KCNK3 Mutation Causes Altered Immune Function in Pulmonary Arterial Hypertension Patients and Mouse Models

Loss of function KCNK3 mutation is one of the gene variants driving hereditary pulmonary arterial hypertension (PAH). KCNK3 is expressed in several cell and tissue types on both membrane and endoplasmic reticulum and potentially plays a role in multiple pathological process associated with PAH. However, the role of various stressors driving the susceptibility of KCNK3 mutation to PAH is unknown. Hence, we exposed kcnk3^fl/fl animals to hypoxia, metabolic diet and low dose lipopolysaccharide (LPS) and performed molecular characterization of their tissue. We also used tissue samples from KCNK3 patients (skin fibroblast derived inducible pluripotent stem cells, blood, lungs, peripheral blood mononuclear cells) and performed microarray, immunohistochemistry (IHC) and mass cytometry time of flight (CyTOF) experiments. Although a hypoxic insult did not alter vascular tone in kcnk3^fl/fl mice, RNASeq study of these lungs implied that inflammatory and metabolic factors were altered, and the follow-up diet study demonstrated a dysregulation of bone marrow cells in kcnk3^fl/fl mice. Finally, a low dose LPS study clearly showed that inflammation could be a possible second hit driving PAH in kcnk3^fl/fl mice. Multiplex, IHC and CyTOF immunophenotyping studies on human samples confirmed the mouse data and strongly indicated that cell mediated, and innate immune responses may drive PAH susceptibility in these patients. In conclusion, loss of function KCNK3 mutation alters various physiological processes from vascular tone to metabolic diet through inflammation. Our data suggests that altered circulating immune cells may drive PAH susceptibility in patients with KCNK3 mutation.     

Maximizing PV peak shaving with solar load control: validation of a web-based economic evaluation tool

We present an evaluation of a new version of the web-based clean power estimator (CPE) capable of evaluating the effectiveness and value of solar load control (SLC) for commercial applications in the US. Three experimental building case studies are used as a validation benchmark. The selected buildings include a large office building near New York City, a department store in Long Island, and another department store in Hawaii. The results of the CPE calculations are compared against results obtained using actual building load and colocated hourly actual solar radiation data.     

Electrochemical measurement of endogenous serotonin release from human blood platelets

Platelet aggregation in the bloodstream is tightly associated with the secretory function of platelets based on several types of cytoplasmic secretory granules, each sequestering distinct chemical messenger species. Dense-body granules are one prominent type of secretory granule responsible for storing small molecule chemical messengers. Upon platelet activation, the timely and rapid release of these small molecules is critical in facilitating platelet aggregation. Therefore, techniques capable of measuring real-time granule content release are needed to understand the fundamental properties of platelet secretion and aggregation. Existing techniques lack adequate time resolution or require potentially toxic exogenous reagents for real-time measurement of granule content release. Herein, we demonstrate a label-free electrochemical method based on the endogenous electroactive chemical messenger serotonin (5-hydroxytryptamine or 5-HT) for the real-time measurement of dense-body granule secretion from platelet suspensions; fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes was chosen on the basis of its excellent temporal resolution, high sensitivity, and the ability to provide the electrochemical signature cyclic voltammograms for molecular identification. Real-time serotonin release from thrombin-stimulated human platelet suspensions was successfully measured, and the amount and time course of the bulk serotonin release were found to agree well with data obtained from single platelet measurements, thus confirming accurate characterization of granular secretion. Furthermore, this electrochemical method was applied to study the stimulation-secretion coupling in platelets, serotonin storage and release dynamics with applied pharmacological agents, and chemical messenger storage deficiency in Hermansky-Pudlak Syndrome (HPS) platelets, and the potential of this method to reveal secretion behavior in both normal and diseased platelets has clearly been demonstrated.     

A Route Towards Sustainability Through Engineered Polymeric Interfaces

Chemical vapor deposition (CVD) of polymer films represent the marriage of two of the most important technological innovations of the modern age. CVD as a mature technology for growing inorganic thin films is already a workhorse technology of the microfabrication industry and easily scalable from bench to plant. The low cost, mechanical flexibility, and varied functionality offered by polymer thin films make them attractive for both macro and micro scale applications. This review article focuses on two energy and resource efficient CVD polymerization methods, initiated Chemical Vapor Deposition (iCVD) and oxidative Chemical Vapor Deposition (oCVD). These solvent‐free, substrate independent techniques engineer multi‐scale, multi‐functional and conformal polymer thin film surfaces and interfaces for applications that can address the main sustainability challenges faced by the world today.     

Understanding the role of gender in bloggers' switching behavior

Blog has become an increasingly popular form of social networking technology in recent years. Many world famous web sites (e.g., Microsoft, Yahoo!, and Google) are providing blog services on the Internet. Bloggers, therefore, can easily establish and maintain their blogs through such services. However, research on blogs' adoption and diffusion is rare. In this study, we attempt to study bloggers' post-adoption behaviors. We examine bloggers' intention to switch their blog services by building upon studies in the marketing and IS literature. Particularly, the role of gender is explored and an online survey is conducted to test the research model. Findings confirm that bloggers' intention to switch their blog services is strongly associated with three factors: satisfaction, sunk costs, and attractive alternatives. Meanwhile, moderating effects are found in gender, but not in sunk costs. Implications for both researchers and practitioners are provided.     

Misunderstanding of multiculturalism: Shouting fire in crowded theaters.

Comments on B. J. Fowers and F. C. Richardson's (see record 83-30335) article on the psychological construct of multiculturalism. It is stressed that the multicultural agenda is to stop imposing any one group's cultural values on all others, whether Eurocentric or not. The existence of separatist movements within multiculturalism should not be surprising, given a cultural context that has often been hostile to persons of color. The intercultural dialog that Fowers and Richardson advocate may be difficult to accomplish if are assumed to not desire a dialog. The interactions between the majority culture and multiculturalism have been primarily a majority monolog. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of Drug, Formulation, and Process Variables on Granulation and Compaction Characteristics of Heterogeneous Matrices: Part II. HPMC and PVP Systems

A heterogeneous matrix comprising hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) at various ratios was granulated using acetaminophen and pseudoephedrine as model drugs. The effect of drug, polymer ratio, total polymer loading, and volume of the granulating fluid on granule growth, granule size distribution, compaction, and tablet properties of the matrix was studied. Formulations containing both acetaminophen and pseudoephedrine required less water to granulate than those containing only acetaminophen. Moreover, the particle sizes of granules prepared with acetaminophen and pseudoephedrine were smaller than those containing only acetaminophen. Tablet hardness increased and friability decreased considerably in all formulations containing pseudoephedrine. In general, the tablet hardness and tablet disintegration time varied with changes in total polymer loading, fraction of HPMC in the matrix, and composition of the model drug(s). All the matrix systems studied showed good flow characteristics at different polymer loadings or HPMC-PVP ratio for matrices formulated with either acetaminophen or both acetaminophen and pseudoephedrine. The results of this study indicate that the presence of drug and/or other excipient(s) in the formulation affects the hydration characteristics of the matrix polymer(s) and compression properties of the granules.     

Development during adolescence: The impact of stage€nvironment fit on young adolescents' experiences in schools and in families.

Although most individuals pass through adolescence without excessively high levels of "storm and stress," many do experience difficulty. Why? Is there something unique about this developmental period that puts adolescents at risk for difficulty? This article focuses on this question and advances the hypothesis that some of the negative psychological changes associated with adolescent development result from a mismatch between the needs of developing adolescents and the opportunities afforded them by their social environments. It provides examples of how this mismatch develops in the school and in the home and how it is linked to negative age-related changes in early adolescents' motivation and self-perceptions. Ways in which more developmentally appropriate social environments can be created are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reliability and validity of the Functional Outcome Questionnaire for Aphasia (FOQ-A).

Objective: To perform a psychometric evaluation of the Functional Outcome Questionnaire for Aphasia (FOQ-A), a 32-item instrument designed to assess the extent to which a person who has had a stroke performs several important functional communication behaviors. Research Design: The FOQ-A was administered to family caregivers of persons with a history of left hemisphere stroke (N = 91) undergoing a comprehensive screening assessment to determine their eligibility for participation in research trials for novel stroke rehabilitation interventions. Results: Statistical analyses provided strong support for the internal consistency reliability and the convergent and discriminant validity of the FOQ-A. An exploratory factor analysis revealed a two-factor solution, Basic Verbal Expression and Conversational Response Skills. Conclusions: The present findings build on earlier evidence indicating that the FOQ-A has good psychometric properties and considerable promise as a measure of functional communication in aphasia rehabilitation. Future research will focus on the test-retest reliability, criterion-oriented validity, and predictive validity of the instrument. (PsycINFO Database Record (c) 2010 APA, all rights reserved)