antibodies.
Anticancer Role of PPARγAgonists in Hematological Malignancies Found in the Vasculature, Marrow, and Eyes (2010)

The use of targeted cancer therapies in combination with conventional chemotherapeutic agents and/or radiation treatment has increased overall survival of cancer patients. However, longer survival is accompanied by increased incidence of comorbidities due, in part, to drug side effects and toxicities. It is well accepted that inflammation and tumorigenesis are linked. Because peroxisome proliferator-activated receptor (PPAR)-gamma agonists are potent mediators of anti-inflammatory responses, it was a logical extension to examine the role of PPARgamma agonists in the treatment and prevention of cancer. This paper has two objectives: first to highlight the potential uses for PPARgamma agonists in anticancer therapy with special emphasis on their role when used as adjuvant or combined therapy in the treatment of hematological malignancies found in the vasculature, marrow, and eyes, and second, to review the potential role PPARgamma and/or its ligands may have in modulating cancer-associated angiogenesis and tumor-stromal microenvironment crosstalk in bone marrow.
Insulin‐Like Growth Factor I Is Required for the Anabolic Actions of Parathyroid Hormone on Mouse Bone (2002)

Parathyroid hormone (PTH) is a potent anabolic agent for bone, but the mechanism(s) by which it works remains imperfectly understood. Previous studies have indicated that PTH stimulates insulin-like growth factor (IGF) I production, but it remains uncertain whether IGF-I mediates some or all of the skeletal actions of PTH. To address this question, we examined the skeletal response to PTH in IGF-I-deficient (knockout [k/o]) mice. These mice and their normal littermates (NLMs) were given daily injections of PTH (80 microg/kg) or vehicle for 2 weeks after which their tibias were examined for fat-free weight (FFW), bone mineral content, bone structure, and bone formation rate (BFR), and their femurs were assessed for mRNA levels of osteoblast differentiation markers. In wild-type mice, PTH increased FFW, periosteal BFR, and cortical thickness (C.Th) of the proximal tibia while reducing trabecular bone volume (BV); these responses were not seen in the k/o mice. The k/o mice had normal mRNA levels of the PTH receptor and increased mRNA levels of the IGF-I receptor but markedly reduced basal mRNA levels of the osteoblast markers. Surprisingly, these mRNAs in the k/o bones increased several-fold more in response to PTH than the mRNAs in the bones from their wild-type littermates. These results indicate that IGF-I is required for the anabolic actions of PTH on bone formation, but the defect lies distal to the initial response of the osteoblast to PTH.
FRETS‐VWF73, a first fluorogenic substrate for ADAMTS13 assay (2005)

Summary A plasma metalloprotease, ADAMTS13, cleaves von Willebrand factor (VWF) multimers and downregulates their activity in platelet aggregation. Functional ADAMTS13 deficiency leads to the accumulation of hyperactive large VWF multimers, inducing a life‐threatening disease, thrombotic thrombocytopenic purpura (TTP). Although measuring ADAMTS13 activity is important in TTP diagnosis, existing methods require time and skill. Here, we report a fluorescence resonance energy transfer (FRET) assay for ADAMTS13 activity. We developed a synthetic 73‐amino‐acid peptide, FRETS‐VWF73. Cleavage of this substrate between two modified residues relieves the fluorescence quenching in the intact peptide. Incubation of FRETS‐VWF73 with normal human plasma quantitatively increased fluorescence over time, while ADAMTS13‐deficient plasma had no effect. Quantitative analysis could be achieved within a 1‐h period using a 96‐well format in commercial plate readers with common filters. The FRETS‐VWF73 assay will be useful for the characterization of thrombotic microangiopathies like TTP and may clarify the importance of ADAMTS13 activity as a predictive marker for various thrombotic diseases.