gebhart/patrepeval huggingface dataset:
Antiplatelet therapy in acute coronary syndromes (2008)

Antiplatelet agents are an essential component of the treatment of acute coronary syndromes (ACS). In numerous clinical trials, aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors have been shown to reduce the incidence of ischaemic events in patients with unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction. Aspirin is appropriate for lifelong therapy in patients with ACS. Clopidogrel is recommended for most patients with ACS for short- or long-term therapy, depending on the patient’s level of risk. New antiplatelet agents with distinct pharmacological properties may offer advantages, including faster onset of action, greater potency, and reversibility of effects. The treatment of ACS has evolved considerably in the past decade, with a trend towards greater consistency of care and more widespread provision of evidence-based therapies. Registries and surveys offer opportunities to educate health care providers on compliance with current guideline recommendations for the management of patients with ACS, which should lead to improved clinical outcomes.
Tight gas detection based on the reflectivity dispersion technology (2014)

The study focuses on the reflectivity dispersion caused by velocity dispersion related to pore fluid and its application to identify tight gas reservoirs. Seismic attenuation in viscoelastic media has two effects: (1) the change in frequency content and amplitude of a pulse propagating through attenuating media; (2) reflection coefficients are frequency dependent. Based on linear viscoelastic theory of velocity dispersion and the linearization of Zoeppritz equations, a new approximate reflection coefficient is presented considering P & S wave velocity dispersion, which adds the effects of frequencies and quality factors in reflection coefficient formula, representing the characteristics of reflection coefficient dependent by frequency, incident angle, quality factor etc. Based on the relationship between P-wave velocity and gas saturation, the reflected energy changes induced by reflectivity dispersion can be calculated and used to directly detect gas reservoirs, combining with seismic velocity, amplitude and energy attenuation mechanism caused by gas, such as squirt flow mechanism. This method has been successfully applied to characterize the distribution of tight gas sands in the GA101 well area of Sichuan Basin, and the results offer reliable foundations for seismic prospecting and well designing.
Naphthalene degradation via salicylate and gentisate by Rhodococcus sp. strain B4 (1992)

Rhodococcus sp. strain B4, isolated from a soil sample contaminated with polycyclic aromatic hydrocarbons, grows with naphthalene as the sole source of carbon and energy. Salicylate and gentisate were identified as intermediates in the catabolism of naphthalene. In contrast to the well-studied catabolic pathway encoded by the NAH7 plasmid of Pseudomonas putida, salicylate does not induce the genes of the naphthalene-degradative pathway in Rhodococcus sp. strain B4. The key enzymes of naphthalene degradation in Rhodococcus sp. strain B4 have unusual cofactor requirements. The 1,2-dihydroxynaphthalene oxygenase activity depends on NADH and the salicylate 5-hydroxylase requires NADPH, ATP, and coenzyme A.
Trypsin Stimulates Integrin α5β1-dependent Adhesion to Fibronectin and Proliferation of Human Gastric Carcinoma Cells through Activation of Proteinase-activated Receptor-2 (2000)

Trypsin is widely expressed in various non-pancreatic tissues at low levels and overexpressed in some types of human cancers. In the present study, we found that trypsin stimulates integrin-dependent adhesion and growth of MKN-1 human gastric carcinoma cells. MKN-1 cells expressed both proteinase-activated receptor-1 (PAR-1) and PAR-2, which are activated by thrombin and trypsin, respectively. Both trypsin and the PAR-2 ligand SLIGKV promoted integrin alpha(5)beta(1)-mediated adhesion of MKN-1 cells to fibronectin, and less effectively integrin alpha(v)beta(3)-mediated cell adhesion to vitronectin, but not that to type IV collagen or laminin-1 at all. Thrombin and the PAR-1 ligand SFLLRN promoted the cell adhesion to vitronectin more strongly than trypsin or the PAR-2 ligand, but not the cell adhesion to fibronectin at all. The cell adhesion-stimulating effect of the PAR-2 ligand was significantly reduced by the pre-treatment of cells with trypsin, indicating that the effect of trypsin is mediated by PAR-2 activation. The trypsin-stimulated cell adhesion to vitronectin, but not to fibronectin, was effectively inhibited by the G(i) protein blocker pertussis toxin, and both cell adhesions were completely inhibited by the Src kinase inhibitor herbimycin A. Furthermore, trypsin and the PAR-2 ligand stimulated growth of MKN-1 cells more strongly than thrombin or the PAR-1 ligand. These results show that trypsin regulates cellular adhesion and proliferation by inducing PAR-2/G protein signalings, and that the integrin alpha(5)beta(1)- and integrin alpha(v)beta(3)-dependent cell adhesions are regulated by different PAR/G protein signalings.
Synthesis and biological activity of selected 2,6-disubstituted(2-deoxy-.alpha.- and -.beta.-D-erythro-pentofuranosyl)purines (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and biological activity of selected 2,6-disubstituted(2-deoxy-.alpha.- and -.beta.-D-erythro-pentofuranosyl)purinesLeon F. Christensen, Arthur D. Broom, Morris J. Robins, and Alexander BlochCite this: J. Med. Chem. 1972, 15, 7, 735–739Publication Date (Print):July 1, 1972Publication History Published online1 May 2002Published inissue 1 July 1972https://pubs.acs.org/doi/10.1021/jm00277a010https://doi.org/10.1021/jm00277a010research-articleACS PublicationsRequest reuse permissionsArticle Views358Altmetric-Citations90LEARN 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
Autocorrelation and regularization in digital images. II. Simple image models (1989)

For pt.I see ibid., vol.26, no.4, p.463-73, July 1988. The variogram function used in geostatistical analysis is a useful statistic in the analysis of remotely sensed images. Using the results derived in Part I, the basic second-order, or covariance, properties of scenes modeled by simple disks of varying size and spacing after imaging into disk-shaped pixels are analyzed to explore the relationship between the image variograms and discrete object scene structure. The models provide insight into the nature of real images of the Earth's surface and the tools for a complete analysis of the more complex case of three-dimensional illuminated discrete-object images.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Stereochemical studies on medicinal agents. 31. Only one pharmacophore is required for the .kappa. opioid antagonist selectivity of norbinaltorphimine (1988)

We have investigated whether one or two pharmacophores are required for the kappa opioid receptor selectivity of the bivalent opioid antagonist norbinaltorphimine, (-)-1 (nor-BNI), by the synthesis and testing of its meso isomer 2. In smooth muscle preparations 2 was more potent than 1 and about half as selective as a kappa antagonist. Since 2 contains only one antagonist pharmacophore but yet retains substantial kappa selectivity, it is concluded that kappa selectivity is not dependent on the presence of two (-)-naltrexone-derived pharmacophores of 1. It is suggested that the kappa selectivity of (-)-1 and 2 is derived from the portions of the second halves of these molecules in that they mimic key "address" components of dynorphin at kappa opioid receptors.
Studies of polyarthritis and other lesions induced in rats by injection of mycobacterial adjuvant. I. General clinical and pathologic characteristics and some modifying factors (1959)

A reproducible polyarthritis was induced in rats by administering an emulsion of mineral oil and certain mycobacteria. Associated nonarticular lesions were observed. Pathogenesis of this experimental disease apparently involves hypersensitivity. Un reproducibile polyarthritis esseva inducite in rattos per le administration de un emulsion de oleo mineral e certe mycobacterios. Associate lesiones non-articular esseva observate. Le pathogenese de iste morbo experimental es apparentemente un question de hypersensibilitate.
Gene therapy strategies for hemophilia: benefits versus risks (2010)

Hemophilia is an inherited bleeding disorder caused by a deficiency of functional clotting factors VIII or IX in the blood plasma. The drawbacks of the classical protein substitution therapy fueled interest in alternative treatments by gene therapy. Hemophilia has been recognized as an ideal target disease for gene therapy because a relatively modest increase in clotting factor levels can result in a significant therapeutic benefit. Consequently, introducing a functional FVIII or FIX gene copy into the appropriate target cells could ultimately provide a cure for hemophilic patients. Several cell types have been explored for hemophilia gene therapy, including hepatocytes, muscle, endothelial and hematopoietic cells. Both nonviral and viral vectors have been considered for the development of hemophilia gene therapy, including transposons, γ-retroviral, lentiviral, adenoviral and adeno-associated viral vectors. Several of these strategies have resulted in stable correction of the bleeding diathesis in hemophilia A and B murine as well as canine models, paving the way towards clinical trials. Although clotting factor expression has been detected in hemophilic patients treated by gene therapy, the challenge now lies in obtaining prolonged therapeutic FVIII or FIX levels in these patients. This review highlights the benefits and potential risks of the different gene therapy strategies for hemophilia that have been developed.
Methods of Parallel Voxel Manipulation for 3D Digital Printing (2007)

A novel digital printing concept is explored for desktop fabrication of multimaterial objects with arbitrary 3D geometry. Digital objects are composed of many discrete, self-aligning voxels instead of continuous (analog) deposition techniques. Overall accuracy is determined by the individual voxels instead of the printer, and digital properties such as perfect replication and error correction are physically meaningful. The key challenge in digital printing is massively parallel, deterministic voxel manipulation. To quickly print millions of voxels while keeping errors low, we propose a parallel manufacturing process that exploits electrostatic forces to place an entire 2D pattern of voxels concurrently. Using a custom charged print head, we demonstrate selective 1.5mm voxel pick-up within a larger, self-aligned layer. We expect the principle to scale to million voxel layers using currently available technology.
Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary (1999)

It has recently been shown that androgens increase the growth of immature follicles in the primate ovary. In the present study the effect of androgens on ovarian insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression was investigated. The study groups included five follicular phase, placebo-treated controls, and four testosterone- and three dihydrotestosterone (DHT)-treated rhesus monkeys. The treatment period was 5 days. Both testosterone and DHT treatment resulted in significant, 3-4-fold increases in IGF-I mRNA concentration in granulosa, thecal and interstitial compartments. Likewise, both androgens induced significant increases in the amount of IGF-I receptor mRNA, most notably in thecal cells and less markedly in granulosa and interstitium (P < 0.05). These changes in amounts of IGF system mRNA were documented in growing follicles up to the small antral (</=1 mm diameter) stage. Larger follicles were too few in number for significant comparisons. By contrast, amounts of ovarian insulin receptor mRNA were not appreciably altered by androgen treatment. These data suggest that IGF-I and its cognate receptor may mediate androgen-induced ovarian follicular and thecal-interstitial growth.
A review of treatments for macular degeneration: a synopsis of currently approved treatments and ongoing clinical trials (2004)

Currently a patient with wet macular degeneration may have multiple investigational options that were unavailable several years ago. Ongoing clinical trials are aimed at determining the long-term safety and efficacy of these new pharmacologic and combination therapy modalities.
Excess soluble vascular endothelial growth factor receptor-1 in amniotic fluid impairs lung growth in rats: linking preeclampsia with bronchopulmonary dysplasia (2011)

Epidemiological studies have shown that maternal preeclampsia (PE) increases the risk of bronchopulmonary dysplasia (BPD), but the underlying mechanism is unknown. Soluble vascular endothelial growth factor receptor-1 (soluble VEGFR1, known as soluble fms-like tyrosine kinase 1, or sFlt-1), an endogenous antagonist of vascular endothelial growth factor (VEGF), is markedly elevated in amniotic fluid and maternal blood in PE. Therefore, we hypothesized that antenatal exposure to excess sFlt-1 disrupts lung development through impaired VEGF signaling in utero, providing a mechanistic link between PE and BPD. To determine whether increased sFlt-1 in amniotic fluid is sufficient to cause sustained abnormalities of lung structure during infancy, sFlt-1 or saline was injected into amniotic sacs of pregnant Sprague-Dawley rats at 20 days of gestation (term, 22 days). After birth, pups were observed through 14 days of age for study. We found that intra-amniotic sFlt-1 treatment decreased alveolar number, reduced pulmonary vessel density, and caused right and left ventricular hypertrophy in 14-day-old rats. In addition, intra-amniotic sFlt-1 treatment suppressed activation of lung VEGF receptor-2 and increased apoptosis in endothelial and mesenchymal cells in the newborn lung. We conclude that exposure to excess sFlt-1 in amniotic fluid during late gestation causes sustained reductions in alveolarization and pulmonary vascular growth during infancy, accompanied by biventricular hypertrophy suggesting pulmonary and systemic hypertension. We speculate that impaired VEGF signaling in utero due to exposure of high amniotic fluid levels of sFlt-1 in PE disrupts lung growth and contributes to the increased risk of BPD in infants born to mothers with PE.
Development of COX Inhibitors in Cancer Prevention and Therapy (2003)

On the strength of in vitro, in vivo, observational, and clinical data, nonsteroidal antiinflammatory drugs (NSAIDs)-also referred to as COX inhibitors-have emerged as lead compounds for cancer prevention, and possible adjuncts to cancer therapy. Thus far, the routine use of NSAIDs for these indications is limited, largely owing to toxicity concerns, the paucity of efficacy data for any specific target organ, and uncertainties with regard to the most appropriate regimen (i.e., the best agent, formulation, dose, route of administration, and duration). Strategies to address these concerns primarily aim to improve the therapeutic index (i.e., benefit:risk ratio) of COX inhibitors by 1) minimizing systemic exposures whenever feasible, 2) achieving greater mechanistic specificity, 3) coadministering agents that provide prophylaxis against common toxicities, and 4) coadministering other effective anticancer agents. Clinical trials testing most of these strategies have been completed or are under way. The National Cancer Institute has a substantial research portfolio dedicated to the identification, testing, and development of NSAIDs as preventive and therapeutic anticancer agents. Discovering how to apply NSAIDs in persons with-or at risk for-cancer, although challenging, has the potential for considerable clinical and public health benefits.
Role of AMP-activated protein kinase in mechanism of metformin action (2001)

Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism. Here we report that metformin activates AMPK in hepatocytes; as a result, acetyl-CoA carboxylase (ACC) activity is reduced, fatty acid oxidation is induced, and expression of lipogenic enzymes is suppressed. Activation of AMPK by metformin or an adenosine analogue suppresses expression of SREBP-1, a key lipogenic transcription factor. In metformin-treated rats, hepatic expression of SREBP-1 (and other lipogenic) mRNAs and protein is reduced; activity of the AMPK target, ACC, is also reduced. Using a novel AMPK inhibitor, we find that AMPK activation is required for metformin's inhibitory effect on glucose production by hepatocytes. In isolated rat skeletal muscles, metformin stimulates glucose uptake coincident with AMPK activation. Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders.
Results of a prototype television bandwidth compression scheme (1967)

The transmitter/receiver system for bandwidth or data-rate compression of television signals, described herein, is a prototype model of the experimental system of Cherry et al. [1]. The system is suitable for both black-and-white or half-tone pictures, in realistic noise conditions. The system parameters my be adjusted so that an optimum run-length encoding may be found; the great advantages of run-length quantizing are shown, especially with regard to practical instrumentation, leading to the use of buffer stores of modest capacity. One particular cheap form of receiver operates on a quantized-variable-velocity principle and, being much more simple and cheap than the transmitter, is suitable for use in situations requiring many receivers.
Whey Proteins Are More Efficient than Casein in the Recovery of Muscle Functional Properties following a Casting Induced Muscle Atrophy (2013)

The purpose of this study was to investigate the effect of whey supplementation, as compared to the standard casein diet, on the recovery of muscle functional properties after a casting-induced immobilization period. After an initial (I0) evaluation of the contractile properties of the plantarflexors (isometric torque-frequency relationship, concentric power-velocity relationship and a fatigability test), the ankle of 20 male adult rats was immobilized by casting for 8 days. During this period, rats were fed a standard diet with 13% of casein (CAS). After cast removal, rats received either the same diet or a diet with 13% of whey proteins (WHEY). A control group (n = 10), non-immobilized but pair-fed to the two other experimental groups, was also studied and fed with the CAS diet. During the recovery period, contractile properties were evaluated 7 (R7), 21 (R21) and 42 days (R42) after cast removal. The immobilization procedure induced a homogeneous depression of average isometric force at R7 (CAS: 2 19.068.2%; WHEY: 2 21.768.4%; P,0.001) and concentric power (CAS: 2 26.8616.4%, P,0.001; WHEY: 2 13.5621.8%, P,0.05) as compared to I0. Conversely, no significant alteration of fatigability was observed. At R21, isometric force had fully recovered in WHEY, especially for frequencies above 50 Hz, whereas it was still significantly depressed in CAS, where complete recovery occurred only at R42. Similarly, recovery of concentric power was faster at R21 in the 5002700u/s range in the WHEY group. These results suggest that recovery kinetics varied between diets, the diet with the whey proteins promoting a faster recovery of isometric force and concentric power output as compared to the casein diet. These effects were more specifically observed at force level and movement velocities that are relevant for functional abilities, and thus natural locomotion.
‘RNA walk’ a novel approach to study RNA–RNA interactions between a small RNA and its target (2009)

In this study we describe a novel method to investigate the RNA-RNA interactions between a small RNA and its target that we termed 'RNA walk'. The method is based on UV-induced AMT cross-linking in vivo followed by affinity selection of the hybrid molecules and mapping the intermolecular adducts by RT-PCR or real-time PCR. Domains carrying the cross-linked adducts fail to efficiently amplify by PCR compared with non-cross-linked domains. This method was calibrated and used to study the interaction between a special tRNA-like molecule (sRNA-85) that is part of the trypanosome signal recognition particle (SRP) complex and the ribosome. Four contact sites between sRNA-85 and rRNA were identified by 'RNA walk' and were further fine-mapped by primer extension. Two of the contact sites are expected; one contact site mimics the interaction of the mammalian Alu domain of SRP with the ribosome and the other contact sites include a canonical tRNA interaction. The two other cross-linked sites could not be predicted. We propose that 'RNA walk, is a generic method to map target RNA small RNAs interactions in vivo.
Peptide-specific Antibodies as Probes of the Topography of the Voltage-gated Channel in the Mitochondrial Outer Membrane of Neurospora crassa (1995)

The voltage-dependent anion-selective channel (VDAC) in mitochondrial outer membranes is formed by a polypeptide (M(r) 31,000) coded by a nuclear gene whose cDNA sequence is known for several organisms. Antibodies have been raised against synthetic peptides corresponding to four different regions in the predicted sequence of the VDAC polypeptide of the fungus Neurospora crassa (residues 1-20, amino terminus; 195-210, 251-268, and 272-283, carboxyl terminus). Specificity of the antibodies has been characterized in terms of binding to peptides or fungal mitochondria on microtiter plates and binding to mitochondrial proteins of several species in Western blots. Reactivity of three of the four antibodies with fungal mitochondria in suspension increases with lysis of outer membranes, indicating that the respective epitopes (including those near the amino and carboxyl termini) are exposed on the surface of the outer membrane that faces inside the mitochondrion. Preincubation of mitochondria with a polyanion that modulates VDAC voltage dependence strongly inhibits binding of the antibody against residues 251-268, whose epitopes are on the outer mitochondrial surface.