Molecular Matchmaking: A Computational Study of the Electrostatic Interaction Between Chronic Myeloid Leukemia Drugs and Bcr-Abl Oncoprotein

In this project, we systematically use several computational techniques such as charge optimization and component analysis to study molecular recognition and binding in the chronic myeloid leukemia (CML) drug systems. Using CML drugs and their biological target, the Bcr-Abl oncoprotein, we systematically conduct a comparative analysis on five CML drugs bound to both the wild-type (WT) and T315I mutant Abl kinase. While early generation drugs (imatinib, nilotinib, and dasatinib) interact with Thr315 via a hydrogen bond, novel drugs ponatinib and PPY-A bypass interacting with Thr315 altogether. With the mutation to Ile at position 315, early generation drugs may experience a significant loss in favorable binding due to loss of electrostatic interaction and introduction of steric hindrance. To investigate the differential binding of these drugs to the WT and mutant, we optimize each of the drugs to the Abl kinase, allowing us to study how each drug binds to the native form. We also optimize PPY-A and ponatinib to the mutant T315I, comparing this charge distribution with the one generated from optimizing to the native form. Using component analysis, we identify chemical moieties of each drug that contribute favorably or unfavorably to the electrostatic free energy of binding. Taken together, we hope that by studying CML drugs, we will gain some insight into the larger picture of electrostatic binding interaction and potentially provide future direction for rational drug design and battling drug resistance

High Fill-Out, Extreme Mass Ratio Overcontact Binary Systems. X. The new discovered binary XY Leonis Minoris

The new discovered short-period close binary star, XY LMi, was monitored photometrically since 2006. It is shown that the light curves are typical EW-type and show complete eclipses with an eclipse duration of about 80 minutes. By analyzing the complete B, V, R, and I light curves with the 2003 version of the W-D code, photometric solutions were determined. It is discovered that XY LMi is a high fill-out, extreme mass ratio overcontact binary system with a mass ratio of q=0.148 and a fill-out factor of f=74.1%, suggesting that it is on the late evolutionary stage of late-type tidal-locked binary stars. As observed in other overcontact binary stars, evidence for the presence of two dark spots on both components are given. Based on our 19 epoches of eclipse times, it is found that the orbital period of the overcontact binary is decreasing continuously at a rate of dP/dt=-1.67\times10^{-7}\,days/year, which may be caused by the mass transfer from the primary to the secondary or/and angular momentum loss via magnetic stellar wind. The decrease of the orbital period may result in the increase of the fill-out, and finally, it will evolve into a single rapid-rotation star when the fluid surface reaching the outer critical Roche Lobe.Comment: 19 pages, 4 figures, 9 table

WEAR BEHAVIOR OF W-DLC COATING UNDER RECIPROCATING SLIDING MOTION

ABSTRACT Tungsten containing diamond like coatings have been used to improve reliability and durability of rubbing surfaces, thus their degradation becomes critical to predict component life. The gradual wear of such coatings is studied in this work using a high frequency reciprocating rig with the ball (coated)-flat configuration. In order to study the relationship between wear behavior and coating properties, two deposition recipes are used to deposit coatings on steel balls and these specimens have been tested in an interrupted manner under the same loading, frequency, and lubrication conditions. The coating wear quantified by measuring the wear scar on the balls with a surface profilometer shows nonlinear relationship with sliding distance. Recipe B with more Tungsten content in the top layer has better wear resistance. INTRODUCTION Tungsten containing diamond like coatings (W-DLC or WC/C) have been received considerable attention for tribological application in the past decade The focus of this experimental study is on the gradual wear. In order to study the relationship between wear rate and coating properties, two coating deposition recipes are used to deposit coatings on steel ball specimens. These specimens have been tested under the same loading, frequency, and lubrication conditions with a high frequency reciprocating rig (HFRR). The coating wear is quantified by measuring the wear scar on coated steel ball

Measuring Coverage in MNCH:A Validation Study Linking Population Survey Derived Coverage to Maternal, Newborn, and Child Health Care Records in Rural China

Accurate data on coverage of key maternal, newborn, and child health (MNCH) interventions are crucial for monitoring progress toward the Millennium Development Goals 4 and 5. Coverage estimates are primarily obtained from routine population surveys through self-reporting, the validity of which is not well understood. We aimed to examine the validity of the coverage of selected MNCH interventions in Gongcheng County, China.We conducted a validation study by comparing women's self-reported coverage of MNCH interventions relating to antenatal and postnatal care, mode of delivery, and child vaccinations in a community survey with their paper- and electronic-based health care records, treating the health care records as the reference standard. Of 936 women recruited, 914 (97.6%) completed the survey. Results show that self-reported coverage of these interventions had moderate to high sensitivity (0.57 [95% confidence interval (CI): 0.50-0.63] to 0.99 [95% CI: 0.98-1.00]) and low to high specificity (0 to 0.83 [95% CI: 0.80-0.86]). Despite varying overall validity, with the area under the receiver operating characteristic curve (AUC) ranging between 0.49 [95% CI: 0.39-0.57] and 0.90 [95% CI: 0.88-0.92], bias in the coverage estimates at the population level was small to moderate, with the test to actual positive (TAP) ratio ranging between 0.8 and 1.5 for 24 of the 28 indicators examined. Our ability to accurately estimate validity was affected by several caveats associated with the reference standard. Caution should be exercised when generalizing the results to other settings.The overall validity of self-reported coverage was moderate across selected MNCH indicators. However, at the population level, self-reported coverage appears to have small to moderate degree of bias. Accuracy of the coverage was particularly high for indicators with high recorded coverage or low recorded coverage but high specificity. The study provides insights into the accuracy of self-reports based on a population survey in low- and middle-income countries. Similar studies applying an improved reference standard are warranted in the future

IGG purity assay using a new high resolution SDS-GEL

Comunicaciones a congreso

Spectra of supernovae in the nebular phase

When supernovae enter the nebular phase after a few months, they reveal spectral fingerprints of their deep interiors, glowing by radioactivity produced in the explosion. We are given a unique opportunity to see what an exploded star looks like inside. The line profiles and luminosities encode information about physical conditions, explosive and hydrostatic nucleosynthesis, and ejecta morphology, which link to the progenitor properties and the explosion mechanism. Here, the fundamental properties of spectral formation of supernovae in the nebular phase are reviewed. The formalism between ejecta morphology and line profile shapes is derived, including effects of scattering and absorption. Line luminosity expressions are derived in various physical limits, with examples of applications from the literature. The physical processes at work in the supernova ejecta, including gamma-ray deposition, non-thermal electron degradation, ionization and excitation, and radiative transfer are described and linked to the computation and application of advanced spectral models. Some of the results derived so far from nebular-phase supernova analysis are discussed.Comment: Book chapter for 'Handbook of Supernovae,' edited by Alsabti and Murdin, Springer. 51 pages, 14 figure

Barriers to Antiretroviral Initiation in HIV-1–Discordant Couples

In Kenya and much of sub-Saharan Africa, nearly half of all couples affected by HIV are discordant. Antiretroviral therapy (ART) slows disease progression in HIV-1-infected individuals, and reduces transmission to uninfected partners. We examined time to ART initiation and factors associated with delayed initiation in HIV-1-discordant couples in Nairobi

Co-developed implementation guidelines to maximize acceptability, feasibility, and usability of mobile phone supervision in Kenya

Opportunities exist to leverage mobile phones to replace or supplement in-person supervision of lay counselors. However, contextual variables, such as network connectivity and provider preferences, must be considered. Using an iterative and mixed methods approach, we co-developed implementation guidelines to support the implementation of mobile phone supervision with lay counselors and supervisors delivering a culturally adapted trauma-focused cognitive behavioral therapy in Western Kenya. Guidelines were shared and discussed with lay counselors in educational outreach visits led by supervisors. We evaluated the impact of guidelines and outreach on the acceptability, feasibility, and usability of mobile phone supervision. Guidelines were associated with significant improvements in acceptability and usability of mobile phone supervision. There was no evidence of a significant difference in feasibility. Qualitative interviews with lay counselors and supervisors contextualized how guidelines impacted acceptability and feasibility – by setting expectations for mobile phone supervision, emphasizing importance, increasing comfort, and sharing strategies to improve mobile phone supervision. Introducing and discussing co-developed implementation guidelines significantly improved the acceptability and usability of mobile phone supervision. This approach may provide a flexible and scalable model to address challenges with implementing evidence-based practices and implementation strategies in lower-resourced areas