bluuebunny/crossref_metadata_2025 huggingface dataset:
Cleaning graphene: Comparing heat treatments in air and in vacuum
Authors: Tripathi Mukesh , Mittelberger Andreas , Mustonen Kimmo , Mangler Clemens , Kotakoski Jani , Meyer Jannik C. , Susi Toma
Published: July 2017

Surface impurities and contamination often seriously degrade the properties of two‐dimensional materials such as graphene. To remove contamination, thermal annealing is commonly used. We present a comparative analysis of annealing treatments in air and in vacuum, both ex situ and “pre situ,” where an ultra‐high vacuum treatment chamber is directly connected to an aberration‐corrected scanning transmission electron microscope. While ex situ treatments do remove contamination, it is challenging to obtain atomically clean surfaces after ambient transfer. However, pre situ cleaning with radiative or laser heating appears reliable and well suited to clean graphene without damage to most suspended areas.

Pre situ annealing of typical dirty graphene samples yields atomically clean areas several hundred nm2 in size.
Combining drones and satellite tracking as an effective tool for informing policy change in riparian habitats: a proboscis monkey case study
Authors: Stark Danica J. , Vaughan Ian P. , Evans Luke J. , Kler Harjinder , Goossens Benoit
Published: July 2017

Rapid reaction times to undesirable events are becoming increasingly important for the protection and conservation of habitats and species. This study demonstrates how Unmanned Aerial Vehicles, or drones, and satellite tracking of individual animals can be combined to identify important conservation issues (e.g. deforestation). When quickly disseminated, the information can lead to a rapid change in conservation policy. An adult male proboscis monkey, belonging to a one‐male social group, wasGPStracked for 6 months in Sabah, Malaysian Borneo during 2012. Riparian habitats featured heavily (25.4% of total time, 88.6% of all sleeping sites) in the group's home range. A fixed‐wing drone was used in 2015 to map the habitat in high‐resolution. These data revealed that 47.54 ha of forest had been cleared shortly before the drone flights.GPStagging data revealed the importance of this area for a one‐male proboscis monkey group. A total of 30.1% of the proboscis monkeys' home range area had been cleared, as well as 11.4% of sleeping sites. Furthermore, drone images revealed that the felling extended to the river's edge, disregarding water resources laws requiring riparian reserves of a minimum of 20 m. Following this discovery, a press release including drone imagery combined withGPSdata, was published linking habitat destruction to a species that is economically important for the tourism industry in Sabah. The day following dissemination of the data, the Sabah State Government ordered an immediate cessation on further land clearing at sensitive riparian reserves along the river. We propose that this combination of satellite and aerial data provides potential for an effective conservation tool for endangered, iconic and economically important species. This visually compelling data, feasible over large spatial scales, can directly inform policy change in a quick and timely manner.
Physiological insights of recent clinical diagnostic and therapeutic technologies for cardiovascular diseases
Authors: Shigemi Kenji , Fuke Soichiro , Une Dai , Saku Keita , Shimizu Shuji , Kawada Toru , Shishido Toshiaki , Sunagawa Kenji , Sugimachi Masaru
Published: July 2017

Diagnostic and therapeutic methods for cardiovascular diseases continue to be developed in the 21st century. Clinicians should consider the physiological characteristics of the cardiovascular system to ensure successful diagnosis and treatment. In this review, we focus on the roles of cardiovascular physiology in recent diagnostic and therapeutic technologies for cardiovascular diseases. In the first section, we discuss how to evaluate and utilize left ventricular arterial coupling in the clinical settings. In the second section, we review unique characteristics of pulmonary circulation in the diagnosis and treatment of pulmonary hypertension. In the third section, we discuss physiological and anatomical factors associated with graft patency after coronary artery bypass grafting. In the last section, we discuss the usefulness of mechanical ventricular unloading after acute myocardial infarction. Clinical development of diagnostic methods and therapies for cardiovascular diseases should be based on physiological insights of the cardiovascular system.
Education Gains Attributable to Fertility Decline: Patterns by Gender, Period, and Country in Latin America and Asia
Authors: Li Jing , Dow William H. , Rosero-Bixby Luis
Published: July 2017

We investigate the heterogeneity across countries and time in the relationship between mother’s fertility and children’s educational attainment—the quantity-quality (Q-Q) trade-off—by using census data from 17 countries in Asia and Latin America, with data from each country spanning multiple census years. For each country-year, we estimate micro-level instrumental variables models predicting secondary school attainment using number of siblings of the child, instrumented by the sex composition of the first two births in the family. We then analyze correlates of Q-Q trade-off patterns across countries. On average, one additional sibling in the family reduces the probability of secondary education by 6 percentage points for girls and 4 percentage points for boys. This Q-Q trade-off is significantly associated with the level of son preference, slightly decreasing over time and with fertility, but it does not significantly differ by educational level of the country.
Postmarital Living Arrangements in Historically Patrilocal Settings: Integrating Household Fission and Migration Perspectives
Authors: Pearlman Jessica , Pearce Lisa D. , Ghimire Dirgha J. , Bhandari Prem , Hargrove Taylor
Published: July 2017

This study integrates theory and research on household fission (or partition) and migration to better understand living arrangements following marriage, especially in historically patrilocal and primarily agricultural settings. Using panel data from the Chitwan Valley Family Study to analyze the sequential decision-making process that influences men’s living arrangements subsequent to first marriage, we demonstrate the importance of distinguishing among extended family living, temporary migration, and the establishment of an independent household. We find that community economic characteristics, such as access to markets or employment, as well as household wealth affect the initial decision to leave the natal home. Household resources and use of farmland, along with the young men’s own education, media exposure, travel, and marital behavior, influence the decision to make the departure from the natal home permanent. Our findings explain why previous results regarding household fission and those focused on migration have provided such mixed results, and we establish a new framework for thinking about how families and individuals manage living situations.
Relevance versus reliability of accounting information with unlimited and limited commitment
Authors: Schöndube-Pirchegger Barbara , Schöndube Jens Robert
Published: July 2017

We consider a two-period LEN-type agency problem. The principal needs to implement one out of two accounting systems. One emphasizes relevance, the other reliability. Both systems produce identical inter-temporally correlated signals. The relevant system reports an accounting signal in the period in which it is produced. The reliable system reports a more precise signal, but with a one period delay. Accounting information is contractible only if it is reported within the two-period horizon of the game. Accordingly, accounting information produced in the second period becomes uncontractible with the reliable system in place. Non-accounting information needs to be used for contracting to provide any second period incentives at all. We derive optimal compensation contracts in a full and in a limited commitment setting. With full commitment, the reliable system trades-off more precise first and less precise second-period contractible information, as compared to the relevant system. If the reduction of noise in the accounting signals is strong and the distortion in the non-accounting measure is weak, the reliable system is preferred. With limited commitment we identify a similar trade-off if intertemporal correlation of the signals is negative. If it is positive, this trade-off might reverse: The reliable system is possibly preferred if noise reduction is small and the non-accounting measure is heavily distorted. Noisiness in performance measures then serves as a commitment device. It reduces otherwise overly high powered incentives and thus benefits the principal.
Italy and the Fiscal Compact: Why does a country commit to permanent austerity?
Authors: Moschella Manuela
Published: July 2017

The paper investigates the factors that led the Italian government to accede to the Fiscal Compact in spite of its demanding requirements for the country’s budgetary policy. Specifically, the paper assesses the extent to which Italian government’s support for the Fiscal Compact was driven by the logic of the ‘vincolo esterno’ in a replication of the pattern that led Italy to sign the Maastricht Treaty. The paper finds only limited support to the ‘vincolo esterno’ argument. Rather than being motivated by domestic dysfunctions or socialization to the fiscal discipline doctrine, the Italian government acted mainly out of market punishment fears. Interestingly, however, three factors filtered such external pressures and contributed shaping government’s support for the new Treaty. First, the Economic and Monetary Union unfinished architecture, and in particular the lack of a European financial firewall, weakened opposition to the new Treaty. That is to say, the institutional context constrained the choices that Italian policymakers could pursue. Second, the pro-European orientations of government members contributed to elevating the new Treaty to a symbol of European integration. Finally, the Italian government confronted a quite large domestic win-set during the negotiations, as the parties supporting the Monti government also supported Italy’s participation to the new Treaty.
The Italian foreign policy: challenges and continuities
Authors: Isernia Pierangelo , Longo Francesca
Published: July 2017

Italian foreign politics is facing tough challenges in the near future. For more than 60 years, the Italian foreign policy compass was set on two poles, the European Union and the United States. Sometimes alternatively, much more often conjointly, these two polar stars oriented each and every Italian government’s choice since the end of Second World War. All this has been changing over the last few years. In this context, the article intends to introduce the special issue on Italian foreign policy drawing a stylized map of theoretical approaches that knits together the dispersed theoretical and empirical studies of Italian foreign policy, using a couple of theoretical perspectives as light posts in orienting the articles in this special issue. This introduction is organized in four sections. First, it discusses the approaches that explicitly combine together domestic and international factors in explaining foreign policy. Next, it maps studies on the Italian foreign policy within these frameworks. Then the main characteristics of Italian foreign policy, using these theoretical perspectives, are discussed. The article concludes summarizing how the contributions in this special issue fits into these theoretical frameworks and help shed light on present Italian foreign policy.
Borrowing and the perception of English vowels in Russian
Authors: Holden Kyril T.
Published: July 2017

Data from the phonological assimilation of borrowings have typically been employed in linguistic literature in an ad hoc manner for the justification of various proposals concerning the present or past states of the source or target languages. These data are sometimes found in orthographic form, transcribed phonetically or transliterated into native orthography either by speakers of the target language or by linguists describing the language. Whenever borrowings are utilized as evidence for a particular linguistic claim, it is assumed that there exists some well-defined theory of loan-word assimilation which elevates the data beyond question or doubt. Until recently few such theories have been formulated, and the reasons for this are reasonably clear. The nativization of borrowings involves perception, analysis and production in terms of the target system, and unless we already know exactly what the units and processes comprising this system are, it is difficult to propose intelligent hypotheses to account for the loan-word data. In other words, any account of loan–word assimilation is necessarily predicated on an adequate theory of language, or in the absence of such a theory, can be used as evidence in its construction. Our objective here is not to discuss the pros and cons of those few theories of phonological adaptation which have been proposed, or their interaction with phonological theories in general, but rather to caution against the indiscriminate use of orthographic loan–words in (a) the formulation of theories of borrowing, (b) the empirical justification of general theories of language or (c) making specific claims about the phonologies of the source or target languages.
Forensic Linguistics?
Authors: Canale Michael , Mougeon Raymond , Klokeid Terry J.
Published: July 2017

The application of linguistics to legal issues—what some have labelled “forensic linguistics”—has become increasingly common, varied and consequential (see Brackenridge 1981 for a brief overview). Recently, we three served as language experts in Toronto’s first bilingual jury trial (Regina vs. Lapointe and Sicotte, 1981). Since each of us was assigned a different linguistic problem and since our roles were partially adversary ones (two of us worked for the defence and the other for the prosecution), we were able to draw upon a variety of linguistic concepts and analyses as well as to assess their effectiveness when applied to legal issues. The present paper reports not only on the nature of our involvement but, more importantly, on our joint perception of disturbing language-related problems in the legal process and of equally disturbing inadequacies in the responses that linguistics can currently offer to many of these problems.
Vers un Modele Concret de la Phonologie des Emprunts
Authors: Picard Marc , Nicol Janet
Published: July 2017

Depuis une douzaine d’années, un certain nombre de principes ont été énoncés en phonologie générative pour tenter de rendre compte de l’adaptation et de la modification des mots d’emprunt. A l’aide des données qui ont été recueillies dans une étude détaillée de la phonologie des emprunts du québécois de la région de Montréal (cf. Nicol 1979), où l’anglais (A) constitue la langue d’origine (LO) et le québécois (Q) la langue emprunteuse (LE), nous essaierons de démontrer que tous les principes de ce genre, et en particulier ceux qu’ont émis Hyman (1970) et Kaye et Nykiel (1979), semblent faire de mauvaises prédictions dans nombre de cas. Ceci nous amènera à examiner des alternatives plus concrètes à ces contraintes phonotactiques abstraites que l’on a proposées dans le cadre de la phonologie générative transformationnelle.
How Formal Anglican Pew-Renting Worked in Practice, 1800–1950
Authors: BENNETT J. C.
Published: July 2017

Before the early nineteenth century pew-renting was comparatively rare in Anglican churches, and where it existed the practice was generally administered as a less serious means of fund-raising. But just before 1800 or so, methods of administering the letting of sittings became more businesslike and impersonal. The frequency of pew-renting grew exponentially with the advent of the Church Building Acts beginning in 1818, but the profits realised were usually less than is assumed. The often offensive and sometimes dishonest administration of pew-rent schemes, when later combined with waning churchgoing and a consequent surfeit of rentable sittings, marked the system's decline.
Invariants of GLn(𝔽q) in polynomials modulo Frobenius powers
Authors: Lewis J. , Reiner V. , Stanton D.
Published: July 2017

Conjectures are given for Hilbert series related to polynomial invariants of finite general linear groups: one for invariants mod Frobenius powers of the irrelevant ideal and one for cofixed spaces of polynomials.
Dietary fibre in Europe: current state of knowledge on definitions, sources, recommendations, intakes and relationships to health
Authors: Stephen Alison M. , Champ Martine M.-J. , Cloran Susan J. , Fleith Mathilde , van Lieshout Lilou , Mejborn Heddie , Burley Victoria J.
Published: July 2017

Research into the analysis, physical properties and health effects of dietary fibre has continued steadily over the last 40–50 years. From the knowledge gained, countries have developed guidelines for their populations on the optimal amount of fibre to be consumed each day. Food composition tables from many countries now contain values for the dietary fibre content of foods, and, from these, combined with dietary surveys, population intakes have been determined. The present review assessed the uniformity of the analytical methods used, health claims permitted, recommendations and intakes, particularly from national surveys across Europe and around the world. It also assessed current knowledge on health effects of dietary fibre and related the impact of different fibre types on health. The overall intent was to be able to provide more detailed guidance on the types of fibre which should be consumed for good health, rather than simply a total intake figure, the current situation. Analysis of data indicated a fair degree of uniformity in the definition of dietary fibre, the method used for analysis, the recommended amount to be consumed and a growing literature on effects on digestive health and disease risk. However, national dietary survey data showed that intakes do not reach recommendations and very few countries provide guidance on the types of fibre that are preferable to achieve recommended intakes. Research gaps were identified and ideas suggested to provide information for more detailed advice to the public about specific food sources that should be consumed to achieve health benefits.
Refined and Crass Supernaturalism
Authors: Sprigge T. L. S.
Published: July 2017

In the postscript to The Varieties of Religious Experience William James distinguishes two types of belief in the supernatural, conceived as an essential component in religion, crass or piecemeal supernaturalism, on the one hand, and refined supernaturalism on the other.
Moral Values as Religious Absolutes
Authors: Mackey James P.
Published: July 2017

Those who have had the benefit of a reasonably lengthy familiarity with the philosophy of religion, and more particularly with the God question, may be so kind to a speaker long in exile from philosophy and only recently returned, as to subscribe, initially at least, to the following rather enormous generalization: meaning and truth, which to most propositions are the twin forces by which they are maintained, turn out in the case of claims about God, to be the centrifugal forces by which they disintegrate. In simpler language, the greater the amount of intelligible meaning that can be given to the idea of God, the less grounds there would appear to be for assuming let alone asserting, that God exists, at least as a being distinguishable from all the things in this empirical world which are the source of the range of meanings available to us; on the other hand, the more we insist that God exists, a being over and above the things that make up this empirical world (the more we take the proposition ‘God exists’ to be a true proposition in this particular transcendent sense, for the adjective ‘transcendent’ has many uses) the less the amount of commonly available meaning we appear to be able to apply to God. Or, to put this in a manner which might obviate an obvious objection to it; either everything we know is tout ensemble, God, and then nothing in the world that we know is distinctively divine; or else nothing in this world is God, and then nothing that we appear to be able to know is God. That same formulation will work, it should be noted, even if we substitute for ‘things in the world’, ‘an aspect or aspects of things in the world’.
‘Know Thyself’: What Kind of an Injunction?
Authors: Williams Rowan
Published: July 2017

To be told, ‘know thyself’ is to be told that I don't know myself yet: it carries the assumption that I am in some sense distracted from what or who I actually am, that I am in error or at least ignorance about myself. It thus further suggests that my habitual stresses, confusions and frustrations are substantially the result of failure or inability to see what is most profoundly true of me: the complex character of my injuries or traumas, the distinctive potential given me by my history and temperament. I conceal my true feelings from my knowing self; I am content to accept the ways in which other people define me, and so fail to ‘take my own authority’ and decide for myself who or what I shall be. The therapy-orientated culture of the North Atlantic world in the past couple of decades has increasingly taken this picture as foundational, looking to ‘self-discovery’ or ‘self-realization’ as the precondition of moral and mental welfare. And the sense of individual alienation from a true and authoritative selfhood mirrors the political struggle for the right of hitherto disadvantaged groups, especially non-white and non-male, to establish their own self-definition. The rhetoric of discovering a true but buried identity spreads over both private and political spheres. The slogan of the earliest generation of articulate feminists, ‘The personal is the political’, expresses the recognition of how this connection might be made.
Miniaturized filtering SIW power divider with arbitrary power-dividing ratio loaded by open complementary split-ring resonators
Authors: Danaeian Mostafa , Moznebi Ali-Reza , Afrooz Kambiz , Hakimi Ahmad
Published: July 2017

A miniaturized substrate-integrated waveguide (SIW) power divider with embedded filter response and arbitrary power-dividing ratio loaded by open complementary split-ring resonators (OCSRRs) is presented. In the proposed power divider, the miniaturization and filtering response are realized by a pair of OCSRRs, which are etched on the metal cover of the SIW structure. The design procedure indicates that the power division ratio can be adjusted by changing the locations of the output ports. In this study, three miniaturized filtering SIW power dividers with different power division ratios (1:1, 1:4, and 1:8) are implemented to evaluate the performance of the proposed structure on the size reduction. These power dividers (1:1, 1:4, and 1:8) have the overall sizes of 0.31λg× 0.14λg, 0.25λg× 0.17λg, and 0.25λg× 0.18λg, respectively. The measured results also agree well with the simulated results.
Décompensation pulmonaire ou cardiaque chez l’adulte, à quand les soins intensifs?
Authors: Ltaief Zied , Liaudet Lucas , Manzon Cyril
Published: July 2017

Zusammenfassung. Zusammenfassung: Respiratorische Insuffizienz aufgrund von pulmonaler oder kardialer Dekompensation ist ein medizinischer Notfall, der durch eine Gasaustauschstörung (Hypoxämie, isoliert oder in Verbindung mit Hyperkapnie) gekennzeichnet ist. Die Hauptursachen sind Lungenödem, Pneumonie, dekompensierte chronisch-obstruktive Lungenerkrankung, Lungenembolie und Asthma. Die unmittelbare Versorgung umfasst die Beurteilung der Schwere-Kriterien, wie Schock, verändertes Bewusstsein oder Atemnot mit schwerer Hypoxämie und/oder Hyperkapnie mit Azidose, die einen Transfer auf die Intensivstation erfordern. Die Behandlung umfasst Sauerstofftherapie und nicht-invasive Beatmung. Das Ansprechen auf die Behandlung in der ersten Stunde sollte unbedingt ausgewertet werden, und dessen Ausbleiben erfordert einen sofortigen Transfer auf die Intensivstation.
Das St. Galler Konzept zur Versorgung der proximalen Humerusfraktur
Authors: Spross Christian , Jost Bernhard
Published: July 2017

Zusammenfassung. Zusammenfassung: Die Komplikationsrate nach Osteosynthese von proximalen Humerusfrakturen ist trotz neu entwickelten Implantaten hoch. Wir sind der Meinung, dass die hohe Individualität der Patienten auch einen möglichst individuellen Therapieansatz benötigt. Somit definierten wir einen evidenzbasierten Behandlungsalgorithmus, der die Patientenindividualität und das ganze Behandlungsspektrum beinhalten sollte. Wir suchten dabei nach einem optimalen Weg zwischen Risiko (Komplikationen) und Ertrag (Schulterfunktion). Vor allem die Lebensqualität sollte nach der Frakturbehandlung wieder möglichst gut sein. Die ersten Resultate unserer prospektiven Untersuchung sind vielversprechend. Die konservativen Wege im Algorithmus scheinen gut zu funktionieren, nur sehr selten musste davon abgewichen werden. Es zeigt sich jedoch, dass vor allem die Osteosynthesen noch immer komplikationsbelastet sind. Diesbezüglich gilt es, den Algorithmus und die chirurgische Technik in Zukunft noch zu verbessern.
Brain network dynamics in high-functioning individuals with autism
Authors: Watanabe Takamitsu , Rees Geraint
Published: July 2017

Theoretically, autism should be underpinned by aberrant brain dynamics. However, how brain activity changes over time in individuals with autism spectrum disorder (ASD) remains unknown. Here we characterize brain dynamics in autism using an energy-landscape analysis applied to resting-state fMRI data. Whereas neurotypical brain activity frequently transits between two major brain states via an intermediate state, high-functioning adults with ASD show fewer neural transitions due to an unstable intermediate state, and these infrequent transitions predict the severity of autism. Moreover, in contrast to the controls whose IQ is correlated with the neural transition frequency, IQ scores of individuals with ASD are instead predicted by the stability of their brain dynamics. Finally, such brain–behaviour associations are related to functional segregation between brain networks. These findings suggest that atypical functional coordination in the brains of adults with ASD underpins overly stable neural dynamics, which supports both their ASD symptoms and cognitive abilities.
Transcription factor Hlx controls a systematic switch from white to brown fat through Prdm16-mediated co-activation
Authors: Huang Lei , Pan Dongning , Chen Qingbo , Zhu Lihua J. , Ou Jianhong , Wabitsch Martin , Wang Yong-Xu
Published: July 2017

Browning of subcutaneous white fat (iWAT) involves several reprograming events, but the underlying mechanisms are incompletely understood. Here we show that the transcription factor Hlx is selectively expressed in brown adipose tissue (BAT) and iWAT, and is translationally upregulated by β3-adrenergic signaling-mediated suppression of the translational inhibitor 4E-BP1. Hlx interacts with and is co-activated by Prdm16 to control BAT-selective gene expression and mitochondrial biogenesis. Hlx heterozygous knockout mice have defects in brown-like adipocyte formation in iWAT, and develop glucose intolerance and high fat-induced hepatic steatosis. Conversely, transgenic expression of Hlx at a physiological level drives a full program of thermogenesis and converts iWAT to brown-like fat, which improves glucose homeostasis and prevents obesity and hepatic steatosis. The adipose remodeling phenotypes are recapitulated by fat-specific injection of Hlx knockdown and overexpression viruses, respectively. Our studies establish Hlx as a powerful regulator for systematic white adipose tissue browning and offer molecular insights into the underlying transcriptional mechanism.
A new energy transfer channel from carotenoids to chlorophylls in purple bacteria
Authors: Feng Jin , Tseng Chi-Wei , Chen Tingwei , Leng Xia , Yin Huabing , Cheng Yuan-Chung , Rohlfing Michael , Ma Yuchen
Published: July 2017

It is unclear whether there is an intermediate dark state between the S2 and S1 states of carotenoids. Previous two-dimensional electronic spectroscopy measurements support its existence and its involvement in the energy transfer from carotenoids to chlorophylls, but there is still considerable debate on the origin of this dark state and how it regulates the energy transfer process. Here we use ab initio calculations on excited-state dynamics and simulated two-dimensional electronic spectrum of carotenoids from purple bacteria to provide evidence supporting that the dark state may be assigned to a new Ag+ state. Our calculations also indicate that groups on the conjugation backbone of carotenoids may substantially affect the excited-state levels and the energy transfer process. These results contribute to a better understanding of carotenoid excited states.
Identification of differentially methylated BRCA1 and CRISP2 DNA regions as blood surrogate markers for cardiovascular disease
Authors: Istas Geoffrey , Declerck Ken , Pudenz Maria , Szic Katarzyna Szarc vel , Lendinez-Tortajada Veronica , Leon-Latre Montserrat , Heyninck Karen , Haegeman Guy , Casasnovas Jose A. , Tellez-Plaza Maria , Gerhauser Clarissa , Heiss Christian , Rodriguez-Mateos Ana , Berghe Wim Vanden
Published: July 2017

Genome-wide Illumina InfiniumMethylation 450 K DNA methylation analysis was performed on blood samples from clinical atherosclerosis patients (n = 8) and healthy donors (n = 8) in the LVAD study (NCT02174133, NCT01799005). Multiple differentially methylated regions (DMR) could be identified in atherosclerosis patients, related to epigenetic control of cell adhesion, chemotaxis, cytoskeletal reorganisations, cell proliferation, cell death, estrogen receptor pathways and phagocytic immune responses. Furthermore, a subset of 34 DMRs related to impaired oxidative stress, DNA repair, and inflammatory pathways could be replicated in an independent cohort study of donor-matched healthy and atherosclerotic human aorta tissue (n = 15) and human carotid plaque samples (n = 19). Upon integrated network analysis, BRCA1 and CRISP2 DMRs were identified as most central disease-associated DNA methylation biomarkers. Differentially methylated BRCA1 and CRISP2 regions were verified by MassARRAY Epityper and pyrosequencing assays and could be further replicated in blood, aorta tissue and carotid plaque material of atherosclerosis patients. Moreover, methylation changes at BRCA1 and CRISP2 specific CpG sites were consistently associated with subclinical atherosclerosis measures (coronary calcium score and carotid intima media thickness) in an independent sample cohort of middle-aged men with subclinical cardiovascular disease in the Aragon Workers’ Health Study (n = 24). Altogether, BRCA1 and CRISP2 DMRs hold promise as novel blood surrogate markers for early risk stratification and CVD prevention.
Ion Concentration Polarization by Bifurcated Current Path
Authors: Kim Junsuk , Cho Inhee , Lee Hyomin , Kim Sung Jae
Published: July 2017

Ion concentration polarization (ICP) is a fundamental electrokinetic process that occurs near a perm-selective membrane under dc bias. Overall process highly depends on the current transportation mechanisms such as electro-convection, surface conduction and diffusioosmosis and the fundamental characteristics can be significantly altered by external parameters, once the permselectivity was fixed. In this work, a new ICP device with a bifurcated current path as for the enhancement of the surface conduction was fabricated using a polymeric nanoporous material. It was protruded to the middle of a microchannel, while the material was exactly aligned at the interface between two microchannels in a conventional ICP device. Rigorous experiments revealed out that the propagation of ICP layer was initiated from the different locations of the protruded membrane according to the dominant current path which was determined by a bulk electrolyte concentration. Since the enhancement of surface conduction maintained the stability of ICP process, a strong electrokinetic flow associated with the amplified electric field inside ICP layer was significantly suppressed over the protruded membrane even at condensed limit. As a practical example of utilizing the protruded device, we successfully demonstrated a non-destructive micro/nanofluidic preconcentrator of fragile cellular species (i.e. red blood cells).
Homer binds to Orai1 and TRPC channels in the neointima and regulates vascular smooth muscle cell migration and proliferation
Authors: Jia Shuping , Rodriguez Miguel , Williams Arthur G. , Yuan Joseph P.
Published: July 2017

The molecular components of store-operated Ca2+ influx channels (SOCs) in proliferative and migratory vascular smooth muscle cells (VSMCs) are quite intricate with many channels contributing to SOCs. They include the Ca2+-selective Orai1 and members of the transient receptor potential canonical (TRPC) channels, which are activated by the endoplasmic reticulum Ca2+ sensor STIM1. The scaffolding protein Homer assembles SOC complexes, but its role in VSMCs is not well understood. Here, we asked whether these SOC components and Homer1 are present in the same complex in VSMCs and how Homer1 contributes to VSMC SOCs, proliferation, and migration leading to neointima formation. Homer1 expression levels are upregulated in balloon-injured vs. uninjured VSMCs. Coimmunoprecipitation assays revealed the presence and interaction of all SOC components in the injured VSMCs, where Homer1 interacts with Orai1 and various TRPC channels. Accordingly, knockdown of Homer1 in cultured VSMCs partially inhibited SOCs, VSMC migration, and VSMC proliferation. Neointimal area was reduced after treatment with an adeno-associated viral vector expressing a short hairpin RNA against Homer1 mRNA (AAV-shHomer1). These findings stress the role of multiple Ca2+ influx channels in VSMCs and are the first to show the role of Homer proteins in VSMCs and its importance in neointima formation.
SmMYB36, a Novel R2R3-MYB Transcription Factor, Enhances Tanshinone Accumulation and Decreases Phenolic Acid Content in Salvia miltiorrhiza Hairy Roots
Authors: Ding Kai , Pei Tianlin , Bai Zhengqing , Jia Yanyan , Ma Pengda , Liang Zongsuo
Published: July 2017

Phenolic acids and tanshinones are two major bioactive components in Salvia miltiorrhiza Bunge. A novel endogenous R2R3-MYB transcription factor, SmMYB36, was identified in this research. This transcript factor can simultaneously influence the content of two types of components in SmMYB36 overexpression hairy roots. SmMYB36 was mainly localized in the nucleus of onion epidermis and it has transactivation activity. The overexpression of SmMYB36 promoted tanshinone accumulation but inhibited phenolic acid and flavonoid biosynthesis in Salvia miltiorrhiza hairy roots. The altered metabolite content was due to changed metabolic flow which was regulated by transcript expression of metabolic pathway genes. The gene transcription levels of the phenylpropanoid general pathway, tyrosine derived pathway, methylerythritol phosphate pathway and downstream tanshinone biosynthetic pathway changed significantly due to the overexpression of SmMYB36. The wide distribution of MYB binding elements (MBS, MRE, MBSI and MBSII) and electrophoretic mobility shift assay results indicated that SmMYB36 may be an effective tool to regulate metabolic flux shifts.
Heart rhythm characterization through induced physiological variables
Authors: Pons Jean-François , Haddi Zouhair , Deharo Jean-Claude , Charaï Ahmed , Bouchakour Rachid , Ouladsine Mustapha , Delliaux Stéphane
Published: July 2017

Atrial fibrillation remains a major cause of morbi-mortality, making mass screening desirable and leading industry to actively develop devices devoted to automatic AF detection. Because there is a tendency toward mobile devices, there is a need for an accurate, rapid method for studying short inter-beat interval time series for real-time automatic medical monitoring. We report a new methodology to efficiently select highly discriminative variables between physiological states, here a normal sinus rhythm or atrial fibrillation. We generate induced variables using the first ten time derivatives of an RR interval time series and formally express a new multivariate metric quantifying their discriminative power to drive state variable selection. When combined with a simple classifier, this new methodology results in 99.9% classification accuracy for 1-min RR interval time series (n = 7,400), with heart rate accelerations and jerks being the most discriminant variables. We show that the RR interval time series can be drastically reduced from 60 s to 3 s, with a classification accuracy of 95.0%. We show that heart rhythm characterization is facilitated by induced variables using time derivatives, which is a generic methodology that is particularly suitable to real-time medical monitoring.
Effects of Aortic Valve Replacement on Severe Aortic Stenosis and Preserved Systolic Function: Systematic Review and Network Meta-analysis
Authors: Zheng Qishi , Djohan Andie H. , Lim Enghow , Ding Zee Pin , Ling Lieng H. , Shi Luming , Chan Edwin Shih-Yen , Chin Calvin Woon Loong
Published: July 2017

The survival benefits of aortic valve replacement (AVR) in the different flow-gradient states of severe aortic stenosis (AS) is not known. A comprehensive search in PubMed/MEDLINE, Embase, Cochrane Library, CNKI and OpenGrey were conducted to identify studies that investigated the prognosis of severe AS (effective orifice area ≤1.0 cm2) and left ventricular ejection fraction ≥50%. Severe AS was stratified by mean pressure gradient [threshold of 40 mmHg; high-gradient (HG) and low-gradient (LG)] and stroke volume index [threshold of 35 ml/m2; normal-flow (NL) and low-flow (LF)]. Network meta-analysis was conducted to assess all-cause mortality among each AS sub-type with rate ratio (RR) reported. The effects of AVR on prognosis were examined using network meta-regression. In the pooled analysis (15 studies and 9,737 patients), LF states (both HG and LG) were associated with increased mortality rate (LFLG: RR 1.88; 95% CI: 1.43-2.46; LFHG: RR: 1.77; 95% CI: 1.16-2.70) compared to moderate AS; and NF states in both HG and LG had similar prognosis as moderate AS (NFLG: RR 1.11; 95% CI: 0.81-1.53; NFHG: RR 1.16; 95% CI: 0.82-1.64). AVR conferred different survival benefits: it was most effective in NFHG (RR
with AVR
/RR
without AVR
: 0.43; 95% CI: 0.22-0.82) and least in LFLG (RR
with AVR
/RR
without AVR
: 1.19; 95% CI: 0.74-1.94).
Functional analyses of a novel missense and other mutations of the vitamin D receptor in association with alopecia
Authors: Tamura Mayuko , Ishizawa Michiyasu , Isojima Tsuyoshi , Özen Samim , Oka Akira , Makishima Makoto , Kitanaka Sachiko
Published: July 2017

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is a rare disorder, caused by bialellic mutations of the vitamin D receptor (VDR) gene, sometimes associated with alopecia. The aim of this study is to elucidate the mechanism of functional disruption of a novel mutation, detected in a patient with HVDRR, comparing to other mutations with or without alopecia. The patient was a 2-year-old girl with alopecia, who was clinically diagnosed as HVDRR. Genetic analysis revealed a novel homozygous mutation, S360P, located in ligand binding domain (LBD). The mutation was predicted as not disease causing by Polyphen2 and SIFT. But the transcriptional activity of S360P was disrupted as well as other reported mutations, Q152X (located in the hinge lesion), and R274L, H305Q (located in LBD). Following assays revealed no ligand binding affinity, no interaction with cofactors or RXR and no functioning of nuclear localization signals. Our results provide an additional evidence for the previous findings suggesting that DNA binding by the VDR/RXR heterodimer is essential for the function of the VDR in hair development. In conclusion, we identified a novel missense mutation of VDR causing HVDRR with alopecia. Functional analyses revealed that the single amino acid substitution could disrupt the function of the protein.
Metabolic reprogramming is associated with flavopiridol resistance in prostate cancer DU145 cells
Authors: Li Xiaoran , Lu Jie , Kan Quancheng , Li Xiaoli , Fan Qiong , Li Yaqing , Huang Ruixia , Slipicevic Ana , Dong Hiep Phuc , Eide Lars , Wang Junbai , Zhang Hongquan , Berge Viktor , Goscinski Mariusz Adam , Kvalheim Gunnar , Nesland Jahn M. , Suo Zhenhe
Published: July 2017

Flavopiridol (FP) is a pan-cyclin dependent kinase inhibitor, which shows strong efficacy in inducing cancer cell apoptosis. Although FP is potent against most cancer cells in vitro, unfortunately it proved less efficacious in clinical trials in various aggressive cancers. To date, the molecular mechanisms of the FP resistance are mostly unknown. Here, we report that a small fraction human prostate cancer DU145 cells can survive long-term FP treatment and emerge as FP-resistant cells (DU145FP). These DU145FP cells show accumulated mitochondrial lesions with stronger glycolytic features, and they proliferate in slow-cycling and behave highly migratory with strong anti-apoptotic potential. In addition, the cells are less sensitive to cisplatin and docetaxel-induced apoptotic pressure, and over-express multiple stem cell associated biomarkers. Our studies collectively uncover for the first time that FP-resistant prostate cancer cells show metabolic remodeling, and the metabolic plasticity might be required for the FP resistance-associated cancer cell stemness up-regulation.
Dynamics and extreme plasticity of metallic microparticles in supersonic collisions
Authors: Xie Wanting , Alizadeh-Dehkharghani Arash , Chen Qiyong , Champagne Victor K. , Wang Xuemei , Nardi Aaron T. , Kooi Steven , Müftü Sinan , Lee Jae-Hwang
Published: July 2017

Metallic microparticles can acquire remarkable nanoscale morphologies after experiencing high velocity collisions, but materials science regarding the extreme events has been limited due to a lack of controlled experiments. In this work, collision dynamics and nonlinear material characteristics of aluminum microparticles are investigated through precise single particle collisions with two distinctive substrates, sapphire and aluminum, across a broad range of collision velocities, from 50 to 1,100 m/s. An empirical constitutive model is calibrated based on the experimental results, and is used to investigate the mechanics of particle deformation history. Real-time and post-impact characterizations, as well as model based simulations, show that significant material flow occurs during the impact, especially with the sapphire substrate. A material instability stemming from plasticity-induced heating is identified. The presented methodology, based on the use of controlled single particle impact data and constitutive models, provides an innovative approach for the prediction of extreme material behavior.
An allelic variant of the PmrB sensor kinase responsible for colistin resistance in an Escherichia coli strain of clinical origin
Authors: Cannatelli Antonio , Giani Tommaso , Aiezza Noemi , Di Pilato Vincenzo , Principe Luigi , Luzzaro Francesco , Galeotti Cesira L. , Rossolini Gian Maria
Published: July 2017

We investigated the colistin resistance mechanism in an Escherichia coli strain (LC711/14) isolated in Italy in 2014, from an urinary tract infection, which was previously shown to express a colistin resistance mechanism different from mcr-1. LC711/14 was found to carry a novel mutation in the pmrB gene, resulting in a leucine to proline amino acid substitution at position 10 of the PmrB sensor kinase component of the PmrAB signal transduction system. The role of this substitution in colistin resistance was documented by expression of the wild-type and mutated alleles in a pmrB deletion derivative of the E. coli reference strain MG1655, in which expression of the mutated allele conferred colistin resistance and upregulation of the endogenous pmrHFIJKLM lipid A modification system. Complementation of LC711/14 with the wild-type pmrB allele restored colistin susceptibility and decreased expression of pmrHFIJKLM, confirming the role of this PmrB mutation. Substitution of leucine at position 10 of PmrB with other amino acids (glycine and glutamine) resulted in loss of function, underscoring a key role of this residue which is located in the cytoplasmic secretion domain of the protein. This work demonstrated that mutation in this domain of the PmrB sensor kinase can be responsible for acquired colistin resistance in E. coli strains of clinical origin.
Electrospray mode transition of microdroplets with semiconductor nanoparticle suspension
Authors: Castillo-Orozco Eduardo , Kar Aravinda , Kumar Ranganathan
Published: July 2017

Electrosprays operate in several modes depending on the flow rate and electric potential. This allows the deposition of droplets containing nanoparticles into discrete nanodot arrays to fabricate various electronic devices. In this study, seven different suspensions with varying properties were investigated. In the dripping mode, the normalized dropsize decreases linearly with electric capillary number, Ca
e
, (ratio of electric to surface tension forces) up to Ca
e
 ≈ 1.0. The effect of viscous forces is found to be negligible in the dripping mode since the capillary number is small. For flow rates with low Reynolds number, the mode changes to microdripping mode, and then to a planar oscillating microdripping mode as Ca
e
increases. The normalized dropsize remains nearly constant at 0.07 for Ca
e
 > 3.3. The microdripping mode which is important for depositing discrete array of nanodots is found to occur in the range, 2 ≤ Ca
e
 ≤ 2.5. The droplet frequency increases steadily from dripping to microdripping mode, but stays roughly constant in the oscillating microdripping mode. This work provides a physical basis by which the flow rate and the voltage can be chosen for any nanosuspension to precisely operate in the microdripping mode at a predetermined dropsize and droplet frequency.
Anaerobic oxidation of methane coupled with extracellular electron transfer to electrodes
Authors: Gao Yaohuan , Lee Jangho , Neufeld Josh D. , Park Joonhong , Rittmann Bruce E. , Lee Hyung-Sool
Published: July 2017

Anaerobic oxidation of methane (AOM) is an important process for understanding the global flux of methane and its relation to the global carbon cycle. Although AOM is known to be coupled to reductions of sulfate, nitrite, and nitrate, evidence that AOM is coupled with extracellular electron transfer (EET) to conductive solids is relatively insufficient. Here, we demonstrate EET-dependent AOM in a biofilm anode dominated by Geobacter spp. and Methanobacterium spp. using carbon-fiber electrodes as the terminal electron sink. The steady-state current density was kept at 11.0 ± 1.3 mA/m2 in a microbial electrochemical cell, and isotopic experiments supported AOM-EET to the anode. Fluorescence in situ hybridization images and metagenome results suggest that Methanobacterium spp. may work synergistically with Geobacter spp. to allow AOM, likely by employing intermediate (formate or H2)-dependent inter-species electron transport. Since metal oxides are widely present in sedimentary and terrestrial environments, an AOM-EET niche would have implications for minimizing the net global emissions of methane.