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Search Results: 1 - 10 of 217740 matches for " Luis G Valerio "
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In silico toxicology models and databases as FDA Critical Path Initiative toolkits
Luis G Valerio
Human Genomics , 2011, DOI: 10.1186/1479-7364-5-3-200
Abstract: Born out of computational chemistry and chemoinformatics, in silico methods for toxicology testing have brought new insight into several areas of toxicology, including new predictive tools and data-mining approaches to help make more effective use of large repositories of the results from in vitro and animal toxicology studies with xenobiotics. Substances that have been examined with these approaches include human pharmaceuticals, food ingredients, environmental agents and other chemicals to which there is significant human exposure. The use of in silico methods directed towards the evaluation of safety endpoints, as well as the deployment of chemoinformatics approaches in the analysis of genome responses after exposure to xenobiotics, has been supported by authorities through enacted legislation in the European Union--eg the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) legislation--to help to reduce, refine and replace animal testing [1]. In addition, recommendations recently made by the US National Research Council in its report, Toxicity Testing for the 21st Century: A Vision and a Strategy, also lend strong support to the use of computer-based technologies for the assessment of toxicities, with an emphasis on those relevant to protecting public health [2]. The US Food and Drug Administration (FDA) recognises the need to develop and identify new product development and technical tools, for example, using computational, statistical, bioinformatics and genomics methods as part of its broad-based national strategy for transforming the way that FDA-regulated products are developed, evaluated and manufactured [3]. The FDA's Critical Path Initiative describes this goal in its landmark report, Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products [4]. Among other opportunities, the publication points out the potential to develop computer-based (in silico) methods as tools for the early detection of
La importancia de la formación del recurso humano en salud
Emilio Valerio Gómez
Salud en Tabasco , 2006,
Abstract:
Modeling Chemical Interaction Profiles: I. Spectral Data-Activity Relationship and Structure-Activity Relationship Models for Inhibitors and Non-inhibitors of Cytochrome P450 CYP3A4 and CYP2D6 Isozymes
Brooks McPhail,Yunfeng Tie,Huixiao Hong,Bruce A. Pearce,Laura K. Schnackenberg,Weigong Ge,Luis G. Valerio,James C. Fuscoe,Weida Tong,Dan A. Buzatu,Jon G. Wilkes,Bruce A. Fowler,Eugene Demchuk,Richard D. Beger
Molecules , 2012, DOI: 10.3390/molecules17033383
Abstract: An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals—drugs, pesticides, and environmental pollutants—interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP) enzymes. In the present work, spectral data-activity relationship (SDAR) and structure-activity relationship (SAR) approaches were used to develop machine-learning classifiers of inhibitors and non-inhibitors of the CYP3A4 and CYP2D6 isozymes. The models were built upon 602 reference pharmaceutical compounds whose interactions have been deduced from clinical data, and 100 additional chemicals that were used to evaluate model performance in an external validation (EV) test. SDAR is an innovative modeling approach that relies on discriminant analysis applied to binned nuclear magnetic resonance (NMR) spectral descriptors. In the present work, both 1D 13C and 1D 15N-NMR spectra were used together in a novel implementation of the SDAR technique. It was found that increasing the binning size of 1D 13C-NMR and 15N-NMR spectra caused an increase in the tenfold cross-validation (CV) performance in terms of both the rate of correct classification and sensitivity. The results of SDAR modeling were verified using SAR. For SAR modeling, a decision forest approach involving from 6 to 17 Mold2 descriptors in a tree was used. Average rates of correct classification of SDAR and SAR models in a hundred CV tests were 60% and 61% for CYP3A4, and 62% and 70% for CYP2D6, respectively. The rates of correct classification of SDAR and SAR models in the EV test were 73% and 86% for CYP3A4, and 76% and 90% for CYP2D6, respectively. Thus, both SDAR and SAR methods demonstrated a comparable performance in modeling a large set of structurally diverse data. Based on unique NMR structural descriptors, the new SDAR modeling method complements the existing SAR techniques, providing an independent estimator that can increase confidence in a structure-activity assessment. When modeling was applied to hazardous environmental chemicals, it was found that up to 20% of them may be substrates and up to 10% of them may be inhibitors of the CYP3A4 and CYP2D6 isoforms. The developed models provide a rare opportunity for the environmental health branch of the public health service to extrapolate to hazardous chemicals directly from human clinical data. Therefore, the pharmacological and environmental health branches are both expected to benefit from these reported models.
Observations on the Web and Behavior of Wendilgarda Spiders (Araneae: Theridiosomatidae)
Jonathan Coddington,Carlos G. Valerio
Psyche , 1980, DOI: 10.1155/1980/69153
Abstract:
Insolvency Regulations and Economic Recession: An Austro-Libertarian Point of View  [PDF]
Valerio Tavormina
Beijing Law Review (BLR) , 2014, DOI: 10.4236/blr.2014.52014
Abstract:

Economic recovery after a crisis requires above all capital to support the most efficient investments. It is therefore counterproductive to delay selling off the assets of insolvent debtors through lengthy insolvency proceedings instead of letting the creditors free to enforce their claims in the speediest way.

Contrasting Wrongs by Privates to Keep the Market Rolling  [PDF]
Valerio Tavormina
Beijing Law Review (BLR) , 2015, DOI: 10.4236/blr.2015.61009
Abstract: The market must be defended (also) against the countrymen’s offenses, minimizing the costs involved and this minimization requires as a precondition the most precise possible predetermination of the offenses. The more effective regulatory device in preventing wrongs seems the threat of sanctions in excess of the redress, entrusting the decision on their application to the injured party, who should at the same time be the only entitled to reap the benefit, without distinctions between crimes and civil wrongs. The credibility of the threat, as well as any actual restauration of the harm and the prevention of reiteration, requires accuracy, speed and effectiveness in the application of sanctions and therefore: 1) the parties should have the duty to tell the truth and the instruments for finding the facts should be strengthened; 2) the judges’ mistakes should be sanctioned as well; 3) the jurisdiction should be drawn so as to favor a rapid application of sanctions against an incontrovertible finding of the facts; 4) any form of penalties’ remission should be subject to the consent of the injured party.
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient
Christopher J Valerio, John G Coghlan
Vascular Health and Risk Management , 2009, DOI: http://dx.doi.org/10.2147/VHRM.S4713
Abstract: osentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient Review (4558) Total Article Views Authors: Christopher J Valerio, John G Coghlan Published Date August 2009 Volume 2009:5 Pages 607 - 619 DOI: http://dx.doi.org/10.2147/VHRM.S4713 Christopher J Valerio, John G Coghlan Department of Cardiology, Royal Free Hospital, London, UK Abstract: Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcomes. Bosentan is an oral endothelin-1 receptor antagonist (ERA) that has been shown in a large randomized placebo-controlled trial (BREATHE-1) to be effective at improving exercise tolerance in patients with PAH in functional class III and IV. Further studies have been conducted showing: benefit in smaller subgroups of PAH, eg, congenital heart disease, efficacy in combination with other PAH therapies, eg, sildenafil, improved long-term survival compared with historical controls. More recently, controlled trials of new ERAs have included patients with milder symptoms; those in functional class II. Analysis of the functional class II data is often limited by small numbers. These trials have generally shown a similar treatment effect to bosentan, but there are no controlled trials directly comparing these new ERAs. The EARLY trial exclusively enrolled functional class II patients and assessed hemodynamics at 6 months. Though significant, the reduction in pulmonary vascular resistance is merely a surrogate marker for the intended aim of delaying disease progression. Significant adverse effects associated with bosentan include edema, anemia and transaminase elevation. These may preclude a long duration of treatment. Further studies are required to determine optimum treatment strategy in mild disease.
Bosentan in the treatment of pulmonary arterial hypertension with the focus on the mildly symptomatic patient
Christopher J Valerio,John G Coghlan
Vascular Health and Risk Management , 2009,
Abstract: Christopher J Valerio, John G CoghlanDepartment of Cardiology, Royal Free Hospital, London, UKAbstract: Pulmonary arterial hypertension (PAH) is a progressive disease with poor survival outcomes. Bosentan is an oral endothelin-1 receptor antagonist (ERA) that has been shown in a large randomized placebo-controlled trial (BREATHE-1) to be effective at improving exercise tolerance in patients with PAH in functional class III and IV. Further studies have been conducted showing: benefit in smaller subgroups of PAH, eg, congenital heart disease, efficacy in combination with other PAH therapies, eg, sildenafil, improved long-term survival compared with historical controls. More recently, controlled trials of new ERAs have included patients with milder symptoms; those in functional class II. Analysis of the functional class II data is often limited by small numbers. These trials have generally shown a similar treatment effect to bosentan, but there are no controlled trials directly comparing these new ERAs. The EARLY trial exclusively enrolled functional class II patients and assessed hemodynamics at 6 months. Though significant, the reduction in pulmonary vascular resistance is merely a surrogate marker for the intended aim of delaying disease progression. Significant adverse effects associated with bosentan include edema, anemia and transaminase elevation. These may preclude a long duration of treatment. Further studies are required to determine optimum treatment strategy in mild disease.Keywords: pulmonary arterial hypertension, bosentan, endothelin-1 receptor antagonist
Three Metrics to Explore the Openness of GitHub projects
Valerio Cosentino,Javier Luis Canovas Izquierdo,Jordi Cabot
Computer Science , 2014,
Abstract: Open source software projects evolve thanks to a group of volunteers that help in their development. Thus, the success of these projects depends on their ability to attract (and keep) developers. We believe the openness of a project, i.e., how easy is for a new user to actively contribute to it, can help to make a project more attractive. To explore the openness of a software project, we propose three metrics focused on: (1) the distribution of the project community, (2) the rate of acceptance of external contributions and (3) the time it takes to become an official collaborator of the project. We have adapted and applied these metrics to a subset of GitHub projects, thus giving some practical findings on their openness.
Distribución potencial de algunas leguminosas arbustivas en el altiplano central de México
Guevara-Escobar, Aurelio;González-Sosa, Enrique;Suzán-Azpiri, Humberto;Malda-Barrera, Guadalupe;Martínez y Díaz, Mahinda;Gómez-Sánchez, Maricela;Hernandez-Sandoval, Luis;Pantoja-Hernández, Yolanda;Olvera-Valerio, Diana;
Agrociencia , 2008,
Abstract: located on the central highlands of méxico, el bajío is an important agricultural region that faces water shortage, and therefore, it is necessary to increase aquifer recharge and decrease irrigated area. reforestation and agricultural reconversion based on tropical deciduous forest shrub species can help to achieve these goals. probability maps of predicted presence (pp) in el bajío were generated for twelve shrub species. pp probability was considered representative of the potential distribution of the species. biophysical variables spatially digitalized by instituto nacional de estadística, geografía e informática (inegi), botanical records from regional collections, and shared comisión nacional para el conocimiento y uso de la biodiversidad (conabio) data bases were used. the data were processed with the genetic algorithm garp (genetic algorithm for rule-setting prediction). the resulting predictions were different among the legumes, but the following species were outstanding for their high pp: caesalpinia spp. and pithecellobium dulce in central and southwestern el bajío; calliandra spp., eysenhardtia polystachya, lysiloma microphylla, and senna polyantha in the north; and most of the legumes in the eastern zone. contrary to expectations, prosopis laevigata and acacia farnesiana were not the species with the largest area of high pp.
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