Regulation of vacuolar H+-ATPase activity by the Cdc42 effector Ste20 in Saccharomyces cerevisiae

In the budding yeast Saccharomyces cerevisiae, the Cdc42 effector Ste20 plays a crucial role in the regulation of filamentous growth, a response to nutrient limitation. Using the split-ubiquitin technique, we found that Ste20 forms a complex with Vma13, an important regulatory subunit of vacuolar H(+)-ATPase (V-ATPase). This protein-protein interaction was confirmed by a pulldown assay and coimmunoprecipitation. We also demonstrate that Ste20 associates with vacuolar membranes and that Ste20 stimulates V-ATPase activity in isolated vacuolar membranes. This activation requires Ste20 kinase activity and does not depend on increased assembly of the V1 and V0 sectors of the V-ATPase, which is a major regulatory mechanism. Furthermore, loss of V-ATPase activity leads to a strong increase in invasive growth, possibly because these cells fail to store and mobilize nutrients efficiently in the vacuole in the absence of the vacuolar proton gradient. In contrast to the wild type, which grows in rather small, isolated colonies on solid medium during filamentation, hyperinvasive vma mutants form much bigger aggregates in which a large number of cells are tightly clustered together. Genetic data suggest that Ste20 and the protein kinase A catalytic subunit Tpk2 are both activated in the vma13Δ strain. We propose that during filamentous growth, Ste20 stimulates V-ATPase activity. This would sustain nutrient mobilization from vacuolar stores, which is beneficial for filamentous growth.The project was supported by Deutsche Forschungsgemeinschaft grant HO 2098/3 to T.H. and NIH grant R01 GM50322 to P.M.K

Chromatic, Photometric and Thermal Modeling of LED Systems with Nonidentical LED Devices

published_or_final_versio

Hydrocarbon ratios during PEM-WEST A: A model perspective

A useful application of the hydrocarbon measurements collected during the Pacific Exploratory Mission (PEM-West A) is as markers or indices of atmospheric processing. Traditionally, ratios of particular hydrocarbons have been interpreted as photochemical indices, since much of the effect due to atmospheric transport is assumed to cancel by using ratios. However, an ever increasing body of observatonial and theoretical evidence suggests that turbulent mixing associated with atmospheric transport influences certain hydrocarbon ratios significantly. In this study a three-dimensional mesoscale photochemical model is used to study the interaction of photochemistry and atmospheric mixing on select hydrocarbons. In terms of correlations and functional relationships between various alkanes the model results and PEM-West A hydrocarbon observations share many similar characteristics as well as explainable differences. When the three-dimensional model is applied to inert tracers, hydrocarbon ratios and other relationships exactly follow those expected by simple dilution with model-imposed "background air," and the three-dimensional results for reactive hydrocarbons are quite consistent with a combined influence of photochemistry and simple dilution. Analogous to these model results, relationships between various hydrocarbons collected during the PEM-West A experiment appear to be consistent with this simplified picture of photochemistry and dilution affecting individual air masses. When hydrocarbons are chosen that have negligeble contributions to clean background air, unambiguous determinations of the relative contributions to photochemistry and dilution can be estimated from the hydrocarbon samples. Both the three-dimensional model results and the observations imply an average characteristic lifetime for dilution with background air roughly equivalent to the photochemical lifetime of butane for the western Pacific lower troposphere. Moreover, the dominance of OH as the primary photochemical oxidant downwind of anthropogenic source regions can be inferred from correlations between the highly reactive alkane ratios. By incorporating back-trajectory information within the three-dimensional model analysis, a correspondence between time and a particular hydrocarbon or hydrocarbon ratio can be determined, and the influence of atmospheric mixing or photochemistry can be quantified. Results of the three-dimensional model study are compared and applied to the PEM-West A hydrocarbon dataset, yielding a practical methodology for determining average OH concentrations and atmospheric mixing rates from the hydrocarbon measurements. Aircraft data taken below 2 km during wall flights east of Japan imply a diurnal average OH concentration of ∼3 × 106 cm-3. The characteristic time for dilution with background air is estimated to be ∼2.5 days for the two study areas examined in this work. Copyright 1996 by the American Geophysical Union

Basel risk weights, asset correlations, and book-to-market equity: evidence from Asian countries

We examine the effect of firm book-to-market equity values (BE/ME) on asset correlations which play an important role in determining risk weights under the current Basel capital requirements. Using firms in China, Hong Kong, Japan, Korea, Singapore and Taiwan over a sample period from 1988 to 2013, we find that BE/ME has a negative effect on asset correlations. This suggests a role for BE/ME as an additional factor in determining asset correlations, and thus risk weights, also potentially reducing incentives for regulatory capital arbitrage

A Partition-Based Random Search Method for Multimodal Optimization

Practical optimization problems are often too complex to be formulated exactly. Knowing multiple good alternatives can help decision-makers easily switch solutions when needed, such as when faced with unforeseen constraints. A multimodal optimization task aims to find multiple global optima as well as high-quality local optima of an optimization problem. Evolutionary algorithms with niching techniques are commonly used for such problems, where a rough estimate of the optima number is required to determine the population size. In this paper, a partition-based random search method is proposed, in which the entire feasible domain is partitioned into smaller and smaller subregions iteratively. Promising regions are partitioned faster than unpromising regions, thus, promising areas will be exploited earlier than unpromising areas. All promising areas are exploited in parallel, which allows multiple good solutions to be found in a single run. The proposed method does not require prior knowledge about the optima number and it is not sensitive to the distance parameter. By cooperating with local search to refine the obtained solutions, the proposed method demonstrates good performance in many benchmark functions with multiple global optima. In addition, in problems with numerous local optima, high-quality local optima are captured earlier than low-quality local optima

Birth weight and risk of ischemic heart disease: A Mendelian randomization study

published_or_final_versio

Precise Color Control of Red-Green-Blue Light-Emitting Diode Systems

postprin

Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study

published_or_final_versio

A predictive continuum dynamic user-optimal model for a polycentric urban city

A predictive continuum dynamic user-optimal model is extended to investigate the traffic equilibrium problem for a polycentric urban city with multiple central business districts (CBDs). The road network within the city is assumed to be dense and can be viewed as a continuum in which travellers can choose their routes in a two-dimensional space. Travellers are assumed to choose their route to minimise the actual total cost to the destination (i.e. the CBD). The model consists of two parts: the conservation law part and the Hamilton–Jacobi part. The finite volume method is used to solve each part on unstructured meshes. Because the two parts are closely interconnected and have different initial times, solving the model can be treated as a fixed-point problem, which is solved using a self-adaptive method of successive averages. Numerical experiments for an urban city with two CBDs are presented to demonstrate the effectiveness of the model and the numerical algorithm.postprin

Dynamic EMCUD for knowledge acquisition

[[abstract]]Due to the knowledge explosion, the new objects will be evolved in a dynamic environment. Hence, the knowledge can be classified into static knowledge and dynamic knowledge. Although many knowledge acquisition methodologies, based upon the Repertory Grid technique, have been proposed to systematically elicit useful rules from static grid from domain experts, they lack the ability of grid evolution to incrementally acquire the dynamic knowledge of new evolved objects. In this paper, we propose dynamic EMCUD, a new Repertory Grid-based knowledge acquisition methodology to elicit the embedded meanings of knowledge (embedded rules bearing on m objects and k object attributes), to enhance the ability of original EMCUD to iteratively integrate new evolved objects and new added attributes into the original Acquisition Table (AT) and original Attribute Ordering Table (AOT). The AOT records the relative importance of each attribute to each object in EMCUD to capture the embedded meanings with acceptable certainty factor value by relaxing or ignoring some minor attributes. In order to discover the new evolved objects, a collaborative framework including local knowledge based systems (KBSs) and a collaborative KBS is proposed to analyze the correlations of inference behaviors of embedded rules between multiple KBSs in a dynamic environment. Each KBS monitors the frequent inference behaviors of interesting embedded rules to construct a small AT increment to facilitate the acquisition of dynamic knowledge after experts confirming the new evolved objects. Moreover, the significance of knowledge may change after a period of time, a trend of all attributes to each evolved object is used to construct a new AOT increment to help experts automatically adjust the relative importance of each attribute to each object using time series analysis approach. Besides, three cases are considered to assist experts in adjusting the certainty factor values of the dynamic knowledge of the new evolved objects from the collection of inference logs in the collaborative KBS. To evaluate the performance of dynamic EMCUD in incrementally integrating new knowledge into the knowledge base, a worm detection prototype system is implemented. (c) 2006 Elsevier Ltd. All rights reserved