Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders

Genome-wide association studies (GWAS) of complex traits, such as alcohol use disorders (AUD), usually identify variants in non-coding regions and cannot by themselves distinguish whether the associated variants are functional or in linkage disequilibrium with the functional variants. Transcriptome studies can identify genes whose expression differs between alcoholics and controls. To test which variants associated with AUD may cause expression differences, we integrated data from deep RNA-seq and GWAS of four postmortem brain regions from 30 subjects with AUD and 30 controls to analyze allele-specific expression (ASE). We identified 88 genes with differential ASE in subjects with AUD compared to controls. Next, to test one potential mechanism contributing to the differential ASE, we analyzed single nucleotide polymorphisms (SNPs) in the 3′ untranslated regions (3′UTR) of these genes. Of the 88 genes with differential ASE, 61 genes contained 437 SNPs in the 3′UTR with at least one heterozygote among the subjects studied. Using a modified PASSPORT-seq (parallel assessment of polymorphisms in miRNA target-sites by sequencing) assay, we identified 25 SNPs that affected RNA levels in a consistent manner in two neuroblastoma cell lines, SH-SY5Y and SK-N-BE(2). Many of these SNPs are in binding sites of miRNAs and RNA-binding proteins, indicating that these SNPs are likely causal variants of AUD-associated differential ASE. In sum, we demonstrate that a combination of computational and experimental approaches provides a powerful strategy to uncover functionally relevant variants associated with the risk for AUD

Modeling and optimization for energy efficient large scale cooling operation

textOptimal chiller loading (OCL) is described as a means to improve the energy efficiency of a chiller plant operation. It is formulated as a multi-period constrained mixed integer non-linear optimization problem to optimize the total cooling load distribution through accurate chiller models. OCL is solved as a set of quadratic programs using sequential programming algorithm (SQP) in MATLAB. Based on application of the methodology to chiller systems at UT Austin and a semiconductor manufacturing facility, OCL can result in an annual energy savings of about 8%. However, the savings may reduce considerably in case of additional physical constraints on overall plant operation. With the addition of thermal energy storage (TES) to the system, OCL can reduce the daily cooling costs in the case of time varying electricity prices by 13.45% on an average. The energy efficiency of a chiller plant as a function of its chiller arrangement is studied by using fitted chiller models. If all other variables are kept same, chillers operating in parallel consume up to 9.62% less power as compared to when they are operated in series. Otherwise, chillers may operate up to 12.26% more efficiently in series depending on their chilled water outlet temperature values. The answer to the optimal chiller arrangement can be straightforward in some cases or can be a complex optimization problem in others.Chemical Engineerin

Practising Feminist Law, Some Reflections

The following article by two advocates examines the reasons why law reform in the areas of rape and violence against women in recent years, has proved ineffective. This is primarily because women continue to be denied the basic dignity of being believed. Little wonder then, that the way the law perceives women in violence has changed marginally while the way feminist practitioners view law and legal reforms has changed considerably. This paper was presented at the Indian Association of Women\u27s Studies Conference, Mysore, May 31- June, 1993

Improved Large-Scale Process Cooling Operation through Energy Optimization

This paper presents a study based on real plant data collected from chiller plants at the University of Texas at Austin. It highlights the advantages of operating the cooling processes based on an optimal strategy. A multi-component model is developed for the entire cooling process network. The model is used to formulate and solve a multi-period optimal chiller loading problem, posed as a mixed-integer nonlinear programming (MINLP) problem. The results showed that an average energy savings of 8.57% could be achieved using optimal chiller loading as compared to the historical energy consumption data from the plant. The scope of the optimization problem was expanded by including a chilled water thermal storage in the cooling system. The effect of optimal thermal energy storage operation on the net electric power consumption by the cooling system was studied. The results include a hypothetical scenario where the campus purchases electricity at wholesale market prices and an optimal hour-by-hour operating strategy is computed to use the thermal energy storage tank