Novel signaling pathways in pulmonary arterial hypertension (2015 Grover Conference Series)

The proliferative endothelial and smooth muscle cell phenotype, inflammation, and pulmonary vascular remodeling are prominent features of pulmonary arterial hypertension (PAH). Mutations in bone morphogenetic protein type 2 receptor (BMPR2) have been identified as the most common genetic cause of PAH and females with BMPR2 mutations are 2.5 times as likely to develop heritable forms of PAH than males. Higher levels of estrogen have also been observed in males with PAH, implicating sex hormones in PAH pathogenesis. Recently, the estrogen metabolite 16α-OHE1 (hydroxyestrone) was implicated in the regulation of miR29, a microRNA involved in modulating energy metabolism. In females, decreased miR96 enhances serotonin’s effect by upregulating the 5-hydroxytryptamine 1B (5HT1B) receptor. Because PAH is characterized as a quasi-malignant disease, likely due to BMPR2 loss of function, altered signaling pathways that sustain this cancer-like phenotype are being explored. Extracellular signal–regulated kinases 1 and 2 and p38 mitogen-activated protein kinases (MAPKs) play a critical role in proliferation and cell motility, and dysregulated MAPK signaling is observed in various experimental models of PAH. Wnt signaling pathways preserve pulmonary vascular homeostasis, and dysregulation of this pathway could contribute to limited vascular regeneration in response to injury. In this review, we take a closer look at sex, sex hormones, and the interplay between sex hormones and microRNA regulation. We also focus on MAPK and Wnt signaling pathways in the emergence of a proproliferative, antiapoptotic endothelial phenotype, which then orchestrates an angioproliferative process of vascular remodeling, with the hope of developing novel therapies that could reverse the phenotype

Effective Tools for Projects Delivered by Construction Manager–General Contractor Method

Construction manager–general contractor (CMGC) is an alternative project delivery method that is fast becoming more prevalently used to accelerate the delivery of highway projects. FHWA\u27s Every Day Counts program is encouraging state departments of transportation (DOTs) to adopt CMGC as a tool to deliver badly needed rapid renewal projects. As part of the program, a CMGC Peer Exchange conference was held in June 2011 in Salt Lake City, Utah. This paper synthesizes the tools used in implementing CMGC project delivery that were reported in those conference presentations by state DOTs with CMGC experience. That information is compared with similar information found in the literature to document the current state-of-the-practice in CMGC highway project delivery. It is concluded that jointly managing risk and developing a collaborative business climate are the two most important aspects of successful CMGC project delivery

Integrated Regressors and Tests of the Permanent Income Hypothesis

We use recent research on estimation and testing in the presence of unit roots to argue that Hall's (1978) t and F tests of whether consumption is predicted by lagged income, or by lags of consumption beyond the first, are asymptotically valid. A Monte Carlo experiment suggests that the asymptotic t and F distributions provide a good approximation to the actual finite sample distribution.

Climate adaptation by crop migration.

Many studies have estimated the adverse effects of climate change on crop yields, however, this literature almost universally assumes a constant geographic distribution of crops in the future. Movement of growing areas to limit exposure to adverse climate conditions has been discussed as a theoretical adaptive response but has not previously been quantified or demonstrated at a global scale. Here, we assess how changes in rainfed crop area have already mediated growing season temperature trends for rainfed maize, wheat, rice, and soybean using spatially-explicit climate and crop area data from 1973 to 2012. Our results suggest that the most damaging impacts of warming on rainfed maize, wheat, and rice have been substantially moderated by the migration of these crops over time and the expansion of irrigation. However, continued migration may incur substantial environmental costs and will depend on socio-economic and political factors in addition to land suitability and climate

Remote Sensing of Soils for Environmental Assessment and Management.

The next generation of imaging systems integrated with complex analytical methods will revolutionize the way we inventory and manage soil resources across a wide range of scientific disciplines and application domains. This special issue highlights those systems and methods for the direct benefit of environmental professionals and students who employ imaging and geospatial information for improved understanding, management, and monitoring of soil resources

Plasma proteome correlates of lipid and lipoprotein: biomarkers of metabolic diversity and inflammation in children of rural Nepal.

Proteins involved in lipoprotein metabolism can modulate cardiovascular health. While often measured to assess adult metabolic diseases, little is known about the proteomes of lipoproteins and their relation to metabolic dysregulation and underlying inflammation in undernourished child populations. The objective of this population study was to globally characterize plasma proteins systemically associated with HDL, LDL, and triglycerides in 500 Nepalese children. Abnormal lipid profiles characterized by elevated plasma triglycerides and low HDL-cholesterol (HDL-C) concentrations were common, especially in children with subclinical inflammation. Among 982 proteins analyzed, the relative abundance of 11, 12, and 52 plasma proteins was correlated with LDL-cholesterol (r = -0.43∼0.70), triglycerides (r = -0.39∼0.53), and HDL-C (r = -0.49∼0.79) concentrations, respectively. These proteins included apolipoproteins and numerous unexpected intracellular and extracellular matrix binding proteins, likely originating in hepatic and peripheral tissues. Relative abundance of two-thirds of the HDL proteome varied with inflammation, with acute phase reactants higher by 4∼40%, and proteins involved in HDL biosynthesis, cholesterol efflux, vitamin transport, angiogenesis, and tissue repair lower by 3∼20%. Untargeted plasma proteomics detects comprehensive sets of both known and novel lipoprotein-associated proteins likely reflecting systemic regulation of lipoprotein metabolism and vascular homeostasis. Inflammation-altered distributions of the HDL proteome may be predisposing undernourished populations to early chronic disease

Educating Pharmacy Students to Improve Quality (EPIQ) in Colleges and Schools of Pharmacy

Objective. To assess course instructors’ and students’ perceptions of the Educating Pharmacy Students and Pharmacists to Improve Quality (EPIQ) curriculum. Methods. Seven colleges and schools of pharmacy that were using the EPIQ program in their curricula agreed to participate in the study. Five of the 7 collected student retrospective pre- and post-intervention questionnaires. Changes in students’ perceptions were evaluated to assess their relationships with demographics and course variables. Instructors who implemented the EPIQ program at each of the 7 colleges and schools were also asked to complete a questionnaire. Results. Scores on all questionnaire items indicated improvement in students’ perceived knowledge of quality improvement. The university the students attended, completion of a class project, and length of coverage of material were significantly related to improvement in the students’ scores. Instructors at all colleges and schools felt the EPIQ curriculum was a strong program that fulfilled the criteria for quality improvement and medication error reduction education. Conclusion. The EPIQ program is a viable, turnkey option for colleges and schools of pharmacy to use in teaching students about quality improvement

Effect of semi-solid forging on microstructure and mechanical properties of in-situ cast Al-Cu-TiB2 composites

The present work deals with the effect of semisolid processing on microstructure and mechanical properties of Al-4.5% Cu – 5% TiB2 in-situ cast composites. The composite was prepared by flux assisted synthesis in which TiB2 particles were formed in-situ through an exothermic reaction between K2TiF6 and KBF4 halide salts. Al-4.5 wt% Cu alloy and Al-4.5% Cu-5% TiB2 composite samples were forged in semisolid state with 0.3 vol fraction of liquid. Semisolid forging was carried out for two forge reductions (30% and 50% forge reductions). Microstructure studies show that the semi-solid forging results in uniform distribution of TiB2 particles and Al2Cu particles in the composite. Further, TiB2 particles play a dual role as grain refiners as well as reinforcements of composites. EBSD and nano indentation studies shows that semisolid forging results in dynamic recrystallization of grains in the composite with significant grain refinement which leads to a marked increase in hardness and elastic modulus of the alloy as well as the composite