bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear Magnetic Resonance Characterization of Renewable Products from a Two‐Step Ex‐Situ Hydropyrolysis Vapor Upgrading Process
Authors: Lai Jinfeng , Zhang Liang , Gong Kening
Published: January 2018

A novel two‐step ex‐situ hydropyrolysis vapor upgrading (HPVU) process can generate tailored oxygenated hydrocarbon products from lignocellulosic biomass by adjusting vapor upgrading temperature. Such products, containing varied oxygen contents (ranging from 2 to 17 wt%), are different from traditional petroleum hydrocarbons and conventional biomass‐derived pyrolysis oil. Elucidation of the comprehensive structural motif of these unconventional products is critical for development and deployment of the HPVU process. To this end, two‐dimensional heteronuclear 1H‐13C NMR techniques were employed to first provide single‐ and multiple‐bond correlations between protons and carbons characteristic of different organic functional groups. The distribution of carbon functional groups was further determined by quantitative 13C NMR spectroscopy with full relaxation and well‐defined chemical shift regions obtained from diverse NMR methods. Phenols and ketones were identified as the main oxygenate species in these renewable products. At higher vapor upgrading temperatures, a decrease in oxygenate species and an increase in alkylation on aromatic rings were observed. Of particular importance, compared to pyrolysis oil, the amounts of thermally unstable oxygenate species, such as aldehyde, carboxylic acid, and carbohydrate, were found to be minimal, suggesting good thermal stability of these renewable hydrocarbon products.
High Tap Density Li4Ti5O12 Anode Materials Synthesized for High Rate Performance Lithium Ion Batteries
Authors: Gao Yuanrui , Cheng Chongling , An Juan , Liu Hongjiang , Zhang Dengsong , Chen Guorong , Shi Liyi
Published: January 2018

We report a simple strategy to synthesize high tap density Li4Ti5O12 particles with excellent electrochemical performance, whose tap density could be controlled by the starting materials. A series of high tap density Li4Ti5O12 particles are successfully synthesized with high tap density TiO2 through hydrothermal process with a short post‐annealing. The electrochemistry performances of them were carefully researched in this work. The high tap density Li4Ti5O12 showed similar performance with normal Li4Ti5O12 particles. The highest tap density of Li4Ti5O12 particles is 1.4 g⋅cm−3, whose capacity is 134 mAh⋅g−1 at 10 C. Those high tap density Li4Ti5O12 display their promising commercial application in high‐energy density lithium ion batteries.
CI24‐Si: a Semiconducting Silicon Phase with an All‐sp3 Bonding Network
Authors: Lu Yihua , Zhu Xi , Wang Min
Published: January 2018

A silicon allotrope which consists of 24 atoms in a body centered cubic cell and displays an symmetry (termed as cI24‐Si) with a mass density of 2.38 g/cm3, is theoretically investigated. This silicon phase has an all‐sp3 network with hexagons. Phonon dispersion confirms its dynamical stability and elastic constant implies it is mechanically stable. The analysis of electronic band structure performing by HSE06 functional shows that cI24‐Si is an indirect semiconductor with a small band gap of 0.83 eV. Additionally, its direct band gap is only 0.02 eV larger than the indirect band gap, indicating that cI24‐Si possesses a quasi‐direct band gap. The calculations of imaginary part of dielectric function and optical absorption for cI24‐Si show that it has better optical properties than diamond‐like Si−I phase as it can capture more sunlight from visible to ultraviolet range. To provide more characterizations for future experimental observations, X‐ray diffraction patterns and Raman spectra are also theoretically simulated. Due to its small band gap, cI24‐Si may possess potential electronic, optical and photovoltaic applications.
Confinement of Reagents in Crystalline Matrix with the Help of Magnetic Field
Authors: Luo Yang‐Hui , Chen Chen , Wang Jing‐Wen , He Xiao‐Tong , Hong Dan‐Li , An Pei‐Jing , Wu Hong‐Shuai , Sun Bai‐Wang
Published: January 2018

Alkyl‐amines with formula CnH2n+1‐NH2 (n=8, 10, 12, 14 and 16), either liquid or solid at room temperature, can form a stripe‐like crystalline matrix with 1.6‐2.1 nm width when in the presence of an external magnetic field, that able to confine the H2dcbp (4,4’‐diacarboxy‐2,2’‐bipyridine) molecules within the stripes interval with stoichiometry of 2:1. This confinement, which can improve the alcohol solubility of H2dcbp remarkably, has facilitated the construction of mononuclear spin‐crossover complex Fe(H2Bpz)2(H2dcbp) (H2Bpz=dihydrobis(1‐pyrazolyl)borate). Thus, the crystalline matrix may provide a convenient method for construction of new hybrid materials derived from H2dcbp and its analogue, through hierarchy control of both the coordination bonding and the hydrogen bonding of H2dcbp at a mild condition.
Synergistic Bronsted‐Lewis Acidity Effect on Upgrading Biomass‐Derived Phenolic Compounds: Statistical Optimization of Process Parameters, Kinetic Investigations and DFT Study
Authors: Patra Tanmoy , Afreen Gul , Parveen Firdaus , Kumar Komal , Bahri Shashank , Upadhyayula Sreedevi
Published: January 2018

Biomass‐derived phenolic compounds and small oxygenates obtained from pyrolysis of lignocellulosic biomass needs to be upgraded to obtain the C10‐C13 range fuel precursors. In this context, iso‐propylation of m‐cresol was performed in batch reactors using multifunctional ionic liquids (ILs) as catalysts. Environmentally benign Bronsted‐Lewis acidic ILs were synthesized and characterized using 1H NMR, 13C NMR and Raman spectroscopic data. Relative Bronsted and Lewis acidity of these ILs were compared using UV‐Visible and FTIR spectroscopic data and the effect of acidity on the catalytic activity and product selectivity in alkylation of m‐cresol with iso‐propyl alcohol was investigated. Correlation of acidity and catalytic activity was confirmed by theoretical DFT study on IL structures. High conversion of m‐cresol (95.6%) was obtained using ZnCl2 containing IL, at 393 K temperature and 2:1:1 alcohol: m‐cresol: IL molar ratio, within 5 h of reaction time. The activity and recoverability of these ILs were retained even after 8 recycles. The effect of process parameters like reaction time, temperature, reactant mole ratio and catalyst to reactant mole ratio was investigated and optimized from design of experiments results. A plausible reaction mechanism was formulated based on the product distribution and a kinetic model was developed to estimate the activation energy (45.70 kJ mol−1) and pre‐exponential factor (247.78 lit. mol−1 min−1).
Synthesis of Carbolines via Microwave‐Assisted Cadogan Reactions of Aryl‐Nitropyridines
Authors: Limbach Daniel , Geffe Mario , Detert Heiner
Published: January 2018

Suzuki‐Miyaura‐couplings to aryl‐nitropyridines followed by Cadogan reactions is a straight‐forward method for the synthesis of δ‐ and β‐carbolines. Microwave irradiation of the nitrobiaryls in triethyl phosphite solutions conveniently gives moderate to very good yields of the carbolines. Reduction to the amines without cyclization occurs on certain substrates, and alkylation of the products is observed as a follow‐up reaction. Instead of α‐carbolines, naphthonitriles are generated by phosphite reduction and ring transformation.
Chemoselective Suzuki Coupling of Bromoarenes Catalysed by Palladium(II)‐Complexing Macrocycles in Aqueous Media
Authors: Ogawa Masahiro , Sogawa Hiromitsu , Mizuno Shunya , Aoki Daisuke , Takata Toshikazu
Published: January 2018

Palladium‐complexing macrocyclic catalysts efficiently and chemoselectively catalysed the Suzuki coupling reaction of bromoarenes. Bromobenzene and 2‐bromopyridine were efficiently monoarylated with 4‐methoxyphenylboronic acid when catalysed by macrocyclic catalysts comprising cyclic pyridine‐2,6‐bisamide pincer‐type ligands with palladium (II) located in the inner cavity (PdMCs). The Suzuki coupling of 2,6‐dibromopyridine to aryl boronic acids catalysed by PdMCs afforded the corresponding monoarylpyridines with high selectivity and yield, whereas a mixture of mono‐ and di‐arylpyridines was obtained when palladium chloride was used as the catalyst. Interestingly, the chemoselectivity increased as the cavity size of the PdMCs decreased. The high chemoselectivity seemed to arise from the steric effect of the macrocyclic ligand. Moreover, an unsymmetrical 2,6‐diarylpyridine was successfully synthesised in high yield by two sequential couplings employing PdMCs followed by palladium chloride.
Transaction surplus superiority in canonical market segments: Using the profit map to guide positioning and investment choices across price‐rivalry regimes
Authors: Postrel Steven
Published: January 2018

Research Summary: Strategy needs an “intermediate measure” of competitive strength easily linked to management choices. “Competitive advantage” fails to accomplish this because most formulations of it violate important criteria and because these formulations are so diverse. I show that one intermediate measure, transaction surplus superiority (TSS), potentially solves both problems. Critically, TSS is defined independently of prices and its usefulness is independent of the degree of price competition: In “canonical” market segments, firms with TSS always make superior segment profits (gross of sunk investments) compared to rivals. When combined with a restriction to “incentive‐compatible pricing behavior,” TSS limits or solves the theoretical problem of indeterminate rivalry among oligopolists. Finally, TSS allows precise explanation of when sunk investments to improve efficiency are stimulated or suppressed by the “spur of competition.”

Managerial Summary: Executives need a conceptual “instrument panel”—“intermediate measures” of competitive strength—to help choose their products and processes. Profit itself is too causally remote from these choices to serve. “Competitive advantage” has been defined in ways that either just mean superior profits or that depend on strong assumptions about price competition that frequently don't apply. Transaction Surplus Superiority (TSS) solves these problems. In an important special case, a “profit map” completely describes each firm's profitability for any combination of price competition and TSS. For choices where sunk cost differences typically aren't important (e.g., product color or inventory policy), TSS is a universal guide to action. TSS helps decide whether to increase price competition to gain market share, and it largely determines whether a given investment in efficiency makes sense.
Vom Brandversuch zum Feuerwiderstand: Neues Prüf‐ und Bewertungsverfahren für filigrane Stahlzugglieder mit reaktivem Brandschutzsystem
Authors: Häßler Dustin , Hothan Sascha
Published: January 2018

Im Stahlbau wird die feuerwiderstandserhöhende Wirkung reaktiver Brandschutzsysteme (RBS) bereits seit Jahrzehnten erfolgreich und mit stetig wachsender Nachfrage genutzt. Die Anwendung dieser Systeme wird durch Zulassungen geregelt. Die Ermittlung des Beitrages reaktiver Brandschutzsysteme zur Feuerwiderstandsdauer von Stahlbauteilen wird in der Regel mit Hilfe von mechanisch belasteten und unbelasteten Brandversuchen beurteilt. Ein entsprechendes Prüf‐ und Bewertungsverfahren war bisher für Träger und Stützen, jedoch nicht für Zugglieder vorhanden [1]. Mehrjährige Forschungen [2], [3] haben in Deutschland zur Entwicklung eines neuen Prüf‐ und Bewertungsverfahrens geführt, so dass der durch Zulassungen geregelte Anwendungsbereich reaktiver Brandschutzsysteme auf filigrane Stahlzugglieder, insbesondere mit Vollprofil, erweitert werden konnte. Der Beitrag beschreibt die Besonderheiten und Herausforderungen für den Einsatz von reaktiven Brandschutzsystemen auf filigranen Stahlzuggliedern, die wesentlichen Einflussparameter sowie die maßgebenden Versagensmechanismen. Ferner wird gezeigt, wie anhand von Brandversuchen, Materialuntersuchungen im Hochtemperaturbereich und numerischen Simulationen das neue Prüf‐ und Bewertungsverfahren entwickelt, validiert und angewendet wurde. Abschließend erfolgt ein Ausblick auf noch zu untersuchende Fragestellungen, z. B. hinsichtlich der Bauteilorientierung sowie zum Umgang mit den Anschlussbauteilen von Stahlzuggliedern.
50 Jahre Rheinbrücke Bonn‐Nord (Friedrich‐Ebert‐Brücke)
Authors: Saul Reiner , Angelmaier Volkhard , Stockmann Rico
Published: January 2018

Herrn Univ.‐Prof. em. Dr.‐Ing. Dr.‐Ing. E.h. Joachim Scheer zur Vollendung seines 90. Lebensjahres gewidmet

Die am 28. Juni 1967 eingeweihte Rheinbrücke Bonn‐Nord war weltweit die erste Schrägseilbrücke mit einem in Brückenachse angeordneten Vielseilsystem (80 vollverschlossene Seile) und hat eine Mittelöffnung von 280 m. Der 36,3 m breite Überbau besteht aus einem Hohlkasten und breiten Kragarmen. Die 49,4 m hohen Pylone sind ebenfalls aus Stahl. Die Seitenöffnungen wurden auf den endgültigen und Hilfspfeilern montiert, die Mittelöffnung im Freivorbau. Es wird über den Entwurf, die Werkstattfertigung und die Montage berichtet sowie über eine kürzliche Untersuchung des baulichen Zustands und die Nachrechnung nach den Eurocodes. Obwohl die Brücke nicht in allen Punkten den heutigen rechnerischen Anforderungen genügt, wurden keine gravierenden Mängel der Tragkonstruktion festgestellt. Die Lebensdauer der Brücke wird also nicht durch ihre Tragfähigkeit bestimmt, sondern durch das in Zukunft noch größere Verkehrsaufkommen, das möglicherweise um 2040 eine breitere Brücke erfordern könnte.
Visionäre und Alltagshelden – Zur kulturellen und technologischen Relevanz des Bauingenieurwesens
Authors: Möller Eberhard
Published: January 2018

Das Oskar von Miller Forum in München präsentiert vom 10. November 2017 bis zum 14. Januar 2018 eine Ausstellung mit dem Titel „Visionäre und Alltagshelden. Ingenieure – Bauen – Zukunft” in Kooperation mit dem M:AI Museum für Architektur und Ingenieurkunst NRW. Als Erfinder, Gestalter, Unternehmer und Macher stellen Ingenieurinnen und Ingenieure im Bauwesen die Erfüllung der Grundbedürfnisse der Gesellschaft sicher. Die Ausstellung setzt sich zum Ziel, den Beruf von Bauingenieurinnen und ‐ingenieuren sowie die Bauwirtschaft selbst als eine der Schlüsselindustrien in wirtschaftlicher, sozialer und gesellschaftlicher Hinsicht zu zeigen. Gleichzeitig wird der spannende und vielseitige Leistungsumfang der Ingenieurinnen und Ingenieure und damit auch der Bauwirtschaft in allen Facetten dargestellt: faszinierend, umfassend, innovativ und lösungsorientiert. Von der Historie kommend mit dem Schwerpunkt auf aktuellen Projekten werden Ingenieurpersönlichkeiten, ihre Netzwerke und Innovationen sowie herausragende Bauwerke vor dem Hintergrund der jeweiligen gesellschaftlichen, wirtschaftlichen und politischen Einflüsse in Szene gesetzt.
Überblick zur Anwendung reaktiver Brandschutzsysteme auf Stahlzuggliedern
Authors: Häßler Dustin , Hothan Sascha
Published: January 2018

Die Feuerwiderstandsdauer von ungeschützten Stahlbauteilen lässt sich durch den Einsatz reaktiver Brandschutzsysteme (RBS) signifikant erhöhen. Durch den profilfolgenden Auftrag der Brandschutzbeschichtung und die hierfür erforderlichen geringen Trockenschichtdicken, welche in der Regel nur wenige Millimeter betragen, können neben den brandschutztechnischen Anforderungen auch die an die Stahlkonstruktion gestellten gestalterischen Ansprüche erfüllt werden. Kommt es zu einem Brand, schäumt das reaktive Brandschutzsystem auf und bildet eine thermische Schutzschicht um das Stahlbauteil aus. Dadurch wird die Erwärmung des Stahls verlangsamt und der Festigkeitsverlust infolge Temperatur wird verzögert. Die Verwendung von reaktiven Brandschutzsystemen auf Stahlbauteilen wird durch Zulassungen geregelt. In Bezug auf den durch die Zulassung geregelten Anwendungsbereich von reaktiven Brandschutzsystemen auf zugbeanspruchten Stahlbauteilen haben sich in den vergangenen Jahren verschiedene Änderungen ergeben. Der nachfolgende Beitrag gibt hierzu einen aktuellen Überblick und beschreibt die Hintergründe, welche zu den neuen Regelungen geführt haben. Ferner erfolgt in diesem Zusammenhang ein Ausblick auf noch zu untersuchende Fragestellungen, welche bisher noch nicht durch die Regelungen in den Zulassungen abgedeckt werden. Bei den nachfolgenden Ausführungen handelt es sich um einen Auszug des Beitrages für die 18. EIPOS‐Sachverständigentage Brandschutz [1].
Concise Review: Optimized Strategies for Stem Cell-Based Therapy in Myocardial Repair: Clinical Translatability and Potential Limitation
Authors: Wu Rongrong , Hu Xinyang , Wang Jian'an
Published: January 2018

Ischemic heart diseases (IHDs) remain major public health problems with high rates of morbidity and mortality worldwide. Despite significant advances, current therapeutic approaches are unable to rescue the extensive and irreversible loss of cardiomyocytes caused by severe ischemia. Over the past 16 years, stem cell-based therapy has been recognized as an innovative strategy for cardiac repair/regeneration and functional recovery after IHDs. Although substantial preclinical animal studies using a variety of stem/progenitor cells have shown promising results, there is a tremendous degree of skepticism in the clinical community as many stem cell trials do not confer any beneficial effects. How to accelerate stem cell-based therapy toward successful clinical application attracts considerate attention. However, many important issues need to be fully addressed. In this Review, we have described and compared the effects of different types of stem cells with their dose, delivery routes, and timing that have been routinely tested in recent preclinical and clinical findings. We have also discussed the potential mechanisms of action of stem cells, and explored the role and underlying regulatory components of stem cell-derived secretomes/exosomes in myocardial repair. Furthermore, we have critically reviewed the different strategies for optimizing both donor stem cells and the target cardiac microenvironments to enhance the engraftment and efficacy of stem cells, highlighting their clinical translatability and potential limitation.
In this issue of Weather
Authors: Galvin Jim
Published: January 2018

Although we may have an image of snow as a typical feature of winter in Britain, its occurrence is variable and, of course, few records go back beyond the establishment of formal observation networks, little more than 100 years ago. However, we are fortunate that keen amateur observers, as well as many parish records, included the occurrence of snow. The establishment of a long‐term climatological series is also important to our growing knowledge of climate change. The winter of 1614/15 (new calendar) saw deep snow in many areas, as revealed by Lucy Veale, Georgina Endfield and James Bowen in ‘The “Great Snow” of winter 1614/1615 in England’, beginning on p. 3.

Large bodies of water often remain relatively warm well into the winter months – not least the Caspian Sea, the main inland water body of western Asia. The surrounding continent becomes very cold by the end of January, but the southern Caspian Sea may be more than 10 degC warmer, remaining unfrozen. This is a great source of humidity for convection, and potentially unstable northeasterly air masses may bring significant snow to its southwestern coasts. This was the case in winter 2014, as described by Parvin Ghafarian, Nafiseh Pegahfar and Elaheh Owlad in ‘Multiscale analysis of lake‐effect snow over the southwest coast of the Caspian Sea (31 January‐5 February 2014)’ on p. 9.

Snowfall is a feature of winter on the slopes of the Himalaya. As elsewhere, accumulations and its significance vary. However, Kashmir experienced significant snowfall, causing loss of life and damage at this time last year. This is described by Mohammd Rafiq and Anoop Kumar Mishra in ‘A study of heavy snowfall in Kashmir, India in January 2017’ on p. 15.

On p. 20, we move on to look at the effect of a mid‐latitude storm. Storms bring not only strong winds, but usually, copious rainfall and the associated risk of floods. This was the case from the storm of 22–24 December 2013 in the British Isles. The study by Bruno de Campos and Vanessa Silveira Barreto Carvalho, ‘The effect of the Welsh mountains on rainfall distribution over Wales and England: a case study of a severe extratropical storm’ looks at the role of orography in the development and amount of rainfall.

The Yellow River and its tributaries occupy much of northern China, rising high in the mountains of Qing‐Hi, meandering eastwards into the East China Sea. On p. 27, ‘Spatio‐temporal temperature variations in the Chinese Yellow River basin from 1981 to 2013’ by Lei Wu, Xia Liu and Xiaoyi Ma studies this area, mapping temperature changes across the area in recent times.
Enterprise dynamics and employment growth
Authors: Corley‐Coulibaly Marva , Kizu Takaaki , Manrique Elizabeth Echeverria , Hiriyur Salonie
Published: January 2018

This chapter investigates how employment outcomes vary with respect to firm size, age and sector and over time. It provides an in‐depth analysis of formal private sector enterprises in 132 developing, emerging and developed economies by identifying the types of firms (by size and age) that created and destroyed jobs during the pre‐ and post‐crisis periods. The chapter finds that both firm size and age are related to the employment situation. In particular, relative toSMEs, large enterprises are the principal source of employment in the formal private sector. ButSMEs and young firms are more dynamic than large firms, both with respect to employment growth and as an important source of employment and firm ownership, particularly women. Since the crisis, for certain types of employment the contribution of young firms andSMEs has declined, owing in part to the faster rate of job destruction seen inSMEs relative to large enterprises. Finally, region‐specific (and by extension country‐specific) characteristics play a stronger role in influencing firm size than the specific sectoral composition.

These findings shed light on the importance of an enabling environment for enterprise survival and growth. Indeed, there is a need for policies to better promoteSMEs’ and young firms’ access to resources, particularly in the post‐crisis era.
Identification as a Mutation Carrier and Effects on Life According to Experiences of Finnish Male BRCA1/2 Mutation Carriers
Authors: Kajula Outi , Kuismin Outi , Kyngäs Helvi
Published: January 2018

Earlier studies have explored post‐identification experiences of male BRCA1/2 mutation carriers, but more detailed knowledge of both their experiences and effects of identification as a carrier on their lives is required to improve genetic counseling. Thus, the aim of this study was to acquire deeper and broader insights into their experiences. Qualitative data were collected from theme‐based interviews with 31 men carrying BRCA1/2 mutations in Finland, and analyzed using inductive content analysis. Three categories of the participants’ responses to identification as BRCA1/2 mutation carriers were identified (personal, offspring‐related and related to other relatives), mainly concerning issues associated with cancer, hereditary transmission of their mutations, and life decisions. Although there were many neutral responses regarding the issues, there were also strong emotional reactions and cancer worries. Identification as a carrier also had several effects on participants’ lifestyles, including adoption of healthier and disease‐preventing behavior, and social well‐being, such as family planning and attitudes to life. The results provide detailed information about several aspects of male BRCA1/2 mutation carriers’ experiences, which could be used to develop a tentative model of tailored genetic counseling for them.
Tests Indicate Which Edible Plants Could Thrive on Mars
Authors: Cartier Kimberly
Published: January 2018

An undergraduate experiment grew vegetables and herbs in simulated Martian soil under Mars-like reduced daylight. The tasty results suggest that Mars colonists could farm their own produce.
The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin
Authors: Lim Chol Seung , Han Jung-Soo
Published: January 2018

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory properties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced oxidative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and reduced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP activities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD.
Subaru Hyper Suprime-Cam Survey for an optical counterpart of GW170817
Authors: Tominaga Nozomu , Tanaka Masaomi , Morokuma Tomoki , Utsumi Yousuke , Yamaguchi Masaki S , Yasuda Naoki , Tanaka Masayuki , Yoshida Michitoshi , Fujiyoshi Takuya , Furusawa Hisanori , Kawabata Koji S , Lee Chien-Hsiu , Motohara Kentaro , Ohsawa Ryou , Ohta Kouji , Terai Tsuyoshi , Abe Fumio , Aoki Wako , Asakura Yuichiro , Barway Sudhanshu , Bond Ian A , Fujisawa Kenta , Honda Satoshi , Ioka Kunihito , Itoh Youichi , Kawai Nobuyuki , Kim Ji Hoon , Koshimoto Naoki , Matsubayashi Kazuya , Miyazaki Shota , Saito Tomoki , Sekiguchi Yuichiro , Sumi Takahiro , Tristram Paul J ,   the J-GEM collaboration
Published: January 2018

We perform a z-band survey for an optical counterpart of the binary neutron star coalescence GW170817 with Subaru/Hyper Suprime-Cam. Our untargeted transient search covers 23.6 deg2 corresponding to the 56.6% credible region of GW170817 and reaches the 50% completeness magnitude of 20.6 mag on average. As a result, we find 60 candidate extragalactic transients, including J-GEM17btc (also known as SSS17a/DLT17ck). While J-GEM17btc is associated with NGC 4993, which is firmly located inside the 3D skymap of GW170817, the other 59 candidates do not have distance information in the GLADE v2 catalog or NASA/IPAC Extragalactic Database. Among 59 of the candidates, 58 are located at the center of extended objects in the Pan-STARRS1 catalog, while one candidate has an offset. We present location, z-band apparent magnitude, and time variability of the candidates and evaluate the probabilities that they are located within the 3D skymap of GW170817. The probability for J-GEM17btc is 64%, which is much higher than for the other 59 candidates (9.3 × 10−3–2.1 × 10−1%). Furthermore, the possibility that at least one of the other 59 candidates is located within the 3D skymap is only 3.2%. Therefore, we conclude that J-GEM17btc is the most likely and distinguished candidate to be the optical counterpart of GW170817.
The Politics of Narcotic Medicines in Early Twentieth-Century South Africa
Authors: Waetjen Thembisa
Published: January 2018

Controls over trade and consumption of narcotic medicines emerged as both a concern and emblem of progressive governance around the turn of the twentieth century. This article traces political struggles over drugs regulation in the case of colonial South Africa. It focuses on two parallel streams of law-making by the British occupation regime in the Transvaal, following the Anglo-Boer war. Controversies over the availability of traditional ‘Dutch medicines’ to Boer farmers and prohibitions of certain patent medicines to African consumers were elements of, and contradictions within, the process of building a modern pharmaceutical economy. An influx to the region of new curatives coincided with the growth of vernacular newspapers as well as temperance campaigns. Working to nurture white national cohesion and support a mining industry premised on unskilled black labour, the South African state created race-based drugs controls. These developments proved significant to regulatory statecraft later in the century.
Genome analysis and data sharing informs timing of molecular events in pancreatic neuroendocrine tumour
Authors: Quevedo Rene , Spreafico Anna , Bruce Jeff , Danesh Arnavaz , Giesler Amanda , Hanna Youstina , Have Cherry , Li Tiantian , Yang S.Y. Cindy , Zhang Tong , Asa Sylvia L. , Haibe-Kains Benjamin , Kamel-Reid Suzanne , Krzyzanowska Monika , Smith Adam , Singh Simron , Siu Lillian L. , Pugh Trevor J.
Published: January 2018

Neuroendocrine tumours (NETs) are rare, slow growing cancers that present in a diversity of tissues. To understand molecular underpinnings of gastrointestinal (GINET) and pancreatic NETs (PNETs), we profiled 45 tumours combining exome, RNA, and shallow whole genome sequencing, as well as fluorescent in situ hybridization. In addition to expected somatic mutations and copy number alterations, we found that PNETs contained a highly consistent copy neutral loss-of-heterozygosity (CN-LOH) profile affecting over half of the genome; a greater percentage than any cancer analyzed to date. Our data indicates that onset of extreme autozygosity may be progressive, associated with metastasis, and initially triggered by the loss ofDAXX/ATRX, and subsequent biallelic loss ofMEN1. We confirmed this molecular timing model using targeted clinical sequencing data from an additional 43 NETs made available by the AACR GENIE project. Against this background of CN-LOH, several chromosomal regions consistently retained heterozygosity, suggesting selection for crucial allele-specific components specific to PNET progression and potential new therapeutic targets.

Statement of significance

We have discovered that pancreatic neuroendocrine tumours contain a characteristic pattern of copy neutral loss-of-heterozygosity affecting the majority of the genome following mutations ofMEN1andATRX/DAXX. Against this background of loss-of-heterozygosity, specific genomic regions are consistently retained and may therefore contain vulnerable therapeutic targets for pancreatic neuroendocrine tumours.
Massive postglacial gene flow between European white oaks uncovered genes underlying species barriers
Authors: Leroy Thibault , Rougemont Quentin , Dupouey Jean-Luc , Bodénès Catherine , Lalanne Céline , Belser Caroline , Labadie Karine , Le Provost Grégoire , Aury Jean-Marc , Kremer Antoine , Plomion Christophe
Published: January 2018

Abstract

Oaks are dominant forest tree species widely distributed across the Northern Hemisphere, where they constitute natural resources of economic, ecological, social and historical value. Hybridization and adaptive introgression have long been thought to be major drivers of their ecological success. Thus, the maintenance of species barriers remains a key question, given the extent of interspecific gene flow. In this study, we scanned the genomes of four European white oak species for reproductive barriers. We identified the ecological and phylogenic relationships of these species and inferred a long-term strict isolation followed by a recent and extensive postglacial contact. Then, we made use of the tremendous genetic variation among these species (31 million SNPs) to identify genomic regions for reproductive isolation. A literature-based functional annotation of the underlying genes highlighted important functions driving the reproductive isolation between these sister species. These functions were consistent with their ecological preferences and included tolerance to biotic and abiotic constraints. This study holds important implications for the renewal of European forests under global warming.
Systematic Analyses of Autosomal Recombination Rates from the 1000 Genomes Project Uncovers the Global Recombination Landscape in Humans
Authors: Manu Shivakumara , Acharya Kshitish K , Thiyagarajan Saravanamuthu
Published: January 2018

Background

Meiotic recombination plays an important role in evolution by shuffling different alleles along the chromosomes, thus generating the genetic diversity across generations that is vital for adaptation. The plasticity of recombination rates and presence of hotspots of recombination along the genome has attracted much attention over two decades due to their contribution to the evolution of the genome. Yet, the variation in genome-wide recombination landscape and the differences in the location and strength of hotspots across worldwide human populations remains little explored.

Results

We make use of the untapped linkage disequilibrium (LD) based genetic maps from the 1000 Genomes Project (1KGP) to perform in-depth analyses of finescale variation in the autosomal recombination rates across 20 human populations to uncover the global recombination landscape. We have generated a detailed map of human recombination landscape comprising of a comprehensive set of 88,841 putative hotspots and 80,129 coldspots with their respective strengths across populations, about 2/3rd of which were previously unknown. We have validated and assessed the number of historical putative hotspots derived from the patterns of LD that are currently active in the contemporary populations using a recently published high-resolution pedigree-based genetic map, constructed and refined using 3.38 million crossovers from various populations. For the first time, we provide statistics regarding the conserved, shared, and unique hotspots across all the populations studied.

Conclusions

Our analysis yields clusters of continental groups, reflecting their shared ancestry and genetic similarities in the recombination rates that are linked to the migratory and evolutionary histories of the populations. We provide the genomic locations and strengths of hotspots and coldspots across all the populations studied which are a valuable set of resources arising out our analyses of 1KGP data. The findings are of great importance for further research on human hotspots as we approach the dusk of retiring HapMap-based resources.
The influence of everyday events on prospective timing “in the moment”
Authors: Bangert Ashley S. , Kurby Christopher A. , Zacks Jeffrey M.
Published: January 2018

We conducted two experiments to investigate how the eventfulness of everyday experiences influences people’s prospective timing ability. Specifically, we investigated whether events contained within movies of everyday activities serve as markers of time, as predicted by Event Segmentation Theory, or whether events pull attention away from the primary timing task, as predicted by the Attentional Gate theory. In the two experiments reported here, we asked participants to reproduce a previously learned 30 second target duration while watching a movie that contained eventful and uneventful intervals. In Experiment 2, reproduction also occurred during “blank movies” while watching a fixation. In both experiments, participants made shorter and more variable reproductions while simultaneously watching eventful as compared to uneventful movie intervals. Moreover, in Experiment 2, the longest reproductions were produced when participants had to watch the blank movies, which contained no events. These results support Event Segmentation Theory and demonstrate that the elapsing events during prospective temporal reproduction appear to serve as markers of temporal duration rather than distracting from the timing task.
Cell transformation disrupts the efficiency of chromosome segregation through microtubule detyrosination
Authors: Silió Virginia , Millar Jonathan B. , McAinsh Andrew D.
Published: January 2018

The general principles of chromosome segregation are highly conserved throughout eukaryotic evolution. However, it is unknown whether there are differences in spindle or kinetochore composition or architecture which influence the efficiency chromosome segregation in different cell types. Here we show that the transition of human retinal pigment epithelial cells to a mesenchymal phenotype causes a stabilisation of kinetochore-microtubule attachments and an increase in the frequency of chromosome mis-segregation, due to inefficient error-correction, during mitosis. We find that this is caused by microtubule detyrosination during the epithelial-to-mesenchymal transition and that parthenolide, a tubulin carboxypeptidase inhibitor, efficiently reverts mes-enchymal cells to the epithelial mode of chromosome segregation. We propose that reprogramming the post-translational modifications of the mitotic spindle decreases mitotic fidelity and may contribute to CIN in mesenchymal cell populations during tumorigenesis.
Coronavirus S protein-induced fusion is blocked prior to hemifusion by Abl kinase inhibitors
Authors: Sisk Jeanne M. , Frieman Matthew B. , Machamer Carolyn E.
Published: January 2018

Enveloped viruses gain entry into host cells by fusing with cellular membranes, a step required for virus replication. Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and infectious bronchitis virus (IBV), fuse at the plasma membrane or use receptor-mediated endocytosis and fuse with endosomes depending on the cell or tissue type. The virus Spike (S) protein mediates fusion with the host cell membrane. We have shown previously that an Abl kinase inhibitor, imatinib, significantly reduces SARS-CoV and MERS-CoV viral titers and prevents endosomal entry by HIV SARS S and MERS S pseudotyped virions. SARS-CoV and MERS-CoV are classified as BSL-3 viruses, which can make experimentation into the cellular mechanisms involved in infection more challenging. Here, we use IBV, a BSL-2 virus, as a model for studying the role of Abl kinase activity during coronavirus infection. We found that imatinib and two specific Abl kinase inhibitors, GNF2 and GNF5, reduce IBV titers by blocking the first round of virus infection. Additionally, all three drugs prevented IBV S-induced syncytia formation prior to the hemifusion step. Our results indicate that membrane fusion (both virus-cell and cell-cell) is blocked in the presence of Abl kinase inhibitors. Studying the effects of Abl kinase inhibitors on IBV will be useful in identifying host cell pathways required for coronavirus infection. This will provide insight into possible therapeutic targets to treat infections by current as well as newly emerging coronaviruses.
Consistency in predicting functions from anatomical and functional connectivity profiles across the cortical cortex
Authors: Wu Dongya , Fan Lingzhong , Jiang Tianzi
Published: January 2018

More and more studies had used connectivity profiles to predict functions of the brain. However, whether anatomical connectivity can predict functions consistently with functional connectivity in various functional domains and whether the connectivity-function relationship is universal across the whole cortex are unknown. Using a linear model, we discovered that anatomical connectivity was comparative to functional connectivity in explaining the variance of functions in most cortical regions, with the exception that anatomical connectivity had poor explaining abilities in brain areas which had high individual task variations. In addition, anatomical connectivity were not that good at capturing individual functional differences and had less inter-subject variation than functional connectivity, however anatomical connectivity could be regarded as more stable in the perspective of parcellation. The current results provided the first comprehensive picture of the relationships between functions and connectivity in the whole human cortex at a fine-grained brain atlas.
A laboratory demand optimisation project in primary care
Authors: Bucholc Magda , O’Kane Maurice , O’Hare Brendan , Mullan Ciaran , Cavanagh Paul , Ashe Siobhan , Wong-Lin KongFatt
Published: January 2018

Background

There is evidence of increasing use of laboratory tests with substantial variation between clinical teams which is difficult to justify on clinical grounds. The aim of this project was to assess the effect of a demand optimisation intervention on laboratory test requesting in primary care.

Methods

The intervention comprised educational initiatives, feedback to 55 individual practices on test request rates with ranking relative to other practices, and a small financial incentive for practices to engage and reflect on their test requesting activity. Data on test request numbers were collected from the laboratory databases for consecutive 12 month periods; pre‐intervention 2011-12, intervention 2012-13, 2013-14, 2014-15, and post-intervention 2015-16.

Results

The intervention was associated with a 3.6% reduction in the mean number of profile test requests between baseline and 2015-16, although this was seen only in rural practices. In both rural and urban practices, there was a significant reduction in-between practice variability in request rates. The mean number of HbA1crequests increased from 1.9 to 3.0 per practice patient with diabetes. Variability in HbA1crequest rates increased from 23.8% to 36.6%. At all considered time points, test request rates and variability were higher in rural than in urban areas.

Conclusions

The intervention was associated with a reduction in both the volume and between practice variability of profile test requests, with differences noted between rural and urban practices. The increase in HbA1crequests may reflect a more appropriate rate of diabetes monitoring and also the adoption of HbA1cas a diagnostic test.

Strengths & limitations of the study

We assessed the effect of a laboratory demand optimisation intervention both on the value and between GP practice variability in laboratory test requesting.

The changes in laboratory test requesting were separately evaluated for rural and urban GP practices.

Other factors (GP practice organisation, characteristics of general practitioners) potentially affecting between practice differences in laboratory test ordering were not taken into account due to data unavailability.

The demand management initiative was not accompanied by the cost-effectiveness analysis.

The demand optimisation intervention was conducted in a Northern Ireland (NI) Western Health and Social Care Trust and the findings have not been independently replicated in any other NI trusts.
Type-2 CD8+T lymphocytes responsive to PGD2and LTE4in severe eosinophilic asthma
Authors: Hilvering Bart , Hinks Timothy SC , Stöger Linda , Marchi Emanuele , Salimi Maryam , Shrimanker Rahul , Liu Wei , Chen Wentao , Luo Jian , Go Simei , Powell Timothy , Cane Jennifer , Thulborn Samantha , Kurioka Ayako , Leng Tianqi , Matthews Jamie , Connolly Clare , Borg Catherine , Bafadhel Mona , Willberg Christian B , Ramasamy Adaikalavan , Djukanović Ratko , Ogg Graham , Pavord Ian D , Klenerman Paul , Xue Luzheng
Published: January 2018

The functions andin vivoroles of type-2 CD8+T cells in humans have not been well defined and this cell type has been largely overlooked in models of disease. We investigated this in the context of severe asthma with persistent airway eosinophilia - a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+CRTH2+(Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2(PGD2) and cysteinyl leukotriene E4(LTE4) are also increased in the airways of the same group of patients.In vitroPGD2and LTE4function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.
Engineering of a Polydisperse Small Heat-Shock Protein Reveals Conserved Motifs of Oligomer Plasticity
Authors: Mishra Sanjay , Chandler Shane A. , Williams Dewight , Claxton Derek P. , Koteiche Hanane A. , Stewart Phoebe L. , Benesch Justin L.P. , Mchaourab Hassane S.
Published: January 2018

Small heat-shock proteins (sHSP) are molecular chaperones that bind and sequester partially and globally unfolded states of their client proteins. Of paramount importance to their physiological roles is the assembly into large oligomers, which for mammalian sHSP are polydisperse and undergo subunit exchange. The flexibility and dynamic nature of these oligomers mediates functional regulation by phosphorylation and underpins the deleterious effects of disease-linked mutations. Previously, we discovered that the archaeal Hsp16.5, which natively forms ordered and symmetric 24-subunit oligomers, can be engineered to transition to an ordered and symmetric 48-subunit oligomer by insertion of a peptide from human HspB1 (Hsp27) at the junction of the N-terminal and α-crystallin domains. Here, we carried out a detailed analysis of the determinants of Hsp16.5 oligomeric plasticity by altering the sequence and length of the inserted peptide. Utilizing light scattering, blue native gel electrophoresis, native mass spectrometry and electron microscopy, we uncovered the existence of an array of oligomeric states (30 to 38 subunits) that can be populated as a consequence of different insertions. These oligomers are intermediate states on the assembly pathway of the 48-subunit oligomer as two of the variants can concurrently form 24-subunit or 30-38 subunit polydisperse oligomers. Polydisperse Hsp16.5 oligomers displayed higher affinity to a model client protein consistent with a general mechanism for recognition and binding that involves increased access of the hydrophobic N-terminal region. Our findings, which integrate structural and functional analyses from evolutionarily-distant sHSP, support a model wherein the modular architecture of these proteins encodes motifs of oligomer polydispersity, dissociation and expansion to achieve functional diversity and regulation.