Causal variation in yeast sporulation tends to reside in a pathway bottleneck

There has been extensive debate over whether certain classes of genes are more likely than others to contain the causal variants responsible for phenotypic differences in complex traits between individuals. One hypothesis states that input/output genes positioned in signal transduction bottlenecks are more likely than other genes to contain causal natural variation. The IME1 gene resides at such a signaling bottleneck in the yeast sporulation pathway, suggesting that it may be more likely to contain causal variation than other genes in the sporulation pathway. Through crosses between natural isolates of yeast, we demonstrate that the specific causal nucleotides responsible for differences in sporulation efficiencies reside not only in IME1 but also in the genes that surround IME1 in the signaling pathway, including RME1, RSF1, RIM15, and RIM101. Our results support the hypothesis that genes at the critical decision making points in signaling cascades will be enriched for causal variants responsible for phenotypic differences

Online Payment Systems: Are We on the Same Page?

Although scholars have enhanced our understanding of online payment systems (OPSs), our literature review shows that extant research has not fully addressed the way in which scholars have conceptualized OPSs and what roles organizations have played in establishing the OPSs. This study reviews the literature on OPSs and synthesizes the definitions of OPSs. This study also discusses the theoretical and practical implications of the roles of regulators, service providers, and technologies. Using the literature review method, we analyze the definitions of online payment systems from perspectives of academics, regulators, and practitioners. This study deepens our understanding of the concepts of OPSs by providing a conceptual framework of the roles of regulators, service providers, and technologies in shaping OPSs. Finally, this study goes beyond online shopping and the trust relationship in order to show a big picture of OPSs

An integrated machine learning approach for predicting DosR-regulated genes in Mycobacterium tuberculosis.

BACKGROUND: DosR is an important regulator of the response to stress such as limited oxygen availability in Mycobacterium tuberculosis. Time course gene expression data enable us to dissect this response on the gene regulatory level. The mRNA expression profile of a regulator, however, is not necessarily a direct reflection of its activity. Knowing the transcription factor activity (TFA) can be exploited to predict novel target genes regulated by the same transcription factor. Various approaches have been proposed to reconstruct TFAs from gene expression data. Most of them capture only a first-order approximation to the complex transcriptional processes by assuming linear gene responses and linear dynamics in TFA, or ignore the temporal information in data from such systems. RESULTS: In this paper, we approach the problem of inferring dynamic hidden TFAs using Gaussian processes (GP). We are able to model dynamic TFAs and to account for both linear and nonlinear gene responses. To test the validity of the proposed approach, we reconstruct the hidden TFA of p53, a tumour suppressor activated by DNA damage, using published time course gene expression data. Our reconstructed TFA is closer to the experimentally determined profile of p53 concentration than that from the original study. We then apply the model to time course gene expression data obtained from chemostat cultures of M. tuberculosis under reduced oxygen availability. After estimation of the TFA of DosR based on a number of known target genes using the GP model, we predict novel DosR-regulated genes: the parameters of the model are interpreted as relevance parameters indicating an existing functional relationship between TFA and gene expression. We further improve the prediction by integrating promoter sequence information in a logistic regression model. Apart from the documented DosR-regulated genes, our prediction yields ten novel genes under direct control of DosR. CONCLUSIONS: Chemostat cultures are an ideal experimental system for controlling noise and variability when monitoring the response of bacterial organisms such as M. tuberculosis to finely controlled changes in culture conditions and available metabolites. Nonlinear hidden TFA dynamics of regulators can be reconstructed remarkably well with Gaussian processes from such data. Moreover, estimated parameters of the GP can be used to assess whether a gene is controlled by the reconstructed TFA or not. It is straightforward to combine these parameters with further information, such as the presence of binding motifs, to increase prediction accuracy.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Exploring Planets with Directed Aerial Robot Explorers

Global Aerospace Corporation (GAC) is developing a revolutionary system architecture for exploration of planetary atmospheres and surfaces from atmospheric altitudes. The work is supported by the NASA Institute for Advanced Concepts (NIAC). The innovative system architecture relies upon the use of Directed Aerial Robot Explorers (DAREs), which essentially are long-duration-flight autonomous balloons with trajectory control capabilities that can deploy swarms of miniature probes over multiple target areas. Balloon guidance capabilities will offer unprecedented opportunities in high-resolution, targeted observations of both atmospheric and surface phenomena. Multifunctional microprobes will be deployed from the balloons once over the target areas, and perform a multitude of functions, such as atmospheric profiling or surface exploration, relaying data back to the balloons or an orbiter. This architecture will enable low-cost, low-energy, long-term global exploration of planetary atmospheres and surfaces. This paper focuses on a conceptual analysis of the DARE architecture capabilities and science applications for Venus, Titan and Jupiter. Preliminary simulations with simplified atmospheric models show that a relatively small trajectory control wing can enable global coverage of the atmospheres of Venus and Titan by a single balloon over a 100-day mission. This presents unique opportunities for global in situ sampling of the atmospheric composition and dynamics, atmospheric profiling over multiple sites with small dropsondes and targeted deployment of surface microprobes. At Jupiter, path guidance capabilities of the DARE platforms permits targeting localized regions of interest, such as "hot spots" or the Great Red Spot. A single DARE platform at Jupiter can sample major types of the atmospheric flows (zones and belts) over a 100-day mission. Observations by deployable probes would reveal if the differences exist in radiative, dynamic and compositional environments at these sites

A Bayesian Change point model for differential gene expression patterns of the DosR regulon of Mycobacterium tuberculosis.

BACKGROUND: Low oxygen availability has been shown previously to stimulate M. tuberculosis to establish non-replicative persistence in vitro. The two component sensor/regulator dosRS is a major mediator in the transcriptional response of M. tuberculosis to hypoxia and controls a regulon of approximately 50 genes that are induced under this condition. The aim of this study was to determine whether the induction of the entire DosR regulon is triggered as a synchronous event or if induction can unfold as a cascade of events as the differential expression of subsets of genes is stimulated by different oxygen availabilities. RESULTS: A novel aspect of our work is the use of chemostat cultures of M. tuberculosis which allowed us to control environmental conditions very tightly. We exposed M. tuberculosis to a sudden drop in oxygen availability in chemostat culture and studied the transcriptional response of the organism during the transition from a high oxygen level (10% dissolved oxygen tension or DOT) to a low oxygen level (0.2% DOT) using DNA microarrays. We developed a Bayesian change point analysis method that enabled us to detect subtle shifts in the timing of gene induction. It results in probabilities of a change in gene expression at certain time points. A computational analysis of potential binding sites upstream of the DosR-controlled genes shows how the transcriptional responses of these genes are influenced by the affinity of these binding sites to DosR. Our study also indicates that a subgroup of DosR-controlled genes is regulated indirectly. CONCLUSION: The majority of the dosR-dependent genes were up-regulated at 0.2% DOT, which confirms previous findings that these genes are triggered by hypoxic environments. However, our change point analysis also highlights genes which were up-regulated earlier at levels of about 8% DOT indicating that they respond to small fluctuations in oxygen availability. Our analysis shows that there are pairs of divergent genes where one gene in the pair is up-regulated before the other, presumably for a flexible response to a constantly changing environment in the host.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Structural and superconducting properties of MgB2−x_{2-x}Bex_x

We prepared MgB$_{2-x}$Be$_{x}$ ($x=0$, 0.2, 0.3, 0.4, and 0.6) samples where B is substituted with Be. MgB$_{2}$ structure is maintained up to $x=0.6$. In-plane and inter-plane lattice constants were found to decrease and increase, respectively. Superconducting transition temperature $T_{c}$ decreases with $x$. We found that the $T_{c}$ decrease is correlated with in-plane contraction but is insensitive to carrier doping, which is consistent with other substitution studies such as Mg$_{1-x}$Al$_{x}$B$_{2}$ and MgB$_{2-x}$C$_{x}$. Implication of this work is discussed in terms of the 2D nature of $\sigma$-band.Comment: 3 pages,4 figures, to be published in Phys. Rev.

Performance analysis of a flux-concentrating field-modulated permanent-magnet machine for direct-drive applications

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Diagnosis of the significance of inconsistencies in software designs: a framework and its experimental evaluation

This paper presents: (a) a framework for assessing the significance of inconsistencies which arise in object-oriented design models that describe software systems from multiple perspectives, and (b) the findings of a series of experiments conducted to evaluate it. The framework allows the definition of significance criteria and measures the significance of inconsistencies as beliefs for the satisfiability of these criteria. The experiments conducted to evaluate it indicate that criteria definable in the framework have the power to create elaborate rankings of inconsistencies in models

Self Selection Does Not Increase Other-Regarding Preferences among Adult Laboratory Subjects, but Student Subjects May Be More Self-Regarding than Adults

We use a sequential prisoner's dilemma game to measure the other-regarding behavior in samples from three related populations in the upper Midwest of the United States: 100 college students, 94 non-student adults from the community surrounding the college and 1,069 adult trainee truckers in a residential training program. Both of the first two groups were recruited according to procedures commonly used in experimental economics (i.e., via e-mail and bulletin-board advertisements) and therefore subjects self-selected into the experiment. Because the structure of their training program reduced the opportunity cost of participating dramatically, 91% of the solicited trainees participated in the third group, so there was little scope for self-selection in this sample. We find no differences in the elicited other-regarding preferences between the self-selected adults and the adult trainees, suggesting that selection into this type of experiment is unlikely to bias inferences with respect to non-student adult subjects. We also test (and reject) the more specific hypothesis that approval-seeking subjects are the ones most likely to select into experiments. At the same time, we find a large difference between the self-selected students and the self-selected adults from the surrounding community: the students appear considerably less pro-social. Regression results controlling for demographic factors confirm these basic findings.methodology, selection bias, laboratory experiment, field experiment, other-regarding behavior, social preferences, truckload, trucker