SAMQA: error classification and validation of high-throughput sequenced read data

<p>Abstract</p> <p>Background</p> <p>The advances in high-throughput sequencing technologies and growth in data sizes has highlighted the need for scalable tools to perform quality assurance testing. These tests are necessary to ensure that data is of a minimum necessary standard for use in downstream analysis. In this paper we present the SAMQA tool to rapidly and robustly identify errors in population-scale sequence data.</p> <p>Results</p> <p>SAMQA has been used on samples from three separate sets of cancer genome data from The Cancer Genome Atlas (TCGA) project. Using technical standards provided by the SAM specification and biological standards defined by researchers, we have classified errors in these sequence data sets relative to individual reads within a sample. Due to an observed linearithmic speedup through the use of a high-performance computing (HPC) framework for the majority of tasks, poor quality data was identified prior to secondary analysis in significantly less time on the HPC framework than the same data run using alternative parallelization strategies on a single server.</p> <p>Conclusions</p> <p>The SAMQA toolset validates a minimum set of data quality standards across whole-genome and exome sequences. It is tuned to run on a high-performance computational framework, enabling QA across hundreds gigabytes of samples regardless of coverage or sample type.</p

"Courting the multinational": Subnational institutional capacity and foreign market insidership

peer-reviewedSignificant contemporary challenges face an internationalizing firm, including the non-ergodic nature of investment, and the liability of outsidership. Recent revisions to the Uppsala internationalization process model reflect these challenges, whereby “insidership” is represented as realized, successful foreign market entry. Drawing upon socio-spatial concepts from international business and economic geography, this paper demonstrates the endogeneity of subnational institutions in shaping foreign market insidership within an advanced economy. Employing a multi-method research design with almost 60 subnational actors, the role and interaction of subnational institutions within the internationalization process are explored. Our findings illustrate how customized coalitions of subnational institutions effectively initiate, negotiate and accelerate insidership of inward investment within the foreign market both prior to and during formal entry. Key aspects of this dynamic include communicating tangible and intangible locational resources, initiating functional and relevant business relationships, and facilitating access to codified and tacit knowledge. This paper embellishes the Uppsala internationalization process model by demonstrating the capacity of subnational institutions to participate actively with foreign market insidership, and in so doing advances understanding of how the risk and uncertainty associated with foreign market entry are currently navigated.ACCEPTEDpeer-reviewe

Neural correlates of sexual cue reactivity in individuals with and without compulsive sexual behaviours

Although compulsive sexual behaviour (CSB) has been conceptualized as a "behavioural" addiction and common or overlapping neural circuits may govern the processing of natural and drug rewards, little is known regarding the responses to sexually explicit materials in individuals with and without CSB. Here, the processing of cues of varying sexual content was assessed in individuals with and without CSB, focusing on neural regions identified in prior studies of drug-cue reactivity. 19 CSB subjects and 19 healthy volunteers were assessed using functional MRI comparing sexually explicit videos with non-sexual exciting videos. Ratings of sexual desire and liking were obtained. Relative to healthy volunteers, CSB subjects had greater desire but similar liking scores in response to the sexually explicit videos. Exposure to sexually explicit cues in CSB compared to non-CSB subjects was associated with activation of the dorsal anterior cingulate, ventral striatum and amygdala. Functional connectivity of the dorsal anterior cingulate-ventral striatum-amygdala network was associated with subjective sexual desire (but not liking) to a greater degree in CSB relative to non-CSB subjects. The dissociation between desire or wanting and liking is consistent with theories of incentive motivation underlying CSB as in drug addictions. Neural differences in the processing of sexual-cue reactivity were identified in CSB subjects in regions previously implicated in drug-cue reactivity studies. The greater engagement of corticostriatal limbic circuitry in CSB following exposure to sexual cues suggests neural mechanisms underlying CSB and potential biological targets for interventions

‘It used to be brutal, now it’s an art’:changing negotiations of violence and masculinity in British karate

In most western (and indeed eastern) cultures, fighting is seen as an ultimate symbol of masculinity – an embodied display of dominance, control and violence (Bourdieu, 2001). As a space legitimising and praising performances of mimetic violence (Dunning, 1999), combat sports provide an arena where the virtues of dominance and power at the heart of conceptions of orthodox masculinity (Anderson, 2010 ) or hegemonic masculinity (Connell, 2005) can be symbolically presented by men through bodily displays of strength, physical aggression, and the taking and overcoming of pain (Bourdieu, 2001; Messner, 1990; Wacquant, 2004). Yet, over the last twenty years the focus of karate in Britain has been perceived to shift from aggressive acts of 'hitting hard' to developing and displaying controlled, acrobatic and technically precise movements. Drawn from a nine-month ethnography and 7 semi-structured interviews, this chapter explores how British male karate practitioners re/negotiate ideas of masculinity and embodiments of a masculine identity in the context of karate’s changing emphasis on, and practices of, 'violence'. This paper suggests that a 'civilising' shift (Elias and Dunning, 1986) in the competition rules increases in women’s participation in karate with men, and subsequent negotiations of mimetic violence, complicate the use of violence as a symbol of praised masculine identity within British karate . A praised masculine identity is crafted by carefully blending traits conventional deemed feminine such as technical precision, elegance and agility alongside displays of strength and dominance. Such performances challenge conceptions of an orthodox sporting masculinity and notions of hierarchical gender distinction

Random-phase approximation and its applications in computational chemistry and materials science

The random-phase approximation (RPA) as an approach for computing the electronic correlation energy is reviewed. After a brief account of its basic concept and historical development, the paper is devoted to the theoretical formulations of RPA, and its applications to realistic systems. With several illustrating applications, we discuss the implications of RPA for computational chemistry and materials science. The computational cost of RPA is also addressed which is critical for its widespread use in future applications. In addition, current correction schemes going beyond RPA and directions of further development will be discussed.Comment: 25 pages, 11 figures, published online in J. Mater. Sci. (2012

Red clover-derived isoflavones and mammographic breast density: a double-blind, randomized, placebo-controlled trial [ISRCTN42940165]

INTRODUCTION: Isoflavones are hypothesized to protect against breast cancer, but it is not clear whether they act as oestrogens or anti-oestrogens in breast tissue. Our aim was to determine the effects of taking a red clover-derived isoflavone supplement daily for 1 year on mammographic breast density. Effects on oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), lymphocyte tyrosine kinase activity and menopausal symptoms were also assessed. METHODS: A total of 205 women (age range 49–65 years) with Wolfe P2 or DY mammographic breast patterns were randomly assigned to receive either a red clover-derived isoflavone tablet (26 mg biochanin A, 16 mg formononetin, 1 mg genistein and 0.5 mg daidzein) or placebo. Change in mammographic breast density, serum oestradiol, FSH, LH, menopausal symptoms and lymphocyte tyrosine kinase activity from baseline to 12 months were assessed. RESULTS: A total of 177 women completed the trial. Mammographic breast density decreased in both groups but the difference between the treatment and placebo was not statistically significant. There was a significant interaction between treatment group and oestrogen receptor (ESR1) PvuII polymorphism for the change in estimated percentage breast density (mean ± standard deviation): TT isoflavone 1.4 ± 12.3% and TT placebo -9.6 ± 14.2%; CT isoflavone -5.2 ± 12.0% and CT placebo -2.8 ± 10.3%; and CC isoflavone -3.4 ± 9.7% and CC placebo -1.1 ± 9.5%. There were no statistically significant treatment effects on oestradiol, FSH, or LH (assessed only in postmenopausal women), or on lymphocyte tyrosine kinase activity. Baseline levels of menopausal symptoms were low, and there were no statistically significant treatment effects on frequency of hot flushes or other menopausal symptoms. CONCLUSION: In contrast to studies showing that conventional hormone replacement therapies increase mammographic breast density, the isoflavone supplement did not increase mammographic breast density in this population of women. Furthermore, there were no effects on oestradiol, gonadotrophins, lymphocyte tyrosine kinase activity, or menopausal symptoms

Balancing equity and efficiency in the Dutch basic benefits package using the principle of proportional shortfall

Economic evaluations are increasingly used to inform decisions regarding the allocation of scarce health care resources. To systematically incorporate societal preferences into these evaluations, quality-adjusted life year gains could be weighted according to some equity principle, the most suitable of which is a matter of frequent debate. While many countries still struggle with equity concerns for priority setting in health care, the Netherlands has reached a broad consensus to use the concept of proportional shortfall. Our study evaluates the concept and its support in the Dutch health care context. We discuss arguments in the Netherlands for using proportional shortfall and difficulties in transitioning from principle to practice. In doing so, we address universal issues leading to a systematic consideration of equity concerns for priority setting in health care. The article thus has relevance to all countries struggling with the formalization of equity concerns for priority setting

From Acting What’s next to Speeding Trap: Co-Evolutionary Dynamics of an Emerging Technology-Leader

JEL Classifications: O33, O53, L63[[abstract]]How does technological innovation emerge and evolve? We approach such an inquiry by synthesizing the perspectives of dynamic capabilities and co-evolutionary dynamics to portray organizational routines and multi-phase strategic renewals of an emerging technology-leader. To untangle the emergence of technological innovation, we conducted a longitudinal case study on the first and the largest dedicated semiconductor foundry, TSMC, located in the emerging economy of Taiwan. The firm-case of TSMC illustrates two unique co-evolutionary paths, that is, transforming from industry-latecomer to technology-leader and from process innovation to product innovation. We found multi-motor co-evolutionary dynamics between TSMC and the semiconductor industry, where its co-evolutionary mechanism of managed selection in its creating phase of mature process-innovation (1987-1998) has migrated to hierarchical renewal in its extending phase of advanced process-innovation (1999-2001), and then to holistic renewal in its modifying phase of product-innovation (2002-2007). During such paths, our research discovered a unique type of organizational routines, acting what’s next because TSMC has proactively searched for potential problems sooner than its competitors. However, such routines, although driving technological innovation, also lead to a unique type of success-trap, that is, speeding trap. When an emerging technology-leader fundamentally changes the industrial structures to over-specs, the growth driven by technology speeding may trap such a leader in a loop of over-exploration.[[sponsorship]]The authors are grateful to the research grant from the National Science Council (NSC) in Taiwan. The earlier manuscript of this paper was presented at the 2009 Annual Meeting of Academy of International Business (AIB) in San Diego, USA.[[notice]]補正完畢[[journaltype]]國外[[ispeerreviewed]]Y[[booktype]]紙本[[booktype]]電子版[[countrycodes]]CA

Evidence for Paternal Leakage in Hybrid Periodical Cicadas (Hemiptera: Magicicada spp.)

Mitochondrial inheritance is generally assumed to be maternal. However, there is increasing evidence of exceptions to this rule, especially in hybrid crosses. In these cases, mitochondria are also inherited paternally, so “paternal leakage” of mitochondria occurs. It is important to understand these exceptions better, since they potentially complicate or invalidate studies that make use of mitochondrial markers. We surveyed F1 offspring of experimental hybrid crosses of the 17-year periodical cicadas Magicicada septendecim, M. septendecula, and M. cassini for the presence of paternal mitochondrial markers at various times during development (1-day eggs; 3-, 6-, 9-week eggs; 16-month old 1st and 2nd instar nymphs). We found evidence of paternal leakage in both reciprocal hybrid crosses in all of these samples. The relative difficulty of detecting paternal mtDNA in the youngest eggs and ease of detecting leakage in older eggs and in nymphs suggests that paternal mitochondria proliferate as the eggs develop. Our data support recent theoretical predictions that paternal leakage may be more common than previously estimated