bluuebunny/crossref_metadata_2025 huggingface dataset:
Ubiquitin‐Conjugating Enzyme E2 L3 is Downregulated by the Chikungunya Virus nsP2 Protease
Authors: Ramphan Suwipa , Khongwichit Sarawut , Saisawang Chonticha , Kovanich Duangnapa , Ketterman Albert J. , Ubol Sukathida , Auewarakul Prasert , Roytrakul Sittiruk , Smith Duncan R. , Kuadkitkan Atichat
Published: October 2017

Purpose

Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that causes chikungunya fever in humans. The CHIKV non‐structural protein 2 (nsP2) is a multifunctional protein that additionally modulates the host cell to dampen the innate immune response and inhibit other cellular processes.

Experimental design

To further investigate the interactions of nsP2 with host cells, the protease domain of CHIKV nsP2 (nsP2‐pro) is transfected into Hela cells, and differential protein expression is detected by 2D polyacrylamide gel electrophoresis.

Results

A total of 21 differentially regulated (six upregulated, 15 downregulated) spots are observed, of which five are identified by mass spectrometry. The downregulation of one of the identified proteins, ubiquitin‐conjugating enzyme E2 L3 (UBE2L3) is confirmed by western blotting of both nsP2‐pro transfection and CHIKV natural infection, and the downregulation of UBE2L3 is additionally shown to require an enzymatically active nsP2 protease domain. Transfection of full length UBE2L3 into HEK293T/17 cells prior to CHIKV infection reduce levels of infection and E protein expression but do not alter RNA genome levels.

Conclusion

These results suggest that UBE2L3 is a cellular target of the CHIKV nsP2 protease, and this possibly mediates the pathogenesis of chikungunya fever.
Hysteresis Phenomena in Relaxor Ferroelectrics: Consideration of Polar Nanoregions
Authors: Starkov Alexander S. , Starkov Ivan A. , Dedyk Antonina I. , Suchaneck Gunnar , Gerlach Gerald
Published: October 2017

Hysteresis phenomena of relaxor ferroelectrics have been modeled by considering spheroidal polar nanoregions covered by a thin shell of a linear dielectric both embedded into a ferroelectric matrix. The electric field within the spheroid is described by the Landau–Ginzburg–Devonshire equation. The resulting phase transition temperature is strongly dependent on the field direction. Calculations for single spheroids are generalized for an ensemble of random oriented spheroids. Finally, the temperature dependence of P–E hysteresis curve has been described with good accuracy for 0.7PbMg1/3Nb2/3O3–0.3PbTiO3 as an exemplary relaxor ferroelectric.
3‐D Coupled Analysis of Deformation of the Strip and Rolls in Flat Rolling by FEM
Authors: Park Hyojin , Hwang Sangmoo
Published: October 2017

In flat rolling mills, while demands for precise process set‐up and control are increasing than ever before, it is difficult to improve the prediction accuracy of the existing models to the level of satisfaction. This seems particularly true for the models for the prediction of the strip profile. The breakthrough may be achieved, if new models are to be developed on the basis of powerful and rigorous finite element simulation capabilities. In this paper, the authors present a rigorous finite element (FE) approach for 3‐D coupled analysis of the elastic‐plastic deformation of the strip and the elastic deformation of rolls in the roll‐stack of a mill stand. FE formulations, strategies for the treatment of the 3‐D coupled nature of the problem, and the related computational schemes are described in detail, with some examples and illustrations. The prediction accuracy of the proposed approach is also examined through comparison with measurements.
Non‐alcoholic fatty liver disease satisfactorily treated with traditional Japanese kampo medicine
Authors: Shimada Yutaka , Fujimoto Makoto , Nogami Tatsuya , Watari Hidetoshi , Kitahara Hideyuki , Misawa Hiroki , Kimbara Yoshiyuki
Published: October 2017

Case

An obese 17‐year‐old male patient with right hemiparesis secondary to cerebral infarction presented for kampo treatment. The hemiparesis and resultant lack of exercise had led to an increase in bodyweight. Serum alanine aminotransferase (ALT) was elevated and abdominal ultrasound identified fatty liver. The patient was diagnosed with non‐alcoholic fatty liver disease (NAFLD). Aspirin and tocopherol acetate (vitamin E), previously prescribed, were continued, and kampo medicines were prescribed.

Outcome

Two years and 6 months after the initial visit, we prescribed keishikashakuyakuto (Gui Zhi Jia Shao Yao Tang) extract, in addition to keishibukuryogan (Gui Zhi Fu Ling Wan) extract. Thereafter, serum ALT gradually decreased, despite no significant change in bodyweight or blood platelet count.

Conclusion

Kampo medicine may be effective for the treatment of NAFLD.
Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study
Authors: Kovacevic A. , Öhman A. , Tulzer G. , Herberg U. , Dangel J. , Carvalho J. S. , Fesslova V. , Jicinska H. , Sarkola T. , Pedroza C. , Averiss I. E. , Mellander M. , Gardiner H. M. ,   the Fetal Working Group of the AEPC
Published: October 2017

Objective

Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not.

Methods

This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV‐circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14–0.9, to create a final cohort for analysis of 42 FV and 29 NH cases.

Results

FV was technically successful in 59/67 fetuses at a median age of 26 (21–34) weeks. There were 7/72 (10%) procedure‐related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23–0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01).

Conclusions

We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow‐up. However, FV is associated with a 10% procedure‐related loss and increased prematurity compared with the NH cohort, and therefore the risk‐to‐benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center‐specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Cerebrovascular response to maternal hyperoxygenation in fetuses with hypoplastic left heart syndrome depends on gestational age and baseline cerebrovascular resistance
Authors: Szwast A. , Putt M. , Gaynor J. W. , Licht D. J. , Rychik J.
Published: October 2017

Objectives

Compared with normal fetuses, fetuses with hypoplastic left heart syndrome (HLHS) have smaller brain volumes and are at higher risk of brain injury, possibly due to diminished cerebral blood flow and oxygen content. By increasing cerebral oxygen delivery, maternal hyperoxygenation (MH) might improve brain development and reduce the risk of brain injury in these fetuses. This study investigated whether gestational age and baseline cerebrovascular resistance affect the response to MH in fetuses with HLHS.

Methods

The study population comprised 43 fetuses with HLHS or HLHS variant referred for fetal echocardiography between January 2004 and September 2008. Middle cerebral artery (MCA) pulsatility index (PI), a surrogate measure of cerebrovascular resistance, was assessed between 20 and 41 weeks' gestation at baseline in room air (RA) and after 10 min of MH. Z‐scores of MCA‐PI were generated. A mixed‐effects model was used to determine whether change in MCA‐PI depends upon gestational age and baseline MCA‐PI.

Results

In RA and following MH, MCA‐PI demonstrated a curvilinear relationship with gestational age in fetuses with HLHS, peaking at around 28 weeks and then falling more steeply near term. MCA‐PI Z‐score declined in a linear manner, such that it was 1.4 SD below that in normal fetuses at 38 weeks. Increase in MCA‐PI Z‐score after MH was first seen at ≥ 28 weeks. A baseline MCA‐PI Z‐score ≤ −0.96 was predictive of an increase in cerebrovascular resistance in response to MH.

Conclusion

In fetuses with HLHS, MCA‐PI first increases in response to MH at ≥ 28 weeks' gestation. A baseline MCA‐PI Z‐score ≤ −0.96 predicts an increase in cerebrovascular resistance in response to MH. These results may have implications for clinical trials utilizing MH as a neuroprotective agent. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Unraveling Pancreatic Segmentation
Authors: Renard Yohann , de Mestier Louis , Perez Manuela , Avisse Claude , Lévy Philippe , Kianmanesh Reza
Published: October 2017

Background

Limited pancreatic resections are increasingly performed, but the rate of postoperative fistula is higher than after classical resections. Pancreatic segmentation, anatomically and radiologically identifiable, may theoretically help the surgeon removing selected anatomical portions with their own segmental pancreatic duct and thus might decrease the postoperative fistula rate. We aimed at systematically and comprehensively reviewing the previously proposed pancreatic segmentations and discuss their relevance and limitations.

Methods

PubMed database was searched for articles investigating pancreatic segmentation, including human or animal anatomy, and cadaveric or surgical studies.

Results

Overall, 47/99 articles were selected and grouped into 4 main hypotheses of pancreatic segmentation methodology: anatomic, vascular, embryologic and lymphatic. The head, body and tail segments are gross description without distinct borders. The arterial territories defined vascular segments and isolate an isthmic paucivascular area. The embryological theory relied on the fusion plans of the embryological buds. The lymphatic drainage pathways defined the lymphatic segmentation. These theories had differences, but converged toward separating the head and body/tail parts, and the anterior from posterior and inferior parts of the pancreatic head. The rate of postoperative fistula was not decreased when surgical resection was performed following any of these segmentation theories; hence, none of them appeared relevant enough to guide pancreatic transections.

Conclusion

Current pancreatic segmentation theories do not enable defining anatomical–surgical pancreatic segments. Other approaches should be explored, in particular focusing on pancreatic ducts, through pancreatic ducts reconstructions and embryologic 3D modelization.
Designing distribution systems with reverse flows
Authors: Cilacı Tombuş Ayşe , Aras Necati , Verter Vedat
Published: October 2017

Closed-loop supply chains involve forward flows of products from production facilities to customer zones as well as reverse flows from customer zones back to remanufacturing facilities. We present an integrated modeling framework for configuring a distribution system with reverse flows so as to minimize the total cost of satisfying customer demand and remanufacturing the returned items that are recoverable. Given a set of existing plants and customer zones, our basic model identifies the optimal number and location of distribution centers and return centers assuming that all plants have remanufacturing capability. We devise a Lagrangian heuristic for this problem. The proposed solution method proved to be computationally efficient for solving large-scale instances of the closed-loop supply chain design problem. The potential benefits of the integrated model are demonstrated by comparing its results with those obtained from an alternative approach that determines optimal forward and reverse network structures sequentially. We also extend the basic model to determine the optimal locations for establishing remanufacturing facilities. Using the extended model, we study the conditions under which the return centers can be co-located with remanufacturing facilities rather than being established at the downstream echelons of the supply chain. Different from the existing works on facility location-allocation models for closed-loop supply chain network design, the main focus in this paper is on the investigation of structural properties of the network such as co-locating return centers with remanufacturing facilities and quantifying the benefit of modeling forward and reverse flows simultaneously rather than sequentially.
Modularization in material flow simulation for managing production releases in remanufacturing
Authors: Gaspari Lorenzo , Colucci Lorenzo , Butzer Steffen , Colledani Marcello , Steinhilper Rolf
Published: October 2017

Remanufacturing is recognized as a major circular economy option to recover and upgrade functions from post-use products. However, the inefficiencies associated with operations, mainly due to the uncertainty and variability of material flows and product conditions, undermine the growth of remanufacturing. With the objective of supporting the design and management of more proficient and robust remanufacturing processes, this paper proposes a generic and reconfigurable simulation model of remanufacturing systems. The developed model relies upon a modular framework that enables the user to handle multiple process settings and production control policies, among which token-based policies. Customizable to the characteristics of the process under analysis, this model can support logistics performance evaluation of different production control policies, thus enabling the selection of the optimal policy in specific business contexts. The proposed model is applied to a real remanufacturing environment in order to validate and demonstrate its applicability and benefits in the industrial settings.
Work Disability Among Native-born and Foreign-born Americans: On Origins, Health, and Social Safety Nets
Authors: Engelman Michal , Kestenbaum Bert M. , Zuelsdorff Megan L. , Mehta Neil K. , Lauderdale Diane S.
Published: October 2017

Public debates about both immigration policy and social safety net programs are increasingly contentious. However, little research has explored differences in health within America’s diverse population of foreign-born workers, and the effect of these workers on public benefit programs is not well understood. We investigate differences in work disability by nativity and origins and describe the mix of health problems associated with receiving Social Security Disability Insurance benefits. Our analysis draws on two large national data sources—the American Community Survey and comprehensive administrative records from the Social Security Administration—to determine the prevalence and incidence of work disability between 2001 and 2010. In sharp contrast to prior research, we find that foreign-born adults are substantially less likely than native-born Americans to report work disability, to be insured for work disability benefits, and to apply for those benefits. Overall and across origins, the foreign-born also have a lower incidence of disability benefit award. Persons from Africa, Northern Europe, Canada, and parts of Asia have the lowest work disability benefit prevalence rates among the foreign-born; persons from Southern Europe, Western Europe, the former Soviet Union, and the Caribbean have the highest rates.
Identification of freeplay and aerodynamic nonlinearities in a 2D aerofoil system with via higher-order spectra
Authors: Candon M. , Carrese R. , Ogawa H. , Marzocca P.
Published: October 2017

Higher-Order Spectra (HOS) are used to characterise the nonlinear aeroelastic behaviour of a plunging and pitching 2-degree-of-freedom aerofoil system by diagnosing structural and/or aerodynamic nonlinearities via the nonlinear spectral content of the computed displacement signals. The nonlinear aeroelastic predictions are obtained from high-fidelity viscous fluid-structure interaction simulations. The power spectral, bi-spectral and tri-spectral densities are used to provide insight into the functional form of both freeplay and inviscid/viscous aerodynamic nonlinearities with the system displaying both low- and high-amplitude Limit Cycle Oscillation (LCO). It is shown that in the absence of aerodynamic nonlinearity (low-amplitude LCO) the system is characterised by cubic phase coupling only. Furthermore, when the amplitude of the oscillations becomes large, aerodynamic nonlinearities become prevalent and are characterised by quadratic phase coupling. Physical insights into the nonlinearities are provided in the form of phase-plane diagrams, pressure coefficient distributions and Mach number flowfield contours.
Flow and structure in a dendritic glacier with bedrock steps
Authors: JISKOOT HESTER , FOX THOMAS A , VAN WYCHEN WESLEY
Published: October 2017

We analyse ice flow and structural glaciology of Shackleton Glacier, a dendritic glacier with multiple icefalls in the Canadian Rockies. A major tributary-trunk junction allows us to investigate the potential of tributaries to alter trunk flow and structure, and the formation of bedrock steps at confluences. Multi-year velocity-stake data and structural glaciology up-glacier from the junction were assimilated with glacier-wide velocity derived from Radarsat-2 speckle tracking. Maximum flow speeds are 65 m a−1 in the trunk and 175 m a−1 in icefalls. Field and remote-sensing velocities are in good agreement, except where velocity gradients are high. Although compression occurs in the trunk up-glacier of the tributary entrance, glacier flux is steady state because flow speed increases at the junction due to the funnelling of trunk ice towards an icefall related to a bedrock step. Drawing on a published erosion model, we relate the heights of the step and the hanging valley to the relative fluxes of the tributary and trunk. It is the first time that an extant glacier is used to test and support such model. Our study elucidates the inherent complexity of tributary/trunk interactions and provides a conceptual model for trunk flow restriction by a tributary in surge-type glaciers.
The Garboldisham Macehead: its Manufacture, Date, Archaeological Context and Significance
Authors: Jones Andrew Meirion , Díaz-Guardamino Marta , Gibson Alex , Cox Sylvia
Published: October 2017

The paper discusses the Garboldisham macehead: an unusual decorated macehead carved from red deer antler. The macehead was found in the 1960s deposited in a tributary of the river Little Ouse, Norfolk and is decorated with three spirals, making it especially significant. This paper reports on the analysis of the decoration using digital imaging, discusses a new radiocarbon date recently obtained for the artefact, and discusses its significance alongside other dated antler maceheads.
Morphological and molecular characterization ofTrophurus wuhuensisn. sp. (Nematoda: Telotylenchinae) from soil associated withCinnamomum camphorain China
Authors: Li Y. , Du J. , Wang Z.Y. , Wang K. , Li H.L.
Published: October 2017

A new plant nematode species,Trophurus wuhuensisn. sp., was collected from the soil associated withCinnamomum camphorain Wuhu, Anhui Province, China. The new species is characterized by having a female with a slender body 660.5–801.5 μm in length, stylet 12–14 μm long, knobs directed laterad, lateral field marked by short and scattered grooves, post-vulval uterine sac shorter than vulval body diameter, post-rectal intestinal sac absent, tail cylindroid, terminus with deep wrinkles; and male with a pointed tail terminus and spicules 16–18 μm long. The internal transcribed spacer sequences of ribosomal DNA (ITS rDNA) and partial 18S ribosomal DNA (18S rDNA) fromT. wuhuensisn. sp. were amplified and sequenced. A phylogenetic analysis based on sequences of 18S rDNA fragments is given in this study.
Multilocus phylogenetic analysis and morphological data reveal a new species composition of the genusDrepanocephalusDietz, 1909 (Digenea: Echinostomatidae), parasites of fish-eating birds in the Americas
Authors: Hernández-Cruz E. , Hernández-Orts J.S. , Sereno-Uribe A.L. , Pérez-Ponce de León G. , García-Varela M.
Published: October 2017

Members of the genusDrepanocephalusare endoparasites of fish-eating birds of the families Phalacrocoracidae and Sulidae distributed across the Americas. Currently,Drepanocephaluscontains three species, i.e.D. spathans(type species),D. olivaceusandD. auritus.Two additional species,D. parvicephalusandD. mexicanuswere transferred to the genusPetasiger. In the current study, available DNA sequences ofD. spathans,D. auritusandDrepanocephalussp., were aligned with newly generated sequences ofD. spathansandPetasiger mexicanus. Phylogenetic analyses inferred with three nuclear (LSU, SSU and ITS1, 5.8S, ITS2) and two mitochondrial (cox1,nad1) molecular markers showed that the sequences ofD. spathansandD. auritusare nested together in a single clade with very low genetic divergence, withPetasiger mexicanusas its sister species. Additionally,P. mexicanuswas not a close relative of other members of the genusPetasiger,showing thatP. mexicanusactually belongs to the genusDrepanocephalus,suggesting the need to re-allocatePetasiger mexicanusback into the genusDrepanocephalus, asD. mexicanus.Morphological observations of the newly sampled individuals ofD. spathansshowed that the position of the testes is variable and testes might be contiguous or widely separated, which is one of the main diagnostic traits forD. auritus. Our results suggest thatD. auritusmight be considered a synonym ofD. spathansand, as a result, the latter represents a species with a wide geographic range across the Americas, parasitizing both the Neotropical and the double-crested cormorant in Argentina, Brazil, Paraguay, Venezuela, Colombia, Mexico, USA and Canada.
Replication in task-based language teaching research: Kim (2012) and Shintani (2012)
Authors: Révész Andrea
Published: October 2017

This paper calls for the replication of two task-based language teaching (TBLT) studies, Kim (2012) and Shintani (2012). Kim contributes to the large body of TBLT research on output-based tasks, whereas Shintani initiates research into input-based tasks, a less well researched domain. These studies deserve to be replicated for several reasons. Unlike the bulk of existing TBLT research, they investigate task-based second language (L2) development in addition to performance, and are conducted in actual classroom rather than laboratory contexts. Also, they are well designed studies, including detailed descriptions of the instruments and methodological procedures, making replication feasible. First, this paper provides an overview of the studies. Next, approaches to approximate and conceptual replications are suggested in order to assess the internal and external validity of the original experiments.
CME: Das Schweizer Fallpauschalensystem
Authors: Mehra Tarun , Schaer Dominik
Published: October 2017

Zusammenfassung. Diagnose-bezogene Fallgruppen, DRGs, sind eines der seit den 1960er in den USA entwickelten und erstmals 1983 zu Abrechnungszwecken eingeführten Patientenklassifikationssysteme, die den Anspruch erheben, klinisch ähnliche Fälle, die ähnlich teuer sind, zwecks einer erhöhten Vergleichbarkeit zusammenzufassen. Die Hauptziele, welche mit der Einführung von DRGs zu Abrechnungszwecken verfolgt werden, sind einerseits eine Erhöhung der Transparenz der erbrachten Leistungen, sowie andererseits eine Steigerung der Effizienz durch die pauschale Rückvergütung des durchschnittlichen Aufwands der Fälle der selben DRG. In der Schweiz werden seit 2012 sämtliche stationäre, akut-somatische Fälle über DRGs abgerechnet. Obwohl einige Befürchtungen nicht objektiviert werden konnten, haben sich andere bestätigt.
Mastodynie – wie soll man «Brustschmerz» abklären und behandeln?
Authors: Talimi-Schnabel Julia , Fink Daniel
Published: October 2017

Zusammenfassung. Mastodynie ist ein häufig auftretendes Krankheitsbild, das uns im klinischen Alltag regelmässig begegnet. Da die Ursachenpalette äusserst breit von physiologischen Veränderungen bis Malignität reichen kann, ist die Diagnosefindung nicht immer einfach. Der Ausschluss der Malignität führt bereits bei vielen Betroffenen zu einer grossen Entlastung und zu besserem Umgang mit den Beschwerden. Nach einer sorgfältigen Abklärung kann die adäquate Therapie je nach Form der Mastodynie eingeleitet werden. Grundsätzlich lässt sich sagen: Die medikamentöse Therapie der zyklusunabhängigen Form ist unbefriedigend, operative Vorgehensweisen sind bei symptomatischen Befunden zu diskutieren. Grössere operative Massnahmen stellen hingegen bei der zyklischen Mastodynie keine erfolgversprechende Option dar und hier ist strenge Zurückhaltung geboten. Nicht jede Mastodynie benötigt zwingend ein therapeutisches Vorgehen. Das Konzept muss individuell angepasst an den Leidensdruck festgelegt werden. Bekannt sind Spontanremissionen von ca. 20–30 %. Dabei steht die Remission der zyklischen Mastodynie in Zusammenhang mit hormonellen Ereignissen (z.B. Beginn Einnahme einer Antibabypille, Schwangerschaft, Menopause).
Soziale Kompetenzen als Bestandteil von Abschlussprüfungen in der Sekundarstufe
Authors: Döring Melanie , Strobel-Eisele Gabriele , Wacker Albrecht , Heizmann Elke , Kramer Jochen
Published: October 2017

Zusammenfassung. Der Förderung sozialer Kompetenzen wird in den Bildungsplänen ein hoher Stellenwert eingeräumt und in den letzten Jahren zunehmend auch in Prüfungsprozesse integriert. Ziel neu implementierter Abschlussprüfungen ist es, neben fachlich-inhaltlichen Kenntnissen auch soziale Kompetenzen in der Leistungsbeurteilung zu berücksichtigen. Prüfungen, die als projektartige Gruppenprüfungen konzipiert sind, verlangen eine kooperative Arbeitsweise der Lernenden, für die soziale Kompetenzen als wichtige Voraussetzung gelten. Bislang ist jedoch nicht empirisch geklärt, welchen Einfluss soziale Kompetenzen tatsächlich auf den Leistungserfolg in diesen kooperativen Prüfungsarrangements aufweisen. Die vorliegende Studie setzt an diesem Forschungsdefizit an und untersucht am Beispiel der Fächerübergreifenden Kompetenzprüfung an Realschulen in Baden-Württemberg, inwieweit soziale Kompetenzen die Prüfungsleistung beeinflussen. Zudem wurde in einem quasi-experimentellen Interventions- und Kontrollgruppendesign verglichen, ob sich die sozialen Kompetenzen der Lernenden anhand gezielter Trainingseinheiten zum kooperativen Arbeiten steigern lassen und sich Effekte auf die Prüfungsleistung zeigen. Als Ergebnis der Studie ergab sich ein substanzieller Effekt für situationsspezifische soziale Kompetenzen auf die Leistung. Signifikante Veränderungen der sozialen Kompetenzen konnten jedoch nach Durchführung der Intervention nicht nachgewiesen werden.
Keeping Our Focus on the Subseafloor
Authors: Bangs Nathan , Austin Jr. James
Published: October 2017

Hard-pressed funding agencies wonder whether marine seismic facilities are worth the investment. A recent survey gives a resounding yes.
Cardioprotection induced in a mouse model of neuropathic pain via anterior nucleus of paraventricular thalamus
Authors: Cheng Yi-Fen , Chang Ya-Ting , Chen Wei-Hsin , Shih Hsi-Chien , Chen Yen-Hui , Shyu Bai-Chuang , Chen Chien-Chang
Published: October 2017

Myocardial infarction is the leading cause of death worldwide. Restoration of blood flow rescues myocardium but also causes ischemia-reperfusion injury. Here, we show that in a mouse model of chronic neuropathic pain, ischemia-reperfusion injury following myocardial infarction is reduced, and this cardioprotection is induced via an anterior nucleus of paraventricular thalamus (PVA)-dependent parasympathetic pathway. Pharmacological inhibition of extracellular signal-regulated kinase activation in the PVA abolishes neuropathic pain-induced cardioprotection, whereas activation of PVA neurons pharmacologically, or optogenetic stimulation, is sufficient to induce cardioprotection. Furthermore, neuropathic injury and optogenetic stimulation of PVA neurons reduce the heart rate. These results suggest that the parasympathetic nerve is responsible for this unexpected cardioprotective effect of chronic neuropathic pain in mice.
Activating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder
Authors: Huppke Peter , Weissbach Susann , Church Joseph A. , Schnur Rhonda , Krusen Martina , Dreha-Kulaczewski Steffi , Kühn-Velten W. Nikolaus , Wolf Annika , Huppke Brenda , Millan Francisca , Begtrup Amber , Almusafri Fatima , Thiele Holger , Altmüller Janine , Nürnberg Peter , Müller Michael , Gärtner Jutta
Published: October 2017

Transcription factor NRF2, encoded by NFE2L2, is the master regulator of defense against stress in mammalian cells. Somatic mutations of NFE2L2 leading to NRF2 accumulation promote cell survival and drug resistance in cancer cells. Here we show that the same mutations as inborn de novo mutations cause an early onset multisystem disorder with failure to thrive, immunodeficiency and neurological symptoms. NRF2 accumulation leads to widespread misregulation of gene expression and an imbalance in cytosolic redox balance. The unique combination of white matter lesions, hypohomocysteinaemia and increased G-6-P-dehydrogenase activity will facilitate early diagnosis and therapeutic intervention of this novel disorder.
3D integrated superconducting qubits
Authors: Rosenberg D. , Kim D. , Das R. , Yost D. , Gustavsson S. , Hover D. , Krantz P. , Melville A. , Racz L. , Samach G. O. , Weber S. J. , Yan F. , Yoder J. L. , Kerman A. J. , Oliver W. D.
Published: October 2017

As the field of quantum computing advances from the few-qubit stage to larger-scale processors, qubit addressability and extensibility will necessitate the use of 3D integration and packaging. While 3D integration is well-developed for commercial electronics, relatively little work has been performed to determine its compatibility with high-coherence solid-state qubits. Of particular concern, qubit coherence times can be suppressed by the requisite processing steps and close proximity of another chip. In this work, we use a flip-chip process to bond a chip with superconducting flux qubits to another chip containing structures for qubit readout and control. We demonstrate that high qubit coherence (T1, T2,echo > 20 μs) is maintained in a flip-chip geometry in the presence of galvanic, capacitive, and inductive coupling between the chips.
A Bivariate Hypothesis Testing Approach for Mapping the Trait-Influential Gene
Authors: Saunders Garrett , Fu Guifang , Stevens John R.
Published: October 2017

The linkage disequilibrium (LD) based quantitative trait loci (QTL) model involves two indispensable hypothesis tests: the test of whether or not a QTL exists, and the test of the LD strength between the QTaL and the observed marker. The advantage of this two-test framework is to test whether there is an influential QTL around the observed marker instead of just having a QTL by random chance. There exist unsolved, open statistical questions about the inaccurate asymptotic distributions of the test statistics. We propose a bivariate null kernel (BNK) hypothesis testing method, which characterizes the joint distribution of the two test statistics in two-dimensional space. The power of this BNK approach is verified by three different simulation designs and one whole genome dataset. It solves a few challenging open statistical questions, closely separates the confounding between ‘linkage’ and ‘QTL effect’, makes a fine genome division, provides a comprehensive understanding of the entire genome, overcomes limitations of traditional QTL approaches, and connects traditional QTL mapping with the newest genotyping technologies. The proposed approach contributes to both the genetics literature and the statistics literature, and has a potential to be extended to broader fields where a bivariate test is needed.
Transient postnatal overfeeding causes liver stress-induced premature senescence in adult mice
Authors: Yzydorczyk Catherine , Li Na , Chehade Hassib , Mosig Dolores , Bidho Mickael , Keshavjee Basile , Armengaud Jean Baptiste , Nardou Katya , Siddeek Benazir , Benahmed Mohamed , Vergely Catherine , Simeoni Umberto
Published: October 2017

Unbalanced nutrition early in life is increasingly recognized as an important factor in the development of chronic, non-communicable diseases at adulthood, including metabolic diseases. We aimed to determine whether transient postnatal overfeeding (OF) leads to liver stress-induced premature senescence (SIPS) of hepatocytes in association with liver structure and hepatic function alterations. Litters sizes of male C57BL/6 mice were adjusted to 9 pups (normal feeding, NF) or reduced to 3 pups during the lactation period to induce transient postnatal OF. Compared to the NF group, seven-month-old adult mice transiently overfed during the postnatal period were overweight and developed glucose intolerance and insulin resistance. Their livers showed microsteatosis and fibrosis, while hepatic insulin signaling and glucose transporter protein expressions were altered. Increased hepatic oxidative stress (OS) was observed, with increased superoxide anion production, glucose-6-phosphate dehydrogenase protein expression, oxidative DNA damage and decreased levels of antioxidant defense markers, such as superoxide dismutase and catalase proteins. Hepatocyte senescence was characterized by increased p21WAF, p53, Acp53, p16INK4a and decreased pRb/Rb and Sirtuin-1 (SIRT-1) protein expression levels. Transient postnatal OF induces liver OS at adulthood, associated with hepatocyte SIPS and alterations in liver structure and hepatic functions, which could be mediated by a SIRT-1 deficiency.
Multiple Geographical Origins of Environmental Sex Determination enhanced the diversification of Darwin’s Favourite Orchids
Authors: Pérez-Escobar Oscar Alejandro , Chomicki Guillaume , Condamine Fabien L. , de Vos Jurriaan M. , Martins Aline C. , Smidt Eric C. , Klitgård Bente , Gerlach Günter , Heinrichs Jochen
Published: October 2017

Environmental sex determination (ESD) − a change in sexual function during an individual life span driven by environmental cues − is an exceedingly rare sexual system among angiosperms. Because ESD can directly affect reproduction success, it could influence diversification rate as compared with lineages that have alternative reproductive systems. Here we test this hypothesis using a solid phylogenetic framework of Neotropical Catasetinae, the angiosperm lineage richest in taxa with ESD. We assess whether gains of ESD are associated with higher diversification rates compared to lineages with alternative systems while considering additional traits known to positively affect diversification rates in orchids. We found that ESD has evolved asynchronously three times during the last ~5 Myr. Lineages with ESD have consistently higher diversification rates than related lineages with other sexual systems. Habitat fragmentation due to mega-wetlands extinction, and climate instability are suggested as the driving forces for ESD evolution.
Erratum: miR-15a/miR-16 down-regulates BMI1, impacting Ub-H2A mediated DNA repair and breast cancer cell sensitivity to doxorubicin
Authors: Patel Nibedita , Garikapati Koteswara Rao , Pandita Raj K. , Singh Dharmendra Kumar , Pandita Tej K. , Bhadra Utpal , Bhadra Manika Pal
Published: October 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Squeezing giant spin states via geometric phase control in cavity-assisted Raman transitions
Authors: Xia Keyu
Published: October 2017

Squeezing ensemble of spins provides a way to surpass the standard quantum limit in quantum metrology and test the fundamental physics as well, and therefore attracts broad interest. Here we propose an experimentally accessible protocol to squeeze a giant ensemble of spins via the geometric phase control (GPC). Using the cavity-assisted Raman transition (CART) in a double Λ-type system, we realize an effective Dicke model. Under the condition of vanishing effective spin transition frequency, we find a particular evolution time where the cavity decouples from the spins and the spin ensemble is squeezed considerably. Our scheme combines the CART and the GPC, and has the potential to improve the sensitivity in quantum metrology with spins by about two orders.
Geometry Optimization with Machine Trained Topological Atoms
Authors: Zielinski François , Maxwell Peter I. , Fletcher Timothy L. , Davie Stuart J. , Di Pasquale Nicodemo , Cardamone Salvatore , Mills Matthew J. L. , Popelier Paul L. A.
Published: October 2017

The geometry optimization of a water molecule with a novel type of energy function called FFLUX is presented, which bypasses the traditional bonded potentials. Instead, topologically-partitioned atomic energies are trained by the machine learning method kriging to predict their IQA atomic energies for a previously unseen molecular geometry. Proof-of-concept that FFLUX’s architecture is suitable for geometry optimization is rigorously demonstrated. It is found that accurate kriging models can optimize 2000 distorted geometries to within 0.28 kJ mol−1of the correspondingab initioenergy, and 50% of those to within 0.05 kJ mol−1. Kriging models are robust enough to optimize the molecular geometry to sub-noise accuracy, when two thirds of the geometric inputs are outside the training range of that model. Finally, the individual components of the potential energy are analyzed, and chemical intuition is reflected in the independent behavior of the three energy terms$${E}_{{\rm{intra}}}^{{\rm{A}}}$$EintraA(intra-atomic),$${V}_{{\rm{cl}}}^{\text{AA}\text{'}}$$VclAA'(electrostatic) and$${V}_{{\rm{x}}}^{\text{AA}\text{'}}$$VxAA'(exchange), in contrast to standard force fields.
Associative visual learning by tethered bees in a controlled visual environment
Authors: Buatois Alexis , Pichot Cécile , Schultheiss Patrick , Sandoz Jean-Christophe , Lazzari Claudio R. , Chittka Lars , Avarguès-Weber Aurore , Giurfa Martin
Published: October 2017

Free-flying honeybees exhibit remarkable cognitive capacities but the neural underpinnings of these capacities cannot be studied in flying insects. Conversely, immobilized bees are accessible to neurobiological investigation but display poor visual learning. To overcome this limitation, we aimed at establishing a controlled visual environment in which tethered bees walking on a spherical treadmill learn to discriminate visual stimuli video projected in front of them. Freely flying bees trained to walk into a miniature Y-maze displaying these stimuli in a dark environment learned the visual discrimination efficiently when one of them (CS+) was paired with sucrose and the other with quinine solution (CS−). Adapting this discrimination to the treadmill paradigm with a tethered, walking bee was successful as bees exhibited robust discrimination and preferred the CS+ to the CS− after training. As learning was better in the maze, movement freedom, active vision and behavioral context might be important for visual learning. The nature of the punishment associated with the CS− also affects learning as quinine and distilled water enhanced the proportion of learners. Thus, visual learning is amenable to a controlled environment in which tethered bees learn visual stimuli, a result that is important for future neurobiological studies in virtual reality.
Difference in intracellular temperature rise between matured and precursor brown adipocytes in response to uncoupler and β-adrenergic agonist stimuli
Authors: Tsuji Toshikazu , Ikado Kumiko , Koizumi Hideki , Uchiyama Seiichi , Kajimoto Kazuaki
Published: October 2017

Brown adipocytes function to maintain body temperature by heat production. However, direct measurement of heat production at a single cell level remains difficult. Here we developed a method to measure the temperature within primary cultured brown adipocytes using a cationic fluorescent polymeric thermometer. Placement of the thermometer within a matured brown adipocyte and a precursor cell enabled the detection of heat production following uncoupler treatment. The increase in the intracellular temperature due to stimulation with a mitochondrial uncoupler was higher in matured brown adipocytes than in precursor cells. Stimulation with a β-adrenergic receptor (β-AR) agonist, norepinephrine, raised the intracellular temperature of matured brown adipocytes to a level comparable to that observed after stimulation with a β3-AR-specific agonist, CL316.243. In contrast, neither β-AR agonist induced an intracellular temperature increase in precursor cells. Further, pretreatment of brown adipocytes with a β3-AR antagonist inhibited the norepinephrine-stimulated elevation of temperature. These results demonstrate that our novel method successfully determined the difference in intracellular temperature increase between matured brown adipocytes and precursor cells in response to stimulation by an uncoupler and β-AR agonists.
Systematic Moiety Variations of Ultrashort Peptides Produce Profound Effects on Self-Assembly, Nanostructure Formation, Hydrogelation, and Phase Transition
Authors: Chan Kiat Hwa , Xue Bo , Robinson Robert C. , Hauser Charlotte A. E.
Published: October 2017

Self-assembly of small biomolecules is a prevalent phenomenon that is increasingly being recognised to hold the key to building complex structures from simple monomeric units. Small peptides, in particular ultrashort peptides containing up to seven amino acids, for which our laboratory has found many biomedical applications, exhibit immense potential in this regard. For next-generation applications, more intricate control is required over the self-assembly processes. We seek to find out how subtle moiety variation of peptides can affect self-assembly and nanostructure formation. To this end, we have selected a library of 54 tripeptides, derived from systematic moiety variations from seven tripeptides. Our study reveals that subtle structural changes in the tripeptides can exert profound effects on self-assembly, nanostructure formation, hydrogelation, and even phase transition of peptide nanostructures. By comparing the X-ray crystal structures of two tripeptides, acetylated leucine-leucine-glutamic acid (Ac-LLE) and acetylated tyrosine-leucine-aspartic acid (Ac-YLD), we obtained valuable insights into the structural factors that can influence the formation of supramolecular peptide structures. We believe that our results have major implications on the understanding of the factors that affect peptide self-assembly. In addition, our findings can potentially assist current computational efforts to predict and design self-assembling peptide systems for diverse biomedical applications.
Dissecting the mycobacterial cell envelope and defining the composition of the native mycomembrane
Authors: Chiaradia Laura , Lefebvre Cyril , Parra Julien , Marcoux Julien , Burlet-Schiltz Odile , Etienne Gilles , Tropis Maryelle , Daffé Mamadou
Published: October 2017

The mycobacterial envelope is unique, containing the so-called mycomembrane (MM) composed of very-long chain fatty acids, mycolic acids (MA). Presently, the molecular composition of the MM remains unproven, due to the diversity of methods used for determining its composition. The plasma membranes (PM) and the native MM-containing cell walls (MMCW) of two rapid-growing mycobacterial species, Mycobacterium aurum and M. smegmatis, were isolated from their cell lysates by differential ultracentrifugation. Transmission electron microscopy and biochemical analyses demonstrated that the two membranes were virtually pure. Bottom-up quantitative proteomics study indicated a different distribution of more than 2,100 proteins between the PM and MMCW. Among these, the mannosyltransferase PimB, galactofuranosyltransferase GlfT2, Cytochrome p450 and ABC transporter YjfF, were most abundant in the PM, which also contain lipoglycans, phospholipids, including phosphatidylinositol mannosides, and only a tiny amount of other glycolipids. Antigen85 complex proteins, porins and the putative transporters MCE protein family were mostly found in MMCW fraction that contains MA esterifying arabinogalactan, constituting the inner leaflet of MM. Glycolipids, phospholipids and lipoglycans, together with proteins, presumably composed the outer leaflet of the MM, a lipid composition that differs from that deduced from the widely used extraction method of mycobacterial cells with dioctylsulfosuccinate sodium.
ADAR1 polymorphisms are related to severity of liver fibrosis in HIV/HCV-coinfected patients
Authors: Medrano Luz M. , Berenguer Juan , Jiménez-Sousa María A. , Aldámiz-Echevarria Teresa , Tejerina Francisco , Diez Cristina , Vigón Lorena , Fernández-Rodríguez Amanda , Resino Salvador
Published: October 2017

The adenosine deaminase acting on RNA (ADAR1) gene is an interferon-stimulated gene involved in liver injury protection. Our aim was to analyze the association of polymorphisms within this gene with the severity of liver disease in European HIV/HCV-coinfected patients. We performed a cross-sectional study in 220 patients that underwent a liver biopsy. Five SNPs in the ADAR1 gene (rs1127326, rs1127317, rs1127314, rs1127313, rs2229857) were genotyped by GoldenGate assay. The outcome variables were fibrosis stage and necroinflammatory activity grade by METAVIR-score, aspartate aminotransferase to platelet ratio index (APRI), FIB-4 index, and fibrosis progression rate (FPR). In multivariate analysis, fibrosis progression rate (FPR) (aAMRs = 0.97) decreased in a dose-dependent manner with the presence of rs2229857_T, rs1127313_G, rs1127314_G and rs1127317_G; while rs1127326_T allele had only significant associations with FIB-4 (aAMRs ≤ 0.63) and FPR (aAMRs ≤ 0.97). Moreover, carriers of rs2229857_T, rs1127314_G, rs1127317_G, and rs1127326_T alleles were protected against advanced fibrosis (F ≥ 3) (adjusted ORs (aORs) ≤ 0.44), APRI ≥ 1.5 (aORs ≤ 0.33), and FPR ≥ 0.075 (aORs ≤ 0.45). rs1127313_G carriers showed lower odds of having F ≥ 3 (aORs = 0.39), FIB4 ≥ 3.25 (aOR = 0.22) and FPR ≥ 0.075 (aORs = 0.44). In conclusion, ADAR1 polymorphisms protected against severe liver disease in HIV/HCV-coinfected patients. These results could be used to improve therapeutic decision-making in clinical practice.