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11.
Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels. A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion channel targets accessible for drug screening. Specifically, genuine HTS parallel processing techniques based on arrays of planar silicon chips are being developed, but also lower throughput sequential techniques may be of value in compound screening, lead optimization, and safety screening. The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery.  相似文献   
12.
The aim of this study was to characterize patterns of energy balance through lactation of cows kept under constant feeding conditions. Danish Holstein, Danish Red, and Jersey cows were studied during consecutive lactations and remained on the same dietary treatment throughout. They were fed a normal (13.55 MJ of digestible energy/kg of dry matter) or a lower energy diet (12.88 MJ of digestible energy/kg of dry matter) ad libitum throughout lactation. Energy balance was calculated using the effective energy (EE) system in such a way that energy balance equated to body energy reserve change. In the EE system the energy values assigned to feeds are directly equivalent to the energy requirements of the animal; 1 MJ of EE supply has the same energy value as 1 MJ of lipid loss from the body. The resulting body energy change data were analyzed using a linear spline model. There was no evidence to suggest that different combinations of breed and parity required different knot placements. The Holstein mobilized significantly more body energy in early lactation than the Danish Red and Jersey breeds. Parity 1 cows mobilized significantly less than parity 2 and 3 cows. There was a significant interaction between breed and parity in the first half of lactation due to parity 1 Jersey cows having a greater mobilization than would be expected of the difference between parities in the other breeds. As lactation progressed, the differences between parities and between breeds decreased. Cows on the higher energy diet had a more positive energy balance. Within breed and parity, the following possible predictors of individual differences in body energy change were examined: fatness-corrected live weight, condition score at calving, and genotype. There was no difference in the predicted cow effect or residual energy balance profile when grouped according to quartiles of corrected live weight or according to condition score at calving. During the period of most negative energy balance (d 14) there was no significant relationship between live weight and intake, suggesting that, within diet type, the systematic patterns of body energy change through lactation in cows that were kept under stable and sufficient nutritional conditions cannot be accounted for by environmental factors such as constrained intake or condition score at calving. Thus, these patterns appear to have a genetic basis. The proportion of the phenotypic variation (remaining after accounting for fixed effects) accounted for by additive genetic effects varied through lactation from 4.2 to 13.0%. Genetic correlations between early and late lactation energy balances were low and close to zero, suggesting that body energy changes in early and late lactation are genetically independent traits.  相似文献   
13.
In contrast with major theories of attitudes and behavior, the authors propose that individuals are not equally motivated to pursue their self-interests. The authors show that differences in other orientation affect the extent to which actions and attitudes reflect self-interested calculation (instrumental rationality) and the extent to which beliefs represent their external environment (epistemic rationality). These differences have consequences for processes underlying a wide range of attitudes and behavior typically assumed to be rationally self-interested. Thus, the authors' model exposes a common explanation for diverse organizational phenomena. It also clarifies inconsistencies surrounding the validity of certain attitudinal and motivational models, the relationship between job attitudes and actions, cross-cultural differences in attitudes and behavior, escalation of commitment, and the relationship between chief executive officer characteristics and organizational performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
14.
On the basis of H. A. Simon (see record 1991-15229-001), the value of concern for others is proposed to derive from a process whereby individuals accept social information without carefully weighing its personal consequences. This value may thus reflect a sensitivity to social information that is unrelated to helping others. In 3 studies examining individuals' reactions to performance feedback, the reactions of persons high in concern for others were less contingent than those of persons low in concern for others on the personal costs and benefits of accepting and responding to feedback. In contrast, persons low in concern for others were likely to reject feedback that did not result in valued personal outcomes. Because many models of organizational behavior maintain that individuals act on the basis of their evaluation of personal consequences, this value may relate to a wide range of organizational phenomena. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
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The definition of organizational citizenship behavior (OCB) has evolved from one in which the behavior is unrewarded to one in which rewards play a significant role. As a result, little is known about mechanisms that sustain unrewarded OCB. We used the theory of other orientation to examine 2 mechanisms based on the norm of reciprocity: the obligation to reciprocate the benefits already received from another (“paying you back”) and the expected reciprocity that one’s actions will stimulate future benefits from another (“paying me forward”). We propose that these mechanisms are more or less influential depending on one’s motivational orientation. In 3 experiments using both trait and state indicators of other orientation, we found that the prosocial behavior of individuals higher in other orientation was more strongly influenced by the obligation to reciprocate and less affected by the expectation of reciprocity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
17.
This study investigated the proposition that a subordinate's communication style can affect a manager's fairness behavior during decision making and, consequently, can affect the subordinate's attitudes toward the decision, manager, and organization. Two studies were conducted to test these propositions in the context of performance appraisal decisions. First, a laboratory study demonstrated that appraisers engage in more interactionally fair behavior when interacting with an assertive appraisee than with an unassertive appraisee. Second, a quasiexperimental field design showed that training employees on assertiveness, when coupled with self-appraisal, is associated with positive attitudes toward the appraisal and trust in the manager. Implications for understanding the causes of fair behavior and improving the fairness of decisions are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   
18.
A total of 115 Danish dwellings were investigated during the winter season in order to evaluate the indoor environment. The sample was considered representative of Danish dwellings. Measurements of air-exchange rates in the bedrm showed a very low natural venthtion with a median air-exchange rate of 0.28 air changes per hour (ach) (interqmmle range (IQR): 0.12 –0.56).18% of the dwellings had a natural air-exchange below a detectable limit of 0.10 ach and 72% had air-exchanges rates below the requirements in Danish Building Codes of 0.50 ach. The investigations showed a statistically signifiant inverse correlation between air-exchange rates and absolute indoor humidity. Concentrations of formaldehyde and volatile organic compounds were measured in 36 dwellings. The median formaldehyde concentration was 0.037 mg/m3 which is well below the recommended indoor TLV The concentration of VOC in some cases reached a level that may be of importance for persons with sensitive airways. It is concluded that natural ventilation in a great number of Danish dwellings is too low fiom a health point of view and that the requirements in Danish Building codes are insufficient to ensure acceptable air-exchange rates.  相似文献   
19.
This study was conducted to examine the impact of building characteristics and indoor air quality on recurrent wheezing in infants. We followed a birth cohort (BAMSE) comprising 4089 children, born in predefined areas of Stockholm, during their first 2 years of life. Information on exposures was obtained from parental questionnaires when the children were 2 months and on symptoms and diseases when the children were 1 and 2 years old. Children with recurrent wheezing, and two age-matched controls per case, were identified and enrolled in a nested case-control study. The homes were investigated and ventilation rate, humidity, temperature and NO2 measured. We found that living in an apartment erected after 1939, or in a private home with crawl space/concrete slab foundation were associated with an increased risk of recurrent wheezing, odds ratio (OR) 2.5 (1.3-4.8) and 2.5 (1.1-5.4), respectively. The same was true for living in homes with absolute indoor humidity >5.8 g/kg, OR 1.7 (1.0-2.9) and in homes where windowpane condensation was consistently reported over several years, OR 2.2 (1.1-4.5). However, air change rate and type of ventilation system did not seem to affect the risk. In conclusion, relatively new apartment buildings, single-family homes with crawl space/concrete slab foundation, elevated indoor humidity, and reported wintertime windowpane condensation were associated with recurrent wheezing in infants. Thus, improvements of the building quality may have potential to prevent infant wheezing.  相似文献   
20.
A novel micro combined heat and power system and a dynamic model thereof were presented in part one of the publication. In the following, the control system and dynamic performance of the system are presented. The model is subjected to a measured consumption pattern of 25 Danish single family houses with measurements of heat, power and hot water consumption every 15th minute during one year.  相似文献   
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