bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidized Low Density Lipoprotein Among the Elderly in Qinghai-Tibet Plateau
Authors: Sakamoto Ryota , Okumiya Kiyohito , Wang Hongxin , Dai Qingxiang , Fujisawa Michiko , Wada Taizo , Imai Hissei , Kimura Yumi , Ishimoto Yasuko , Fukutomi Eriko , Chen Wingling , Sasiwongsaroj Kwanchit , Kato Emiko , Ge Ri-Li , Matsubayashi Kozo
Published: July 2015

Objective

Several environmental factors including hypoxia have been reported to contribute to oxidative stress in individuals living in the highlands. However, little is known about the role of oxidized low-density lipoprotein (ox-LDL) among community-dwelling elderly in the Qinghai-Tibet plateau.

Methods

The study population comprised 168 community-dwelling elderly subjects aged 60 years or older (male to female ratio, 70:98; mean age, 65.8 years) living in Haiyan County, located 3000 to 3200 m above sea level, 30 km northwest of Xining, Qinghai. The subjects were volunteers who joined a Comprehensive Geriatric Assessment. Plasma ox-LDL was measured in 168 community-dwelling elderly subjects aged 60 years or older (23 Tibetans and 145 Hans) with a monoclonal antibody-based enzyme-linked immunosorbent assay.

Results

Mean ox-LDL level was higher among Tibetan elderly than Han elderly (Tibetan, 79.0 ± 29.6 U/L; Han, 62.8 ± 23.5 U/L; P = .003). Tibetan ethnicity was significantly associated with ox-LDL levels after adjusting for LDL cholesterol levels. In addition, high ox-LDL levels (≥70 U/L) were significantly associated with a homeostasis model assessment insulin resistance index of at least 1.6 (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to 7.15; P = .029) and ankle brachial pressure index of less than 1.0 (OR, 4.85; 95% CI, 1.14 to 10.00; P = .028), after adjusting for age, sex, and ethnicity.

Conclusions

Our findings support the hypothesis that ox-LDL levels are higher among Tibetan elderly highlanders compared with those among Han elderly. As ox-LDL levels can affect insulin resistance and arteriosclerosis, further research is needed to determine how oxidative stress influences the health situation among elderly individuals at high altitudes.
What Climate Information Is Most Useful for Predicting Floods?
Authors: Kollipara Puneet
Published: July 2015

Basing forecasts on data that preserve variations over space yield more reliable predictions than using standard numerical measures of climatic cycles' intensity.
Past Phosphorus Runoff Causes Present Oxygen Depletion in Lakes
Authors: Shultz David
Published: July 2015

Sediment cores show how phosphorus pollution in the 1950s led to current, inherited hypoxia in lakes in the Alps.
Pluto Image Shows First Picture of Its Atmosphere
Authors: Showstack Randy
Published: July 2015

Scientists are amazed by new images that show Pluto's atmosphere and diverse geology.
The effect of selection for residual feed intake on scale-activity and scale-exit scores in Yorkshire gilts
Authors: Sadler L. J. , Johnson A. K. , Nettleton D. , Lewis C. R. G. , Young J. M. , Lonergan S. M. , Dekkers J. C. M.
Published: July 2015

The objectives of the present study were to use scale-activity and scale-exit scores to (1) determine the extent to which selection for improved residual feed intake (RFI) correlates with individual gilt temperament, (2) determine whether the timing of assessment affects the scores, and (3) determine whether gilts habituate to the process of weighing. To achieve these objectives, 192 grow–finish purebred Yorkshire gilts (39.7 ± 5.7 kg; 98 ± 6 days old) were utilised. Ninety-six gilts were from the 5th generation of a line selected for low residual feed intake (LRFI), and 96 gilts were from the 5th generation of a randomly selected control line (CRFI). Gilt activity and exit behaviour were scored on the weigh scale. The activity score was taken at two time points, namely, t = 0 (immediately on the back gate closing on the weight scale) and t = 15 (15 s later). Activity was assessed using a 5-point scoring system (1 = calm, minimal movement; 5 = continuous rapid movement and an escape attempt), and exit score was assessed using a 3-point scoring system (1 = no encouragement needed, full exit; 3 = encouragement needed). Gilts were weighed once every 2 weeks (each weighing considered a testing round) for a maximum of eight scores per gilt. Statistical differences were identified in all rounds for activity between genetic lines, except Rounds 2, 4 and 5. For both lines, gilt-activity scores decreased over rounds. The LRFI line began with a lower activity score (2.31 vs 2.65 ± 0.13), but did not experience as great of a drop in average score over rounds as did the CRFI gilts (0.62 vs 1.21). By the end of the trial, the CRFI gilts scored lower than the LRFI gilts. Activity was greater at t = 15 than at t = 0. Although timing affected the score, the pattern was similar, and so consistency will be more important than timing procedure. For exit scores, in Rounds 5 and 7, the LRFI line scored lower than the CRFI line, and there was a trend for the LRFI line to score lower in Round 6. Across all gilts, the mean exit score increased slowly throughout the trial. In conclusion, selection for lower RFI in purebred Yorkshires has an effect on activity score but this relationship is complex and warrants further research. The observation that gilts become habituated to the process of weighing supports the conclusion that the process is not aversive.
A biological rationale for musical consonance
Authors: Bowling Daniel L. , Purves Dale
Published: July 2015

The basis of musical consonance has been debated for centuries without resolution. Three interpretations have been considered: (i) that consonance derives from the mathematical simplicity of small integer ratios; (ii) that consonance derives from the physical absence of interference between harmonic spectra; and (iii) that consonance derives from the advantages of recognizing biological vocalization and human vocalization in particular. Whereas the mathematical and physical explanations are at odds with the evidence that has now accumulated, biology provides a plausible explanation for this central issue in music and audition.
Local axonal protection by WldS as revealed by conditional regulation of protein stability
Authors: Wang Jack T. , Medress Zachary A. , Vargas Mauricio E. , Barres Ben A.
Published: July 2015

Significance

We investigated the molecular basis of Wallerian degeneration slow (WldS) axon protection by defining a spatial and temporal requirement of WldS activity to promote axonal survival. The findings carry clinical significance in showing that the cellular mechanisms governing degeneration of mammalian axons exhibit a latency period before the axon is irreversibly committed to degradation. Moreover, our findings indicate that the progression of Wallerian axon degeneration can be attenuated or halted altogether even long after an injury has occurred. We believe these findings narrow the molecular mechanisms responsible for orchestrating axonal degeneration to events within the axonal compartment and help identify therapeutic targets to halt or reverse the course of axon degeneration in neurological injuries and diseases.
Evaluation of Probabilistic Sampling Designs for Estimating Abundance of Multiple Species of Migratory Fish Using Video Recordings at Fishways
Authors: McCormick Joshua L. , Jackson Laura S. , Carr Fabian M. , Meyer Daniel H.
Published: July 2015

Fifteen years of video census data from a fishway at Winchester Dam on the North Umpqua River, Oregon, were used to evaluate sampling designs to estimate abundance of spring- and fall-run Chinook Salmon Oncorhynchus tshawytscha, summer- and winter-run steelhead O. mykiss, Coho Salmon O. kisutch, and Pacific Lamprey Entosphenus tridentatus. Five probabilistic sampling designs were evaluated via simulation, with variation in the number of days and the number of hours within a day that were sampled over a 1-year period. For most species, stratified one-stage and two-stage cluster designs were more accurate at estimating abundance than simple random sampling designs. There was very little gain in accuracy beyond sampling 8 h per day for all species. The stratified two-stage cluster nonuniform probability design was more accurate than the stratified two-stage cluster uniform probability design at estimating the abundance of steelhead, spring Chinook Salmon, and Coho Salmon, whereas using uniform probabilities resulted in more accurate estimates of abundance for Pacific Lamprey and fall Chinook Salmon. Additionally, the stratified and nonuniform probability designs can be adjusted for high-priority species through allocation of the sample and assigning selection probabilities of secondary sampling units that optimize efficiency for those species. The consistency in patterns observed among species suggests that the results of this study can be applied to other systems where the abundance of multiple species is of interest.

Received December 5, 2014; accepted March 28, 2015
Pr-SNTX, a short-chain three-finger toxin from Papuan pigmy mulga snake, is an antagonist of muscle-type nicotinic acetylcholine receptor (α2βδε)
Authors: Yamauchi Yoko , Kimoto Hikari , Yang Xianyu , Filkin Sergey , Utkin Yuri , Kubo Tai , Inagaki Hidetoshi
Published: July 2015

Three-finger toxins (3FTxs) are one of the major components in snake venoms. In this study, we isolated a cDNA encoding a short-chain 3FTx, Pr-SNTX, from Pseudechis rossignolii. The amino acid sequence of Pr-SNTX is nearly identical to that of its ortholog in Pseudechis australis. Pr-SNTX protein inhibited muscle-type (α2βδε), but not neuronal α7 nicotinic acetylcholine receptor (nAChR) activity.
Giardini Govi is our spot! When parkour meets Genoa
Authors: Benasso Sebastiano
Published: July 2015

This article focuses on the experience of a group of traceurs (people practising parkour) in the urban context of Genoa. It describes a public area of the town – the ‘spot' most frequently used for training – from the specific point of view of the traceurs. Genoa is made up of different and relatively autonomous public spaces with specific and cultural characters, but parkour originates from the attempt to disrupt and reconfigure the city's institutional framework. Genoese traceurs share some of their orientation with other parkour groups in Europe and North America: they are attempting to define new ways of moving and new meanings for urban spaces and to expand the standard definition of a citizen. However, in the urban environment of Genoa, traceurs have to face diverse forms of opposition to their attempts to define their own pathways through the everyday flow of people, and in the disciplinary gaze of other citizens.
You'll change more than I will: Adults’ predictions about their own and others’ future preferences
Authors: Renoult Louis , Kopp Leia , Davidson Patrick S. R. , Taler Vanessa , Atance Cristina M.
Published: July 2015

It has been argued that adults underestimate the extent to which their preferences will change over time. We sought to determine whether such mispredictions are the result of a difficulty imagining that one's own current and future preferences may differ or whether it also characterizes our predictions about the future preferences of others. We used a perspective-taking task in which we asked young people how much they liked stereotypically young-person items (e.g., Top 40 music, adventure vacations) and stereotypically old-person items (e.g., jazz, playing bridge) now, and how much they would like them in the distant future (i.e., when they are 70 years old). Participants also made these same predictions for a generic same-age, same-sex peer. In a third condition, participants predicted how much a generic older (i.e., age 70) same-sex adult would like items from both categories today. Participants predicted less change between their own current and future preferences than between the current and future preferences of a peer. However, participants estimated that, compared to a current older adult today, their peer would like stereotypically young items more in the future and stereotypically old items less. The fact that peers’ distant-future estimated preferences were different from the ones they made for “current” older adults suggests that even though underestimation of change of preferences over time is attenuated when thinking about others, a bias still exists.
Bad–good constraints on a polarity correspondence account for the spatial–numerical association of response codes (SNARC) and markedness association of response codes (MARC) effects
Authors: Leth-Steensen Craig , Citta Richie
Published: July 2015

Performance in numerical classification tasks involving either parity or magnitude judgements is quicker when small numbers are mapped onto a left-sided response and large numbers onto a right-sided response than for the opposite mapping (i.e., the spatial–numerical association of response codes or SNARC effect). Recent research by Gevers et al. [Gevers, W., Santens, S., Dhooge, E., Chen, Q., Van den Bossche, L., Fias, W., & Verguts, T. (2010). Verbal-spatial and visuospatial coding of number–space interactions. Journal of Experimental Psychology: General, 139, 180–190] suggests that this effect also arises for vocal “left” and “right” responding, indicating that verbal–spatial coding has a role to play in determining it. Another presumably verbal-based, spatial–numerical mapping phenomenon is the linguistic markedness association of response codes (MARC) effect whereby responding in parity tasks is quicker when odd numbers are mapped onto left-sided responses and even numbers onto right-sided responses. A recent account of both the SNARC and MARC effects is based on the polarity correspondence principle [Proctor, R. W., & Cho, Y. S. (2006). Polarity correspondence: A general principle for performance of speeded binary classification tasks. Psychological Bulletin, 132, 416–442]. This account assumes that stimulus and response alternatives are coded along any number of dimensions in terms of – and + polarities with quicker responding when the polarity codes for the stimulus and the response correspond. In the present study, even–odd parity judgements were made using either “left” and “right” or “bad” and “good” vocal responses. Results indicated that a SNARC effect was indeed present for the former type of vocal responding, providing further evidence for the sufficiency of the verbal–spatial coding account for this effect. However, the decided lack of an analogous SNARC-like effect in the results for the latter type of vocal responding provides an important constraint on the presumed generality of the polarity correspondence account. On the other hand, the presence of robust MARC effects for “bad” and “good” but not “left” and “right” vocal responses is consistent with the view that such effects are due to conceptual associations between semantic codes for odd–even and bad–good (but not necessarily left–right).
Solidarisation and its limits: the EU and the transformation of international society
Authors: Ahrens Bettina , Diez Thomas
Published: July 2015

The literature on international societies has widely recognised that the EU has formed a regional international society that has transcended the rules of Westphalian statecentred pluralism. However, the analysis of the consequences of this transcendence for global international society has so far been limited. For the most part, such studies have focused on the EU as a normative power, and even within that literature, there is much more attention given to the question of whether the EU acts as a normative power rather than to the consequences of its actions. This is intriguing given that Ian Manners, who originally coined the term, thought of the EU's ability to fundamentally transform the pluralist international society as the ultimate litmus test of normative power. In this paper, we want to explore this question further. Our argument is that the EU contributes to a solidarisation of international society, and we will show this in relation to two cases, human rights and regionalisation. However, we will also argue that this contribution is not unambiguous. Instead, it is characterised by internal contradictions and tensions.
Regional international society in East Asia? A critical investigation
Authors: Zhang Yongjin
Published: July 2015

This essay conducts a critical investigation of the existence or not of international society at the regional level in East Asia as a critique of the excessive universalism of the existing English School theorization of international society. Through a purposeful engagement with the English School theory, it looks at how primary institutions of the Westphalian society of states such as sovereignty and the imperialism are historically imposed upon and resisted by East Asian states in dismantling the traditional regional order. It considers the way in which East Asian states creatively accept, interpret, engage in and practise certain primary institutions of Western-global international society, sovereignty and the market in particular, on their own terms in the postcolonial context. Variations in interpretation and practice of these two primary institutions, it argues, amount to East Asian regional contestations to Western-global international society through localization of norms. It also examines the peculiar features of great power management as a primary institution as it operates and is practised in East Asia and reflects on how in terms of both power politics and political economy the regional and the global deeply interpenetrate each other and are mutually constitutive. In so doing, the essay offers a social structural view of the contested existence of international society in East Asia, with an emphasis on understanding the contingent nature of the emergence of regional international society, its fluid existence and the problematic nature of its social boundaries.
Imagining the Middle East: the state, nationalism and regional international society
Authors: Göl Ayla
Published: July 2015

The Middle East is commonly perceived as a zone of cultural and political differences within the global international society. Imagining the Middle East as a ‘unique’ region is not a new idea, but relocating this conception within the English School (ES) of International Relations (IR) is. This article challenges the perceived ‘exceptionalism’ of the Middle East, which claims that the European concepts of state, sovereignty and nationalism are alien to Islam, therefore preventing the emergence of a regional international society. The first part highlights the correlation between Eurocentrism in IR and the lack of interest in regional – area – studies through the critique of Orientalism and the ES. The second part moves to demonstrate why the ES is more explanatory than other IR theories in the context of the Ottoman–European relations. The third part explores the ‘institutional distinctiveness’ of the Middle East, disproving the notion of regional ‘exceptionalism’ and IR's foundational Eurocentric assumptions. This article concludes by arguing that there is a strong case for calling the Middle East a ‘regional interstate society’, which remains to be a litmus test of whether or not a truly global international society is possible.
Interactions between African and Global International Societies: the African Peer Review Mechanism (APRM)
Authors: Tan Elaine Shek Yan
Published: July 2015

Through an analysis of the African Peer Review Mechanism (APRM), one of the most visible and ambitious governance exercises undertaken by African states, this paper considers the ways in which an African international society and global international society have interacted. The presence of regional international societies implies the presence of difference in global international society, and therefore the possibility of a breakdown in global consensus and the fragmentation of global international society, a perennial concern of the English School. However, while divergences between African and global international societies on democracy and political governance result in tensions, the APRM can be seen as a way to negotiate between these divergent positions. The APRM is an uneasy and unstable compromise, indicating a highly ambivalent relationship between African and global international societies. This relationship has to be understood in the context of an unequal global international society, dominated by a number of core states with an increasingly solidarist governance agenda, as well as the attempts of a largely pluralist African international society to manage its demands.
Leading or following? International societies, Southeast Asia, and the issue of migrant workers
Authors: Quayle Linda
Published: July 2015

Focusing both on the global domain and on Southeast Asia's regional international society, this article uses the English School's (ES) pluralist/solidarist spectrum to map and compare responses to the issue of migrant workers. This case suggests, firstly, that the complexity of the relationship between global and regional societies is exacerbated by the starkly diverging pluralist and solidarist streams within the former; secondly, that the informal, consensus-oriented methods of the Association of Southeast Asian Nations, though often criticized, have proved useful at global level in moving dialogue forward in this contentious area; and thirdly, that regional international societies provide highly salient arenas for dealing with this issue, but still struggle with interregional difference and trans-regional challenges. The questions that the topic of migration foregrounds – the relationship between different levels of society, solidarist ambition, and regional potential – are questions on which the ES can already provide useful responses, but which also open up promising agendas for future work.
Russia's droit de regard: pluralist norms and the sphere of influence
Authors: Kaczmarska Katarzyna
Published: July 2015

Following the end of the cold war and throughout the 1990s, Russia was described as the readily ‘joining’ international society. According to the English school perspective on IR, this meant that Russia was expected to adjust and accept the norms and rules established and propagated by mostly Western liberal states but hailed as common for the family of states. With Vladimir Putin's ascendance to power and Russia's economic recovery followed by Moscow's more assertive stance on global affairs, Russia was increasingly seen as the supporter of a pluralist vision of the international society, i.e. one characterized by limited cooperation, respect for sovereignty and non-intervention. These depictions ignored the fundamental differences in Russia's approach towards relations between states in the regional and global perspective. While on the global scale Russia cherishes norms of sovereignty and non-intervention, the regional realm has been subject to a variety of moves compromising the sovereignty of post-Soviet states. In the Commonwealth of Independent States, Russia has been ready and willing to engage in undermining states’ sovereignty in a number of ways: attempting to establish a sphere of influence, directly intervening in a civil strives, policing borders, waging wars on ‘humanitarian’ grounds and stimulating separatisms, as well as undertaking less explicit interventionist activities of regional integration, security provision and development assistance. This article discusses these cases in order to make the point that Russia's approach to its most immediate neighbours cannot be subsumed under pluralist or solidarist vision of interstate relations. It highlights the difficulty to approach the Russian global-regional split using the conceptual apparatus of the English school and links it to a more perennial problem – that of the English school disregard for the specifics of post-colonial situations.
‘Do you know what I mean?’ ‘Not exactly’: English School, global international society and the polysemy of institutions
Authors: Costa-Buranelli Filippo
Published: July 2015

The English School has recently focussed on sub-global political developments, inaugurating a new research agenda on how regional international societies are formed and evolve. However, while regional international societies can adopt more or less institutions than those at the global level, they may take some institutions present at the global level to mean something different. In this paper, it is tentatively argued that the development of regional international societies is favouring the polysemy of institutions, a situation in which different international societies adopt the same institutions with different meanings and specific normative contents. If institutions exist at the global level, but then are framed, interpreted and adopted differently in several regional international societies, then what are the prospects for the existence of a global international society? Does it still make sense to speak of a global international society?
The interplay between regional international societies
Authors: Linsenmaier Thomas
Published: July 2015

The increasing salience of ‘multiple worlds’ within the international system makes it necessary to take into account the dynamics operating at the sub-systemic level. This article, utilising the concept of regional international society (RIS), aims to further develop the regional dimension as seen through the lenses of the English School. It suggests accompanying the move to the regional level by reflections on the interregional. For this purpose, it puts forward a conceptualisation of various types of relationships that unfold between RIS's – the inter-regional dimension. The traditional notion of ‘expansion’ is found wanting in capturing the full range of relationships and is complemented by forms of coexistence and confrontation. Understood as ideal types, the three concepts (expansion, coexistence and clash) serve as analytical tools for making sense of the varied nature of inter-regional encounters. This is illustrated with regard to the relationship between the European international society and its Eastern neighbours in the aftermath of the Eastern enlargement of the European Union. A more nuanced reading of the inter-regional highlights a constellation quite different from ‘expansion’ where the European society does not push into empty space, but reaches out into an alternative order, opening the possibility of a clash between the European and a consolidating post-Soviet RIS.
Understanding regional and global diffusion in international law: the case for a non-monolithic approach to institutions
Authors: Lasmar Jorge M. , Zahreddine Danny , Gribel Lage Delber Andrade
Published: July 2015

This article attempts to map the reach of key universal norms and rules of human rights law in international society while also mapping, at the same time, specific regional interpretations and practices of such norms. By mapping the normative architecture of the primary institution of international law through its key human rights’ universal norms and rules, it is possible to undertake a geographic analysis of its diffusion and density throughout international society. Hence, it is also possible to visually assess the reach of norms we take for granted as being universal. On the other hand, the mapping of regional interpretations and practices of ‘global’ norms allows identifying if these regionalisms do construct coexistent regional clusters of different ‘international’ normative systems within the system-level institution governing international society. This mapping exercise hopes to contribute to the English School research agenda and its discussions of regions by trying to trace a clearer picture of the normative and institutional borders within international society and thus provide an additional tool to understand how regional norms and practice constitute, interact and redefine the global international society.
Alternative preprocessing of RNA-Sequencing data in The Cancer Genome Atlas leads to improved analysis results
Authors: Rahman Mumtahena , Jackson Laurie K. , Johnson W. Evan , Li Dean Y. , Bild Andrea H. , Piccolo Stephen R.
Published: July 2015

Motivation: The Cancer Genome Atlas (TCGA) RNA-Sequencing data are used widely for research. TCGA provides ‘Level 3’ data, which have been processed using a pipeline specific to that resource. However, we have found using experimentally derived data that this pipeline produces gene-expression values that vary considerably across biological replicates. In addition, some RNA-Sequencing analysis tools require integer-based read counts, which are not provided with the Level 3 data. As an alternative, we have reprocessed the data for 9264 tumor and 741 normal samples across 24 cancer types using the Rsubread package. We have also collated corresponding clinical data for these samples. We provide these data as a community resource.

Results: We compared TCGA samples processed using either pipeline and found that the Rsubread pipeline produced fewer zero-expression genes and more consistent expression levels across replicate samples than the TCGA pipeline. Additionally, we used a genomic-signature approach to estimate HER2 (ERBB2) activation status for 662 breast-tumor samples and found that the Rsubread data resulted in stronger predictions of HER2 pathway activity. Finally, we used data from both pipelines to classify 575 lung cancer samples based on histological type. This analysis identified various non-coding RNA that may influence lung-cancer histology.

Availability and implementation: The RNA-Sequencing and clinical data can be downloaded from Gene Expression Omnibus (accession number GSE62944). Scripts and code that were used to process and analyze the data are available from https://github.com/srp33/TCGA_RNASeq_Clinical.

Contact:  stephen_piccolo@byu.edu or andreab@genetics.utah.edu

Supplementary information:  Supplementary material is available at Bioinformatics online.
A mutation profile for top-k patient search exploiting Gene-Ontology and orthogonal non-negative matrix factorization
Authors: Kim Sungchul , Sael Lee , Yu Hwanjo
Published: July 2015

Motivation: As the quantity of genomic mutation data increases, the likelihood of finding patients with similar genomic profiles, for various disease inferences, increases. However, so does the difficulty in identifying them. Similarity search based on patient mutation profiles can solve various translational bioinformatics tasks, including prognostics and treatment efficacy predictions for better clinical decision making through large volume of data. However, this is a challenging problem due to heterogeneous and sparse characteristics of the mutation data as well as their high dimensionality.

Results: To solve this problem we introduce a compact representation and search strategy based on Gene-Ontology and orthogonal non-negative matrix factorization. Statistical significance between the identified cancer subtypes and their clinical features are computed for validation; results show that our method can identify and characterize clinically meaningful tumor subtypes comparable or better in most datasets than the recently introduced Network-Based Stratification method while enabling real-time search. To the best of our knowledge, this is the first attempt to simultaneously characterize and represent somatic mutational data for efficient search purposes.

Availability: The implementations are available at: https://sites.google.com/site/postechdm/research/implementation/orgos.

Contact: sael@cs.stonybrook.edu or hwanjoyu@postech.ac.kr

Supplementary information:  Supplementary data are available at Bioinformatics online.
GeneVetter: a web tool for quantitative monogenic assessment of rare diseases
Authors: Gillies Christopher E. , Robertson Catherine C. , Sampson Matthew G. , Kang Hyun Min
Published: July 2015

Summary: When performing DNA sequencing to diagnose affected individuals with monogenic forms of rare diseases, accurate attribution of causality to detected variants is imperative but imperfect. Even if a gene has variants already known to cause a disease, rare disruptive variants predicted to be causal are not always so, mainly due to imperfect ability to predict the pathogenicity of variants. Existing population-scale sequence resources such as 1000 Genomes are useful to quantify the ‘background prevalence’ of an unaffected individual being falsely predicted to carry causal variants. We developed GeneVetter to allow users to quantify the ‘background prevalence’ of subjects with predicted causal variants within specific genes under user-specified filtering parameters. GeneVetter helps quantify uncertainty in monogenic diagnosis and design genetic studies with support for power and sample size calculations for specific genes with specific filtering criteria. GeneVetter also allows users to analyze their own sequence data without sending genotype information over the Internet. Overall, GeneVetter is an interactive web tool that facilitates quantifying and accounting for the background prevalence of predicted pathogenic variants in a population.

Availability and Implementation:  GeneVetter is available at http://genevetter.org/

Contact:  mgsamps@med.umich.edu or hmkang@umich.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Separate Brain Circuits Support Integrative and Semantic Priming in the Human Language System
Authors: Feng Gangyi , Chen Qi , Zhu Zude , Wang Suiping
Published: July 2015

Semantic priming is a crucial phenomenon to study the organization of semantic memory. A novel type of priming effect, integrative priming, has been identified behaviorally, whereby a prime word facilitates recognition of a target word when the 2 concepts can be combined to form a unitary representation. We used both functional and anatomical imaging approaches to investigate the neural substrates supporting such integrative priming, and compare them with those in semantic priming. Similar behavioral priming effects for both semantic (Bread–Cake) and integrative conditions (Cherry–Cake) were observed when compared with an unrelated condition. However, a clearly dissociated brain response was observed between these 2 types of priming. The semantic-priming effect was localized to the posterior superior temporal and middle temporal gyrus. In contrast, the integrative-priming effect localized to the left anterior inferior frontal gyrus and left anterior temporal cortices. Furthermore, fiber tractography showed that the integrative-priming regions were connected via uncinate fasciculus fiber bundle forming an integrative circuit, whereas the semantic-priming regions connected to the posterior frontal cortex via separated pathways. The results point to dissociable neural pathways underlying the 2 distinct types of priming, illuminating the neural circuitry organization of semantic representation and integration.
Seismic attenuation due to heterogeneities of rock fabric and fluid distribution
Authors: Ba Jing , Carcione José M. , Sun Weitao
Published: July 2015

The study of the influence of rock fabric and porefluid distribution on the seismic wavefield is important for the prediction and detection of reservoir properties such as lithology and fluid saturation. Wave-induced local fluid flow (WILFF), which is affected by local heterogeneities of the pore structure and fluid saturation, is believed to be the main mechanism to explain the measured attenuation levels at different frequency bands. These two types of heterogeneity affect seismic waves as a combined WILFF process. In this work, we consider a double-porosity system, each part with a different compressibility and patchy saturation, and derive the wave equations from Hamilton's principle. A plane-wave analysis yields the properties of the classical P-wave and those of the four slow waves. The examples show that patchy fluid saturation dominates the peak frequency of the relaxation mechanism. The relation between seismic anelasticity (velocity dispersion and attenuation) and saturation depends on frequency and on the geometrical features of the two heterogeneities. The proposed theory constitutes the comprehensive description for wave propagation process through reservoirs rocks of shallow Earth and porous media in general, to estimate fluid content and distribution.
Use of data mining at the Food and Drug Administration
Authors: Duggirala Hesha J , Tonning Joseph M , Smith Ella , Bright Roselie A , Baker John D , Ball Robert , Bell Carlos , Bright-Ponte Susan J , Botsis Taxiarchis , Bouri Khaled , Boyer Marc , Burkhart Keith , Steven Condrey G , Chen James J , Chirtel Stuart , Filice Ross W , Francis Henry , Jiang Hongying , Levine Jonathan , Martin David , Oladipo Taiye , O’Neill Rene , Palmer Lee Anne M. , Paredes Antonio , Rochester George , Sholtes Deborah , Szarfman Ana , Wong Hui-Lee , Xu Zhiheng , Kass-Hout Taha
Published: July 2015

Objectives This article summarizes past and current data mining activities at the United States Food and Drug Administration (FDA).

Target audience We address data miners in all sectors, anyone interested in the safety of products regulated by the FDA (predominantly medical products, food, veterinary products and nutrition, and tobacco products), and those interested in FDA activities.

Scope Topics include routine and developmental data mining activities, short descriptions of mined FDA data, advantages and challenges of data mining at the FDA, and future directions of data mining at the FDA.
Inhaled Nitric Oxide as an Adjunctive Treatment for Cerebral Malaria in Children: A Phase II Randomized Open-Label Clinical Trial
Authors: Mwanga-Amumpaire Juliet , Carroll Ryan W. , Baudin Elisabeth , Kemigisha Elisabeth , Nampijja Dorah , Mworozi Kenneth , Santorino Data , Nyehangane Dan , Nathan Daniel I. , De Beaudrap Pierre , Etard Jean-François , Feelisch Martin , Fernandez Bernadette O. , Berssenbrugge Annie , Bangsberg David , Bloch Kenneth D. , Boum Yap , Zapol Warren M.
Published: July 2015

Background.  Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM.

Methods.  This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate. We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment.

Results.  Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N2 for 48 or more hours. Plasma Ang-1 levels increased in both treatment groups, but there was no difference between the groups at 48 hours (P = not significant [NS]). Plasma Ang-2 and cytokine levels (tumor necrosis factor-α, interferon-γ, interleukin [IL]-1β, IL-6, IL-10, and monocyte chemoattractant protein-1) decreased between inclusion and 48 hours in both treatment groups, but there was no difference between the groups (P = NS). Nitric oxide metabolite levels—blood methemoglobin and plasma nitrate—increased in patients treated with NO (both P < .05). Seven patients in the N2 group and 4 patients in the NO group died. Five patients in the N2 group and 6 in the NO group had neurological sequelae at hospital discharge.

Conclusions.  Breathing NO as an adjunctive treatment for CM for a minimum of 48 hours was safe, increased blood methemoglobin and plasma nitrate levels, but did not result in a greater increase of plasma Ang-1 levels at 48 hours.
High-resolution ALMA observations of SDP.81. II. Molecular clump properties of a lensed submillimeter galaxy at z = 3.042
Authors: Hatsukade Bunyo , Tamura Yoichi , Iono Daisuke , Matsuda Yuichi , Hayashi Masao , Oguri Masamune
Published: July 2015

We present spatially resolved properties of molecular gas and dust in a gravitationally lensed submillimeter galaxy H-ATLAS J090311.6+003906 (SDP.81) at z = 3.042 revealed by the Atacama Large Millimeter/submillimeter Array (ALMA). We identified 14 molecular clumps in the CO(5–4) line data. The surface density of molecular gas ($\Sigma _{\rm H_2}$) and star-formation rate (ΣSFR) of the clumps are more than three orders of magnitude higher than those found in local spiral galaxies. The clumps are placed in the “burst” sequence in the $\Sigma _{\rm H_2}$–ΣSFR plane, suggesting that z ∼ 3 molecular clumps follow the star-formation law derived for local starburst galaxies. With our gravitational lens model, the positions in the source plane are derived for the molecular clumps, dust clumps, and stellar components identified in the Hubble Space Telescope image. The molecular and dust clumps are confined within a ∼ 2 kpc region, while the spatial extent of the stellar components is as large as ∼ 6 kpc and offset toward the west. The molecular clumps have a systematic velocity gradient in the north–south direction, which may indicate a rotating gas disk. One possible scenario is that the components of molecular gas, dust, and stars are distributed in a several-kpc-scale rotating disk, and the stellar emission is heavily obscured by dust in the central star-forming region. Alternatively, SDP.81 can be explained by a merging system, where dusty starbursts occur in the region where the two galaxies collide, surrounded by tidal features traced in the stellar components.
Rapid dissipation of protoplanetary disks in Ophiuchus
Authors: Takagi Yuhei , Itoh Yoichi , Arai Akira , Sai Shoko , Oasa Yumiko
Published: July 2015

We present the results of an age determination study for pre-main sequence stars in the Ophiuchus molecular cloud. The ages of eight pre-main sequence stars were estimated from surface gravities derived from high-resolution spectroscopy. The average age of the target stars was 0.7 Myr. By comparing the individual age and the near-infrared color excess, we found that color excess decreases gradually with a constant rate and the lifetime of the inner disk was determined to be 1.2 Myr. The estimated lifetime is nearly a half of the time compared to that of the pre-main sequence stars in the Taurus molecular cloud estimated with the same method. This result indicates that the disk evolution timescale depends on the environment of the star-forming region.
Revisiting a gravity-darkened and precessing planetary system PTFO 8-8695: A spin–orbit non-synchronous case
Authors: Kamiaka Shoya , Masuda Kento , Xue Yuxin , Suto Yasushi , Nishioka Tsubasa , Murakami Risa , Inayama Koichiro , Saitoh Madoka , Tanaka Michisuke , Yonehara Atsunori
Published: July 2015

We reanalyse the time-variable light curves of the transiting planetary system PTFO 8-8695, in which a planet of 3 to 4 Jupiter masses orbits a rapidly rotating pre-main-sequence star. Both the planetary orbital period Porb of 0.448 d and the stellar spin period Ps of less than 0.671 d are unusually short, which makes PTFO 8-8695 an ideal system to check the model of gravity darkening and nodal precession. While the previous analysis of PTFO 8-8695 assumed that the stellar spin and planetary orbital periods are the same, we extend the analysis by discarding the spin–orbit synchronous condition, and find three different classes of solutions roughly corresponding to the nodal precession periods of 199 ± 16, 475 ± 21, and 827 ± 53 d that reproduce the transit light curves observed in 2009 and 2010. We compare the predicted light curves of the three solutions against the photometry data of a few percent accuracy obtained at Koyama Astronomical Observatory in 2014 and 2015, and find that the solution with a precession period of 199 ± 16 d is preferred even though it is preliminary. Future prospects and implications for other transiting systems are briefly discussed.
Percutaneous Subtrochanteric Osteotomy for Painful Dislocated Hips in Patients With Cerebral Palsy
Authors: Martinez Maximilian , Kim Seung-Ju , Sabharwal Sanjeev
Published: July 2015

Background:

Treatment of a painful, chronically dislocated hip in nonambulatory children with cerebral palsy (CP) is challenging and controversial. Although many surgical options have been described, there is limited information, including patient-centered outcomes, following treatment. The purpose of our study was to evaluate the effect of a percutaneous subtrochanteric valgus osteotomy (SVO) using external fixation (EF) on hip abduction, radiographic parameters, and quality of life (QOL) measures in such patients.

Methods:

Fifteen nonambulatory patients (8 male, 7 female) with CP with 19 chronically dislocated hips underwent SVO using EF and adductor tenotomy at an average age of 14.3 years (range, 10.7 to 26.8 y). Changes in hip abduction and radiographic angular correction following surgery were assessed. Caregivers completed 2 surveys detailing differences in the patient’s QOL measures, including severity and duration of pain and ease of nursing care, and the modified Child Health Index of Life with Disabilities (CPCHILD).

Results:

Caregivers of 11 patients completed both surveys at an average follow-up of 50 months (range, 17 to 119 mo) after fixator removal. There was improvement in pain, sitting tolerance, ease of transfers, and perineal care in the majority (9/11) of patients. The modified CPCHILD (possible score, 10 to 50) improved from 27.2 to 16.23 (P=0.05). Hip abduction improved from −7 degrees (range, −32 to 5 degrees) to 24 degrees (range, 0 to 40 degrees) (P<0.0001). The average valgus osteotomy correction was 48.2 degrees (range, 2.2 to 93.2 degrees). The pelvic femoral shaft angle improved from −15.2 degrees (range, −47.7 to 7.4 degrees) to 15.4 degrees (−44.3 to 44.6 degrees). There was some correlation of both, change in hip abduction (R
2=0.55) and osteotomy angle (R
2=0.60), with improvement in QOL measures. There were 3 major complications (20%) in 15 patients.

Conclusions:

On the basis of preliminary results, percutaneous SVO stabilized with EF improves QOL in the majority of nonambulatory CP patients despite untoward events and is a viable alternative to open osteotomy with internal fixation. More robust comparative studies are needed to further assess the optimal salvage technique in this patient population.

Level of Evidence:

Level IV.