Evidence suggesting the role of specific genetic factors in cigarette smoking.

Twin studies suggest that propensity to smoke and ability to quit smoking are influenced by genetic factors. As a means of investigating the risk of smoking associated with genetic polymorphisms in the dopamine transporter (SLC6A3) and the D? dopamine receptor (DRD2) genes, a case-control study of 289 smokers and 233 nonsmoking controls and a case series analysis of smokers were conducted. A significant effect for SLC6A3 and a significant gene-gene interaction were found in a logistic regression model, indicating that individuals with SLC6A3-9 genotypes were significantly less likely to be smokers, especially if they also had DRD2-A2 genotypes. Smokers with SLC6A3-9 genotypes were also significantly less likely to have started smoking before 16 years of age and had prior smoking histories indicating a longer period of prior smoking cessation. This study provides preliminary evidence that the SLC6A3 gene may influence smoking initiation and nicotine dependence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension

Once perceived as a disorder treated by vasodilation, pulmonary artery hypertension (PAH) has emerged as a pulmonary vascular disease with severe endothelial cell dysfunction. In the absence of a cure, many studies seek to understand the detailed mechanisms of EC regulation to potentially create more therapeutic options for PAH. Endothelial dysfunction is characterized by complex phenotypic changes including unchecked proliferation, apoptosis-resistance, enhanced inflammatory signaling and metabolic reprogramming. Recent studies have highlighted the role of epigenetic modifications leading to pro-inflammatory response pathways, endothelial dysfunction, and the progression of PAH. This review summarizes the existing literature on epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, which can lead to aberrant endothelial function. Our goal is to develop a conceptual framework for immune dysregulation and epigenetic changes in endothelial cells in the context of PAH. These studies as well as others may lead to advances in therapeutics to treat this devastating disease.     

Modified fully utilized design (MFUD) method for stress and displacement constraints

The traditional fully stressed method performs satisfactorily for stress-limited structural design. When this method is extended to include displacement limitations in addition to stress constraints, it is known as the Fully Utilized Design (FUD). Typically, the FUD produces an overdesign, which is the primary limitation of this otherwise elegant method. We have modified FUD in an attempt to alleviate the limitation. This new method, called the Modified Fully Utilized Design (MFUD) method, has been tested successfully on a number of problems that were subjected to multiple loads and had both stress and displacement constraints. The solutions obtained with MFUD compare favourably with the optimum results that can be generated by using non-linear mathematical programming techniques. The MFUD method appears to have alleviated the overdesign condition and offers the simplicity of a direct, fully stressed type of design method that is distinctly different from optimization and optimality criteria formulations. The MFUD method is being developed for practicing engineers who favour traditional design methods rather than methods based on advanced calculus and non-linear mathematical programming techniques. The Integrated Force Method (IFM) was found to be the appropriate analysis tool in the development of the MFUD method. In this paper, the MFUD method and its optimality are examined along with a number of illustrative examples. © 1998 This paper was produced under the auspices of the U.S. Government and it is therefore not subject to copyright in the U.S.     

Influence of Risk Factors for Male Infertility on Sperm Protein Composition

Male infertility is a common health problem that can be influenced by a host of lifestyle risk factors such as environment, nutrition, smoking, stress, and endocrine disruptors. These effects have been largely demonstrated on sperm parameters (e.g., motility, numeration, vitality, DNA integrity). In addition, several studies showed the deregulation of sperm proteins in relation to some of these factors. This review inventories the literature related to the identification of sperm proteins showing abundance variations in response to the four risk factors for male infertility that are the most investigated in this context: obesity, diabetes, tobacco smoking, and exposure to bisphenol-A (BPA). First, we provide an overview of the techniques used to identify deregulated proteins. Then, we summarise the main results obtained in the different studies and provide a compiled list of deregulated proteins in relation to each risk factor. Gene ontology analysis of these deregulated proteins shows that oxidative stress and immune and inflammatory responses are common mechanisms involved in sperm alterations encountered in relation to the risk factors.     

Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant

Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R₅₁₀stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G₆₆₀R) that, surprisingly, does not affect the Ca²⁺ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G₆₆₀R and R₅₁₀stop mutants and combinations with wild type TRPV6. We show that both the G₆₆₀R and R₅₁₀stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases.     

Grain velocity distribution in a mixed flow dryer

For corn drying one of the most popular possibilities in Europe is to use a mixed flow dryer. Large differences in the vertical grain particle velocity in this type of dryers are causing differences in the residence time. Hence, uneven drying occurs causing under-drying or over-drying of grain portions. To investigate the influences of the dryer walls and the air ducts on the particle velocity distribution experiments have been carried out in industrial and laboratory sized dryers and the measurements were compared with discrete element models. The particle flow velocity distribution between the air ducts is modelled analytically based on arching hypothesis. Using discrete element models the effects of different possible constructional modifications causing more even vertical grain particle velocity distribution were analyzed.     

Catastrophic misinterpretations as a predictor of symptom change during treatment for panic disorder.

Objective: Cognitive models of panic disorder suggest that change in catastrophic misinterpretations of bodily sensations will predict symptom reduction. To examine change processes, we used a repeated measures design to evaluate whether the trajectory of change in misinterpretations over the course of 12-week cognitive behavior therapy is related to the trajectory of change in a variety of panic-relevant outcomes. Method: Participants had a primary diagnosis of panic disorder (N = 43; 70% female; mean age = 40.14 years). Race or ethnicity was reported as 91% Caucasian, 5% African American, 2.3% biracial, and 2.3% “other.” Change in catastrophic misinterpretations (assessed with the Brief Body Sensations Interpretation Questionnaire; Clark et al., 1997) was used to predict a variety of treatment outcomes, including overall panic symptom severity (assessed with the Panic Disorder Severity Scale [PDSS]; Shear et al., 1997), panic attack frequency (assessed with the relevant PDSS item), panic-related distress/apprehension (assessed by a latent factor, including peak anxiety in response to a panic-relevant stressor—a straw breathing task), and avoidance (assessed by a latent factor, which included the Fear Questionnaire–Agoraphobic Avoidance subscale; Marks & Mathews, 1979). Results: Bivariate latent difference score modeling indicated that, as expected, change in catastrophic misinterpretations predicted subsequent reductions in overall symptom severity, panic attack frequency, distress/apprehension, and avoidance behavior. However, change in the various symptom domains was not typically a significant predictor of later interpretation change (except for the distress/apprehension factor). Conclusions: These results provide considerable support for the cognitive model of panic and speak to the temporal sequence of change processes during therapy. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Application of In Situ Neutron and X-Ray Measurements at High Temperatures in the Development of Co-Re-Based Alloys for Gas Turbines

Co-Re alloy development is prompted by the search for new materials for future gas turbines which can be used at temperatures considerably higher than the current day single crystal Ni-based superalloys. The Co-Re-based alloys have been designed to have very high melting range, and they are meant for application at +373 K (+100 °C) above Ni-superalloys. They are significantly different from the conventional Co-based alloys that are used in static components of today??s gas turbines, and the Co-Re alloys have never been used for structural applications before. The Co-Re-Cr system has complex microstructure with many different phases present. Phase transformations and stabilities of fine strengthening precipitates at high temperatures remain mostly unexplored in the Co-Re alloys, and to develop basic understanding, model ternary and quaternary compositions were studied within the alloy development program. In situ neutron and synchrotron measurements at high temperatures were extensively used for this purpose, and some recent results from the in situ measurements are presented. In particular, the effect of boron doping in Co-Re alloys and the stabilities of the fine TaC precipitates at high temperatures were investigated. A fine dispersion of TaC precipitates strengthens some Co-Re alloys, and their stabilities at the application temperatures are critical. In the beginning, the alloy development strategy is very briefly discussed.     

Acyl Migration Kinetics of Vegetable Oil 1,2-Diacylglycerols

The acyl migration kinetics of long-chain 1,2-diacylglycerol (1,2-DAG) to form 1,3-diacylglycerol (1,3-DAG) over the temperature range of 25–80 °C were examined using ¹H-NMR spectroscopy. Lipase-catalyzed ethanolysis of high-oleic sunflower oil, followed by a series of solvent extraction steps, generated high purity 1,2-DAG (0.93 mol fraction of the DAG content). The 1,2-DAG mole fraction of 0.32 at equilibrium was found to be insensitive to temperature, indicating that long-chain acyl group migration is neither endothermic nor exothermic. Determination of the temperature-dependent, first-order reaction kinetic parameters revealed a 1,2-DAG half life (t _1/2) of 3,425 h and 15.8 h at 25 and 80 °C, respectively. A comparison of 1,2-DAG with 2-monoacylglycerol indicated that there is no difference between the two in the potential energy state (ΔG ^‡) of their respective transitions states or cyclic intermediates. Product names are necessary to report factually on available data; however, the USDA neither guarantees nor warrants the standard of the product, and the use of the name by the USDA implies no approval of the product to the exclusion of others that may be suitable.     

水路和水面

罗德诺霍夫农舍位于奥地利慕维特尔区的偏僻空地上,一对已婚夫妇周末常来此度假。翻修建筑的时候,为更好利用花园,房主和建筑师把原来倾斜的场地修成了台地。场地北边的清水混凝土墙围成一个狭窄的长形水池。房子后方天井的窗户和坐凳是用裸露的混凝土墙建成的。容易引人注意,水生植物在墙上投射下形状不同的影子。水池还具有过滤的功能。在另一头,水流淌过沙砾池底,然后进入地下泳池。一个太阳能水泵把水抽回到过滤池。泳池的四周种着黑刺李树,一棵老樱桃树为池边的观景木台提供了遮荫功能。可循