bluuebunny/crossref_metadata_2025 huggingface dataset:
Porous Silicon Nanowire Arrays for Reversible Optical Gas Sensing
Authors: Georgobiani Veronika A. , Gonchar Kirill A. , Zvereva Elena A. , Osminkina Liubov A.
Published: December 2017

Porous silicon nanowire arrays are shown to be used for optical detection of molecular oxygen (O2). The samples are produced by metal assisted chemical etching of heavily boron‐doped wafers of crystalline silicon. It is found that the photoluminescence signal from porous silicon nanowires quenched in O2 ambience but restored again in N2 atmosphere, which repeated in several cycles. Electron paramagnetic resonance data demonstrate that number of silicon dangling bonds (Pb‐center) increases after O2 adsorption, but then drops in vacuum. The experimental results are explained by a microscopic model taking into account the reversible charging/recharging of surface defects (Pb‐centers) due to the oxygen adsorption/desorption. The obtained results indicate that porous silicon nanowires are prospective for applications as reversible optical gas sensor.
Width‐Dependent Sheet Resistance of Nanometer‐Wide Si Fins as Measured with Micro Four‐Point Probe
Authors: Bogdanowicz Janusz , Folkersma Steven , Sergeant Stefanie , Schulze Andreas , Moussa Alain , Petersen Dirch H. , Hansen Ole , Henrichsen Henrik H. , Nielsen Peter F. , Vandervorst Wilfried
Published: December 2017

This paper extends the applicability of the micro four‐point probe technique from the sheet resistance measurements on large areas toward narrow (<20 nm) semiconducting nanostructures with an elongated fin geometry. Using this technology, it is shown that the sheet resistance of boron‐implanted and laser‐annealed silicon fins with widths ranging from 500 down to 20 nm rises as the width is reduced. Drift‐diffusion simulations show that the observed increase can be partially explained by the carrier depletion induced by interface states at the fin sidewalls.
Development and Synchrotron‐Based Characterization of Al and Cr Nanostructures as Potential Calibration Samples for 3D Analytical Techniques
Authors: Dialameh Masoud , Ferrarese Lupi Federico , Hönicke Philipp , Kayser Yves , Beckhoff Burkhard , Weimann Thomas , Fleischmann Claudia , Vandervorst Wilfried , Dubček Pavo , Pivac Branko , Perego Michele , Seguini Gabriele , De Leo Natascia , Boarino Luca
Published: December 2017

The continuous and aggressive scaling in semiconductor technology results in the integration of increasingly complex 3D architectures and new materials. The realization of these downscaled 3D structures requires also further improvement in 3D characterization techniques. In this work, a potential route to improve the accuracy and reliability of the quantitative analysis of 3D nano‐devices is investigated. 3D organic and inorganic reference nanostructures with dimensions and structural ordering resembling those utilized in industrial applications are fabricated and characterized in detail. The 3D organic nanostructures are fabricated exploiting the self‐assembly capability of di‐block copolymers. Subsequent deposition of a thin Al film lead to the formation and realization of nanostructured Al. In addition, different inorganic nanostructures are fabricated using electron beam lithography. The various nanostructures are characterized with respect to their dimensions as well as composition using various analytical techniques namely reference‐free grazing incidence X‐ray fluorescence, grazing incidence small angle X‐ray scattering, scanning electron microscopy, and spectroscopic ellipsometry.
Application of the unitary group approach to evaluate spin density for configuration interaction calculations in a basis of S2 eigenfunctions
Authors: Polyak Iakov , Bearpark Michael J. , Robb Michael A.
Published: December 2017

We present an implementation of the spin‐dependent unitary group approach to calculate spin densities for configuration interaction calculations in a basis of spin symmetry‐adapted functions. Using S2 eigenfunctions helps to reduce the size of configuration space and is beneficial in studies of the systems where selection of states of specific spin symmetry is crucial. To achieve this, we combine the method to calculate U(n) generator matrix elements developed by Downward and Robb (Theor. Chim. Acta 1977, 46, 129) with the approach of Battle and Gould to calculate U(2n) generator matrix elements (Chem. Phys. Lett. 1993, 201, 284). We also compare and contrast the spin density formulated in terms of the spin‐independent unitary generators arising from the group theory formalism and equivalent formulation of the spin density representation in terms of the one‐ and two‐electron charge densities.
Neurotrophically Induced Mesenchymal Progenitor Cells Derived from Induced Pluripotent Stem Cells Enhance Neuritogenesis via Neurotrophin and Cytokine Production
Authors: Brick Rachel M. , Sun Aaron X. , Tuan Rocky S.
Published: December 2017

Adult tissue-derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal-like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs). We found that several genes were upregulated and proteins were produced in MiMPCs that matched those previously reported for MSCs. Like MSCs, the MiMPCs secreted various neurotrophic and neuroprotective factors, including brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), osteopontin, and osteonectin, and promoted neurite outgrowth in chick embryonic dorsal root ganglia (DRG) cultures compared with control cultures. Cotreatment with a pharmacological Trk-receptor inhibitor did not result in significant decrease in MiMPC-induced neurite outgrowth, which was however inhibited upon Jak/STAT3 blockade. These findings suggest that the MiMPC induction of DRG neurite outgrowth is unlikely to be solely dependent on BDNF, but instead Jak/STAT3 activation by IL-6 and/or LIF is likely to be critical neurotrophic signaling pathways of the MiMPC secretome. Taken together, these findings suggest MiMPCs as a renewable, candidate source of therapeutic cells and a potential alternative to MSCs for peripheral nerve repair, in view of their ability to promote nerve growth by producing many of the same growth factors and cytokines as Schwann cells and signaling through critical neurotrophic pathways.
Relationships Between Cooking Properties and Physicochemical Properties in Brown and White Rice
Authors: Wu Kao , Gunaratne Anil , Gan Renyou , Bao Jinsong , Corke Harold , Jiang Fatang
Published: December 2017

Brown rice presently attracts a growing number of customers due to its perceived health benefits, but its cooking properties differ from white rice. This study aims to investigate the relationship between physicochemical properties and cooking properties of brown rice and white rice. Brown rice samples generally are found to have higher thousand kernel weight, and minimum cooking time, but lower length/breadth ratio, pasting viscosity values (except setback), swelling power, water uptake ratio, gruel solid loss, cooked length/breadth ratio, and elongation ratio than white rice. Brown and white rice from the same cultivar show some differences regarding their gelatinization properties. The cooking property differences between brown and white rice may be explained by impact of embryo and protection by bran layers. Correlation analysis indicate that cooking properties are little correlated to the flour physicochemical properties, except minimum cooking time. Although apparent amylose content show strong correlations with most flour physicochemical properties, gelatinization temperature may be preferred to be used for prediction of minimum cooking time in both brown and white rice.
Exposure to cadmium during gestation and lactation affects development and function of Leydig cells in male offspring
Authors: Tian Huajian , Chen Shaomin , Leng Yang , Li Teng , Li Zengli , Chen Hongxia , Zhang Qihao
Published: December 2017

Toxic effects of maternal exposure to Cadmium (Cd) on Leydig cells of male offspring arises much concern recently, but its toxic effects on the development of Leydig cells and androgen synthesis have not been elucidated. In this study, female rats were exposed to Cd during gestation and lactation, and the development of Leydig cells in the first filial‐generation (F1) male rats was investigated. The steroidogenic signaling pathway and biomarkers related to the development of Leydig cells were detected to disclose how maternal Cd‐exposure caused reproductive damage. F1 male rats with maternal Cd‐exposure gained a low relative weight of testis and declined levels of steroid hormones. Maternal Cd‐exposure interrupted the development of Leydig cells with high expression of SRD5α and cell morphology of immature Leydig cells in adulthood, inhibited the activation of cyclic adenosine monophosphate/ protein kinase A signaling pathway and down‐regulated the steroidogenic enzymes. These results would help to disclose the origin of male sexual dysfunction in the developmental stages of Leydig cells.
Tax certified individual auditors and effective tax rates
Authors: Frey Lisa
Published: December 2017

This study examines how the appointment of tax certified individual auditors is associated with reported effective tax rates of corporate clients. The study uses a unique German institutional setting which makes it possible to track individual auditors that are also certified tax consultants and sign the audit opinion. Empirical results indicate that tax certified individual engagement partners are associated with higher effective tax rates. Further tests reveal that this association also exists for individual parent company financial statements and that it is stronger when tax confirmation services are provided to the audit client. My findings enhance the understanding of the role of individual auditors.
Are you attracted? Do you remain? Meta-analytic evidence on flexible work practices
Authors: Onken-Menke Greta , Nüesch Stephan , Kröll Claudia
Published: December 2017

This meta-analysis investigates how three flexible work practices (FWPs), flexible work schedules, telecommuting and sabbaticals, affect organizational attractiveness for job seekers and the organizational attachment of employees. Based on organizational support theory and signalling theory, we conjecture that anticipated organizational support mediates the positive relationship between FWPs and organizational attractiveness. Applying the conservation of resources theory, we suggest that FWPs increase organizational attachment through increased perceived autonomy. Meta-analytic results based on 68 studies and 52,738 employees indicate that FWPs increase organizational attractiveness and that the positive effects are partially mediated by anticipated organizational support. We also find that flexible work schedules and sabbaticals (but not telecommuting) increase organizational commitment and that all FWPs decrease turnover intention. Furthermore, these effects are partially mediated by perceived autonomy. Implications for practice and future research are discussed.
Lightweight vehicle underbody design
Authors: Dittmar Harri , Plaggenborg Henrik
Published: December 2017

Tepex continuous-fiber-reinforced thermoplastic composite semi-finished products are becoming increasingly popular in lightweight automotive design. Underbody components represent an important field of application with strong growth prospects. These components are manufactured in compression and flow molding processes using thermoplastic molding compounds. The semi-finished products serve as overlays, which significantly increase the mechanical performance of the compression-molded components while offering cost-effective component solutions.
A HARD TIME TO DATE: THE SCOTT COUNTY PUEBLO (14SC1) AND PUEBLOAN RESIDENTS OF THE HIGH PLAINS
Authors: Hill Matthew E. , Beck Margaret E. , Lengyel Stacey , Trabert Sarah J. , Adair Mary J.
Published: December 2017

During the seventeenth and eighteenth centuries, Puebloan women (if not entire families) were incorporated into Apache Dismal River communities in western Kansas. In at least one site (14SC1), Puebloan people lived in a small masonry pueblo. We evaluate the timing and nature of the Puebloan occupation at 14SC1 and its relationship to the Dismal River population at the site. We use a Bayesian analytical framework to evaluate different models of the pueblo's use history, constraining 12 radiocarbon dates by their stratigraphic data and then comparing this framework with different temporal models based on the historical record. We conclude that Dismal River people lived at 14SC1 prior to the appearance of Pueblo migrants, sometime between cal AD 1490 and 1650. Construction and early use of the pueblo by migrants from the Rio Grande valley occurred between cal AD 1630 and 1660, and the pueblo was closed by burning sometime between cal AD 1640 and 1690. Site 14SC1 lacks Rio Grande Glaze Ware, and its residents seem rarely to have engaged with the groups in the Southern Plains Macroeconomy. Our results contribute to studies of indigenous community formation and Puebloan residential mobility during the Spanish colonial period.
Assessing Features of Psychometric Assessment Instruments: A Comparison of the COSMIN Checklist with Other Critical Appraisal Tools
Authors: Rosenkoetter Ulrike , Tate Robyn L.
Published: December 2017

The past 20 years have seen the development of instruments designed to specify standards and evaluate the adequacy of published studies with respect to the quality of study design, the quality of findings, as well as the quality of their reporting. In the field of psychometrics, the first minimum set of standards for the review of psychometric instruments was published in 1996 by the Scientific Advisory Committee of the Medical Outcomes Trust. Since then, a number of tools have been developed with similar aims. The present paper reviews basic psychometric properties (reliability, validity and responsiveness), compares six tools developed for the critical appraisal of psychometric studies and provides a worked example of using the COSMIN checklist, Terwee-m statistical quality criteria, and the levels of evidence synthesis using the method of Schellingerhout and colleagues (2012). This paper will aid users and reviewers of questionnaires in the quality appraisal and selection of appropriate instruments by presenting available assessment tools, their characteristics and utility.
An Introduction to Item Response Theory and Rasch Analysis: Application Using the Eating Assessment Tool (EAT-10)
Authors: Kean Jacob , Bisson Erica F. , Brodke Darrel S. , Biber Joshua , Gross Paul H.
Published: December 2017

Item response theory has its origins in educational measurement and is now commonly applied in health-related measurement of latent traits, such as function and symptoms. This application is due, in large part, to gains in the precision of measurement attributable to item response theory and corresponding decreases in response burden, study costs, and study duration. The purpose of this paper is twofold: introduce basic concepts of item response theory and demonstrate this analytic approach in a worked example, a Rasch model (1PL) analysis of the Eating Assessment Tool (EAT-10), a commonly used measure for oropharyngeal dysphagia. The results of the analysis were largely concordant with previous studies of the EAT-10 and illustrate for brain impairment clinicians and researchers how IRT analysis can yield greater precision of measurement.
Chemotherapeutics of visceral leishmaniasis: present and future developments
Authors: SUNDAR SHYAM , SINGH ANUP
Published: December 2017

Treatment of Visceral Leishmaniasis (VL), a neglected tropical disease, is very challenging with few treatment options. Long duration of treatment and drug toxicity further limit the target of achieving VL elimination. Chemotherapy remains the treatment of choice. Single dose of liposomal amphotericin B (LAmB) and multidrug therapy (LAmB + miltefosine, LAmB + paromomycin (PM), or miltefosine + PM) are recommended treatment regimen for treatment of VL in Indian sub-continent. Combination therapy of pentavalent antimonials (Sbv) and PM in East Africa and LAmB in the Mediterranean region/South America remains the treatment of choice. Various drugs having anti-leishmania properties are in preclinical phase and need further development. An effective treatment and secondary prophylaxis of HIV-VL co-infection should be developed to decrease treatment failure and drug resistance.
Nurturant-involved parenting and adolescent substance use: Examining an internalizing pathway through adolescent social anxiety symptoms and substance refusal efficacy
Authors: Weymouth Bridget B. , Fosco Gregory M. , Feinberg Mark E.
Published: December 2017

Research has clearly established the important role of parents in preventing substance use among early adolescents. Much of this work has focused on deviance (e.g., antisocial behavior, delinquency, and oppositional behavior) as a central pathway linking parenting behaviors and early adolescent substance use. This study proposed an alternative pathway; using a four-wave longitudinal design, we examined whether nurturant-involved parenting (Fall sixth grade) was inversely associated with adolescent drunkenness, marijuana use, and cigarette use (eighth grade) through social anxiety symptoms (Spring sixth grade) and subsequent decreases in substance refusal efficacy (seventh grade). Nurturant-involved parenting is characterized by warmth, supportiveness, low hostility, and low rejection. Analyses were conducted with a sample of 687 two-parent families. Results indicated that adolescents who were in families where fathers exhibited lower levels of nurturant-involved parenting experienced subsequent increases in social anxiety symptoms and decreased efficacy to refuse substances, which in turn was related to more frequent drunkenness, cigarette use, and marijuana use. Indirect effects are discussed. Findings were not substantiated for mothers’ parenting. Adolescent gender did not moderate associations. The results highlight an additional pathway through which parenting influences youth substance use and links social anxiety symptoms to reduced substance refusal efficacy.
Discovery of an important wintering site of the Critically Endangered Spoon-billed Sandpiper Calidris pygmaea in the Meghna Estuary, Bangladesh
Authors: CHOWDHURY SAYAM U. , FOYSAL MOHAMMAD , DIYAN M ABDULLAH ABU , AHMED SAKIB
Published: December 2017

The Critically Endangered Spoon-billed Sandpiper Calidris pygmaeus is one of the most threatened migratory shorebirds in the world, breeding in Russia and wintering in Asia. The global population is declining rapidly and is projected to be extinct within a few decades without intervention. Here, we present the results of shorebird surveys in previously unrecognised site in Bangladesh along the Meghna Estuary, identified for the first time by using species distribution models. Counts and habitat preference of Spoon-billed Sandpipers and other endangered shorebirds are described here with notes on the global importance of the newly discovered site. The sum of the peak counts for each shorebird species across the two surveys was 25,993 including a minimum of 48 Spoon-billed Sandpipers. The majority of the Spoon-billed Sandpipers were observed during low tide while foraging (66.6%) and logistic regression testing for effects on the presence of foraging Spoon-billed Sandpiper indicate that they mainly preferred to forage on shallow mud. We summarise the threats to Spoon-billed Sandpipers and other birds in the new site that is currently not recognized as a Wetland of International Importance under the Ramsar Convention, although it fulfils several Ramsar Criteria. We also propose conservation and monitoring measures for long-term protection of the Spoon-billed Sandpiper and its habitat.
Wickedness, Moral Responsibility, and Access to Transplantable Livers
Authors: TONKENS RYAN
Published: December 2017

Under the current conditions of scarcity of transplantable livers, difficult decisions need to be made about access. There is a growing consensus that it is morally justified to give people with ARESLD lower priority than those whose need is not self-caused. The purpose of this article is to critically examine the conditions under which such prioritization is morally justified, by challenging arguments put forth by Walter Glannon and Daniel Brudney. There are serious theoretical and practical problems with these views, which have to do with the nature and scope of the (putative) moral duty not to contribute to the competition for scarce transplantable livers, and the difficulty in determining whether people are responsible for their weakness or even wickedness of character. These problems need to be resolved if we are to be morally justified in determining access based on causal and moral responsibility for being in need.
The Ethics of Making Patients Responsible
Authors: HANSSON SVEN OVE
Published: December 2017

In their daily clinical work, healthcare professionals generally apply what seems to be a double standard for the responsibility of patients. On the one hand, patients are encouraged to take responsibility for lifestyle changes that can improve their chances of good health. On the other hand, when patients fail to follow such recommendations, they are not held responsible for the failure. This seeming inconsistency is explained in terms of the distinction between task responsibility and blame responsibility. The double standard for responsibility is shown to be epistemologically rational, ethically commendable, and therapeutically advantageous. However, this non-blaming approach to patient responsibility is threatened by proposals to assign lower priority in healthcare to patients who are themselves responsible for their disease. Such responsibility-based priority setting requires that physicians assign blame responsibility to their patients, a practice that would run into conflict with the ethical foundations of the patient–physician relationship. Therefore, such proposals should be rejected.
Fear of Life, Fear of Death, and Fear of Causing Death: How Legislative Changes on Assisted Dying Are Doomed to Fail
Authors: HÄYRY MATTI
Published: December 2017

Fear of life, fear of death, and fear of causing death form a combination that prevents reasoned changes in laws concerning end-of-life situations. This is shown systematically in this article using the methods of conceptual analysis. Prevalent fears are explicated and interpreted to see how their meanings differ depending on the chosen normative stance. When the meanings have been clarified, the impact of the fears on the motivations and justifications of potential legislative reforms are assessed. Two main normative stances are evoked. The first makes an appeal to individual self-determination, or autonomy, and the second to the traditional professional ethics of physicians. These views partly share qualifying elements, including incurability and irreversibility of the patient’s medical condition, proximity of death, the unbearable nature of suffering, and issues of voluntariness further shade the matter. The conclusion is that although many motives to change end-of-life laws are admirable, they are partly contradictory, as are calls for autonomy and appeals to professional ethics; to a degree that good, principled legislative solutions remain improbable in the foreseeable future.
The potential benefits of agricultural adaptation to warming in China in the long run
Authors: Huang Kaixing , Wang Jinxia , Huang Jikun , Findlay Christopher
Published: December 2017

Understanding the extent to which agriculture can adapt to climate change and the determinants of farmers' adaptive capacity are of paramount importance from a policy perspective. Based on household survey data from a large sample in rural China, the present article adopts a panel approach to estimate the potential benefits of long-run adaptation and to identify the determinants of farmers' adaptive capacity. The empirical results suggest that, for various model settings and climate change scenarios, long-run adaptations should mitigate one-third to one-half of the damages of warming on crop profits by the end of this century. These findings support the basic argument of the hedonic approach that omitting long-run adaptations will dramatically overestimate the potential damage of climate change. The paper also finds that household-level capital intensity and farmland size have significant effects on farmers' adaptive capacities.
THE COMMITMENTS OF DEMOCRACY
Authors: RODGERS DANIEL T.
Published: December 2017

It underplays the significance of James Kloppenberg's monumentally ambitious and massively learned Toward Democracy to call it a big book—though at seven hundred pages of text, a hundred pages of notes and another five hundred pages of additional endnotes online it is surely that. It is, in voice and subject, several books in one. The first is a sweeping narrative account of the struggles for self-rule in England, the United States, and France from the seventeenth century through the middle third of the nineteenth century. The great revolutions stand at this history's center—the Puritan Revolution of the 1640s, the British North Americans’ revolt against monarchy and their construction of an enduring kingless polity in the 1770s and 1780s, and the revolutionary upheaval in France in the years after 1789—their origins, struggles, and dramas etched with a skilled narrative historian's hand.
Resonanz – das Andere der Kompetenz?
Authors: Straubenmüller Viola
Published: December 2017

Zusammenfassung. Kompetenzorientierung, die als Programm Handhabbarkeit verspricht, ist legitim und notwendig. Sie zeichnet das Bild einer souveränen Person, die über sich selbst verfügen kann. Im Resonanzbegriff hingegen wird das Begegnende, das, was berührt, als teilweise unverfügbar (vgl. Rosa 2016) verstanden. Ist das pädagogischer Kitsch1? Ist Resonanzpädagogik2 überhaupt etwas Neues? Als Maßstab, an dem sich Pflegebildung gegenüber reiner Outcomeorientierung bewährt (vgl. von Hentig o. J.) lohnt Resonanzorientierung einige weitergehende Gedanken.
Die Einstellung von Auszubildenden der Gesundheits- und Krankenpflege sowie der Gesundheits- und Kinderkrankenpflege zum interprofessionellen Lernen
Authors: Krug Doreen
Published: December 2017

Zusammenfassung. Interprofessionelle Kooperation ist ein wesentlicher Baustein der künftigen professionellen Versorgung von Pflegebedürftigen und Patienten. In der beruflichen Praxis zeigt sich, dass die Gesundheitsberufe wenig voneinander wissen. Anhand der Entwicklung eines Konzeptes der Medizinischen Fakultät der Martin-Luther-Universität Halle / Saale zur Schaffung und Umsetzung interprofessioneller Ausbildungssequenzen soll der Frage nach der Bereitschaft zum interprofessionellen Lernen in den einzelnen Gesundheitsfachberufen nachgegangen werden.
Beginner’s Guide to the AGU Fall Meeting
Authors: Lerback Jory
Published: December 2017

An early-career scientist’s compilation of solicited advice and notes to self on how to effectively use the “conference experience.”
Exciting Section and Focus Group News
Authors: McEntee Chris
Published: December 2017

The American Geophysical Union announces new engagement pilots, simplified naming structure, and new GeoHealth section.
In situ functional dissection of RNA cis-regulatory elements by multiplex CRISPR-Cas9 genome engineering
Authors: Wu Qianxin , Ferry Quentin R. V. , Baeumler Toni A. , Michaels Yale S. , Vitsios Dimitrios M. , Habib Omer , Arnold Roland , Jiang Xiaowei , Maio Stefano , Steinkraus Bruno R. , Tapia Marta , Piazza Paolo , Xu Ni , Holländer Georg A. , Milne Thomas A. , Kim Jin-Soo , Enright Anton J. , Bassett Andrew R. , Fulga Tudor A.
Published: December 2017

RNA regulatory elements (RREs) are an important yet relatively under-explored facet of gene regulation. Deciphering the prevalence and functional impact of this post-transcriptional control layer requires technologies for disrupting RREs without perturbing cellular homeostasis. Here we describe genome-engineering based evaluation of RNA regulatory element activity (GenERA), a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 platform for in situ high-content functional analysis of RREs. We use GenERA to survey the entire regulatory landscape of a 3′UTR, and apply it in a multiplex fashion to analyse combinatorial interactions between sets of miRNA response elements (MREs), providing strong evidence for cooperative activity. We also employ this technology to probe the functionality of an entire MRE network under cellular homeostasis, and show that high-resolution analysis of the GenERA dataset can be used to extract functional features of MREs. This study provides a genome editing-based multiplex strategy for direct functional interrogation of RNA cis-regulatory elements in a native cellular environment.
Dielectric anomalies and interactions in the three-dimensional quadratic band touching Luttinger semimetal Pr2Ir2O7
Authors: Cheng Bing , Ohtsuki T. , Chaudhuri Dipanjan , Nakatsuji S. , Lippmaa Mikk , Armitage N. P.
Published: December 2017

Dirac and Weyl semimetals with linearly crossing bands are the focus of much recent interest in condensed matter physics. Although they host fascinating phenomena, their physics can be understood in terms of weakly interacting electrons. In contrast, more than 40 years ago, Abrikosov pointed out that quadratic band touchings are generically strongly interacting. We have performed terahertz spectroscopy on the films of the conducting pyrochlore Pr2Ir2O7, which has been shown to host a quadratic band touching. A dielectric constant as large as $$\tilde{ \varepsilon} {\mathrm{/}}\epsilon _0 \sim 180$$

ε

̃

∕

ϵ

0

~
180
is observed at low temperatures. In such systems, the dielectric constant is a measure of the relative scale of interactions, which are therefore in our material almost two orders of magnitude larger than the kinetic energy. Despite this, the scattering rate exhibits a T2 dependence, which shows that for finite doping a Fermi liquid state survives—however, with a scattering rate close to the maximal value allowed.
SYK kinase mediates brown fat differentiation and activation
Authors: Knoll Marko , Winther Sally , Natarajan Anirudh , Yang Huan , Jiang Mengxi , Thiru Prathapan , Shahsafaei Aliakbar , Chavarria Tony E. , Lamming Dudley W. , Sun Lei , Hansen Jacob B. , Lodish Harvey F.
Published: December 2017

Brown adipose tissue (BAT) metabolism influences glucose homeostasis and metabolic health in mice and humans. Sympathetic stimulation of β-adrenergic receptors in response to cold induces proliferation, differentiation, and UCP1 expression in pre-adipocytes and mature brown adipocytes. Here we show that spleen tyrosine kinase (SYK) is upregulated during brown adipocyte differentiation and activated by β-adrenergic stimulation. Deletion or inhibition of SYK, a kinase known for its essential roles in the immune system, blocks brown and white pre-adipocyte proliferation and differentiation in vitro, and results in diminished expression of Ucp1 and other genes regulating brown adipocyte function in response to β-adrenergic stimulation. Adipocyte-specific SYK deletion in mice reduces BAT mass and BAT that developed consisted of SYK-expressing brown adipocytes that had escaped homozygous Syk deletion. SYK inhibition in vivo represses β-agonist-induced thermogenesis and oxygen consumption. These results establish SYK as an essential mediator of brown fat formation and function.
Nucleotide– and Mal3-dependent changes in fission yeast microtubules suggest a structural plasticity view of dynamics
Authors: von Loeffelholz Ottilie , Venables Neil A. , Drummond Douglas Robert , Katsuki Miho , Cross Robert , Moores Carolyn A.
Published: December 2017

Using cryo-electron microscopy, we characterize the architecture of microtubules assembled fromSchizosaccharomyces pombetubulin, in the presence and absence of their regulatory partner Mal3. Cryo-electron tomography reveals that microtubules assembled fromS. pombetubulin have predominantly B-lattice interprotofilament contacts, with protofilaments skewed around the microtubule axis. Copolymerization with Mal3 favors 13 protofilament microtubules with reduced protofilament skew, indicating that Mal3 adjusts interprotofilament interfaces. A 4.6-Å resolution structure of microtubule-bound Mal3 shows that Mal3 makes a distinctive footprint on theS. pombemicrotubule lattice and that unlike mammalian microtubules,S. pombemicrotubules do not show the longitudinal lattice compaction associated with EB protein binding and GTP hydrolysis. Our results firmly support a structural plasticity view of microtubule dynamics in which microtubule lattice conformation is sensitive to a variety of effectors and differently so for different tubulins.
Targeted inhibition of STAT/TET1 axis as a therapeutic strategy for acute myeloid leukemia
Authors: Jiang Xi , Hu Chao , Ferchen Kyle , Nie Ji , Cui Xiaolong , Chen Chih-Hong , Cheng Liting , Zuo Zhixiang , Seibel William , He Chunjiang , Tang Yixuan , Skibbe Jennifer R. , Wunderlich Mark , Reinhold William C. , Dong Lei , Shen Chao , Arnovitz Stephen , Ulrich Bryan , Lu Jiuwei , Weng Hengyou , Su Rui , Huang Huilin , Wang Yungui , Li Chenying , Qin Xi , Mulloy James C. , Zheng Yi , Diao Jiajie , Jin Jie , Li Chong , Liu Paul P. , He Chuan , Chen Yuan , Chen Jianjun
Published: December 2017

Effective therapy of acute myeloid leukemia (AML) remains an unmet need. DNA methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) is a critical oncoprotein in AML. Through a series of data analysis and drug screening, we identified two compounds (i.e., NSC-311068 and NSC-370284) that selectively suppress TET1 transcription and 5-hydroxymethylcytosine (5hmC) modification, and effectively inhibit cell viability in AML with high expression of TET1 (i.e., TET1-high AML), including AML carrying t(11q23)/MLL-rearrangements and t(8;21) AML. NSC-311068 and especially NSC-370284 significantly repressed TET1-high AML progression in vivo. UC-514321, a structural analog of NSC-370284, exhibited a more potent therapeutic effect and prolonged the median survival of TET1-high AML mice over three fold. NSC-370284 and UC-514321 both directly target STAT3/5, transcriptional activators of TET1, and thus repress TET1 expression. They also exhibit strong synergistic effects with standard chemotherapy. Our results highlight the therapeutic potential of targeting the STAT/TET1 axis by selective inhibitors in AML treatment.
A pH-gated conformational switch regulates the phosphatase activity of bifunctional HisKA-family histidine kinases
Authors: Liu Yixiang , Rose Joshua , Huang Shaojia , Hu Yangbo , Wu Qiong , Wang Dan , Li Conggang , Liu Maili , Zhou Pei , Jiang Ling
Published: December 2017

Histidine kinases are key regulators in the bacterial two-component systems that mediate the cellular response to environmental changes. The vast majority of the sensor histidine kinases belong to the bifunctional HisKA family, displaying both kinase and phosphatase activities toward their substrates. The molecular mechanisms regulating the opposing activities of these enzymes are not well understood. Through a combined NMR and crystallographic study on the histidine kinase HK853 and its response regulator RR468 from Thermotoga maritima, here we report a pH-mediated conformational switch of HK853 that shuts off its phosphatase activity under acidic conditions. Such a pH-sensing mechanism is further demonstrated in the EnvZ-OmpR two-component system from Salmonella enterica in vitro and in vivo, which directly contributes to the bacterial infectivity. Our finding reveals a broadly conserved mechanism that regulates the phosphatase activity of the largest family of bifunctional histidine kinases in response to the change of environmental pH.
Relationship of corneal hysteresis and optic nerve parameters in healthy myopic subjects
Authors: Qiu Kunliang , Lu Xuehui , Zhang Riping , Wang Geng , Zhang Mingzhi
Published: December 2017

The association between corneal biomechanical properties and glaucoma is an area of much interest. We determined the relationship between corneal hysteresis (CH) and optic nerve parameters in healthy myopic subjects in the current study. CH was measured with Reichert Ocular Response Analyzer in 108 eyes from 108 healthy myopic subjects. All subjects received retinal nerve fiber layer and optic disc imaging Cirrus HD-OCT, GDx ECC, and Heidelberg Retina Tomograph II. None of the tested optic nerve parameters showed statistical significance with CH by using correlation analysis. For RNFL parameters, there was a negative but not statistically significant correlation between CH and average RNFL thickness obtained with OCT (r = −0.15, p = 0.13). For optic disc parameters, there was a negative but not statistically significant correlation between CH and rim area measured with OCT (r = −0.10, p = 0.29). The current study did not find any statistically significant relationship between CH and optic nerve parameters as measured by all three imaging modalities in healthy myopic eyes. Therefore, the relationship observed previously in glaucoma subjects is likely coming to fruition as optic nerve damage is caused by the disease.
Quantification of interacting cognate odorants with olfactory receptors in nanovesicles
Authors: Sanmartí-Espinal Marta , Iavicoli Patrizia , Calò Annalisa , Taulés Marta , Galve Roger , Marco M. Pilar , Samitier Josep
Published: December 2017

This study aims to improve our understanding of the interaction between olfactory receptors and odorants to develop highly selective biosensing devices. Natural nanovesicles (NVs) from Saccharomyces cerevisiae, ~100 nm in diameter, carrying either the human OR17-40 or the chimpanzee OR7D4 olfactory receptor (OR) tagged with the c-myc epitope at their N-terminus, are presented as model systems to quantify the interaction between odorant and olfactory receptors. The level of expression of olfactory receptors was determined at individual NVs using a novel competitive ELISA immunoassay comparing the values obtained against those from techniques involving the solubilization of cell membrane proteins and the identification of c-myc-carrying receptors. Surface Plasmon Resonance (SPR) measurements on L1 Biacore chips indicate that cognate odorants bind to their Ors, thereby quantifying the approximate number of odorants that interact with a given olfactory receptor. The selectivity of OR17-40-carrying NVs towards helional and OR7D4-carrying NVs towards androstenone has been proven in cross-check experiments with non-specific odorant molecules (heptanal and pentadecalactone, respectively) and in control receptors.
Identification of nonsense-mediated mRNA decay pathway as a critical regulator of p53 isoform β
Authors: Cowen Lauren E. , Tang Yi
Published: December 2017

Human TP53 gene encodes the tumor suppressor p53 and, via alternative splicing, the p53β and γ isoforms. Numerous studies have shown that p53β/γ can modulate p53 functions and are critically involved in regulation of cellular response to stress conditions. However, it is not fully understood how the β and γ isoforms are regulated following splicing. Using gene targeting and RNAi, we showed that depletion of the nonsense-mediated mRNA decay (NMD) factor SMG7 or UPF1 significantly induced p53β but had minimal effect on p53γ. Sequence analysis reveals the presence of unique features – key hallmarks of NMD targets in the p53β transcript, which was further confirmed in NMD reporter gene assays. By manipulating splicing components, we found that NMD activities are crucial to control p53β levels under conditions that favor its splicing. Our data demonstrate that the NMD and alternative splicing pathways regulate p53β in a synergistic manner, and NMD plays a critical role in the determination of the p53β following its splicing. As aberrant p53β expression and dysfunctional NMD are both implicated in cancers, our studies may provide a novel insight into the regulation of p53β in tumorigenic settings.
Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage
Authors: Chambers Anna R. , Pilati Nadia , Balaram Pooja , Large Charles H. , Kaczmarek Leonard K. , Polley Daniel B.
Published: December 2017

Higher stages of central auditory processing compensate for a loss of cochlear nerve synapses by increasing the gain on remaining afferent inputs, thereby restoring firing rate codes for rudimentary sound features. The benefits of this compensatory plasticity are limited, as the recovery of precise temporal coding is comparatively modest. We reasoned that persistent temporal coding deficits could be ameliorated through modulation of voltage-gated potassium (Kv) channels that regulate temporal firing patterns. Here, we characterize AUT00063, a pharmacological compound that modulates Kv3.1, a high-threshold channel expressed in fast-spiking neurons throughout the central auditory pathway. Patch clamp recordings from auditory brainstem neurons and in silico modeling revealed that application of AUT00063 reduced action potential timing variability and improved temporal coding precision. Systemic injections of AUT00063 in vivo improved auditory synchronization and supported more accurate decoding of temporal sound features in the inferior colliculus and auditory cortex in adult mice with a near-complete loss of auditory nerve afferent synapses in the contralateral ear. These findings suggest modulating Kv3.1 in central neurons could be a promising therapeutic approach to mitigate temporal processing deficits that commonly accompany aging, tinnitus, ototoxic drug exposure or noise damage.
Ratiometric fluorescence imaging of cell surface pH by poly(ethylene glycol)-phospholipid conjugated with fluorescein isothiocyanate
Authors: Ohgaki Ryuichi , Teramura Yuji , Hayashi Daichi , Quan Lili , Okuda Suguru , Nagamori Shushi , Takai Madoka , Kanai Yoshikatsu
Published: December 2017

Various physiological and pathological processes are accompanied with the alteration of pH at extracellular juxtamembrane region. Accordingly, the methods to analyze the cell surface pH have been demanded in biological and medical sciences. In this study, we have established a novel methodology for cell surface pH imaging using poly(ethylene glycol)-phospholipid (PEG-lipid) as a core structure of ratiometric fluorescent probes. PEG-lipid is a synthetic amphiphilic polymer originally developed for the cell surface modification in transplantation therapy. Via its hydrophobic alkyl chains of the phospholipid moiety, PEG-lipid is, when applied extracellularly, spontaneously inserted into the plasma membrane and retained at the surface of the cells. We have demonstrated that the PEG-lipid conjugated with fluorescein isothiocyanate (FITC-PEG-lipid) can be used as a sensitive and reversible cell-surface-anchored pH probe between weakly alkaline and acidic pH with an excellent spatiotemporal resolution. The remarkably simple procedure for cell-surface labeling with FITC-PEG-lipid would also be advantageous when considering its application to high-throughputin vitroassay. This study further indicates that various probes useful for the investigation of juxtamembrane environments could also be developed by using PEG-lipid as the core structure for bio-membrane anchoring.
The β-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA2DS2-VaSc score
Authors: Hu Xiaofeng , Wang Junjun , Li Yaguo , Wu Jiong , Qiao Song , Xu Shanhu , Huang Jun , Chen Linhui
Published: December 2017

Previous work has suggested that ischemic stroke (IS) may be more likely to occur in individuals with a genetic predisposition. In this study, we investigated the potential association of IS-relevant genetic risk factors with cardioembolic stroke (CES) in atrial fibrillation (AF) patients with low CHA2DS2-VaSc score. Genotyping was performed using the GenomeLab SNPstream genotyping platform for five IS-relevant SNPs (MMP-9 C1562T, ALOX5AP SG13S114A/T, MTHFR 677 C/T, FGB 455 G/A, and eNOS G298A) in 479 AF patients with CES and 580 age and sex-matched AF patients without CES. The multivariate analysis adjusted for potential confounders and demonstrated that FGB 455 G/A was independently associated with increased risk of CES in AF patients and the significance remained after Bonferroni correction in the additive, dominant, and recessive models with ORs of 1.548 (95% CI: 1.251–1.915, P = 0.001), 1.588 (95% CI: (1.226–2.057, P = 0.003), and 2.394 (95% CI: 1.357–4.223, P = 0.015), respectively. Plasma fibrinogen levels were significantly higher in patients with the A allele compared with patients with genotype of GG (3.29 ± 0.38 mg/dl vs. 2.87 ± 0.18 mg/dl, P < 0.001). We found for the first time that the A allele of FGB 455 G/A was a risk factor for CES in AF patients, probably by elevating the level of plasma fibrinogen.
A novel type I cystatin of parasite origin with atypical legumain-binding domain
Authors: Ilgová Jana , Jedličková Lucie , Dvořáková Hana , Benovics Michal , Mikeš Libor , Janda Lubomír , Vorel Jiří , Roudnický Pavel , Potěšil David , Zdráhal Zbyněk , Gelnar Milan , Kašný Martin
Published: December 2017

Parasite inhibitors of cysteine peptidases are known to influence a vast range of processes linked to a degradation of either the parasites’ own proteins or proteins native to their hosts. We characterise a novel type I cystatin (stefin) found in a sanguinivorous fish parasite Eudiplozoon nipponicum (Platyhelminthes: Monogenea). We have identified a transcript of its coding gene in the transcriptome of adult worms. Its amino acid sequence is similar to other stefins except for containing a legumain-binding domain, which is in this type of cystatins rather unusual. As expected, the recombinant form of E. nipponicum stefin (rEnStef) produced in Escherichia coli inhibits clan CA peptidases – cathepsins L and B of the worm – via the standard papain-binding domain. It also blocks haemoglobinolysis by cysteine peptidases in the worm’s excretory-secretory products and soluble extracts. Furthermore, we had confirmed its ability to inhibit clan CD asparaginyl endopeptidase (legumain). The presence of a native EnStef in the excretory-secretory products of adult worms, detected by mass spectrometry, suggests that this protein has an important biological function at the host-parasite interface. We discuss the inhibitor’s possible role in the regulation of blood digestion, modulation of antigen presentation, and in the regeneration of host tissues.
Assessment of low concentration wastewater treatment operations with dewatered alum sludge-based sequencing batch constructed wetland system
Authors: Kang Wei , Chai Hongxiang , Xiang Yu , Chen Wei , Shao Zhiyu , He Qiang
Published: December 2017

Competition of volatile fatty acids between anoxic denitrification and anaerobic phosphorus release is prominent. Therefore, low concentration wastewater has restricted effects on nitrogen and phosphorus removal. The purpose of this study is to treat dormitory sewage with a biochemical oxygen demand (BOD) ranging from 50 to 150 mg/L using dewatered alum sludge-based sequencing batch constructed wetland system. Vegetation in the wetland system was chosen to be Phragmites australis. Three parallel cases were carried out to assess impacts due to different hydraulic retention time (HRT) and artificial aeration. The results showed that this system is effective in removing total nitrogen (TN), ammonia nitrogen (NH3-N) and total phosphorus (TP) under different HRT. However, nitrous oxide (N2O) emission poses to be the greatest challenge in the high HRT cases. Artificial aeration could reduce N2O emission but is associated with high operational cost. Results indicate that dewatered alum sludge-based sequencing batch constructed wetland system is a promising bio-measure in the treatment of low concentration wastewater.