Detection of regulator genes and eQTLs in gene networks

Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure

Institutional distance and foreign subsidiary performance in emerging markets: moderating effects of ownership strategy and host-country experience

Institutional distance has been known to be an important driver of Multinational Enterprises’ strategies and performance in host countries. Based on a large panel dataset of 10562 firms operating in 17 emerging markets and spanning 80 home countries, we re-examine the relationship described by Gaur and Lu (2007) between regulatory institutional distance and subsidiary performance. We extend this research by (1) examining this relationship in the context of emerging markets, (2) examining the moderating effects of ownership strategy and host-country experience within the context of emerging markets and (3) accounting for a greater variety of institutions by including a large number of home and host countries. We find that institutional distance negatively affects subsidiary performance in emerging markets. Our findings also show that the negative effects of institutional distance on subsidiary performance are lesser for subsidiaries with partial ownership (than for subsidiaries with full ownership) and for subsidiaries with greater host-country experience. We discuss our findings with respect to Gaur and Lu’s model, which explores the relationships between these variables in a general context

Topical microbicides to prevent the transmission of HIV: formulation gaps and challenges

The efforts of the topical microbicide field to identify a safe and effective topical microbicide were realized in July of 2010 with the reporting of the results of the Centre for the AIDS Programme of Research in South Africa 004 trial. In this trial, a 1% tenofovir gel was found to reduce women’s risk for HIV acquisition by 39% compared to placebo. To understand the impact of this trial on future microbicide development, we must view it from the historical perspective of previous phases 2 and 3 clinical trials with detergents and sulfated polyanions. This knowledge and emerging information must then be parlayed into the next steps needed to create a safe, effective, and acceptable topical microbicide. This review will look at the lessons learned from preclinical and clinical development of topical microbicides, focusing on two significant future challenges: (1) topical microbicide formulation safety and (2) the critical role that adherence to product use has in determining safety and efficacy in clinical trials and ultimately commercial viability of the licensed product. In addition to framing these issues within our current understanding of formulation and prevention of HIV acquisition, recent advances in our understanding of the mechanism of HIV transmission and how it informs on future formulation strategies will be briefly discussed

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Modelling an integrated impact of fire, explosion and combustion products during transitional events caused by an accidental release of LNG

In a complex processing facility, there is likelihood of occurrence of cascading scenarios, i.e. hydrocarbon release, fire, explosion and dispersion of combustion products. The consequence of such scenarios, when combined, can be more severe than their individual impact. Hence, actual impact can be only representedby integration of above mentioned events. A novel methodology is proposed to model an evolving accident scenario during an incidental release of LNG in a complex processing facility. The methodology is applied to a case study considering transitional scenarios namely spill, pool formation and evaporation of LNG, dispersion of natural gas, and the consequent fire, explosion and dispersion of combustion products using Computational Fluid Dynamics (CFD). Probit functions are employed to analyze individual impacts and a ranking method is used to combine various impacts to identify risk during the transitional events.The results confirmed that in a large and complex facility, an LNG fire can transit to a vapor cloud explosion ifthe necessary conditions are met, i.e.the flammable range, ignition source with enough energy and congestion/confinement level. Therefore, the integrated consequences are more severe than those associated with the individual ones, and need to be properly assessed. This study would provide an insight for an effective analysis of potential consequences of an LNG spill in any LNG processing facility and it can be useful for the safety measured design of process facilities

Incidence and prevalence of patellofemoral pain: a systematic review and meta-analysis

Background: Patellofemoral pain is considered one of the most common forms of knee pain, affecting adults, adolescents, and physically active populations. Inconsistencies in reported incidence and prevalence exist and in relation to the allocation of healthcare and research funding, there is a clear need to accurately understand the epidemiology of patellofemoral pain. Methods: An electronic database search was conducted, as well as grey literature databases, from inception to June 2017. Two authors independently selected studies, extracted data and appraised methodological quality. If heterogeneous, data were analysed descriptively. Where studies were homogeneous, data were pooled through a meta-analysis. Results: 23 studies were included. Annual prevalence for patellofemoral pain in the general population was reported as 22.7%, and adolescents as 28.9%. Incidence rates in military recruits ranged from 9.7 – 571.4/1,000 person-years, amateur runners in the general population at 1080.5/1,000 person-years and adolescents amateur athletes 5.1% - 14.9% over 1 season. One study reported point prevalence within military populations as 13.5%. The pooled estimate for point prevalence in adolescents was 7.2% (95% Confidence Interval: 6.3% - 8.3%), and in female only adolescent athletes was 22.7% (95% Confidence Interval 17.4% - 28.0%). Conclusion: This review demonstrates high incidence and prevalence levels for patellofemoral pain. Within the context of this, and poor long term prognosis and high disability levels, PFP should be an urgent research priority