gebhart/patrepeval huggingface dataset:
Pentadienyl carboxamide derivatives as antagonists of platelet activating factor (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPentadienyl carboxamide derivatives as antagonists of platelet activating factorRobert W. Guthrie, Gerald L. Kaplan, Francis A. Mennona, Jefferson W. Tilley, Richard W. Kierstead, John G. Mullin, Ronald A. LeMahieu, Sonja Zawoiski, Margaret O'Donnell, and Cite this: J. Med. Chem. 1989, 32, 8, 1820–1835Publication Date (Print):August 1, 1989Publication History Published online1 May 2002Published inissue 1 August 1989https://pubs.acs.org/doi/10.1021/jm00128a026https://doi.org/10.1021/jm00128a026research-articleACS PublicationsRequest reuse permissionsArticle Views797Altmetric-Citations31LEARN 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
Cooperative activation of transcription by bovine papillomavirus type 1 E2 can occur over a large distance. (1990)

The viral transcriptional factors encoded by the E2 open reading frame bind to the specific DNA sequence elements ACCGNNNNCGGT, allowing activation or repression of transcription. We have analyzed bovine papillomavirus type 1 E2 transactivation using recombinant genes containing E2-binding sites inserted at either 3' or 5' positions relative to the heterologous transcriptional initiation site of the herpes simplex virus thymidine kinase gene. In these hybrid plasmids, strong transactivation required the presence of a minimum of two E2-binding sites in close proximity to the promoter or five binding sites at a distance. The presence of a single E2-binding motif 5', close to the initiation site, increased the efficiency of E2 transactivation from a distance in a more-than-additive manner. Since each E2-binding site bound a dimer of the E2 protein, these experiments suggest that transactivation by E2 requires the interaction between several E2 dimers with other essential transcription factors. This interaction may be facilitated by DNA looping, which would bring E2 molecules close to the promoter.
Cortical reorganization during recovery from complex regional pain syndrome (2004)

Changes of the somatotopic map within the S1 cortex may depend on CRPS pain and its recovery.
Reseña de dos libros de Domingo F. Sarmiento (1985)

destierro en Ch ile, donde ser periodista activo y jefe de los Itra romnticos emigrados argentinos.Durante el ao de 1845, se anuncia que Juan Manuel e Rosas piensa enviar a un comisionado a Chile, quien reclamar ante ese gobierno por las ctividades de los argentinos ex-patriados.Sarmiento se lanza una vez ms al combate.Durante los meses de mayo y junio aparece en los folletines de "El Progreso" su obra: "Vida e Facundo Quiroga" o~'Civilizacin y Barbarie".Este libro, "Vida de Facundo Quiroga" es una obra difcil de clasificar, ofrece como je central una biografa.En ella se inserta un estudio sociolgico y la exposicin de las opiniones e ideales del autor.Es sobre todo, la reconstruccin de un ambiente y la presentain de su resultado: el caudillismo y la barbarie dominadora.La finalidad poi tica que determ in la obra, fue contrarrestar la influencia de Rosas, on la presentacin de su propia figura y su gobierno y entrelazarlos continuamente con el tema central: "el tipo ingenuo" encarnado en Quiroga.Hechos posteriores se mezclan con otros anteriores, aunque la relacin se explique por qu aqullos, son el resultado de stos.Y la pasin que agita a Sarm iento, al exponer un cuadro que le horroriza por lo que tiene de retroceso para la civilizacin que ansa, igual que la prisa CQn que debi escribirlo, son factores que hacen que resulte a veces oscuro y confuso para quienes no conocen la sucesin cronolgica de los acontecim lentos relatados.Pero estas clrcunsi mcias no hacen mella ni en su fuerza, ni en su poder expresivo.En "Recuerdos de Provincia" el autor se refiere a Civilizacin y Barbarie: "escrib este libro, que deba ser trabajo meditado y enriquecido de datos y documentos histricos, con el fin de hacer conocer en Chile la poi tica de Rosas".Ms adelante escribe: "Este libro contiene en germen muchos otros escritos, y est destinado a perder a Rosas en el concepto del mundo ilustrado.El mismo ha sentido que era un golpe mortal a su poi tica, y en cinco aos de injurias dirigidas contra m , "La Gaceta Mercantil" no ha nombrado jams este libro, no obstante que no hay en Buenos Aires un federal de importancia que no lo tenga o no lo haya ledo, y que circulen
Anatomy and histology of joint innervation. (1997)

Joint diseases are mostly accompanied with hyperalgesia and/or pain in the joint region. As about 60% of the knee joint innervation may be classified as nociceptive, the structure of joint afferents became a matter of interest. The function of a sensory nerve fibre may be defined by its location, its morphology and its biochemical composition. This review is therefore focused on the composition of articular nerves, the morphology of sensory endings, their content of mitochondria and neuropeptides, and the plasticity of neuropeptide synthesis during joint inflammation. As the knee joint of the cat belongs to the best examined articular tissue concerning the sensory function of its afferent innervation, most of the morphological data have also been determined in this model. The histological studies revealed a dense afferent innervation of all parts of joints. Most of the afferents terminate in non-corpuscular endings. Although the ultrastructure of these endings has been examined in great detail, up to now no morphological and biochemical details can be used to discriminate between mechanosensitive and nociceptive afferents. Only the differences in the content of mitochondria in single nerve fibres may be related to different sensory functions. The content of different neuropeptides in joint afferents highlights an additional efferent function of a proportion of joint afferents. The dense innervation with peptidergic joint afferents indicates an important, but up to now mainly unknown role of neuropeptides in a normal joint. Pathological conditions like joint inflammations lead to an enhanced release of neuropeptides into the joint tissue and a specific upregulation of neuropeptide biosynthesis in articular afferents.
Transformation of a non-enzymatic toxin into a toxoid by genetic engineering (1997)

Curaremimetic toxins are typical non-enzymatic toxins that bind to their target [the nicotinic acetylcholine receptor (AChR)] through multiple residues. Nevertheless, we show that the concomitant substitutions of only three of the ten functionally important residues of such a toxin sufficed to cause an affinity decrease of the toxin for AChR that is higher than four orders of magnitude. Despite these triple mutations, the overall conformation of the mutated protein remains similar to that of a related recombinant toxin, as judged from both circular dichroism analysis and investigation of antigenicity, using monoclonal and polyclonal antibodies. Furthermore, we show that the detoxified toxin is capable of eliciting antibodies that neutralize the binding of a wild-type toxin to AChR. Therefore, transformation of a non-enzymatic toxin into a toxoid can be achieved, like in the case of enzymatic toxins, by introducing a small number of mutations at positions identified to be critical for expression of toxicity.
MicroRNA Expression Profiles in Lung Cancer Cooperated with Drug Sensitivity to EGFR Tyrosine Kinase Inhibitor (2009)

Lung cancer is the leading cause of cancer death and the most common cause of smoking-related mortality both in the United States and worldwide. However, approximately 25% of cases of lung cancer are not attributable to smoking. Molecular and clinical characteristics of lung cancers in never-smokers are extremely different from those in smokers. For example, G to T transversions of the p53 gene and K-ras mutations occur more frequently in lung adenocarcinomas from smokers than in lung carcinomas from never-smokers. In contrast, mutations of the epidermal growth factor receptor (EGFR) gene are frequently observed in adenocarcinomas from never-smokers. Striking differences in response rates to EGFR tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib and erlotinib, have been observed between lung cancers in never-smokers and those in smokers. Further understanding of the biological differences between lung cancers in never-smokers and those in smokers is necessary for the treatment strategies of lung cancer in never-smokers. MicroRNAs (miRNAs) are small noncoding RNA molecules comprising 18 to 25 nucleotides which are frequently located at previously reported regions for genetic alterations in cancers, suggesting that miRNAs are a new class of genes involved in human tumorigenesis. Expression levels of miRNAs are altered in most human cancers, including lung cancers. Recently, miRNAs have also been demonstrated to be prognostic biomarkers, including for the response to therapy, in leukemia, lung cancer, and colon cancer. These findings suggest that miRNA could serve as a novel diagnostic marker and a therapeutic target in human cancers, including lung cancer. We have previously analyzed the miRNA profiles of 104 lung cancers and found that high miR-155 expression and low let7a expression, as independent risk factors, have a negative prognostic impact in patients with lung adenocarcinoma. The altered miRNA profiles were reflected primarily by the profiles of lung cancers in smokers. In this study of 28 lung cancers in never-smokers, we found high expression levels of unique miRNAs in tumor tissues with a further statistically significant increase in cases with EGFR mutations by miRNA microarray analyses. In addition, the level of miR-21 was high in the lung adenocarcinoma cell line H3255, which contains an EGFR mutation and is hypersensitive to AG1478, an EGFR-TKI. After treatment with AG1478, expression levels of miR-21 were significantly decreased in H3255 cells with and without epidermal growth factor stimulation. Furthermore, inhibition of the miR-21 by antisense oligonucleotide-enhanced AG1478 induced apoptotic activities in lung cancer cells, which showed intermediate sensitivity to AG1478. These results suggest that aberrant expression of miR-21 contributes to the development of lung cancers in never-smokers through the activation of the EGFR signaling pathway. Our findings support the possibility of developing a treatment combining an EGFR-TKI with the inhibition of miR-21 in lung cancers from never-smokers.
Influence of inter-stimulus interval of spinal cord stimulation in patients with disorders of consciousness: A preliminary functional near-infrared spectroscopy study (2017)

Spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DOC), but the underlying mechanism and most effective procedures remain uncertain. To optimize the protocol, previous studies evaluated the frequency-specific effects of SCS on neurophysiological activities. However, whether and how the inter-stimulus interval (ISI) parameter affects the SCS neuromodulation in DOC remains unknown. We enrolled nine DOC patients who had implanted SCS devices and conducted three different durations of ISIs. Using functional near-infrared spectroscopy (fNIRS), we monitored the blood volume fluctuations in the prefrontal and occipital cortices during the SCS. The results showed that short stimuli (30 s) induced significant cerebral blood volume changes, especially in the prefrontal cortex, an important area in the consciousness system. By comparing the mean value of the responses from the first and the last block in each session, a shorter ISI was found to improve the blood volume in the prefrontal cortex. This phenomenon was more significant for the subgroup of patients with a favorable prognosis. These preliminary results imply that the ISI may be an important factor for SCS. The research paradigm proposed here also provides insights for further quantitative evaluations of the therapeutic effects of neuromodulation.
Effect of timing of insemination, numbers of spermatozoa and extender components on the pregnancy rate in mares inseminated with frozen stallion semen. (1975)

Fertilization rate was highest in mares inseminated with frozen semen within 12 hr of ovulation. Foaling rate was improved (P less than 0-05) by increasing the number of motile spermatozoa inseminated from 40 X 10(6) to 80 X 10(6) but was not further improved by increasing the number to 160 X 10(6) or by increasing the frequency of insemination from once to twice daily. The fertilizing capacity of spermatozoa frozen in one of the hydrogen ion extenders studied was dependent upon relative osmotic pressure and method of freezing (ampoules or pellets). Adjusting glycerol concentration from 7% to 2%, addition of glycerol 15 min before freezing and freezing 2 hr after extension all enhanced the fertilizing capacity of spermatozoa. Pregnancy rate per mare service period was higher (P less than 0-01) for mares inseminated with unextended semen (75%) than for extended semen containing no glycerol (50%) or extended semen containing 7% glycerol (35%). Although wide variability in the fertilizing capacity of spermatozoa from individual stallions was observed when semen was extended or extended and frozen, pregnancy rate was depressed in all stallions. It was concluded, therefore, that hydrogen ion extenders depress fertilizing capacity of stallion spermatozoa immediately after extension and show little promise as semen extenders for short- or long-term storage of stallion semen.
The elastic constants and ultrastructural organization of a basement membrane (lens capsule) (1976)

Abstract The elastic constants and ultrastructure of the basement membrane of the crystalline lens of the adult cat have been investigated. Negatively stained specimens examined by electron microscopy revealed fragments of parallel filaments showing little tendency to cross over or link with each other. High resolution micrographs also showed that the filament spacing was about 4.3 nm while the filaments had a regular periodicity of 4.1 nm along their length. Optical defraction analysis of the filaments suggested a possible helical array, the angle of tilt of the helices being about 50°. The elastic properties of the basement membrane were compared with those of a lightly vulcanized rubber membrane of the same thickness. At low stress values the Young modulus of elasticity of the basement membrane (0.82 x 106 Nm-2) and rubber membrane (1.32 x106 N m-2) were similar, but at moderate extension the basement membrane had a Young modulus of elasticity almost ten times greater than rubber which in contrast showed a slight decrease in elasticity. Also basement membrane had a low percentage of elongation (25%) compared with rubber (750 %) but the ultimate stress required to rupture basement membrane was similar to that of rubber. These data suggest that the extension of coiled superhelices of the filaments rather than the extension of non-extensile randomly linked filaments, would be an appropriate model of basement membrane. This satisfactorily predicts the stress-strain curve, and ultimate stress of the intact membrane, while on the molecular level it predicts the angle of tilt of the superhelix (53°) and indicates that the elasticity modulus of the filaments of which the membrane is composed is similar to the elasticity modulus of collagen filaments. Furthermore the change of entropy (1.0 → 1.6 J K-1 per mole of collagenous protein polypeptide residue) has been calculated from the external work necessary to rupture the membrane. In terms of the model this presumes that all the superhelices of which the membrane is composed have passed from a helical to a non-helical or extended state before rupture. A similar estimate for the growth entropy of polypeptide chains has previously been made from thermodynamic measurements on binary polypeptide solutions which induce either a random or helical configuration.
Transcobalamin II synthesized in the intestinal villi facilitates transfer of cobalamin to the portal blood (1999)

This study was designed to identify the cellular component of the intestinal villus where transcobalamin II (TCII) is synthesized, because this protein provides an essential function in the intestinal absorption of vitamin B(12) (cobalamin, Cbl). When a segment of proximal or distal small intestine of the guinea pig is cultured in medium containing [(57)Co]Cbl, TCII-[(57)Co]Cbl appears within 15 min. Northern blot analysis of RNA from both proximal and distal small intestine identified the TCII transcript. In situ hybridization of the distal ileum with (35)S-labeled TCII antisense transcript localized grains predominantly in crypts and in the lower third and central core of the villi. Grains were also evident at the base of the enterocytes in close apposition with the vascular network, whereas few grains appeared in the apical region of the columnar cells. This study provides evidence that TCII is constitutively expressed in the intestinal villi where vascular endothelium is abundant. In the distal ileum, where the intrinsic factor (IF) receptor is expressed, after uptake of IF-Cbl and the subsequent binding of free Cbl to TCII synthesized in the villi, the TCII-Cbl complex enters the microcirculation and passes into the portal blood.
Bile Acid Transport in Sister of P-Glycoprotein (ABCB11) Knockout Mice (2005)

In vertebrates, bile flow is essential for movement of water and solutes across liver canalicular membranes. In recent years, the molecular motor of canalicular bile acid secretion has been identified as a member of the ATP binding cassette transporter (ABC) superfamily, known as sister of P-glycoprotein (Spgp) or bile salt export pump (Bsep, ABCB11). In humans, mutations in the BSEP gene are associated with a very low level of bile acid secretion and severe cholestasis. However, as reported previously, because the spgp(-)(/)(-) knockout mice do not express severe cholestasis and have substantial bile acid secretion, we investigated the "alternative transport system" that allows these mice to be physiologically relatively normal. We examined the expression levels of several ABC transporters in spgp(-)(/)(-) mice and found that the level of multidrug resistance Mdr1 (P-glycoprotein) was strikingly increased while those of Mdr2, Mrp2, and Mrp3 were increased to only a moderate extent. We hypothesize that an elevated level of Mdr1 in the spgp(-)(/)(-) knockout mice functions as an alternative pathway to transport bile acids and protects hepatocytes from bile acid-induced cholestasis. In support of this hypothesis, we showed that plasma membrane vesicles isolated from a drug resistant cell line expressing high levels of P-glycoprotein were capable of transporting bile acids, albeit with a 5-fold lower affinity compared to Spgp. This finding is the first direct evidence that P-glycoprotein (Mdr1) is capable of transporting bile acids.
Arabidopsis hapless Mutations Define Essential Gametophytic Functions (2004)

In flowering plants, the egg develops within a haploid embryo sac (female gametophyte) that is encased within the pistil. The haploid pollen grain (male gametophyte) extends a pollen tube that carries two sperm cells within its cytoplasm to the embryo sac. This feat requires rapid, precisely guided, and highly polarized growth through, between, and on the surface of the cells of the stigma, style, and ovary. Pollen tube migration depends on a series of long-range signals from diploid female cells as well as a short-range attractant emitted by the embryo sac that guides the final stage of tube growth. We developed a genetic screen in Arabidopsis thaliana that tags mutant pollen with a cell-autonomous marker carried on an insertion element. We found 32 haploid-disrupting (hapless) mutations that define genes required for pollen grain development, pollen tube growth in the stigma and style, or pollen tube growth and guidance in the ovary. We also identified genomic DNA flanking the insertion element for eleven hap mutants and showed that hap1 disrupts AtMago, a gene whose ortholog is important for Drosophila cell polarity.
Mycobacterium tuberculosis appears to lack α‐ketoglutarate dehydrogenase and encodes pyruvate dehydrogenase in widely separated genes (2005)

Mycobacterium tuberculosis (Mtb) persists for prolonged periods in macrophages, where it must adapt to metabolic limitations and oxidative/nitrosative stress. However, little is known about Mtb's intermediary metabolism or antioxidant defences. We recently identified a peroxynitrite reductase-peroxidase complex in Mtb that included products of the genes sucB and lpd, which are annotated to encode the dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) components of alpha-ketoglutarate dehydrogenase (KDH). However, we could detect no KDH activity in Mtb lysates, nor could we reconstitute KDH by combining the recombinant proteins SucA (annotated as the E1 component of KDH), SucB and Lpd. We therefore renamed the sucB product dihydrolipoamide acyltransferase (DlaT). Mtb lysates contained pyruvate dehydrogenase (PDH) activity, which was lost when the dlaT gene (formerly, sucB) was disrupted. Purification of PDH from Mtb yielded AceE, annotated as an E1 component of PDH, along with DlaT and Lpd. Moreover, anti-DlaT antibody coimmunoprecipitated AceE. Finally, recombinant AceE, DlaT and Lpd, although encoded by genes that are widely separated on the chromosome, reconstituted PDH in vitro with Km values typical of bacterial PDH complexes. In sum, Mtb appears to lack KDH. Instead, DlaT and Lpd join with AceE to constitute PDH.
FEATUREIs usability obsolete? (2009)

research-article Share on FEATUREIs usability obsolete? Author: Katie Minardo Scott MAYA Design MAYA DesignView Profile Authors Info & Claims InteractionsVolume 16Issue 3May + June 2009 pp 6–11https://doi.org/10.1145/1516016.1516018Online:01 May 2009Publication History 13citation1,452DownloadsMetricsTotal Citations13Total Downloads1,452Last 12 Months147Last 6 weeks10 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