gebhart/patrepeval huggingface dataset:
Development of Agents to Modulate the Effects of Endothelin (1994)

Abstract: Due partly to a greater understanding of the role of regulatory peptides and proteins in the pathophysiology of human disease there is considerable interest in designing agents that will modulate their effects. Endothelin-1 and its isopeptides belong to a family of novel vasoconstrictor agents first isolated from porcine aortic endothelial cells and subsequently found to be secreted from a variety of cell types. These peptides have potent biological effects on cardiovascular, renal, endocrine and neurological function. The rational design of receptor agonists and antagonists or proce­ ssing inhibitors from a ligand of interest, requires an understanding of the binding mode of the natural ligand(s) to the receptor(s) or enzyme and the relative importance of individual residues to binding. Screening of compound libraries and lead optimization techniques have also lead to pote'lt antagonists and processing enzyme inhibitors. This review will describe the progress achieved to date using both of these techniques to discover novel and potent endothelin agonists and antagonists of differing selectivity for the known ET receptor subtypes. Progress towards to design of endothelin converting enzyme inhibitors is also discussed. the discovery of agents to modulate the effects of endothelin will prove useful in elucidating the role of the endothelin family of peptides in human physiology and pathophysiology.
A minimalist approach to the development of a word processor supporting group writing activities (1991)

article A minimalist approach to the development of a word processor supporting group writing activities Share on Authors: Nicholas Malcolm Knowledge Science Institute, University of Calgary, Calgary, Alberta, Canada T2N 1N4 Knowledge Science Institute, University of Calgary, Calgary, Alberta, Canada T2N 1N4View Profile , Brian R. Gaines Knowledge Science Institute, University of Calgary, Calgary, Alberta, Canada T2N 1N4 Knowledge Science Institute, University of Calgary, Calgary, Alberta, Canada T2N 1N4View Profile Authors Info & Claims ACM SIGOIS BulletinVolume 12Issue 2-3Nov. 1991 pp 147–152https://doi.org/10.1145/127769.122846Published:01 October 1991 9citation340DownloadsMetricsTotal Citations9Total Downloads340Last 12 Months6Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Bioavailability of Iron from Micro-Encapsulated Iron Sprinkle Supplement (2002)

To improve the iron status of infants an effort was made to increase the iron content of complementary foods by adding 12.5 mg of elemental iron to the meal in the form of micro-encapsulated ferrous fumarate coated with a lipid. The contents of the packet were sprinkled directly on to infant foods. Relative absorption of iron from this supplement was determined in a prospective randomized study with 39 infants (mean age 33.6 +/- 5.2 weeks) with initial hemoglobin values greater than 100 g/L. They were fed two complementary foods (rice-based and wheat-based) in which the supplement labeled with stable isotopes of iron 57Fe and 58Fe was incorporated. The erythrocyte iron incorporation was measured in the blood by inductively coupled plasma mass spectrophotometry. The incorporation of iron was significantly higher 11.9% p < .001 and 13.3% p < .001 and no difference was observed with the type of cereal in complementary foods. The use of ferrous fumarate sprinkles has proved to be efficacious in increasing the available iron intake of the infants.
Function of glycoprotein VI and integrin alpha2beta1 in the procoagulant response of single, collagen-adherent platelets. (1999)

Various collagen-based materials were used to assess the structural requirements of collagen for inducing the procoagulant response of adhering platelets, as well as the collagen receptors involved. Cross-linked or monomeric collagen-related peptide (CRP), Gly-Cys-Hyp-(Gly-Pro-Hyp)10-Gly-Cys-Hyp-Gly was highly adhesive for platelets in a glycoprotein VI-(GpVI-)dependent manner. Adhesion was followed by a prolonged increase in cytosolic [Ca2+]i, formation of membrane blebs, exposure of phosphatidylserine (PS) and generation of prothrombinase-stimulating activity. Fibrils of type-I collagen were less adhesive but, once adhered, many of the platelets presented a full procoagulant response. Monomeric type-I collagen was unable to support adhesion, unless Mg(2+)-dependent integrin alpha2beta1 interactions were facilitated by omission of Ca2+ ions. With all surfaces, however, post-addition of CaCl2 to adhering platelets resulted in a potent Ca(2+)-influx signal, followed by PS exposure and bleb formation. The procoagulant response elicited by binding to CRP was inhibited by anti-GpVI Fab fragments, but not by impeding integrin alpha2beta1-mediated events. With fibrillar collagen, it was inhibited by blocking either the GpVI- or integrin alpha2beta1-mediated interactions. This suggests that the triple-helical Gly-Pro-Hyp repeat in CRP and analogous sequences in fibrillar collagen stimulate the procoagulant response of adherent platelets by acting as ligands for GpVI. Influx of Ca2+ is required for this response, and adhesion via integrin alpha2beta1 serves to potentiate the signaling effects of GpVI.
BM mesenchymal stromal cell–derived exosomes facilitate multiple myeloma progression (2013)

BM mesenchymal stromal cells (BM-MSCs) support multiple myeloma (MM) cell growth, but little is known about the putative mechanisms by which the BM microenvironment plays an oncogenic role in this disease. Cell-cell communication is mediated by exosomes. In this study, we showed that MM BM-MSCs release exosomes that are transferred to MM cells, thereby resulting in modulation of tumor growth in vivo. Exosomal microRNA (miR) content differed between MM and normal BM-MSCs, with a lower content of the tumor suppressor miR-15a. In addition, MM BM-MSC-derived exosomes had higher levels of oncogenic proteins, cytokines, and adhesion molecules compared with exosomes from the cells of origin. Importantly, whereas MM BM-MSC-derived exosomes promoted MM tumor growth, normal BM-MSC exosomes inhibited the growth of MM cells. In summary, these in vitro and in vivo studies demonstrated that exosome transfer from BM-MSCs to clonal plasma cells represents a previously undescribed and unique mechanism that highlights the contribution of BM-MSCs to MM disease progression.
Effect of the Orientation of the Ester Bonds on the Properties of Three Isomeric Liquid Crystal Diacrylates before and after Polymerization (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEffect of the Orientation of the Ester Bonds on the Properties of Three Isomeric Liquid Crystal Diacrylates before and after PolymerizationR. A. M. Hikmet, J. Lub, and A. J. W. TolCite this: Macromolecules 1995, 28, 9, 3313–3327Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ma00113a036https://doi.org/10.1021/ma00113a036research-articleACS PublicationsRequest reuse permissionsArticle Views441Altmetric-Citations57LEARN 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
Segregated network polymer/carbon nanotubes composites (2004)

Abstract In this work we present the preparation of conductive polyethylene/carbon nanotube composites based on the segregated network concept. Attention has been focused on the effect of decreasing the amount of filler necessary to achieve low resistivity. Using high- and low-grade single-walled carbon nanotube materials we obtained conductive composites with a low percolation threshold of 0.5 wt.% for high-grade nanotubes, about 1 wt% for commercial nanotubes and 1.5 wt% for low-grade material. The higher percolation threshold for low-grade material is related to low effectiveness of other carbon fractions in the network formation. The electrical conductivity was measured as a function of the single-walled carbon nanotubes content in the polymer matrix and as a function of temperature. It was also found that processing parameters significantly influenced the electrical conductivity of the composites. Raman spectroscopy was applied to study single wall nanotubes in the conductive composites.
A Wide-Scan Printed Planar K-band Microwave Lens (2005)

Microwave lenses are an attractive option for switched beam antenna systems because several beams can share a single aperture. Of particular interest are printed planar lenses due to their light weight, low volume, and ease of fabrication. Several researchers have developed such lenses using two different methods. The first method is to connect the antennas on the transmit and receive side with delay lines to obtain the appropriate phase response (McGrath, D.T., 1986; Popovic, D. and Popovic, Z., 2002; Pozar, D.M., 1996). The second, the antenna-filter-antenna (AFA) method, is to couple the antennas resonantly on the transmit and receive side forming a bandpass filter response and to scale the unit cells to obtain the desired phase response (Abbaspour-Tamijani, A. et al., IEEE AP-S Symp. Dig., p.675-8, 2004). In a switched beam system, it is often desired to have a wide scan angle. A K-band lens is presented with at least /spl plusmn/50/spl deg/ scanning in both the E-plane and the H-plane and no grating lobes using the AFA concept.
Morphine, Gabapentin, or Their Combination for Neuropathic Pain (2005)

Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.
Exosomes Derived from HIV-1 Infected DCs Mediate Viral trans-Infection via Fibronectin and Galectin-3 (2017)

Exosomes are membrane enclosed nano-sized vesicles actively released into the extracellular milieu that can harbor genomic, proteomic and lipid cargos. Functionally, they are shown to regulate cell-cell communication and transmission of pathogens. Though studies have implicated a role for exosomes in HIV-1 pathogenesis, their mechanisms are not well defined. Here, we characterized exosomes derived from uninfected or HIV-1 infected T-cells and DCs. We demonstrate substantial differences in morphological, molecular and biogenesis machinery between exosomes derived from these two immune cell types. In addition, exosomes derived from HIV-1 infected DCs were 4 fold more infective than either cell free HIV-1 or exosomes derived from T-cells. Molecular analysis of exosomes detected the presence of fibronectin and galectin-3 in those derived from DCs, whereas T-cell exosomes lacked these molecules. Addition of anti-fibronectin antibody and β-lactose, a galectin-3 antagonist, significantly blocked DC exosome-mediated HIV-1 infection of T-cells. We also observed increased gene expression of the pro-inflammatory cytokines IFN-γ, TNF-α, IL-1β and RANTES and activation of p38/Stat pathways in T-cells exposed to exosomes derived from HIV-1 infected DCs. Our study provides insight into the role of exosomes in HIV pathogenesis and suggests they can be a target in development of novel therapeutic strategies against viral infection.
Highly accelerated real‐time cardiac cine MRI using k–t SPARSE‐SENSE (2012)

For patients with impaired breath-hold capacity and/or arrhythmias, real-time cine MRI may be more clinically useful than breath-hold cine MRI. However, commercially available real-time cine MRI methods using parallel imaging typically yield relatively poor spatio-temporal resolution due to their low image acquisition speed. We sought to achieve relatively high spatial resolution (∼2.5 × 2.5 mm(2)) and temporal resolution (∼40 ms), to produce high-quality real-time cine MR images that could be applied clinically for wall motion assessment and measurement of left ventricular function. In this work, we present an eightfold accelerated real-time cardiac cine MRI pulse sequence using a combination of compressed sensing and parallel imaging (k-t SPARSE-SENSE). Compared with reference, breath-hold cine MRI, our eightfold accelerated real-time cine MRI produced significantly worse qualitative grades (1-5 scale), but its image quality and temporal fidelity scores were above 3.0 (adequate) and artifacts and noise scores were below 3.0 (moderate), suggesting that acceptable diagnostic image quality can be achieved. Additionally, both eightfold accelerated real-time cine and breath-hold cine MRI yielded comparable left ventricular function measurements, with coefficient of variation <10% for left ventricular volumes. Our proposed eightfold accelerated real-time cine MRI with k-t SPARSE-SENSE is a promising modality for rapid imaging of myocardial function.
Mothers against dpp encodes a conserved cytoplasmic protein required in DPP/TGF-β responsive cells (1996)

The proteins necessary for signal transduction in cells responding to ligands of the TGF-beta family are largely unknown. We have previously identified Mad (Mothers against dpp), a gene that interacts with the TGF-beta family member encoded by decapentaplegic (dpp) in Drosophila. Assay of Mad's role in the DPP-dependent events of embryonic midgut development demonstrates that Mad is required for any response of the visceral mesoderm or endoderm to DPP signals from the visceral mesoderm. Replacement of the normal DPP promoter with a heterologous (hsp70) promoter fails to restore DPP-dependent responses in Mad mutant midguts. Experiments utilizing Mad transgenes regulated by tissue-specific promoters show that MAD is required specifically in cells responding to DPP. Immunohistochemical studies localize MAD to the cytoplasm in all tissues examined. Experiments in Xenopus embryos demonstrate that Drosophila MAD can function in the signaling pathway of BMP-4, a vertebrate homolog of dpp. Based on these results, we propose that Mad is a highly conserved and essential element of the DPP signal transduction pathway.
Mechanisms of deep brain stimulation: Excitation or inhibition (2002)

There is little debate that deep brain stimulation (DBS) has been an effective tool in the treatment of Parkinson's disease as well as other movement disorders. There remains however, considerable debate concerning the mechanism(s) underlying its beneficial effect. The comparable effect of stimulation to ablation in the thalamus on tremor, and in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) on the motor signs associated with PD, have led many investigators to conclude that DBS acts to suppress neuronal activity, decreasing output from the stimulated site. There are, however, data that do not support this argument. Microdialysis studies in GPi showed increased levels of glutamate during STN stimulation, suggesting activation of glutamatergic output from the STN to the GPi. Studies in parkinsonian primates have demonstrated increased mean discharge rates of neurons in GPi during chronic stimulation in STN, and GPi stimulation in humans has been associated with a suppression of neuronal activity in the thalamus. Contrary to what one would expect if stimulation inhibits output from the stimulated structure, stimulation in GPe has been demonstrated to improve bradykinesia. Although arguments for increased output from the stimulated structure seem to conflict with the hypothesis that stimulation acts to inhibit neuronal activity, it is possible to explain these observations through a common mechanism, e.g. activation of fiber pathways. Based on this mechanism, the effect of stimulation on cellular activity in the stimulated site would be increased or decreased dependent on the neurotransmitter of the afferent fibers projecting to that site. However, in addition to activation of afferent fibers, projection axons from neurons in the stimulated structure, also readily excitable by electrical stimulation, would also be tonically activated and discharge independently of the soma, thereby increasing output from the structure during extracellular stimulation. Thus, although high frequency stimulation may inhibit neurons via activation of inhibitory afferents, the output from that structure may be increased as the result of activation of axonal elements leaving the target structure. This hypothesis would explain the present experimental results, is consistent with excitability profiles of neuronal elements based on their biophysical properties, and fits with more recent models emphasizing the role of altered patterns of neuronal activity in the development of hypokinetic and hyperkinetic movement disorders.
Evaluation of Genetic Variants in MicroRNA-Related Genes and Risk of Bladder Cancer (2008)

MicroRNAs (miRNA) are small noncoding RNA molecules involved in a diversity of cellular functions. Although it has been reported that global suppression of the miRNA biogenesis pathway leads to enhanced tumorigenesis, the effect of common genetic variants of miRNA-related genes on cancer predisposition is unclear. To better understand this effect, we genotyped 41 single-nucleotide polymorphisms (SNP) from 24 miRNA-related genes in a case-control study conducted in 746 Caucasian patients with bladder cancer and 746 matched controls. The homozygous variant genotype of a nonsynonymous SNP in the GEMIN3 gene (rs197414) was associated with a significantly increased bladder cancer risk [odds ratios (OR), 2.40; 95% confidence interval (95% CI), 1.04-5.56]. Several additional miRNA-related SNPs were also identified that showed a borderline significant association with bladder cancer risk. Haplotype analysis indicated that a common haplotype of the GEMIN4 gene was associated with a significantly increased bladder cancer risk with an OR of 1.25 (95% CI, 1.01-1.54). To assess the aggregate effects of the promising SNPs, we performed a combined unfavorable genotype analysis that included all SNPs showing at least a borderline statistical significance. We found that, compared with the low-risk reference group with less than two unfavorable genotypes, the medium-risk group with two unfavorable genotypes exhibited a 1.29-fold (0.92-1.81) increased risk whereas the high-risk group with more than two unfavorable genotypes exhibited a 1.92-fold (1.36-2.71) increased risk (P(trend) < 0.0001). Overall, this is the first epidemiologic study showing that miRNA-related genetic variants may affect bladder cancer risk individually and jointly.
Role of Oxides of Nitrogen in Tobacco-Specific Nitrosamine Formation in Flue-Cured Tobacco (2003)

Abstract Tobacco is known to contain a class of nitrosamines known as tobacco-specific nitrosamines or TSNA. Nitrosation of naturally occurring tobacco alkaloids is commonly accepted as the mechanism of TSNA formation in tobacco. Because green and freshly harvested tobaccos are virtually free of TSNA, formation and accumulation of TSNA are generally considered to occur during the curing process. Most recent hypotheses have focused on microbial reduction of nitrate to nitrite and other oxides of nitrogen (NOcompounds) that react with tobacco alkaloids to form TSNA during curing. This natural microbial process remains the prevalent hypothesis for TSNA formation in burley and other air-cured tobaccos. However, a different mechanism for the formation of TSNA in flue-cured tobacco, independent of microbial activity, is documented in this paper. It is common practice to flue-cure Virginia or blonde tobacco in bulk barns that incorporate forced air ventilation and temperature control. For the last thirty-five years, many modern bulk barns in North America generally have used liquid propane gas (LPG) with direct-fired burners that exhaust combustion gases directly into the barn where the tobacco is exposed to those gases. Our studies indicate that LPG combustion by-products in the exhaust stream, namely NO, react with naturally occurring tobacco alkaloids to form TSNA. Heat exchange curing methods preclude exposure of the tobacco to combustion gases and by-products, thereby eliminating this significant source of TSNA formation, without degrading leaf quality or smoking character. Research findings from 1998 and 1999 are presented to demonstrate the role of NOgases in TSNA formation and the significance of direct-fired curing as a primary source of TSNA formation in flue-cured tobacco. Also, data from an extensive barn conversion program in 2000, which resulted in a 94% average reduction in TSNA levels in cured flue-cured leaf, are presented.
Predictive VQ for noisy channel spectrum coding: AR or MA? (2002)

In this paper, the performance of different predictive vector quantization (PVQ) structures is studied and compared for different degrees of channel noise. Predictive quantization schemes with an auto-regressive (AR) decoder structure are compared with schemes that employ a moving average (MA) decoder. For noisy channels MA prediction performs better than AR. It is shown here that a combination of a PVQ scheme (AR or MA) and a memoryless VQ outperforms both types of traditional predictive quantizer schemes in noiseless as well as noisy channels.
Haplotype tagging efficiency and tagSNP sets portability in worldwide populations in NAT2 gene (2007)

Genetic polymorphism in the NAT2 gene is responsible for pronounced interindividual differences in the acetylation activity of the N-acetyltransferase 2 (NAT2) enzyme, which plays a crucial role in the metabolism of many clinically useful drugs and exogenous chemicals. Up to now, most association studies that have attempted to relate the acetylation phenotype in NAT2 to a variety of complex human disorders have led to contradictory results in different populations. Some of these inconsistencies may result from a poor knowledge of linkage patterns at NAT2 and their geographic variation. Using data from an extensive survey of the literature, we investigated the worldwide haplotype diversity and linkage disequilibrium structure of NAT2. For 28 population samples (including 3,994 individuals) from four continental regions (Africa, Europe, Asia, America), we evaluated haplotype tagging efficiency at NAT2 and defined population-specific sets of haplotype tagging SNPs (htSNPs) to be used for future association studies. Tagging common haplotypes yielded 2- to 3-fold savings in European and East Asian samples, while no gains from tagging were observed in samples of African ancestry, which displayed high haplotype diversity at NAT2. htSNPs sets appeared to be portable among populations from a same continent, provided that the continent-specific htSNPs sets were selected with a stringent criterion. A “cosmopolitan” htSNPs set suitable for all human populations could not be identified for the NAT2 gene, but a single four-htSNP set proved to perform successfully in all the non-African populations investigated.