bluuebunny/crossref_metadata_2025 huggingface dataset:
Bottom-up multilingualism in Singapore: Code choice on shop signs
Authors: Shang Guowen , Zhao Shouhui
Published: November 2016

Characterized by a politically censorious and highly regulated society, Singapore is widely considered to be one of the most sophisticated authoritarian systems in history (Lee, 2005). As in many other public and private domains, the government, well known for its paternalistic attitude (Schiffman, 2003), usually practices an active interventional policy on linguistic life, which is extensively explored in language planning and policy study. However, in a few areas where less official intervention is exercised, the linguistic reality has received relatively scant attention. This study sets out to examine to what extent grassroots individuals can use shop signs to express their personal inclinations regarding language use, which may partly demonstrate the virtual vitality of various languages in the multilingual society.
SEMIPARAMETRIC ESTIMATION OF RANDOM COEFFICIENTS IN STRUCTURAL ECONOMIC MODELS
Authors: Hoderlein Stefan , Nesheim Lars , Simoni Anna
Published: November 2016

This paper discusses nonparametric estimation of the distribution of random coefficients in a structural model that is nonlinear in the random coefficients. We establish that the problem of recovering the probability density function (pdf) of random parameters falls into the class of convexly-constrained inverse problems. The framework offers an estimation method that separates computational solution of the structural model from estimation. We first discuss nonparametric identification. Then, we propose two alternative estimation procedures to estimate the density and derive their asymptotic properties. Our general framework allows us to deal with unobservable nuisance variables, e.g., measurement error, but also covers the case when there are no such nuisance variables. Finally, Monte Carlo experiments for several structural models are provided which illustrate the performance of our estimation procedure.
Introducing the Infant Bookreading Database (IBDb)
Authors: HUDSON KAM CARLA L. , MATTHEWSON LISA
Published: November 2016

Studies on the relationship between bookreading and language development typically lack data about which books are actually read to children. This paper reports on an Internet survey designed to address this data gap. The resulting dataset (the Infant Bookreading Database or IBDb) includes responses from 1,107 caregivers of children aged 0–36 months who answered questions about the English-language books they most commonly read to their children. The inclusion of demographic information enables analysis of subsets of data based on age, sex, or caregivers’ education level. A comparison between our dataset and those used in previous analyses reveals that there is relatively little overlap between booklists gathered from proxies such as bestseller lists and the books caregivers reported reading to children in our survey. The IBDb is available for download for use by researchers at .
Assessing ecosystem services in Neotropical dry forests: a systematic review
Authors: CALVO-RODRIGUEZ SOFIA , SANCHEZ-AZOFEIFA ARTURO G. , DURAN SANDRA M. , ESPÍRITO-SANTO MARIO M.
Published: November 2016

There is an increasing consensus on the importance of understanding ecosystem service (ES) provision in order to facilitate decision making and the sustainable management of Neotropical dry forests (NTDFs), yet research on the ESs provided by NTDFs is limited. We identified the main existing gaps and trends in the quantification of provisioning, regulating and supporting ESs in NTDFs. Systematic web-based searches showed that research has been increasing in recent decades in NTDFs, supporting greater ES knowledge and assessment. Carbon storage and biodiversity are the main subjects under study, while ESs relating to water and soil lack investigation. The most common approaches for assessing ES were fauna and plant inventories, carbon dynamics and ecological processes.
Critical Scholarship and Responsible Practice of International Law. How Can the Two be Reconciled?
Authors: FEICHTNER ISABEL
Published: November 2016

How can I as an international lawyer, conscious that international law is deeply implicated in today's global injustices and that the course of history will not be changed by any grand legal design, practice law responsibly? Taking as a point of departure my own desire not to seek comfort in the formulation of a critique of law, but to aspire to a responsible practice, I consult two quite different bodies of work: first, critical theory of law and second, recent scholarship on international law that argues a practice guided by ethics may enhance the legitimacy of international law. I turn then to my own practice of international economic law focusing on my occasional role as legal expert on the so-called megaregionals the EU aims to conclude with Canada and the United States. I propose that the debate on international economic law lacks an investigation into the role of law in shaping political economy; that this lack can be explained by the compartmentalization of expertise which leads to justification gaps with respect to projects such as the megaregionals. One way lawyers can assume responsibility is to work on closing these gaps even if it means leaving the ‘inside’ of the legal discipline. Finally, I suggest that a responsible legal practice of social change might follow Roberto Unger's call for institutional imagination. Maybe I can satisfy my wish for a transformative practice by joining forces with friends in experimenting with institutions, hoping to build an alternative political economy.
Justice on Screen – A Study of Four Documentary Films on the International Criminal Court
Authors: WERNER WOUTER G.
Published: November 2016

In the past ten years or so, several documentaries on international criminal justice have been produced, shown at film festivals, and used for advocacy and educational purposes. On some occasions, artists, humanitarian organizations, and the Office of the Prosecutor of the International Criminal Court (ICC) have worked closely together in the production of documentary films. Documentaries have thus become important tools for education and the spread of imageries of international criminal justice. So far, however, international legal scholars have largely shied away from researching cinematic representations of their field. In this article, I seek to remedy this by focusing on a family of four recent influential documentaries related to the ICC: The Reckoning, The Court, Prosecutor, and Watchers of the Sky. All four use similar modes of representation, narration and promotion and basically communicate the same message about the Court. My article critically analyzes how such artistic interventions have helped create specific images, stories, and sentiments.
The International Court of Justice: Cruising Ahead at 70
Authors: THIRLWAY HUGH
Published: November 2016

The International Court of Justice (ICJ or the Court) continues to hear and determine the contentious cases submitted to it, keeping up what has been referred to as an acceptable ‘cruising pace’. After recalling the extent to which the demands on the Court have increased, and the practical means available to it have been greatly extended, the author (following up an earlier article on the subject in the Netherlands International Law Review) examines the Court's recent case-law (decisions given since 2010) to show how each decision, besides furthering settlement of the specific dispute, has contributed to the enlargement or development of international law. Attention is concentrated, however, on particular questions: the role of peremptory norms (jus cogens); interpretation of treaties; questions of jurisdiction (including the problem of the existence of a justiciable dispute in each case); and certain incidental proceedings contemplated by the Court's Statute and Rules, namely provisional measures and intervention under Articles 62 and 63 of the Statute.
Fragilariopsis kerguelensis size variability from the Indian subtropical Southern Ocean over the last 42 000 years
Authors: Shukla Sunil Kumar , Crosta Xavier
Published: November 2016

In the open Southern Ocean (SO), both modern and past size changes of the diatom Fragilariopsis kerguelensis appear to be strongly controlled by iron availability. Conversely, sea surface temperatures (SST) and sea ice seasonal dynamics take over in the seasonal sea-ice zone where iron is not limiting. No information exists on F. kerguelensis biometry from the subtropical SO, on the other extreme of the thermal and nutrient gradients. We present here new data on mean valve area of F. kerguelensis (FkergArea) from a sediment core covering the last ~42 cal kyrs from the southern Subtropical Front (SSTF) of the Indian sector of the SO, where iron and silica stocks are thought to have been consistently low over this period. Our results suggest that larger F. kerguelensis valves occurred during the Last Glacial period, and declined during the Holocene period. These findings indicate that more favourable SST, within the F. kerguelensis ecological range, during the Last Glacial period may have enabled F. kerguelensis to make better use of the low silica stocks prevailing in the subtropical zone leading to larger valves. Conversely, declining FkergArea during the deglacial and the Holocene periods may have been a result of higher SST which hampered the utilization of silica.
Effect of sperm preparation on development of bovine blastocyst in vitro
Authors: Abraham Maria Celina , Johannisson Anders , Morrell Jane M.
Published: November 2016

Sperm preparation is an important step in the in vitro production of embryos. Centrifugation through colloids has been used to select normal sperm for assisted reproduction in several species. Animal models can sometimes be used as a preliminary step to investigate sperm preparation methods that are potentially of use for human fertility treatments. In this study bovine semen was prepared using three variants of the single-layer centrifugation sperm selection technique (Small, Mini, Mini-EP) with Bovicoll (Androcoll-B). Computer-assisted sperm motility analysis, the hypo-osmotic swelling test, and the sperm chromatin structure assay were performed on unselected (control) and SLC-selected sperm samples. Mini and Mini-EP gave the highest yield of motile spermatozoa, progressive motility and membrane integrity. In vitro fertilization trials were performed to investigate the fertilizing ability of the frozen–thawed bovine spermatozoa selected with Bovicoll. Mini-SLC (single-layer centrifugation) and swim-up (Control) were performed and cleavage rate and blastocyst rate did not differ significantly between groups. As there was a trend to an increased number of cells in blastocysts in the SLC group, the Mini-SLC method is at least as good as swim-up for selecting frozen–thawed bull spermatozoa for in vitro fertilization (IVF). This method could potentially be used to prepare human sperm for assisted reproduction.
Analyses of apoptosis and DNA damage in bovine cumulus cells afterin vitromaturation with different copper concentrations: consequences on early embryo development
Authors: Rosa D.E. , Anchordoquy J.M. , Anchordoquy J.P. , Sirini M.A. , Testa J.A. , Mattioli G.A. , Furnus C.C.
Published: November 2016

The aim of this study was to investigate the influence of copper (Cu) duringin vitromaturation (IVM) on apoptosis and DNA integrity of cumulus cells (CC); and oocyte viability. Also, the role of CC in the transport of Cu during IVM was evaluated on oocyte developmental capacity. Damage of DNA was higher in CC matured without Cu (0 µg/dl Cu,P< 0.01) with respect to cells treated with Cu for cumulus–oocyte complexes (COCs) exposed to 0, 20, 40, or 60 µg/dl Cu). The percentage of apoptotic cells was higher in CC matured without Cu than in CC matured with Cu. Cumulus expansion and viability of CC did not show differences in COC treated with 0, 20, 40, or 60 µg/dl Cu during IVM. Afterin vitrofertilization (IVF), cleavage rates were higher in COC and DO + CC (denuded oocytes + CC) with or without Cu than in DO. Independently of CC presence (COC, DO + CC or DO) the blastocyst rates were higher when 60 µg/dl Cu was added to IVM medium compared to medium alone. These results indicate that Cu supplementation to IVM medium: (i) decreased DNA damage and apoptosis in CC; (ii) did not modify oocyte viability and cumulus expansion; and (iii) improved subsequent embryo development up to blastocyst stage regardless of CC presence during IVM.
Autophagy is required for sea urchin oogenesis and early development
Authors: Agnello Maria , Chiarelli Roberto , Martino Chiara , Bosco Liana , Roccheri Maria Carmela
Published: November 2016

Autophagy is a major intracellular pathway for the degradation and recycling of cytosolic components. Emerging evidence has demonstrated its crucial role during the embryo development of invertebrates and vertebrates. We recently demonstrated a massive activation of autophagy in Paracentrotus lividus embryos under cadmium stress conditions, and the existence of a temporal relationship between induced autophagy and apoptosis. Although there have been numerous studies on the role of autophagy in the development of different organisms, information on the autophagic process during oogenesis or at the start of development in marine invertebrates is very limited. Here we report our recent data on the occurrence of autophagy at these key phases of development. In order to investigate autophagy trends we performed in vivo assays to detect autophagolysomes, as well as in situ analysis with anti-LC3 antibody to detect autophagosomes before the fusion with lysosomes. From data generated through confocal laser scanning microscopy and quantification of autophagic signals we have drawn several unequivocal conclusions. The results showed a copious and rising number of autophagic organelles that had specific localization. Interestingly the increase in autophagy that occurred just after fertilization has been proved to be crucial for correct initiation of the developmental programme: irreversible developmental delays and morphologic anomalies were induced by short autophagic inhibition. This work focused on the sea urchin model system and corroborates evidence on the need for self-digestion during development, enriching the knowledge on autophagy, a biological mechanism belonging to evolutionarily different organisms.
Psychological prognosis after newly diagnosed chronic conditions: socio-demographic and clinical correlates
Authors: Chiu Ching-Ju , Hsu Yu-Ching , Tseng Shuo-Ping
Published: November 2016

Background:

This study was aimed toward discerning depressive symptom trajectories associated with different chronic conditions and toward finding modifiable factors associated with those trajectories.

Methods:

Data were drawn from the 1996–2007 Taiwan Longitudinal Study on Aging. Nine chronic conditions were selected, and mood trajectories were measured with the Center of Epidemiological Studies-Depression scale.

Results:

Among the nine chronic conditions we examined, four patterns of depressive symptom trajectories were identified: (1) elevated depressive symptoms and worsened over time after diagnosed with heart disease (n= 681), arthritis (n= 850), or hypertension (n= 1,207); (2) elevated depressive symptoms without worsening over time after diagnosed with stroke (n= 160), lung diseases (n= 432), gastric conditions (n= 691), or liver diseases (n= 234); (3) no elevated depressive symptoms after diagnosis but an increase in depressive symptoms over time for participants with diabetes (n= 499); and (4) no significant patterns after diagnosed with cancer (n= 57). Cumulative psychological burden over time was significant for participants with hypertension, diabetes, heart diseases, or arthritis. However, these effects disappeared after controlling for comorbidities and physical limitations. Moreover, psychiatric condition was found to play an important role in baseline depressive symptoms among participants diagnosed with lung diseases, arthritis, or liver diseases.

Conclusions:

Findings from this study provide information in addressing psychological burden at different times for different conditions. In addition, minimizing the incidence of comorbidities, physical limitations, or psychiatric conditions may have the prospective effect of avoiding the trend of increased depressive symptoms, especially when adults diagnosed with hypertension, diabetes, heart diseases, arthritis, lung diseases, arthritis, or liver diseases.
Cross-linguistic structural priming in bilinguals: priming of the subject-to-object raising construction between English and Korean
Authors: SONG YOONSANG , DO YOUNGAH
Published: November 2016

A cross-linguistic structural priming experiment explores the issue of whether parallel syntactic constructions of the two languages in bilinguals share a representation when the surface word orders of the constructions differ. The target population was early balanced bilinguals of Korean and English; the tested constructions were structures relevant to the subject-to-object raising (STOR) operation, which until this study have not been used for structural priming research in cross-linguistic contexts (e.g., STOR: Mary believes Jerry to be trustworthy; non-STOR: Mary believes that Jerry is trustworthy). These syntactic structures exist in both English and Korean, but with different surface word orders. The results show that cross-linguistic priming of the STOR construction occurred, suggesting that parallel syntactic constructions of the languages in bilinguals can share a representation independent of surface word order.
Archaeology will be just fine
Authors: Ribeiro Artur
Published: November 2016

Many archaeologists are currently stuck in a mindset in which attention is paid exclusively to ideas that are ‘new’ and ‘revolutionary’. This fetishization of the ‘new’ leads us down a dangerous road as it promotes uncritical disdain of old ideas which remain valid and it advocates fads from neighbouring disciplines which are methodologically vapid and philosophically dubious. The objective of this paper is to question whether archaeology requires constant ‘paradigmatic change’ and my answer to this question is no. By constantly altering the status quo, archaeologists are promoting a culture in which theoretical ‘newness’ is given the spotlight and ideas are considered valid as long as they are original. Against this, I recommend a more critical view of new ideas and a revision of old ones – a culture which prioritizes the quality of archaeological theories regardless of whether they are new or old.
Is it time for an elemental and humoral (re)turn in archaeology?
Authors: Jones Richard , Miller Holly , Sykes Naomi
Published: November 2016

This paper asks whether archaeologists might profitably re-engage with the pre-Enlightenment doctrines of elemental philosophy and humoral theory as paradigms more relevant for archaeological interpretation in certain contexts than much of current theoretical discourse. These ancient cosmologies are here reconceptualized to suggest ways in which archaeologists might provide fairer representations of past cultures, through the readoption of ideas that they understood rather than through the imposition of more recent and thus anachronistic frames of analytical reference. In four brief case studies, the paper seeks to show how the foregrounding of elemental and humoral theories might lead to new ways of thinking about the study and interpretation of the landscape, material culture, consumption and the senses. Through them, the paper looks to encourage reflection on whether elemental and humoral theories represent the intellectual paradigms that archaeologists have been striving to invent since the discipline's creation.
The Forgotten History of Food Security in Multilateral Trade Negotiations
Authors: MARGULIS MATIAS E.
Published: November 2016

Food security emerged as a major source of political deadlock in the WTO Doha Round negotiations. Concerns about food security only intensified at the WTO following the 2008 Global Food Crisis, with the Bali and Nairobi Ministerials revealing polarized views between the US and India on the financing of public food stockholding. These ‘food fights’ at the WTO have attracted significant international media, civil society, and scholarly attention. In this article, I argue that inter-state disagreement on food security is not new or specific to the Doha Round but instead has been a recurrent phenomenon in the multilateral trade system for decades. Employing an historical approach, I show that food security has repeatedly been an item of negotiation in successive GATT negotiating rounds and has been steadily codified in international trade law over time. Today, food security is deeply integrated into the rules of the trade regime, making the WTO an important yet largely unacknowledged institution in global food security governance.
Factors associated with patient preferences for communication of bad news
Authors: Fujimori Maiko , Akechi Tatsuo , Uchitomi Yosuke
Published: November 2016

Objective:

Communication based on patient preferences can alleviate their psychological distress and is an important part of patient-centered care for physicians who have the task of conveying bad news to cancer patients. The present study aimed to explore the demographic, medical, and psychological factors associated with patient preferences with regard to communication of bad news.

Methods:

Outpatients with a variety of cancers were consecutively invited to participate in our study after their follow-up medical visit. A questionnaire assessed their preferences regarding the communication of bad news, covering four factors—(1) how bad news is delivered, (2) reassurance and emotional support, (3) additional information, and (4) setting—as well as on demographic, medical, and psychosocial factors.

Results:

A total of 529 outpatients with a variety of cancers completed the questionnaire. Multiple regression analyses indicated that patients who were younger, female, had greater faith in their physician, and were more highly educated placed more importance on “how bad news is delivered” than patients who were older, male, had less faith in their physician, and a lower level of education. Female patients and patients without an occupation placed more importance on “reassurance and emotional support.” Younger, female, and more highly educated patients placed more importance on “additional information.” Younger, female, and more highly educated patients, along with patients who weren't undergoing active treatment placed more importance on “setting.”

Significance of Results:

Patient preferences with regard to communication of bad news are associated with factors related to patient background. Physicians should consider these characteristics when delivering bad news and use an appropriate communication style tailored to each patient.
Political institutions and financial cooperative development
Authors: KHAFAGY AMR
Published: November 2016

This paper analyses the influence of political institutions on the development of financial cooperatives. It proposes a political economy theory where autocratic regimes deliberately oppose the development of a well-functioning financial cooperative sector to maintain their political influence, and prevent the formation of strong pressure groups that can threaten the current politicalstatus quoand reduce the governing elites’ economic benefits from underdeveloped and exclusive financial sector. Using panel data from 65 developing countries from 1995–2014, the results show that democracy, political rights and civil liberties promote financial cooperative development. These results are robust in controlling for endogeneity as well as other economic and institutional factors.
Emotional Dependency and Dysfunctional Relationship Beliefs as Predictors of Married Turkish Individuals’ Relationship Satisfaction
Authors: Kemer Gülşah , Çetinkaya Yıldız Evrim , Bulgan Gökçe
Published: November 2016

In this study, we examined married individuals’ relationship satisfaction in relation to their emotional dependency and dysfunctional relationship beliefs. Our participants consisted of 203 female and 181 male, a total of 384 married individuals from urban cities of Turkey. Controlling the effects of gender and length of marriage, we performed a hierarchical regression analysis. Results revealed that married Turkish individuals’ relationship satisfaction was significantly explained by their emotional dependency (sr2= .300,p< .001), and perceptions of interpersonal rejection (sr2= .075,p< .001) and unrealistic relationship expectations (sr2= .028,p< .001). However, interpersonal misperception did not make a significant contribution to the participants’ relationship satisfaction (p> .05). When compared to perceptions of interpersonal rejection and unrealistic relationship expectations, emotional dependency had the largest role in explaining participants’ satisfaction with their marriages. We discuss the results in light of current literature as well as cultural relevance. We also provide implications for future research and mental health practices.
Exokrine Pankreasinsuffizienz
Authors: Lenglinger Johannes , Hädrich Marion
Published: November 2016

Zusammenfassung. Die exokrine Pankreasinsuffizienz ist als Verdauungsstörung in Folge einer verminderten pankreatischen Enzym- und Bikarbonatsekretion definiert. Der nicht kompensierbare Ausfall der Pankreaslipase verursacht ein durch Steatorrhoe, Vitaminmangel und Gewichtsverlust gekennzeichnetes Malabsorptionssyndrom. Die Ursachen sind chronische Pankreatitis, Pankreastumore, Zystische Fibrose sowie extrapankreatische Erkrankungen wie Mb. Crohn oder Zöliakie. Bei Fehlen morphologischer Läsionen wird die Diagnose durch nicht invasive Tests der exokrinen Pankreasfunktion gesichert. Die Therapie umfasst Enzymsubstitution sowie Nikotin- und Alkohol-Abstinenz. Der Therapieerfolg wird durch klinische oder funktionsdiagnostische Parameter monitiert. Behandlungsziele sind die Normalisierung der Verdauungsfunktion und die Prävention von Gewichtsverlust und Folgeschäden. Bei unzureichendem Ansprechen kann die Dosis der Enzymersatztherapie gesteigert und ein Protonenpumpenhemmer dazu kombiniert werden.
Akute Pankreatitis
Authors: Aeberhard Carla , Gloor Beat , Stanga Zeno
Published: November 2016

Zusammenfassung. Eine spezifische Therapie der akuten Pankreatitis (AP) existiert nicht. Die wichtigsten therapeutischen Massnahmen neben einer ausreichenden Analgesie ist eine möglichst frühe adäquate Volumen- und Ernährungstherapie. Diesbezüglich hat in den letzten zwei Dekaden ein Paradigmenwechsel stattgefunden. Bei einem milden bis moderaten Verlauf einer AP (miAP, moAP) soll frühzeitig eine orale Nahrungsaufnahme versucht werden, sofern dies aufgrund der Schmerzen und der oft vorliegenden Darmparalyse durchführbar ist. Bei einer schweren AP (sAP) sollte eine früh eingeleitete enterale Ernährung (EE) erfolgen; die Indikation zur parenteralen Ernährung (PE) sollte wegen möglicher Infekt-assoziierter Komplikationen mit Zurückhaltung gestellt werden. Durch diese Massnahmen können Morbidität und Mortalität gesenkt werden. Der Einsatz von Probiotika ist umstritten. Eine Indikation für eine generelle Antibiotikaprophylaxe besteht auch bei sAP nicht. Eine Antibiotikatherapie wird lediglich beim Vorliegen einer Cholangitis oder bei infizierten Nekrosen/Pseudozysten empfohlen.
Hepatitis-E-Virus auf den «differenzialdiagnostischen Radar»!
Authors: Schultze Detlev , Etter Hermann , Mani Bernhard , Dollenmaier Günter
Published: November 2016

Zusammenfassung. Entgegen früherer Annahmen wird die Hepatitis-E-Virus(HEV)-Infektion nicht nur auf Auslandsreisen, sondern auch hierzulande durch kontaminierte Lebensmittel erworben, mit teilweise chronischen Verläufen und neurologischen Komplikationen. Insbesondere Ärzte, die immunsupprimierte Patienten betreuen, sollten HEV-Infektionen auf ihren «differenzialdiagnostischen Radar» nehmen, da chronische Verläufe mit fibrotischem Leberumbau einhergehen können und therapierbar sind.
Ancient Ocean Floor Seashells Improve Model of Past Glaciers
Authors: Underwood Emily
Published: November 2016

More accurate reconstruction of ice sheets over the past 150,000 years could help scientists predict future climate change.
Striped nanoscale phase separation at the metal–insulator transition of heteroepitaxial nickelates
Authors: Mattoni G. , Zubko P. , Maccherozzi F. , van der Torren A.J.H. , Boltje D. B. , Hadjimichael M. , Manca N. , Catalano S. , Gibert M. , Liu Y. , Aarts J. , Triscone J.-M. , Dhesi S. S. , Caviglia A. D.
Published: November 2016

Nucleation processes of mixed-phase states are an intrinsic characteristic of first-order phase transitions, typically related to local symmetry breaking. Direct observation of emerging mixed-phase regions in materials showing a first-order metal–insulator transition (MIT) offers unique opportunities to uncover their driving mechanism. Using photoemission electron microscopy, we image the nanoscale formation and growth of insulating domains across the temperature-driven MIT in NdNiO3 epitaxial thin films. Heteroepitaxy is found to strongly determine the nanoscale nature of the phase transition, inducing preferential formation of striped domains along the terraces of atomically flat stepped surfaces. We show that the distribution of transition temperatures is a local property, set by surface morphology and stable across multiple temperature cycles. Our data provide new insights into the MIT of heteroepitaxial nickelates and point to a rich, nanoscale phenomenology in this strongly correlated material.
Engineering and optimising deaminase fusions for genome editing
Authors: Yang Luhan , Briggs Adrian W. , Chew Wei Leong , Mali Prashant , Guell Marc , Aach John , Goodman Daniel Bryan , Cox David , Kan Yinan , Lesha Emal , Soundararajan Venkataramanan , Zhang Feng , Church George
Published: November 2016

Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2.5% in human cells. However, off-target deaminations were detected more than 150 bp away from the target site. Moreover, whole genome sequencing revealed that edited bacterial cells did not harbour chromosomal abnormalities but demonstrated elevated global cytidine deamination at deaminase intrinsic binding sites. Therefore programmable deaminases represent a promising genome editing tool in prokaryotes and eukaryotes. Future engineering is required to overcome the processivity and the intrinsic DNA binding affinity of deaminases for safer therapeutic applications.
Towards first-principles molecular design of liquid crystal-based chemoresponsive systems
Authors: Roling Luke T. , Scaranto Jessica , Herron Jeffrey A. , Yu Huaizhe , Choi Sangwook , Abbott Nicholas L. , Mavrikakis Manos
Published: November 2016

Nematic liquid crystals make promising chemoresponsive systems, but their development is currently limited by extensive experimental screening. Here we report a computational model to understand and predict orientational changes of surface-anchored nematic liquid crystals in response to chemical stimuli. In particular, we use first-principles calculations to evaluate the binding energies of benzonitrile, a model for 4′-pentyl-4-biphenylcarbonitrile, and dimethyl methylphosphonate to metal cation models representing the substrate chemical sensing surface. We find a correlation between these quantities and the experimental response time useful for predicting the response time of cation–liquid crystal combinations. Consideration of charge donation from chemical species in the surface environment is critical for obtaining agreement between theory and experiment. Our model may be extended to the design of improved chemoresponsive liquid crystals for selectively detecting other chemicals of practical interest by choosing appropriate combinations of metal cations with liquid crystals of suitable molecular structure.
Correction: Corrigendum: A DERL3-associated defect in the degradation of SLC2A1 mediates the Warburg effect
Authors: Lopez-Serra Paula , Marcilla Miguel , Villanueva Alberto , Ramos-Fernandez Antonio , Palau Anna , Leal Lucía , Wahi Jessica E. , Setien-Baranda Fernando , Szczesna Karolina , Moutinho Catia , Martinez-Cardus Anna , Heyn Holger , Sandoval Juan , Puertas Sara , Vidal August , Sanjuan Xavier , Martinez-Balibrea Eva , Viñals Francesc , Perales Jose C. , Bramsem Jesper B. , Ørntoft Torben F. , Andersen Claus L. , Tabernero Josep , McDermott Ultan , Boxer Matthew B. , Vander Heiden Matthew G. , Albar Juan Pablo , Esteller Manel
Published: November 2016

Nature Communications 5: Article number: 4608 (2014); Published: 3 April 2014; Updated: 2 November 2016 During the preparation of the PCR gel panels in Fig. 1b,c, duplicate or otherwise irrelevant lanes were excised; these excisions were not noted in the published figure as per the Nature journal policy.
The ethanopharmacological aspect of carbon nanodots in turmeric smoke
Authors: Chun Sechul , Muthu Manikandan , Gansukh Enkhtaivan , Thalappil Pradeep , Gopal Judy
Published: November 2016

Smoke manifested ever since our ancient’s lit fire; today it has evolved to become an environmental concern. However, medicinal smoke is still part of man’s natural remedies, religious and cultural practices too. The Asiatic household practice of burning turmeric rhizomes to relieve nose and chest congestion is a well known yet never scientifically authenticated or studied practice. For the first time we investigate the components of these turmeric smudges, validate their antimicrobial and anticancer properties and their cell compatibility. With smoke there is always nanoparticulate carbon and turmeric smoke is no exception. If so, what is the role of the nano carbon (NC) in the turmeric smudge effect? This study isolated, characterized and exposed these secret natural NC undercover agents in turmeric smoke. Their unequivocal role in the ethanopharmocological activity of turmeric smudging has been demonstrated. This work opens a new avenue for use of such nano components of smoke for harnessing the ethanopharmacological property of various medicinal smokes, by excluding the smoke factor, through extracting the nano carbon material in them. This is a possibility to realizing the use of such naturally available nanomaterial, as an eco friendly substitute for the notorious anthropogenic nanomaterials.
Staurosporines decrease ORMDL proteins and enhance sphingomyelin synthesis resulting in depletion of plasmalemmal phosphatidylserine
Authors: Maekawa Masashi , Lee Minhyoung , Wei Kuiru , Ridgway Neale D. , Fairn Gregory D.
Published: November 2016

Accumulation of phosphatidylserine in the inner leaflet of the plasma membrane is a hallmark of eukaryotes. Sublethal levels of staurosporine and related compounds deplete phosphatidylserine from the plasma membrane and abrogate K-Ras signaling. Here, we report that low-dose staurosporine and related compounds increase sphingomyelin mass. Mass-spectrometry and metabolic tracer analysis revealed an increase in both the levels and rate of synthesis of sphingomyelin in response to sublethal staurosporine. Mechanistically, it was determined that the abundance of the ORMDL proteins, which negatively regulate serine-palmitoyltransferase, are decreased by low-dose staurosporine. Finally, inhibition of ceramide synthesis, and thus sphingomyelin, prevented the displacement of phosphatidylserine and cholesterol from the inner leaflet of the plasma membrane. The results establish that an optimal level of sphingomyelin is required to maintain the distribution of phosphatidylserine and cholesterol in the plasma membrane and further demonstrate a complex relationship between the trafficking of phosphatidylserine and sphingomyelin.
Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy
Authors: Zhou Xu-Jie , Nath Swapan K , Qi Yuan-Yuan , Sun Celi , Hou Ping , Zhang Yue-Miao , Lv Ji-Cheng , Shi Su-Fang , Liu Li-Jun , Chen Ruoyan , Yang Wanling , He Kevin , Li Yanming , Zhang Hong
Published: November 2016

Known susceptibility loci together can only explain about 6–8% of the disease heritability of IgA nephropathy (IgAN), suggesting that there are still a large number of genetic variants remained to be discovered. We previously identified IgAN and systemic lupus erythematosus (SLE)/lupus nephritis (LN) shared many loci based on GWAS on Chinese populations. The more recent study with high-density genotyping of immune-related loci in individuals with Asian ancestry identified 10 new and 6 suggestive loci in SLE. In the current study, we thus included all the lead SNPs from these 16 loci reported, and firstly tested their associations in 1,248 patients with sporadic IgAN, 737 patients with LN and 1,187 controls. Significant associations identified in IgAN were replicated in additional 500 patients and 2372 controls. rs12022418 in RGS1 (p = 3.0 × 10−6) and rs7170151 in RASGRP1 (p = 1.9 × 10−5) showed novel associations in IgAN. Compared to SNPs that were in LD with them, the associated variants showed higher potential of regulatory features by affecting gene expression. And systemic evaluation of GWAS data supported the pleiotropic effects of RGS1 and RASGRP1 variants in mediating human complex diseases. In conclusion, novel risk loci shared between IgAN and SLE/LN were identified, which may shed new light to exploit the potential pathogenesis for those two diseases.
Distinct roles for primate caudate dopamine D1 and D2 receptors in visual discrimination learning revealed using shRNA knockdown
Authors: Takaji Masafumi , Takemoto Atsushi , Yokoyama Chihiro , Watakabe Akiya , Mizukami Hiroaki , Ozawa Keiya , Onoe Hirotaka , Nakamura Katsuki , Yamamori Tetsuo
Published: November 2016

The striatum plays important motor, associative and cognitive roles in brain functions. However, the rodent dorsolateral (the primate putamen) and dorsomedial (the primate caudate nucleus) striatum are not anatomically separated, making it difficult to distinguish their functions. By contrast, anatomical separation exists between the caudate nucleus and putamen in primates. Here, we successfully decreased dopamine D1 receptor (D1R) or D2R mRNA expression levels selectively in the marmoset caudate using shRNA knockdown techniques, as determined using positron emission tomography imaging with specific D1R and D2R ligands and postmortem in situ hybridization analysis. We then conducted a voxel-based correlation analysis between binding potential values of PET imaging and visual discrimination learning task performance in these genetically modified marmosets to find a critical role for the caudate D2R but no apparent role for the caudate D1R. This latter finding challenges the current understanding of the mechanisms underlying D1R activation in the caudate.
Coral Reef Resilience, Tipping Points and the Strength of Herbivory
Authors: Holbrook Sally J. , Schmitt Russell J. , Adam Thomas C. , Brooks Andrew J.
Published: November 2016

Coral reefs increasingly are undergoing transitions from coral to macroalgal dominance. Although the functional roles of reef herbivores in controlling algae are becoming better understood, identifying possible tipping points in the herbivory-macroalgae relationships has remained a challenge. Assessment of where any coral reef ecosystem lies in relation to the coral-to-macroalgae tipping point is fundamental to understanding resilience properties, forecasting state shifts, and developing effective management practices. We conducted a multi-year field experiment in Moorea, French Polynesia to estimate these properties. While we found a sharp herbivory threshold where macroalgae escape control, ambient levels of herbivory by reef fishes were well above that needed to prevent proliferation of macroalgae. These findings are consistent with previously observed high resilience of the fore reef in Moorea. Our approach can identify vulnerable coral reef systems in urgent need of management action to both forestall shifts to macroalgae and preserve properties essential for resilience.
Systems-wide analysis of manganese deficiency-induced changes in gene activity of Arabidopsis roots
Authors: Rodríguez-Celma Jorge , Tsai Yi-Hsiu , Wen Tuan-Nan , Wu Yu-Ching , Curie Catherine , Schmidt Wolfgang
Published: November 2016

Manganese (Mn) is pivotal for plant growth and development, but little information is available regarding the strategies that evolved to improve Mn acquisition and cellular homeostasis of Mn. Using an integrated RNA-based transcriptomic and high-throughput shotgun proteomics approach, we generated a comprehensive inventory of transcripts and proteins that showed altered abundance in response to Mn deficiency in roots of the model plant Arabidopsis. A suite of 22,385 transcripts was consistently detected in three RNA-seq runs; LC-MS/MS-based iTRAQ proteomics allowed the unambiguous determination of 11,606 proteins. While high concordance between mRNA and protein expression (R = 0.87) was observed for transcript/protein pairs in which both gene products accumulated differentially upon Mn deficiency, only approximately 10% of the total alterations in the abundance of proteins could be attributed to transcription, indicating a large impact of protein-level regulation. Differentially expressed genes spanned a wide range of biological functions, including the maturation, translation, and transport of mRNAs, as well as primary and secondary metabolic processes. Metabolic analysis by UPLC-qTOF-MS revealed that the steady-state levels of several major glucosinolates were significantly altered upon Mn deficiency in both roots and leaves, possibly as a compensation for increased pathogen susceptibility under conditions of Mn deficiency.
Kisspeptin and RFRP-3 differentially regulate food intake and metabolic neuropeptides in the female desert jerboa
Authors: Talbi Rajae , Laran-Chich Marie-Pierre , Magoul Rabia , El Ouezzani Seloua , Simonneaux Valérie
Published: November 2016

Jerboas are wild rodents exhibiting exceptional adaptation to their desert environment. Under harsh autumn conditions, they shut down reproduction, increase body weight and hibernate, while during spring they become sexually active even under negative energy-balance. We recently reported that these rhythms are associated with synchronized changes in genes expressing reproductive (Kiss1, Rfrp) and metabolic (Npy and Pomc) peptides, raising the hypothesis of coordinated seasonal regulation of both functions. Here we analyzed whether kisspeptin and RFRP-3 regulate food-intake in parallel to their established reproductive functions. Intracerebroventricular administration of kisspeptin inhibited food intake by 1.5-fold in fasted, but not ad-libitum fed, female jerboas captured in spring, an effect associated with an increase in Pomc and decrease in Rfrp mRNA levels. By contrast, intracerebroventricular injection of RFRP-3 induced a 4-fold increase in food-intake in ad-libitum female jerboas, together with a decrease in Pomc and increase in Npy mRNA levels. This orexigenic effect of RFRP-3 was observed in both spring and autumn, whereas kisspeptin’s anorexigenic effect was only observed in spring. Altogether, this study reports opposite metabolic effects of kisspeptin and RFRP-3 in the female jerboa and strengthens our hypothesis of a coordinated, season-dependent, regulation of reproductive activity and food intake through interactions of these hypothalamic peptides.
Passively synchronized Q-switched and mode-locked dual-band Tm3+:ZBLAN fiber lasers using a common graphene saturable absorber
Authors: Jia Chenglai , Shastri Bhavin J. , Abdukerim Nurmemet , Rochette Martin , Prucnal Paul R. , Saad Mohammed , Chen Lawrence R.
Published: November 2016

Dual-band fiber lasers are emerging as a promising technology to penetrate new industrial and medical applications from their dual-band properties, in addition to providing compactness and environmental robustness from the waveguide structure. Here, we demonstrate the use of a common graphene saturable absorber and a single gain medium (Tm3+:ZBLAN fiber) to implement (1) a dual-band fiber ring laser with synchronized Q-switched pulses at wavelengths of 1480 nm and 1840 nm, and (2) a dual-band fiber linear laser with synchronized mode-locked pulses at wavelengths of 1480 nm and 1845 nm. Q-switched operation at 1480 nm and 1840 nm is achieved with a synchronized repetition rate from 20 kHz to 40.5 kHz. For synchronous mode-locked operation, pulses with full-width at half maximum durations of 610 fs and 1.68 ps at wavelengths of 1480 nm and 1845 nm, respectively, are obtained at a repetition rate of 12.3 MHz. These dual-band pulsed sources with an ultra-broadband wavelength separation of ~360 nm will add new capabilities in applications including optical sensing, spectroscopy, and communications.
Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer
Authors: Mezheyeuski Artur , Hrynchyk Ina , Karlberg Mia , Portyanko Anna , Egevad Lars , Ragnhammar Peter , Edler David , Glimelius Bengt , Östman Arne
Published: November 2016

The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study. Metrics obtained with the method acted as independent markers for natural course of the disease, and for benefit of adjuvant treatment. Comparative analyses demonstrated that MF metrics out-performed standard histomorphological features such as tumor grade, budding and configuration of invasive front. Notably, the MF analyses-derived “αmax” –metric constitutes the first response-predictive biomarker in stage II-III colon cancer showing significant interactions with treatment in analyses using a randomized trial-derived study population. Based on these results the method appears as an attractive and easy-to-implement tool for biomarker identification.
A Low-loss Metasurface Antireflection Coating on Dispersive Surface Plasmon Structure
Authors: Jeon Jiyeon , Bhattarai Khagendra , Kim Deok-Kee , Kim Jun Oh , Urbas Augustine , Lee Sang Jun , Ku Zahyun , Zhou Jiangfeng
Published: November 2016

Over the years, there has been increasing interest in the integration of metal hole array (MHA) with optoelectronic devices, as a result of enhanced coupling of incident light into the active layer of devices via surface plasmon polariton (SPP) resonances. However, not all incident light contributes to the SPP resonances due to significant reflection loss at the interface between incident medium and MHA. Conventional thin-film antireflection (AR) coating typically does not work well due to non-existing material satisfying the AR condition with strong dispersion of MHA’s effective impedances. We demonstrate a single-layer metasurface AR coating that completely eliminates the refection and significantly increases the transmission at the SPP resonances. Operating at off-resonance wavelengths, the metasurface exhibits extremely low loss and does not show resonant coupling with the MHA layer. The SPP resonance wavelengths of MHA layer are unaffected whereas the surface wave is significantly increased, thereby paving the way for improved performance of optoelectronic devices. With an improved retrieval method, the metasurface is proved to exhibit a high effective permittivity ("Equation missing") and extremely low loss (tan δ ~ 0.005). A classical thin-film AR coating mechanism is identified through analytical derivations and numerical simulations.