Determinación de la Envolvente de Falla por Corte mediante el Ajuste con el Método Estadístico de Error en Variables a través de la Relación entre las Tensiones Principales

El presente trabajo se fundamentó en el desarrollo de la representación paramétrica de la envolvente de falla a los círculos de Mohr en roca intacta, en función de las tensiones principales. En el método propuesto, las tensiones se ajustan utilizando el método estadístico EIV (error en las variables), el cual no hace distinciones artificiales entre las variables independientes y dependientes. Para complementar la transformación desde el plano de esfuerzos principales al plano de Mohr, se utilizó el método de Balmer mediante la aplicación del análisis algebraico computacional. Para ilustrar y verificar la aplicación de la metodología propuesta, se usó el bien documentado conjunto de datos coleccionados de trabajos previos de Pincus y Sheorey. Para probar las mejoras provistas por este método, se comparó la función objetivo calculada (minimizar la probabilidad de una decisión errónea) con la representación de la ecuación paramétrica obtenida, usando varios métodos de mínimos cuadrados. Se encontró que la metodología propuesta y la transformación del método de Balmer, tienen dos ventajas: i) simplifica el proceso de crear una envolvente de falla para aplicaciones prácticas, y ii) minimiza la posibilidad de un juicio erróneo durante las aplicaciones (como es indicar falla en un estado estable o viceversa)

Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease

β-Blockers reduce mortality and improve symptoms in people with heart disease. However, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-threatening bronchospasm and a reduction in the efficacy of β2-agonist emergency rescue therapy. Thus current life-prolonging β-blockers are contraindicated in people with both heart disease and asthma. Here we describe NDD-713 and NDD-825, novel highly β1-selective neutral antagonists with good pharmaceutical properties that can potentially overcome this limitation. Radioligand binding studies and functional assays using human receptors expressed in CHO cells demonstrate that NDD-713 and NDD-825 have nanomolar β1-AR affinity, greater than 500-fold β1-AR vs β2-AR selectivity and no agonism. Studies in conscious rats demonstrated that they are orally bioavailable and cause pronounced β1-mediated reduction of heart rate while showing no effect on β2-mediated hindquarters vasodilatation. The compounds also have good disposition properties and show no adverse toxicological effects. They potentially offer a truly cardioselective β-blocker therapy for the large number of people with heart and respiratory, or peripheral vascular comorbidities

Genomic Phenotyping by Barcode Sequencing Broadly Distinguishes between Alkylating Agents, Oxidizing Agents, and Non-Genotoxic Agents, and Reveals a Role for Aromatic Amino Acids in Cellular Recovery after Quinone Exposure

Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N′-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic ‘barcode’, were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput ‘barcode’ sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.Unilever (Firm)National Cancer Institute (U.S.) (R01-CA055042 (now R01-ES022872))Massachusetts Institute of Technology. Center for Environmental Health Sciences (Grant NIEHS P30-ES002109

A new concept of wellbore-boundary condition for modeling liquid loading in gas wells

A new formulation of the wellbore-boundary condition in multiphase-reservoir simulation is suggested, allowing automatic determination of the direction of the flow at any time. It is particularly useful in coupled transient modeling of the liquid-loading phenomenon in gas wells. The traditional inflow-performance relationship (IPR) uses a common-wellblock productivity index (PI), but determines the inflow/outflow of the individual phases through a wellbore connection in an otherwise detached manner. The new approach takes into account that all phases should flow in the same direction and should have a common zero-flow condition. The restriction leads to the definition of a new state variable: the multiphase zero-flow pressure (MPZFP or P0). According to the new formulation, the flow direction at the connection is determined by the sign of the difference between this gridblock variable and the wellbore-flowing pressure. Advantages of the new formulation include that the flow is always cocurrent through a single connection (but multiple connections can lead to crossflow); that the meaning of wellblock PI is preserved; that the phase composition of the connection stream is determined by the upstream condition; that when wellbore pressure is far from the MPZFP, the traditional (detached) IPRs are recovered; and, last but not least, that previous numerical-convergence problems are completely eliminated during coupled dynamic simulation of the wellbore/reservoir system in the presence of significant capillary pressure. Examples illustrate the application of the new wellbore boundary condition in coupled modeling of the complex phenomena usually referred to as liquid loading

ON A MATHEMATICAL MODEL OF THE PRODUCTIVITY INDEX OF A WELL FROM RESERVOIR ENGINEERING ∗

Abstract. Motivated by the reservoir engineering concept of the productivity index of a producing oil well in an isolated reservoir, we analyze a time dependent functional, diffusive capacity, on the solutions to initial boundary value problems for a parabolic equation. Sufficient conditions providing for time independent diffusive capacity are given for different boundary conditions. The dependence of the constant diffusive capacity on the type of the boundary condition (Dirichlet, Neumann, or third boundary condition) is investigated using a known variational principle and confirmed numerically for various geometrical settings. An important comparison between two principal constant values of a diffusive capacity is made, leading to the establishment of criteria when the so-called pseudo-steady-state and boundary-dominated productivity indices of a well significantly differ from each other. The third boundary condition is shown to model the thin skin effect for the constant wellbore pressure production regime for a damaged well. The questions of stabilization and uniqueness of the time independent values of the diffusive capacity are addressed. The derived formulas are used in numerical study of evaluating the productivity index of a well in a general three-dimensional reservoir for a variety of well configurations

Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes

Background: Selenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation. Objective: We examined the association between baseline plasma concentrations of selenium and the prevalence of T2D, as well as whether participant characteristics or intake of other antioxidant nutrients modified this relation. Methods: We conducted cross-sectional analyses of 1727 participants from the Selenium Trial, a randomized clinical trial of selenium supplementation for colorectal adenoma chemoprevention that had data for baseline selenium plasma concentrations, T2D status, and dietary intake. Logistic regression modeling was used to evaluate the associations between plasma selenium concentrations and prevalent T2D, adjusting for confounding factors. Heterogeneity of effect by participant characteristics was evaluated utilizing likelihood-ratio tests. Results: Mean +/- SD plasma selenium concentrations for those with T2D compared with those without T2D were 143.6 +/- 28.9 and 138.7 +/- 27.2 ng/mL, respectively. After adjustment for confounding, higher plasma selenium concentrations were associated with a higher prevalence of T2D, with ORs (95% CIs) of 1.25 (0.80, 1.95) and 1.77 (1.16, 2.71) for the second and third tertiles of plasma selenium, respectively, compared with the lowest tertile (P-trend = 0.007). No significant effect modification was observed for age, sex, body mass index, smoking, or ethnicity. Increased odds of T2D were seen among those who were in the highest tertile of plasma selenium and the highest category of intake of ss-cryptoxanthin (P-trend = 0.03) and lycopene (P-trend = 0.008); however, interaction terms were not significant. Conclusions: These findings show that higher plasma concentrations of selenium were significantly associated with prevalent T2D among participants in a selenium supplementation trial. Future work is needed to elucidate whether there are individual characteristics, such as blood concentrations of other antioxidants, which may influence this relation.National Cancer Institute Cancer (NCI) Center Support Grant [P30 CA023074]; NIH/NCI [R01CA151708, P01 CA041108]12 month embargo; published online: 19 June 2018This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]