Accurate Prediction of Protein Structural Class

Because of the increasing gap between the data from sequencing and structural genomics, the accurate prediction of the structural class of a protein domain solely from the primary sequence has remained a challenging problem in structural biology. Traditional sequence-based predictors generally select several sequence features and then feed them directly into a classification program to identify the structural class. The current best sequence-based predictor achieved an overall accuracy of 74.1% when tested on a widely used, non-homologous benchmark dataset 25PDB. In the present work, we built a multiple linear regression (MLR) model to convert the 440-dimensional (440D) sequence feature vector extracted from the Position Specific Scoring Matrix (PSSM) of a protein domain to a 4-dimensinal (4D) structural feature vector, which could then be used to predict the four major structural classes. We performed 10-fold cross-validation and jackknife tests of the method on a large non-homologous dataset containing 8,244 domains distributed among the four major classes. The performance of our approach outperformed all of the existing sequence-based methods and had an overall accuracy of 83.1%, which is even higher than the results of those predicted secondary structure-based methods

Accreting Millisecond X-Ray Pulsars

Accreting Millisecond X-Ray Pulsars (AMXPs) are astrophysical laboratories without parallel in the study of extreme physics. In this chapter we review the past fifteen years of discoveries in the field. We summarize the observations of the fifteen known AMXPs, with a particular emphasis on the multi-wavelength observations that have been carried out since the discovery of the first AMXP in 1998. We review accretion torque theory, the pulse formation process, and how AMXP observations have changed our view on the interaction of plasma and magnetic fields in strong gravity. We also explain how the AMXPs have deepened our understanding of the thermonuclear burst process, in particular the phenomenon of burst oscillations. We conclude with a discussion of the open problems that remain to be addressed in the future.Comment: Review to appear in "Timing neutron stars: pulsations, oscillations and explosions", T. Belloni, M. Mendez, C.M. Zhang Eds., ASSL, Springer; [revision with literature updated, several typos removed, 1 new AMXP added

Effectiveness of national cervical cancer screening programme in Taiwan: 12-year experiences

BACKGROUND: We examined cervical cancer incidence before and after nationwide cervical cancer screening was initiated in Taiwan in mid-1995. RESULTS: The invasive cancer incidence decreased by 47.8% during 1995-2006 . The carcinoma in situ incidence increased 1.7-fold during 1995-2000, and decreased by 19.6% during 2000-2006. CONCLUSION: The Taiwan national programme has significantly decreased invasive cervical cancer

Vegetation forcing modulates global land monsoon and water resources in a CO2-enriched climate

The global monsoon is characterised by transitions between pronounced dry and wet seasons, affecting food security for two-thirds of the world’s population. Rising atmospheric CO2 influences the terrestrial hydrological cycle through climate-radiative and vegetation-physiological forcings. How these two forcings affect the seasonal intensity and characteristics of monsoonal precipitation and runoff is poorly understood. Here we use four Earth System Models to show that in a CO2-enriched climate, radiative forcing changes drive annual precipitation increases for most monsoon regions. Further, vegetation feedbacks substantially affect annual precipitation in North and South America and Australia monsoon regions. In the dry season, runoff increases over most monsoon regions, due to stomatal closure-driven evapotranspiration reductions and associated atmospheric circulation change. Our results imply that flood risks may amplify in the wet season. However, the lengthening of the monsoon rainfall season and reduced evapotranspiration will shorten the water resources scarcity period for most monsoon regions

Integration of Women Veterans into VA Quality Improvement Research Efforts: What Researchers Need to Know

The Department of Veterans Affairs (VA) and other federal agencies require funded researchers to include women in their studies. Historically, many researchers have indicated they will include women in proportion to their VA representation or pointed to their numerical minority as justification for exclusion. However, women’s participation in the military—currently 14% of active military—is rapidly changing veteran demographics, with women among the fastest growing segments of new VA users. These changes will require researchers to meet the challenge of finding ways to adequately represent women veterans for meaningful analysis. We describe women veterans’ health and health-care use, note how VA care is organized to meet their needs, report gender differences in quality, highlight national plans for women veterans’ quality improvement, and discuss VA women’s health research. We then discuss challenges and potential solutions for increasing representation of women veterans in VA research, including steps for implementation research

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Collapse risk and residual drift performance of steel buildings using post-tensioned MRFs and viscous dampers in near-fault regions

The potential of post-tensioned self-centering moment-resisting frames (SC-MRFs) and viscous dampers to reduce the collapse risk and improve the residual drift performance of steel buildings in near-fault regions is evaluated. For this purpose, a prototype steel building is designed using different seismic-resistant frames, i.e.: moment-resisting frames (MRFs); MRFs with viscous dampers; SC-MRFs; and SC-MRFs with viscous dampers. The frames are modeled in OpenSees where material and geometrical nonlinearities are taken into account as well as stiffness and strength deterioration. A database of 91 near-fault, pulse-like ground motions with varying pulse periods is used to conduct incremental dynamic analysis (IDA), in which each ground motion is scaled until collapse occurs. The probability of collapse and the probability of exceeding different residual story drift threshold values are calculated as a function of the ground motion intensity and the period of the velocity pulse. The results of IDA are then combined with probabilistic seismic hazard analysis models that account for near-fault directivity to assess and compare the collapse risk and the residual drift performance of the frames. The paper highlights the benefit of combining the post-tensioning and supplemental viscous damping technologies in the near-source. In particular, the SC-MRF with viscous dampers is found to achieve significant reductions in collapse risk and probability of exceedance of residual story drift threshold values compared to the MRF. © 2016 Springer Science+Business Media Dordrech

T2 Values of Posterior Horns of Knee Menisci in Asymptomatic Subjects

[[abstract]]Purpose: The magnetic resonance (MR) T2 value of cartilage is a reliable indicator of tissue properties and therefore may be used as an objective diagnostic tool in early meniscal degeneration. The purpose of this study was to investigate age, gender, location, and zonal differences in MR T2 value of the posterior horns of knee menisci in asymptomatic subjects. Methods: Sixty asymptomatic volunteers (30 men and 30 women) were enrolled and divided into three different age groups: 20–34, 35–49 and 50–70 years. The inclusion criteria were BMI＜30 kg/cm2, normalized Western Ontario and McMaster Universities (WOMAC) pain score of zero, and no evidence of meniscal and ligamentous abnormalities on routine knee MR imaging. The T2 values were measured on images acquired with a T2-weighted fat-suppressed turbo spin-echo sequence at 3T. Results: The mean T2 values in both medial and lateral menisci for the 20–34, 35–49, and 50–70 age groups were 9.94 msec±0.94, 10.73 msec±1.55, and 12.36 msec±2.27, respectively, for women and 9.17 msec±0.74, 9.64 msec±0.67, and 10.95 msec±1.33, respectively, for men. The T2 values were significantly higher in the 50–70 age group than the 20–34 age group (P＜0.001) and in women than in men (P = 0.001, 0.004, and 0.049 for each respective age group). T2 values were significantly higher in medial menisci than in lateral menisci only in women age 50–70 (3.33 msec, P = 0.006) and in the white zone and red/white zone of the 50–70 and 35–49 age groups than that of the 20–34 age group (2.47, 1.02; 2.77, 1.16 msec, respectively, all P＜0.01). Conclusion: The MR T2 values of the posterior meniscal horns increase with increasing age in women and are higher in women than in men. The age-related rise of T2 values appears to be more severe in medial menisci than in lateral menisci. Differences exist in the white zone and red/white zone.[[incitationindex]]SCI[[booktype]]電子

Implementing and evaluating a regional strategy to improve testing rates in VA patients at risk for HIV, utilizing the QUERI process as a guiding framework: QUERI Series

<p>Abstract</p> <p>Background</p> <p>We describe how we used the framework of the U.S. Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) to develop a program to improve rates of diagnostic testing for the Human Immunodeficiency Virus (HIV). This venture was prompted by the observation by the CDC that 25% of HIV-infected patients do not know their diagnosis – a point of substantial importance to the VA, which is the largest provider of HIV care in the United States.</p> <p>Methods</p> <p>Following the QUERI steps (or process), we evaluated: 1) whether undiagnosed HIV infection is a high-risk, high-volume clinical issue within the VA, 2) whether there are evidence-based recommendations for HIV testing, 3) whether there are gaps in the performance of VA HIV testing, and 4) the barriers and facilitators to improving current practice in the VA.</p> <p>Based on our findings, we developed and initiated a QUERI step 4/phase 1 pilot project using the precepts of the Chronic Care Model. Our improvement strategy relies upon electronic clinical reminders to provide <it>decision support</it>; audit/feedback as a <it>clinical information system</it>, and appropriate changes in <it>delivery system design</it>. These activities are complemented by academic detailing and social marketing interventions to achieve <it>provider activation</it>.</p> <p>Results</p> <p>Our preliminary formative evaluation indicates the need to ensure leadership and team buy-in, address facility-specific barriers, refine the reminder, and address factors that contribute to inter-clinic variances in HIV testing rates. Preliminary unadjusted data from the first seven months of our program show 3–5 fold increases in the proportion of at-risk patients who are offered HIV testing at the VA sites (stations) where the pilot project has been undertaken; no change was seen at control stations.</p> <p>Discussion</p> <p>This project demonstrates the early success of the application of the QUERI process to the development of a program to improve HIV testing rates. Preliminary unadjusted results show that the coordinated use of audit/feedback, provider activation, and organizational change can increase HIV testing rates for at-risk patients. We are refining our program prior to extending our work to a small-scale, multi-site evaluation (QUERI step 4/phase 2). We also plan to evaluate the durability/sustainability of the intervention effect, the costs of HIV testing, and the number of newly identified HIV-infected patients. Ultimately, we will evaluate this program in other geographically dispersed stations (QUERI step 4/phases 3 and 4).</p