bluuebunny/crossref_metadata_2025 huggingface dataset:
Formic Acid or Formate Derivatives as the In Situ Hydrogen Source in Au‐Catalyzed Reduction of para‐Chloronitrobenzene
Authors: Hu Zhun , Tan Shunquan , Mi Rongli , Li Xiang , Bai Jing , Guo Xiaoyan , Hu Guoyang , Hang Peng , Li Juan , Li Dan , Yang Yang , Yan Xianghui
Published: March 2018

Formic acid and formate derivatives as hydrogen source on the hydrogenation of para‐chloronitrobenzene (p‐CNB) over supported gold catalysts were investigated. The hydrogenation activity in various formate derivatives followed the order: HCOOH < HCOONa < HCOOK < HCOONH4, which was in accordance with the decrement of electronegativity of cation species in formate derivatives. Moreover, in the case of HCOONH4 as hydrogen source, the p‐CNB conversion could enhance ten‐fold as the hydrogen source of H2 at 60 oC. This promotion effect was also found in other supported Au catalysts. These results provide a general alternative hydrogen source to replace conventional H2 as reducing agent for fine chemical processes.
Magnetically Reusable MnFe2O4 Nanoparticles Modified with Oxo‐Peroxo Mo (VI) Schiff‐Base Complexes: A High Efficiency Catalyst for Olefin Epoxidation under Solvent‐Free Conditions
Authors: Babaei Behnam , Bezaatpour Abolfazl , Amiri Mandana , Szunerits Sabine , Boukherroub Rabah
Published: March 2018

In this research work, we report on the preparation of a new catalyst based on MnFe2O4 nanoparticles modified with an oxo‐peroxo molybdenum (VI) Schiff base complex. The catalyst was characterized by various techniques, including Fourier transform infrared (FT‐IR) spectroscopy, X‐ray diffraction (XRD), diffuse reflectance spectroscopy (DRS), vibrating sample magnetometer (VSM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X‐ray photoelectron spectroscopy (XPS). The epoxidation catalytic activity of the developed catalyst was tested on various alkenes by t‐butyl hydroperoxide (TBHP) as oxidant under solvent‐free condition. The catalyst showed excellent conversion (>99%), selectivity (100%), turn over frequency (9504 h−1), and a short reaction time (5 min). Moreover, the catalyst is recoverable up to five cycles with no significant loss in selectivity towards epoxide.
Abnormal Tetrel Bonds between Formamidine and TH3F: Substituent Effects
Authors: Xu Huili , Cheng Jianbo , Yu Xuefang , Li Qingzhong
Published: March 2018

Ab initio calculations have been performed for the complexes of formamidine (FA) with TH3F (T=C, Si, Ge, and Sn) as well as the complexes of FA derivatives including CH3, NH2, OH, OCH3, CH2CH3, CH2CH2CH3, CH(CH3)2, CF3, and F with SiH3F. In general, each complex is stabilized by both a main tetrel bond and a secondary interaction. The stability of the complex increases in the order T=C < Ge < Si < Sn, inconsistent with the magnitude of the σ‐hole on the tetrel atom. The (Z)‐FA complex is more stable than the (E)‐FA analogue. The imino nitrogen atom of FA is a better tetrel acceptor than most nitrogenated bases; it shows a particularly strong affinity for SiH3F with an interaction energy of ∼60 kJ/mol. Four electron‐donating groups give rise to the opposite effect on the strength of the tetrel bond: a weakening effect for OH and OCH3 but an enhancement for CH3 and NH2; the largest interaction energy occurs in CH3‐(Z)‐FA‐SiH3F, amounting to a magnitude of 80 kJ/mol. Two electron‐withdrawing groups have a larger weakening effect than OH and OCH3. The effect of the larger alkyl group is dependent on the type of complex. The weak complexes of CH3F are driven by electrostatic and dispersion interactions, while the strong complexes of TH3F (T=Si, Ge, and Sn) are dominated by electrostatic and polarization interactions, as well as orbital interactions.
Ni(II)‐Diphosphine‐Catalyzed One‐Pot Synthesis of Aromatic 1,5‐Diketones
Authors: Venkatesh Sadhana , Leninkumar Vardi , Reddy Manne Madhava , Desikan Rajagopal , Akella Sivaramakrishna
Published: March 2018

A new synthetic route for the preparation of aromatic 1,5‐diketones was developed through Ni(II)‐diphosphine‐catalyzed one‐pot reactions of various aromatic ketones with aromatic aldehydes in presence of KOH and 1,4‐dioxane in moderate yields. This protocol provides expeditious access to aromatic 1,5‐diones with a single step through cross‐aldol reaction followed by Michael 1,4‐addition and does not require expensive metal complexes as catalysts. All the synthesized catalysts and the products derived from the carbonyl compounds were fully characterized by spectroscopic and analytical data. The factors influencing the rate of reaction were discussed.
Anomalous dimensions in the WF O(N) model with a monodromy line defect
Authors: Söderberg Alexander
Published: March 2018

Abstract

Implications of inserting a conformal, monodromy line defect in three dimensional O(N) models are studied. We consider then the WF O(N) model, and study the two-point Green’s function for bulk-local operators found from both the bulk-defect expansion and Feynman diagrams. This yields the anomalous dimensions for bulk- and defect-local primaries as well as one of the OPE coefficients as ϵ-expansions to the first loop order. As a check on our results, we study the (ϕ

k
)2
ϕ

j
operator both using the bulk-defect expansion as well as the equations of motion.
R2 inflation to probe non-perturbative quantum gravity
Authors: Koshelev Alexey S. , Sravan Kumar K. , Starobinsky Alexei A.
Published: March 2018

Abstract

It is natural to expect a consistent inflationary model of the very early Universe to be an effective theory of quantum gravity, at least at energies much less than the Planck one. For the moment,R+R2, or shortlyR2, inflation is the most successful in accounting for the latest CMB data from the PLANCK satellite and other experiments. Moreover, recently it was shown to be ultra-violet (UV) complete via an embedding into an analytic infinite derivative (AID) non-local gravity. In this paper, we derive a most general theory of gravity that contributes to perturbed linear equations of motion around maximally symmetric space-times. We show that such a theory is quadratic in the Ricci scalar and the Weyl tensor with AID operators along with the Einstein-Hilbert term and possibly a cosmological constant. We explicitly demonstrate that introduction of the Ricci tensor squared term is redundant. Working in this quadratic AID gravity framework without a cosmological term we prove that for a specified class of space homogeneous space-times, a space of solutions to the equations of motion is identical to the space of backgrounds in a localR2model. We further compute the full second order perturbed action around any background belonging to that class. We proceed by extracting the key inflationary parameters of our model such as a spectral index (ns), a tensor-to-scalar ratio (r) and a tensor tilt (nt). It appears thatnsremains the same as in the localR2inflation in the leading slow-roll approximation, whilerandntget modified due to modification of the tensor power spectrum. This class of models allows for any value ofr< 0.07 with a modified consistency relation which can be fixed by future observations of primordialB-modes of the CMB polarization. This makes the UV completeR2gravity a natural target for future CMB probes.
Is Palliative Percutaneous Drainage for Malignant Biliary Obstruction Useful?
Authors: Niemelä Jarmo , Kallio Raija , Ohtonen Pasi , Perälä Jukka , Saarnio Juha , Syrjälä Hannu
Published: March 2018

Background

Malignant biliary obstruction is a challenging problem for cancer patients. Here we evaluate predictive factors for survival following percutaneous drainage for malignant biliary obstruction in patients in whom endoscopic drainage was unsuccessful or insufficient.

Methods

A retrospective register study in a tertiary‐level university hospital.

Results

A total of 643 cancer patients (317 females and 326 males) with malignant biliary obstruction were treated with percutaneous drainage at our hospital between 1999 and 2016. Their median overall survival rate was 2.6 months, with a 95% confidence interval (CI) of 2.2–3.0. Independent factors predicting poor outcome were metastatic cancer, with a hazard ratio (HR) of 2.2 (95% CI 1.8–2.7); Eastern Cooperative Oncology Group performance status (ECOG PS) of 2 (HR 2.3; 95% CI 1.8–2.8); ECOG PS of 3–4 (HR 3.5; 95% CI 2.8–4.4), American Society of Anesthesiologists physical status classification (ASA) of 4 (HR 2.1; 95% CI 1.5–2.9); and bilirubin of ≥60.0 µmol/L within 30 days post‐drainage (HR 1.3; 95% CI 1.1–1.6). During the time periods 1999–2004 and 2005–2010, patients had poorer outcomes (HR 1.4; 95% CI 1.1–1.7 and HR 1.4; 95% CI 1.2–1.8) than during the last period 2011–2016.

Conclusion

Patients with cancer who underwent percutaneous biliary drainage for biliary obstruction had a poor median overall survival. The usefulness of biliary drainage, especially in patients with metastatic cancer, poor ECOG PS, and high ASA class, should be critically considered.
Factors driving adaptive radiation in plants of oceanic islands: a case study from the Juan Fernández Archipelago
Authors: Takayama Koji , Crawford Daniel J. , López-Sepúlveda Patricio , Greimler Josef , Stuessy Tod F.
Published: March 2018

Adaptive radiation is a common evolutionary phenomenon in oceanic islands. From one successful immigrant population, dispersal into different island environments and directional selection can rapidly yield a series of morphologically distinct species, each adapted to its own particular environment. Not all island immigrants, however, follow this evolutionary pathway. Others successfully arrive and establish viable populations, but they remain in the same ecological zone and only slowly diverge over millions of years. This transformational speciation, or anagenesis, is also common in oceanic archipelagos. The critical question is why do some groups radiate adaptively and others not? The Juan Fernández Islands contain 105 endemic taxa of angiosperms, 49% of which have originated by adaptive radiation (cladogenesis) and 51% by anagenesis, hence providing an opportunity to examine characteristics of taxa that have undergone both types of speciation in the same general island environment. Life form, dispersal mode, and total number of species in progenitors (genera) of endemic angiosperms in the archipelago were investigated from literature sources and compared with modes of speciation (cladogenesis vs. anagenesis). It is suggested that immigrants tending to undergo adaptive radiation are herbaceous perennial herbs, with leaky self-incompatible breeding systems, good intra-island dispersal capabilities, and flexible structural and physiological systems. Perhaps more importantly, the progenitors of adaptively radiated groups in islands are those that have already been successful in adaptations to different environments in source areas, and which have also undergone eco-geographic speciation. Evolutionary success via adaptive radiation in oceanic islands, therefore, is less a novel feature of island lineages but rather a continuation of tendency for successful adaptive speciation in lineages of continental source regions.
Characterization of Phase Chemistry and Partitioning in a Family of High-Strength Nickel-Based Superalloys
Authors: Lapington M. T. , Crudden D. J. , Reed R. C. , Moody M. P. , Bagot P. A. J.
Published: March 2018

A family of novel polycrystalline Ni-based superalloys with varying Ti:Nb ratios has been created using computational alloy design techniques, and subsequently characterized using atom probe tomography and electron microscopy. Phase chemistry, elemental partitioning, and γ′ character have been analyzed and compared with thermodynamic predictions created using Thermo-Calc. Phase compositions and γ′ volume fraction were found to compare favorably with the thermodynamically predicted values, while predicted partitioning behavior for Ti, Nb, Cr, and Co tended to overestimate γ′ preference over the γ matrix, often with opposing trends vs Nb concentration.
Ethical dilemmas and reflexivity in qualitative research
Authors: Reid Anne-Marie , Brown Jeremy M. , Smith Julie M. , Cope Alexandra C. , Jamieson Susan
Published: March 2018

Context For medical education researchers, a key concern may be the practicalities of gaining ethical approval where this is a national or local requirement. However, in qualitative studies, where the dynamics of human interaction pervade, ethical considerations are an ongoing process which continues long after approval has been granted. Responding to ethical dilemmas arising ‘in the moment’ requires a reflexive approach whereby the researcher questions his/her own motivations, assumptions and interests. Drawing on empirical studies and their experiences in academic and clinical research practice, the authors share their reflections on adhering to ethical principles throughout the research process to illustrate the complexities and nuances involved.

Objectives and findings These reflections offer critical insights into dilemmas arising in view of the ethical principles driving good conduct, and through domains which distinguish between procedural ethics, situational ethics, ethical relationships and ethical issues in exiting the study. The accounts consider integrity and altruism in research, gatekeeping and negotiating access, consent and confidentiality, power dynamics and role conflict, and challenges in dissemination of findings. The experiences are based on a range of examples of research in a UK context from managing difficult conversations in the classroom to video-ethnography in the operating theatre.

Discussion and conclusions These critical reflections make visible the challenges encountered and decisions that must be taken in the moment and on reflection after the event. Through sharing our experiences and debating the decisions we made, we offer insights into reflexivity in qualitative research which will be of value to others.
Difficult but important questions about the ethics of qualitative research
Authors: Paradis Elise , Varpio Lara
Published: March 2018

None
MARKET SHOCKS IN SALMON AQUACULTURE: THE IMPACT OF THE CHILEAN DISEASE CRISIS
Authors: ASCHE F. , COJOCARU A.L. , SIKVELAND M.
Published: March 2018

Several studies indicate an integrated global market for salmon. However, there is increasing evidence of market segmentation for various seafood species. A disease crisis in Chile that reduced production by two-thirds provides a strong market shock that can shed light on how strongly integrated the salmon market is. Our results indicate that Chilean producers changed the product mix and export markets as a result of the disease shock. Yet, the relative prices remained constant, indicating a high degree of market integration. Moreover, Chilean prices are endogenous to the Norwegian price, indicating that prices are determined at the global market.
A claim in need of ‘special treatment’: compensating for Greek tobacco seized by the German occupation authorities during World War II
Authors: Konstantinakou Despina-Georgia
Published: March 2018

Before World War II, tobacco was the most important Greek export, but just days after the German invasion in April 1941, the occupation authorities rushed to seize the tobacco production. While this article will document the seizure, most importantly, it will take a deeper look at how Greek tobacco producers and traders sought compensation for losses incurred as the result of the confiscation of their tobacco. It will also present how the German and the Greek postwar authorities handled these claims, taking into consideration Greek and German archival sources, which have hitherto been relatively neglected.
Take no care for the morrow! The rejection of landed property in eleventh- and twelfth-century Byzantine monasticism
Authors: Krausmüller Dirk
Published: March 2018

In the eleventh and twelfth centuries Byzantium saw the rise of an influential monastic reform movement, which found its expression in rules and saints' lives. In these texts the question of worldly possessions was repeatedly broached. The authors challenged the hitherto common practice of allowing monks some private property and insisted that in their monasteries nobody should own money or other goods. Yet when it came to communal property the situation was starkly different. Most reformers accepted the traditional view that monasteries should be endowed with land in order to meet the material needs of the communities, and if anything were even more acquisitive than their forebears. There was, however, a small group of monastic founders, which challenged this consensus. They insisted that their monasteries should not accept donations of land because such behaviour went against Christ's demand not to take thought for the morrow and displayed a lack of trust in divine providence. This article presents the surviving evidence and seeks to explain how communities without landed property ensured their survival.
Occupying and transcending a provincial see: the career of Euthymios Malakes
Authors: Ewing Hannah
Published: March 2018

Despite a distinguished reputation as an orator and bishop in his own time, comparatively little scholarship focuses upon Euthymios Malakes, metropolitan of Neopatras during the later twelfth century. Using his extant works and contemporary sources, this article reconstructs elements of Malakes’ career in both Constantinople and Hellas. He was active in each, balancing his intellectual credentials, participation in synods, and elite connections to the capital, with immersion in more local contests. This combination allowed him to expand his pursuits and reputation beyond his minor see, in the capital and also in the province of his see.
Garden of Eden and specification
Authors: LI HANFENG
Published: March 2018

We establish a Garden of Eden theorem for expansive algebraic actions of amenable groups with the weak specification property, i.e. for any continuous equivariant map
$T$
from the underlying space to itself,
$T$
is pre-injective if and only if it is surjective. In particular, this applies to all expansive principal algebraic actions of amenable groups and expansive algebraic actions of
$\mathbb{Z}^{d}$
with completely positive entropy.
Organizational Form and Corporate Payout Policy
Authors: Jordan Bradford D. , Liu Mark H. , Wu Qun
Published: March 2018

We examine how organizational form affects corporate payouts. Conglomerates pay out more than pure plays in both cash dividends and total payouts (cash dividends plus share repurchases). Furthermore, their payouts are more sensitive to cash flows compared to pure-play firms. The sensitivity of payouts to cash flow increases as the cross-segment correlation in a conglomerate decreases. Corporate payouts increase after mergers and acquisitions (M&As), especially among M&As in which acquirers and targets are less correlated. These results suggest that the coinsurance among different divisions of a conglomerate allows them to pay out more cash flow to their shareholders than pure-play firms.
Assessing the effectiveness of a protected area network: a case study of Bhutan
Authors: Lham Dechen , Wangchuk Sonam , Stolton Sue , Dudley Nigel
Published: March 2018

An assessment of management effectiveness was carried out for all the protected areas in the Kingdom of Bhutan. During 2014–2016 the Royal Government of Bhutan developed a custom-made tool for assessing management effectiveness: the Bhutan Management Effectiveness Tracking Tool Plus (Bhutan METT +). This was implemented in Bhutan's 10 protected areas and one botanical park, and the results were verified through field trips and expert reviews. The assessment indicates that protected areas in Bhutan are well managed and there are generally good relationships with local communities, despite an increase in livestock predation and crop damage. However, effectiveness is limited by a low level of resources (both financial and appropriate technical resources) and by gaps in monitoring and research data, which limits the ability to understand the impact of conservation, react to changing conditions and undertake adaptive management to improve efficiency and effectiveness. Bhutan is in the midst of mobilizing considerable conservation funding. The Government is working in partnership with WWF to create an innovative funding mechanism for the protected area system: the Bhutan for Life initiative. The Bhutan METT + study provides an example of how to develop a baseline against which to measure the effectiveness of protected areas over time and assess the impact of conservation inputs.
Overlap of heritable influences between cannabis use disorder, frequency of use and opportunity to use cannabis: trivariate twin modelling and implications for genetic design
Authors: Hines Lindsey A. , Morley Katherine I. , Rijsdijk Fruhling , Strang John , Agrawal Arpana , Nelson Elliot C. , Statham Dixie , Martin Nicholas G. , Lynskey Michael T.
Published: March 2018

Background

The genetic component of Cannabis Use Disorder may overlap with influences acting more generally on early stages of cannabis use. This paper aims to determine the extent to which genetic influences on the development of cannabis abuse/dependence are correlated with those acting on the opportunity to use cannabis and frequency of use.

Methods

A cross-sectional study of 3303 Australian twins, measuring age of onset of cannabis use opportunity, lifetime frequency of cannabis use, and lifetime DSM-IV cannabis abuse/dependence. A trivariate Cholesky decomposition estimated additive genetic (A), shared environment (C) and unique environment (E) contributions to the opportunity to use cannabis, the frequency of cannabis use, cannabis abuse/dependence, and the extent of overlap between genetic and environmental factors associated with each phenotype.

Results

Variance components estimates were A = 0.64 [95% confidence interval (CI) 0.58–0.70] and E = 0.36 (95% CI 0.29–0.42) for age of opportunity to use cannabis, A = 0.74 (95% CI 0.66–0.80) and E = 0.26 (95% CI 0.20–0.34) for cannabis use frequency, and A = 0.78 (95% CI 0.65–0.88) and E = 0.22 (95% CI 0.12–0.35) for cannabis abuse/dependence. Opportunity shares 45% of genetic influences with the frequency of use, and only 17% of additive genetic influences are unique to abuse/dependence from those acting on opportunity and frequency.

Conclusions

There are significant genetic contributions to lifetime cannabis abuse/dependence, but a large proportion of this overlaps with influences acting on opportunity and frequency of use. Individuals without drug use opportunity are uninformative, and studies of drug use disorders must incorporate individual exposure to accurately identify aetiology.
The Nature of Nurture: Using a Virtual-Parent Design to Test Parenting Effects on Children's Educational Attainment in Genotyped Families
Authors: Bates Timothy C. , Maher Brion S. , Medland Sarah E. , McAloney Kerrie , Wright Margaret J. , Hansell Narelle K. , Kendler Kenneth S. , Martin Nicholas G. , Gillespie Nathan A.
Published: March 2018

Research on environmental and genetic pathways to complex traits such as educational attainment (EA) is confounded by uncertainty over whether correlations reflect effects of transmitted parental genes, causal family environments, or some, possibly interactive, mixture of both. Thus, an aggregate of thousands of alleles associated with EA (a polygenic risk score; PRS) may tap parental behaviors and home environments promoting EA in the offspring. New methods for unpicking and determining these causal pathways are required. Here, we utilize the fact that parents pass, at random, 50% of their genome to a given offspring to create independent scores for the transmitted alleles (conventional EA PRS) and a parental score based on allelesnot transmittedto the offspring (EA VP_PRS). The formal effect of non-transmitted alleles on offspring attainment was tested in 2,333 genotyped twins for whom high-quality measures of EA, assessed at age 17 years, were available, and whose parents were also genotyped. Four key findings were observed. First, the EA PRS and EA VP_PRS were empirically independent, validating the virtual-parent design. Second, in this family-based design, children's own EA PRS significantly predicted their EA (β = 0.15), ruling out stratification confounds as a cause of the association of attainment with the EA PRS. Third, parental EA PRS predicted the SES environment parents provided to offspring (β = 0.20), and parental SES and offspring EA were significantly associated (β = 0.33). This would suggest that the EA PRS is at least as strongly linked to social competence as it is to EA, leading to higher attained SES in parents and, therefore, a higher experienced SES for children. In a full structural equation model taking account of family genetic relatedness across multiple siblings the non-transmitted allele effects were estimated at similar values; but, in this more complex model, confidence intervals included zero. A test using the forthcoming EA3 PRS may clarify this outcome. The virtual-parent method may be applied to clarify causality in other phenotypes where observational evidence suggests parenting may moderate expression of other outcomes, for instance in psychiatry.
Meridional heat transport variability induced by mesoscale processes in the subpolar North Atlantic
Authors: Zhao Jian , Bower Amy , Yang Jiayan , Lin Xiaopei , Penny Holliday N.
Published: March 2018

The ocean’s role in global climate change largely depends on its heat transport. Therefore, understanding the oceanic meridional heat transport (MHT) variability is a fundamental issue. Prevailing observational and modeling evidence suggests that MHT variability is primarily determined by the large-scale ocean circulation. Here, using new in situ observations in the eastern subpolar North Atlantic Ocean and an eddy-resolving numerical model, we show that energetic mesoscale eddies with horizontal scales of about 10–100 km profoundly modulate MHT variability on time scales from intra-seasonal to interannual. Our results reveal that the velocity changes due to mesoscale processes produce substantial variability for the MHT regionally (within sub-basins) and the subpolar North Atlantic as a whole. The findings have important implications for understanding the mechanisms for poleward heat transport variability in the subpolar North Atlantic Ocean, a key region for heat and carbon sequestration, ice–ocean interaction, and biological productivity.
CtIP fusion to Cas9 enhances transgene integration by homology-dependent repair
Authors: Charpentier M. , Khedher A. H. Y. , Menoret S. , Brion A. , Lamribet K. , Dardillac E. , Boix C. , Perrouault L. , Tesson L. , Geny S. , De Cian A. , Itier J. M. , Anegon I. , Lopez B. , Giovannangeli C. , Concordet J. P.
Published: March 2018

In genome editing with CRISPR–Cas9, transgene integration often remains challenging. Here, we present an approach for increasing the efficiency of transgene integration by homology-dependent repair (HDR). CtIP, a key protein in early steps of homologous recombination, is fused to Cas9 and stimulates transgene integration by HDR at the human AAVS1 safe harbor locus. A minimal N-terminal fragment of CtIP, designated HE for HDR enhancer, is sufficient to stimulate HDR and this depends on CDK phosphorylation sites and the multimerization domain essential for CtIP activity in homologous recombination. HDR stimulation by Cas9–HE, however, depends on the guide RNA used, a limitation that may be overcome by testing multiple guides to the locus of interest. The Cas9–HE fusion is simple to use and allows obtaining twofold or more efficient transgene integration than that with Cas9 in several experimental systems, including human cell lines, iPS cells, and rat zygotes.
An evolutionary hotspot defines functional differences between CRYPTOCHROMES
Authors: Rosensweig Clark , Reynolds Kimberly A. , Gao Peng , Laothamatas Isara , Shan Yongli , Ranganathan Rama , Takahashi Joseph S. , Green Carla B.
Published: March 2018

Mammalian circadian clocks are driven by a transcription/translation feedback loop composed of positive regulators (CLOCK/BMAL1) and repressors (CRYPTOCHROME 1/2 (CRY1/2) and PER1/2). To understand the structural principles of regulation, we used evolutionary sequence analysis to identify co-evolving residues within the CRY/PHL protein family. Here we report the identification of an ancestral secondary cofactor-binding pocket as an interface in repressive CRYs, mediating regulation through direct interaction with CLOCK and BMAL1. Mutations weakening binding between CLOCK/BMAL1 and CRY1 lead to acceleration of the clock, suggesting that subtle sequence divergences at this site can modulate clock function. Divergence between CRY1 and CRY2 at this site results in distinct periodic output. Weaker interactions between CRY2 and CLOCK/BMAL1 at this pocket are strengthened by co-expression of PER2, suggesting that PER expression limits the length of the repressive phase in CRY2-driven rhythms. Overall, this work provides a model for the mechanism and evolutionary variation of clock regulatory mechanisms.
Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus
Authors: Gonzalez Malagon Sandra G. , Lopez Muñoz Anna M. , Doro Daniel , Bolger Triòna G. , Poon Evon , Tucker Elizabeth R. , Adel Al-Lami Hadeel , Krause Matthias , Phiel Christopher J. , Chesler Louis , Liu Karen J.
Published: March 2018

Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest inXenopusand mouse models. We demonstrate that GSK3 is tyrosine phosphorylated (pY) in mouse neural crest cells and that loss of GSK3 leads to increased pFAK and misregulation of Rac1 and lamellipodin, key regulators of cell migration. Genetic reduction of GSK3 results in failure of migration. We find that pY-GSK3 phosphorylation depends on anaplastic lymphoma kinase (ALK), a protein associated with neuroblastoma. Consistent with this, neuroblastoma cells with increased ALK activity express high levels of pY-GSK3, and blockade of GSK3 or ALK can affect migration of these cells. Altogether, this work identifies a role for GSK3 in cell migration during neural crest development and cancer.
Nitrogen-rich organic soils under warm well-drained conditions are global nitrous oxide emission hotspots
Authors: Pärn Jaan , Verhoeven Jos T. A. , Butterbach-Bahl Klaus , Dise Nancy B. , Ullah Sami , Aasa Anto , Egorov Sergey , Espenberg Mikk , Järveoja Järvi , Jauhiainen Jyrki , Kasak Kuno , Klemedtsson Leif , Kull Ain , Laggoun-Défarge Fatima , Lapshina Elena D. , Lohila Annalea , Lõhmus Krista , Maddison Martin , Mitsch William J. , Müller Christoph , Niinemets Ülo , Osborne Bruce , Pae Taavi , Salm Jüri-Ott , Sgouridis Fotis , Sohar Kristina , Soosaar Kaido , Storey Kathryn , Teemusk Alar , Tenywa Moses M. , Tournebize Julien , Truu Jaak , Veber Gert , Villa Jorge A. , Zaw Seint Sann , Mander Ülo
Published: March 2018

Nitrous oxide (N2O) is a powerful greenhouse gas and the main driver of stratospheric ozone depletion. Since soils are the largest source of N2O, predicting soil response to changes in climate or land use is central to understanding and managing N2O. Here we find that N2O flux can be predicted by models incorporating soil nitrate concentration (NO3−), water content and temperature using a global field survey of N2O emissions and potential driving factors across a wide range of organic soils. N2O emissions increase with NO3− and follow a bell-shaped distribution with water content. Combining the two functions explains 72% of N2O emission from all organic soils. Above 5 mg NO3−-N kg−1, either draining wet soils or irrigating well-drained soils increases N2O emission by orders of magnitude. As soil temperature together with NO3− explains 69% of N2O emission, tropical wetlands should be a priority for N2O management.
The MerR-like protein BldC binds DNA direct repeats as cooperative multimers to regulate Streptomyces development
Authors: Schumacher Maria A. , den Hengst Chris D. , Bush Matthew J. , Le T. B. K. , Tran Ngat T. , Chandra Govind , Zeng Wenjie , Travis Brady , Brennan Richard G. , Buttner Mark J.
Published: March 2018

Streptomycetes are notable for their complex life cycle and production of most clinically important antibiotics. A key factor that controls entry into development and the onset of antibiotic production is the 68-residue protein, BldC. BldC is a putative DNA-binding protein related to MerR regulators, but lacks coiled-coil dimerization and effector-binding domains characteristic of classical MerR proteins. Hence, the molecular function of the protein has been unclear. Here we show that BldC is indeed a DNA-binding protein and controls a regulon that includes other key developmental regulators. Intriguingly, BldC DNA-binding sites vary significantly in length. Our BldC-DNA structures explain this DNA-binding capability by revealing that BldC utilizes a DNA-binding mode distinct from MerR and other known regulators, involving asymmetric head-to-tail oligomerization on DNA direct repeats that results in dramatic DNA distortion. Notably, BldC-like proteins radiate throughout eubacteria, establishing BldC as the founding member of a new structural family of regulators.
Spatially heterogeneous dynamics in a metallic glass forming liquid imaged by electron correlation microscopy
Authors: Zhang Pei , Maldonis Jason J. , Liu Ze , Schroers Jan , Voyles Paul M.
Published: March 2018

Supercooled liquids exhibit spatial heterogeneity in the dynamics of their fluctuating atomic arrangements. The length and time scales of the heterogeneous dynamics are central to the glass transition and influence nucleation and growth of crystals from the liquid. Here, we report direct experimental visualization of the spatially heterogeneous dynamics as a function of temperature in the supercooled liquid state of a Pt-based metallic glass, using electron correlation microscopy with sub-nanometer resolution. An experimental four-point space-time correlation function demonstrates a growing dynamic correlation length, ξ, upon cooling of the liquid toward the glass transition temperature. ξ as a function of the relaxation time τ are in good agreement with Adam-Gibbs theory, inhomogeneous mode-coupling theory and random first-order transition theory of the glass transition. The same experiments demonstrate the existence of a nanometer thickness near-surface layer with order of magnitude shorter relaxation time than inside the bulk.
Author Correction: Liquid crystal elastomer coatings with programmed response of surface profile
Authors: Babakhanova Greta , Turiv Taras , Guo Yubing , Hendrikx Matthew , Wei Qi-Huo , Schenning Albert P. H. J. , Broer Dirk J. , Lavrentovich Oleg D.
Published: March 2018

The original version of this Article contained errors in Figs. 1a, 2a, 3a, and 4b, in which the units on the scale bars incorrectly read ‘µm’ rather than the correct ‘nm.’ This has been corrected in both the PDF and HTML versions of the Article.
Carbon dioxide sequestration through silicate degradation and carbon mineralisation: promises and uncertainties
Authors: Daval Damien
Published: March 2018

Turning carbon dioxide (CO2) into rocks: controlling this process, which naturally operates at the Earth’s surface over geological timescales, is likely to represent a major technological challenge of this century. One of the recurring criticisms with the carbonation reactions is their sluggishness, as it is commonly admitted that converting silicates into carbonates within geologic reservoirs may take up to several thousands of years, i.e., a duration which is hardly compatible with the goal of achieving net zero emissions by mid-century. Last year, a study that generated substantial interest suggested that after 2 years, more than 95% of the CO2 injected over the course of a pilot project of CO2 injection in lava flows in Iceland might have been mineralised into carbonates. While such results could have been considered as a green light for industrial applications, a new high-profile study based on the same pilot experiment tempered this idea, as it revealed unexpected modifications of deep ecosystems in response to CO2 injection, evidencing a bloom of chemolithoautotrophic bacteria, which have the ability to promote autotrophic C-fixation. Stated in other words, part of the CO2 that was initially thought to be mineralised under the form of stable carbonates might instead have been converted into (much more labile) biomass. Assessing the respective contributions of carbonates and biomass to the C-sequestration should therefore represent a prerequisite prior to large-scale carbon capture and storage through mineral carbonation, to make sure that the cure is not worse than the disease.
Impact of directionality and correlation on contagion
Authors: Xu Xin-Jian , Li Jia-Yan , Fu Xinchu , Zhang Li-Jie
Published: March 2018

The threshold model has been widely adopted for modelling contagion processes on social networks, where individuals are assumed to be in one of two states: inactive or active. This paper studies the model on directed networks where nodal inand out-degrees may be correlated. To understand how directionality and correlation affect the breakdown of the system, a theoretical framework based on generating function technology is developed. First, the effects of degree and threshold heterogeneities are identified. It is found that both heterogeneities always decrease systematic robustness. Then, the impact of the correlation between nodal in- and out-degrees is investigated. It turns out that the positive correlation increases the systematic robustness in a wide range of the average in-degree, while the negative correlation has an opposite effect. Finally, a comparison between undirected and directed networks shows that the presence of directionality and correlation always make the system more vulnerable.
Longitudinal demographic study of wild populations of African annual killifish
Authors: Vrtílek Milan , Žák Jakub , Polačik Matej , Blažek Radim , Reichard Martin
Published: March 2018

The natural history of model organisms is often overlooked despite its importance to correctly interpret the outcome of laboratory studies. Ageing is particularly understudied in natural populations. To address this gap, we present lifetime demographic data from wild populations of an annual species, the turquoise killifish,Nothobranchius furzeri, a model species in ageing research, and two other species of coexisting annual killifishes. Annual killifish hatch synchronously, have non-overlapping generations, and reproduce daily after reaching sexual maturity. Data from 13 isolated savanna pools in southern Mozambique demonstrate that the pools supporting killifish populations desiccated 1–4 months after their filling, though some pools persisted longer. Declines in population size over the season were stronger than predicted, because they exceeded the effect of steady habitat shrinking on population density that, contrary to the prediction, decreased. Populations ofN. furzerialso became more female-biased with progressing season suggesting that males had lower survival.Nothobranchiuscommunity composition did not significantly vary across the season. Our data clearly demonstrate that natural populations ofN. furzeriand its congeners suffer strong mortality throughout their lives, with apparent selective disappearance (condition-dependent mortality) at the individual level. This represents selective force that can shape the evolution of lifespan, and its variation across populations, beyond the effects of the gradient in habitat persistence.
Successful knock-in of Hypertrophic Cardiomyopathy-mutation R723G into the MYH7 gene mimics HCM pathology in pigs
Authors: Montag J. , Petersen B. , Flögel A. K. , Becker E. , Lucas-Hahn A. , Cost G. J. , Mühlfeld C. , Kraft T. , Niemann H. , Brenner B.
Published: March 2018

Familial Hypertrophic Cardiomyopathy (HCM) is the most common inherited cardiac disease. About 30% of the patients are heterozygous for mutations in the MYH7 gene encoding the ß-myosin heavy chain (MyHC). Hallmarks of HCM are cardiomyocyte disarray and hypertrophy of the left ventricle, the symptoms range from slight arrhythmias to sudden cardiac death or heart failure. To gain insight into the underlying mechanisms of the diseases’ etiology we aimed to generate genome edited pigs with an HCM-mutation. We used TALEN-mediated genome editing and successfully introduced the HCM-point mutation R723G into the MYH7 gene of porcine fibroblasts and subsequently cloned pigs that were heterozygous for the HCM-mutation R723G. No off-target effects were determined in the R723G-pigs. Surprisingly, the animals died within 24 h post partem, probably due to heart failure as indicated by a shift in the a/ß-MyHC ratio in the left ventricle. Most interestingly, the neonatal pigs displayed features of HCM, including mild myocyte disarray, malformed nuclei, and MYH7-overexpression. The finding of HCM-specific pathology in neonatal R723G-piglets suggests a very early onset of the disease and highlights the importance of novel large animal models for studying causative mechanisms and long-term progression of human cardiac diseases.
Photoresponse of graphene field-effect-transistor with n-type Si depletion layer gate
Authors: Kobayashi Shiho , Anno Yuki , Takei Kuniharu , Arie Takayuki , Akita Seiji
Published: March 2018

Graphene/semiconductor Schottky junctions are an emerging field for high-performance optoelectronic devices. This study investigates not only the steady state but also the transient photoresponse of graphene field-effect transistor (G-FET) of which gate bias is applied through the Schottky barrier formed at an n-type Si/graphene interface with a thin oxide layer, where the oxide thickness is sufficiently thin for tunneling of the charge carrier. To analyze the photoresponse, we formulate the charge accumulation process at the n-Si/graphene interface, where the tunneling process through the SiOx layer to graphene occurs along with recombination of the accumulated holes and the electrons in the graphene at the surface states on the SiOx layer. Numerical calculations show good qualitative agreement with the experimentally obtained results for the photoresponse of G-FET.
Analysis of the neurotoxic effects of neuropathic organophosphorus compounds in adult zebrafish
Authors: Faria Melissa , Fuertes Inmaculada , Prats Eva , Abad Jose Luis , Padrós Francesc , Gomez-Canela Cristian , Casas Josefina , Estevez Jorge , Vilanova Eugenio , Piña Benjamin , Raldúa Demetrio
Published: March 2018

Inhibition and aging of neuropathy target esterase (NTE) by exposure to neuropathic organophosphorus compounds (OPs) can result in OP-induced delayed neuropathy (OPIDN). In the present study we aimed to build a model of OPIDN in adult zebrafish. First, inhibition and aging of zebrafish NTE activity were characterized in the brain by using the prototypic neuropathic compounds cresyl saligenin phosphate (CBDP) and diisopropylphosphorofluoridate (DFP). Our results show that, as in other animal models, zebrafish NTE is inhibited and aged by both neuropathic OPs. Then, a neuropathic concentration inhibiting NTE activity by at least 70% for at least 24 h was selected for each compound to analyze changes in phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs) and glycerolphosphocholine (GPC) profiles. In spite to the strong inhibition of the NTE activity found for both compounds, only a mild increase in the LPCs level was found after 48 h of the exposure to DFP, and no effect were observed by CBDP. Moreover, histopathological evaluation and motor function outcome analyses failed to find any neurological abnormalities in the exposed fish. Thus, our results strongly suggest that zebrafish is not a suitable species for the development of an experimental model of human OPIDN.
Author Correction: Anion-conducting channelrhodopsins with tuned spectra and modified kinetics engineered for optogenetic manipulation of behavior
Authors: Wietek Jonas , Rodriguez-Rozada Silvia , Tutas Janine , Tenedini Federico , Grimm Christiane , Oertner Thomas G. , Soba Peter , Hegemann Peter , Wiegert J. Simon
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Experimental infection of Cynomolgus Macaques with highly pathogenic H5N1 influenza virus through the aerosol route
Authors: Watanabe Tokiko , Iwatsuki-Horimoto Kiyoko , Kiso Maki , Nakajima Noriko , Takahashi Kenta , Jose da Silva Lopes Tiago , Ito Mutsumi , Fukuyama Satoshi , Hasegawa Hideki , Kawaoka Yoshihiro
Published: March 2018

Several animal models are used to study influenza viruses. Intranasal inoculation of animals with a liquid inoculum is one of the main methods used to experimentally infect animals with influenza virus; however, this method does not reflect the natural infection with influenza virus by contact or aerosol route. Aerosol inhalation methods have been established with several influenza viruses for mouse and ferret models, but few studies have evaluated inoculation routes in a nonhuman primates (NHP) model. Here, we performed the experimental infection of NHPs with a highly pathogenic H5N1 influenza virus via the aerosol route and demonstrated that aerosol infection had no effect on clinical outcome, but caused broader infection throughout all of the lobes of the lung compared with a non-aerosolized approach. Aerosol infection therefore represents an option for inoculation of NHPs in future studies.
Improvement of the transient expression system for production of recombinant proteins in plants
Authors: Yamamoto Tsuyoshi , Hoshikawa Ken , Ezura Kentaro , Okazawa Risa , Fujita Satoshi , Takaoka Miyo , Mason Hugh S. , Ezura Hiroshi , Miura Kenji
Published: March 2018

An efficient and high yielding expression system is required to produce recombinant proteins. Furthermore, the transient expression system can be used to identify the localization of proteins in plant cells. In this study, we demonstrated that combination of a geminiviral replication and a double terminator dramatically enhanced the transient protein expression level in plants. The GFP protein was expressed transiently in lettuce, Nicotiana benthamiana, tomatoes, eggplants, hot peppers, melons, and orchids with agroinfiltration. Compared to a single terminator, a double terminator enhanced the expression level. A heat shock protein terminator combined with an extensin terminator resulted in the highest protein expression. Transiently expressed GFP was confirmed by immunoblot analysis with anti-GFP antibodies. Quantitative analysis revealed that the geminiviral vector with a double terminator resulted in the expression of at least 3.7 mg/g fresh weight of GFP in Nicotiana benthamiana, approximately 2-fold that of the geminiviral vector with a single terminator. These results indicated that combination of the geminiviral replication and a double terminator is a useful tool for transient expression of the gene of interest in plant cells.