bluuebunny/crossref_metadata_2025 huggingface dataset:
Peroxydisulfate as an Oxidant in the Site‐Selective Functionalization of sp3 C–H Bonds
Authors: Sathyamoorthi Shyam , Banerjee Shibdas
Published: November 2017

The development of methodology for the site‐selective functionalization of sp3 C–H bonds has irrevocably altered the state of organic synthesis. These methods often rely on the use of strong oxidants in conjunction with transition‐metal catalysis. Peroxydisulfate (S2O82–) salts are some of the strongest inorganic oxidants known. They are low‐cost crystalline solids that are stable at room temperature. Harmless sulfate salts are produced as a byproduct of their reactions, allowing S2O82– to serve as a ‘green’ alternative to other commonly employed oxidants. Despite these attractive properties, it has only been in the last ten years that the majority of sp3 C–H functionalization reactions utilizing S2O82– for the diversification of complex molecules have been reported. The objective of this review is to provide a useful reference regarding the recent advancement of sp3 C–H functionalization using S2O82– and to inspire the invention of new protocols utilizing this remarkable oxidant.
Tetranuclear Polypyridylruthenium(II) Complexes as Inhibitors and Down‐Regulators of Phosphatase Enzymes
Authors: Sundaraneedi Madhu K. , Ammit Alaina J. , Tedla Bemnet A. , Pearson Mark S. , Loukas Alex , Keene F. Richard , Collins J. Grant
Published: November 2017

Mitogen‐activated protein kinase phosphatases (MKPs) are over‐expressed in many cancers. The increased levels of MKP enzymes protect cells from apoptosis induced by anticancer drugs, and thereby decrease the efficacy of the drug. Consequently, there is considerable interest in the development of agents that can down‐regulate the production of the MKP enzymes or inhibit their catalytic activities. We have examined the ability of a series of oligonuclear polypyridylruthenium(II) complexes to inhibit the activity of MKP‐1 and MKP‐3. The results demonstrated that two tetranuclear complexes inhibit the activity of MKP‐1 and MKP‐3 at 10‐20 μM concentrations. The ability of the ruthenium complexes to inhibit the production of MKP‐1 in live cancer cells was demonstrated through Western blotting assays, while real‐time reverse transcription polymerase chain reaction assays demonstrated the tetranuclear complexes decreased the amount of mkp‐1 mRNA produced in cancer cells. The results of this study suggest that tetranuclear ruthenium complexes could be used to enhance the antiproliferative effect of anticancer drugs.
Defects and Interfaces on PtPb Nanoplates Boost Fuel Cell Electrocatalysis
Authors: Sun Yingjun , Liang Yanxia , Luo Mingchuan , Lv Fan , Qin Yingnan , Wang Lei , Xu Chuan , Fu Engang , Guo Shaojun
Published: November 2017

Nanostructured Pt is the most efficient single‐metal catalyst for fuel cell technology. Great efforts have been devoted to optimizing the Pt‐based alloy nanocrystals with desired structure, composition, and shape for boosting the electrocatalytic activity. However, these well‐known controls still show the limited ability in maximizing the Pt utilization efficiency for achieving more efficient fuel cell catalysis. Herein, a new strategy for maximizing the fuel cell catalysis by controlling/tuning the defects and interfaces of PtPb nanoplates using ion irradiation technique is reported. The defects and interfaces on PtPb nanoplates, controlled by the fluence of incident C+ ions, make them exhibit the volcano‐like electrocatalytic activity for methanol oxidation reaction (MOR), ethanol oxidation reaction (EOR), and oxygen reduction reaction (ORR) as a function of ion irradiation fluence. The optimized PtPb nanoplates with the mixed structure of dislocations, subgrain boundaries, and small amorphous domains are the most active for MOR, EOR, and ORR. They can also maintain high catalytic stability in acid solution. This work highlights the impact and significance of inducing/controlling the defects and interfaces on Pt‐based nanocrystals toward maximizing the catalytic performance by advanced ion irradiation strategy.
Strength and post‐yield behavior of T‐section steel encased by structural concrete
Authors: Nzabonimpa J.D. , Hong Won‐Kee , Kim Jisoon
Published: November 2017

In this study, the seismic performance of unsymmetrical steel–concrete composite precast beams with T‐shaped steel section were numerically explored and validated by their earlier experimental investigation. This design is based on the proposed calibrated finite element model in which key damage parameters for the evaluation of the nonlinear, post‐yield behavior of the precast composite steel beams were identified. The proposed nonlinear finite‐element‐based numerical model uses various parameters, including the dilatation angle and concrete‐damaged plasticity, to simulate the nonlinear behavior of unsymmetrical composite precast beams with T‐section steel. Greater seismic capacity with greater ductility, contributing to a maximized structural capacity within the composite precast beams was introduced by the effective use of the 2 materials, steel and concrete, and shown by the nonlinear hysteretic investigation of unsymmetrical steel–concrete composite precast beams that was validated experimentally. The post‐yield structural capacity found via the numerical analysis agrees with experimental results when the concrete‐damaged plasticity of the plastic‐damaged seismic model for concrete and the von Mises criteria of the steel section were introduced into the finite element model. Practical design parameters and recommendations were eventually suggested by examining the influence of precast composite beams with unsymmetrical steel sections on the concrete degradations and damage evolution.
Constrained mean‐variance mapping optimization for truss optimization problems
Authors: Aslani Mohamad , Ghasemi Parnian , Gandomi Amir H.
Published: November 2017

Truss optimization is a complex structural problem that involves geometric and mechanical constraints. In the present study, constrained mean‐variance mapping optimization (MVMO) algorithms have been introduced for solving truss optimization problems. Single‐solution and population‐based variants of MVMO are coupled with an adaptive exterior penalty scheme to handle geometric and mechanical constraints. These tools are explained and tuned for weight minimization of trusses with 10 to 200 members and up to 1,200 nonlinear constraints. The results are compared with those obtained from the literature and classical genetic algorithm. The results show that a MVMO algorithm has a rapid rate of convergence and its final solution can obviously outperform those of other algorithms described in the literature. The observed results suggest that a constrained MVMO is an attractive tool for engineering‐based optimization, particularly for computationally expensive problems in which the rate of convergence and global convergence are important.
Analytical estimation of lateral resistance of low‐shear strength masonry infilled reinforced concrete frames with openings
Authors: Mansouri Ali , Marefat Mohammad Sadegh , Khanmohammadi Mohammad
Published: November 2017

Presence of openings in an infill wall alters its behavior and reduces load resistance and stiffness of the infilled frame. In this paper, a simple method for estimating the lateral resistance of infilled frames with openings is proposed based on experimental data. Six half‐scale, single‐story single‐bay reinforced concrete frame specimens were tested under in‐plane lateral loading. The lateral strength of reinforced concrete (RC) frame could be estimated by assuming the formation of plastic hinges in the end regions of the members. In the specimens with central openings, the major load resistance mechanism of the infill panel was the formation of a compression strut and lateral strength of infill panel could be considered as the smallest values of the diagonal tension and corner crushing modes. In the specimens with eccentric openings, the load resistance mechanism of masonry infill was the formation of a compression strut and bed‐joint sliding in 2 opposite loading directions; thus, the lateral resistance of infill panel could be estimated in diagonal tension and corner crushing modes in one direction and bed‐joint sliding mode in another direction. Furthermore, the deformation capacity and structural performance levels are suggested for solid and perforated infill panels based on test observations.
Developing TESOL teacher intercultural identity: An intercultural communication competence approach
Authors: Yang Ping
Published: November 2017

This article conceptually examines TESOL teacher intercultural identity development in the Australian multicultural context. Using intercultural communication competence theory, the author discusses how TESOL teacher intercultural identity is developed and transformed in action and across languages and cultures. The in‐progress formation of TESOL teacher intercultural identity is discussed from three perspectives. First, TESOL teachers must have second language knowledge and demonstrate ability to manage intercultural verbal communicative skills and styles. Second, they need to have more than one set of body languages and demonstrate ability to manage intercultural nonverbal communicative style and sensitivity. Third, they are engaged in social co‐construction of intercultural identity through teacher–stakeholder interaction, having positive impact on themselves and on their students, particularly those with a refugee background. The author also proposes three strategies for TESOL teacher intercultural identity development and points out the future research on its potential contributing and/or interfering factors.
Continuous-spin field propagator and interaction with matter
Authors: Bekaert Xavier , Mourad Jihad , Najafizadeh Mojtaba
Published: November 2017

Abstract

Action principles for the single and double valued continuous-spin representations of the Poincaré group have been recently proposed in a Segal-like formulation. We address three related issues: first, we explain how to obtain these actions directly from the Fronsdal-like and Fang-Fronsdal-like equations by solving the traceless constraints in Fourier space. Second, we introduce a current, similar to the one of Berends, Burgers and Van Dam, which is bilinear in a pair of scalar matter fields, to which the bosonic continuous-spin field can couple minimally. Third, we investigate the current exchange mediated by a continuous-spin particle obtained from this action principle and investigate whether it propagates the right degrees of freedom, and whether it reproduces the known result for massless higher-spin fields in the helicity limit.
Quiver theories and formulae for nilpotent orbits of Exceptional algebras
Authors: Hanany Amihay , Kalveks Rudolph
Published: November 2017

Abstract

We treat the topic of the closures of the nilpotent orbits of the Lie algebras of Exceptional groups through their descriptions as moduli spaces, in terms of Hilbert series and the highest weight generating functions for their representation content. We extend the set of known Coulomb branch quiver theory constructions for Exceptional group minimal nilpotent orbits, or reduced single instanton moduli spaces, to include all orbits of Characteristic Height 2, drawing on extended Dynkin diagrams and the unitary monopole formula. We also present a representation theoretic formula, based on localisation methods, for the normal nilpotent orbits of the Lie algebras of any Classical or Exceptional group. We analyse lower dimensioned Exceptional group nilpotent orbits in terms of Hilbert series and the Highest Weight Generating functions for their decompositions into characters of irreducible representations and/or Hall Littlewood polynomials. We investigate the relationships between the moduli spaces describing different nilpotent orbits and propose candidates for the constructions of some non-normal nilpotent orbits of Exceptional algebras.
Thermodynamics with pressure and volume under charged particle absorption
Authors: Gwak Bogeun
Published: November 2017

Abstract

We investigate the variation of the charged anti-de Sitter black hole under charged particle absorption by considering thermodynamic volume. When the energy of the particle is considered to contribute to the internal energy of the black hole, the variation exactly corresponds to the prediction of the first law of thermodynamics. Nevertheless, we find the decrease of the Bekenstein-Hawking entropy for extremal and near-extremal black holes under the absorption, which is an irreversible process. This violation of the second law of thermodynamics is only found when considering thermodynamic volume. We test the weak cosmic censorship conjecture affected by the violation. Fortunately, the conjecture is still valid, but extremal and near-extremal black holes do not change their configurations when any particle enters the black hole. This result is quite different from the case in which thermodynamic volume is not considered.
Pauli-Lubanski limit and stress-energy tensor for infinite-spin fields
Authors: Rehren Karl-Henning
Published: November 2017

Abstract

String-localized quantum fields transforming in Wigner’s infinite-spin representations were originally introduced in [18, 19]. We construct these fields as limits of fields of finite massm→ 0 and finite spins→ ∞. We determine a string-localized infinite-spin quantum stress-energy tensor with a novel prescription that does not refer to a classical Lagrangean.
Robustness of dark matter constraints and interplay with collider searches for New Physics
Authors: Arbey A. , Boudaud M. , Mahmoudi F. , Robbins G.
Published: November 2017

Abstract

We study the implications of dark matter searches, together with collider constraints, on the phenomenological MSSM with neutralino dark matter and focus on the consequences of the related uncertainties in some detail. We consider, inter alia, the latest results from AMS-02, Fermi-LAT and XENON1T. In particular, we examine the impact of the choice of the dark matter halo profile, as well as the propagation model for cosmic rays, for dark matter indirect detection and show that the constraints on the MSSM differ by one to two orders of magnitude depending on the astrophysical hypotheses. On the other hand, our limited knowledge of the local relic density in the vicinity of the Earth and the velocity of Earth in the dark matter halo leads to a factor 3 in the exclusion limits obtained by direct detection experiments. We identified the astrophysical models leading to the most conservative and the most stringent constraints and for each case studied the complementarities with the latest LHC measurements and limits from Higgs, SUSY and monojet searches. We show that combining all data from dark matter searches and colliders, a large fraction of our supersymmetric sample could be probed. Whereas the direct detection constraints are rather robust under the astrophysical assumptions, the uncertainties related to indirect detection can have an important impact on the number of the excluded points.
Hypoxia Increases Thyroid Cancer Stem Cell‐Enriched Side Population
Authors: Mahkamova K. , Latar N. , Aspinall S. , Meeson A.
Published: November 2017

Introduction

Hypoxic stress is a feature of rapidly growing thyroid tumours. Cancer progression is thought to be driven by a small population of tumour cells possessing stem cell properties. Hypoxia‐inducible factors (HIFs) are important mediators of hypoxia. Both HIF‐1alpha and HIF‐2alpha have been reported to be expressed in thyroid cancers. There is growing evidence that the HIF pathway plays a significant role in the maintenance of thyroid cancer stem cells (CSC).

Methodology

We have isolated thyroid CSC from a papillary thyroid cancer‐derived cell line (BCPAP) and an anaplastic thyroid cancer‐derived cell line (SW1736) as side population (SP) cells (a putative stem cell population) and treated them with cobalt chloride (II) to induce hypoxia.

Results and discussion

We observed an increase in the SP of cells within the thyroid cancer cell lines following induction of hypoxia.
Making Sense of SNPs: Women's Understanding and Experiences of Receiving a Personalized Profile of Their Breast Cancer Risks
Authors: Young Mary‐Anne , Forrest Laura Elenor , Rasmussen Victoria‐Mae , James Paul , Mitchell Gillian , Sawyer Sarah Dilys , Reeve Katrina , Hallowell Nina
Published: November 2017

Genome wide association studies have identified a number of common genetic variants ‐ single nucleotide polymorphisms (SNPs) – that combine to increase breast cancer risk. SNP profiling may enhance the accuracy of risk assessment and provides a personalized risk estimate. SNP testing for breast cancer risks may supplement other genetic tests in the future, however, before it can be implemented in the clinic we need to know how it will be perceived and received. Semi‐structured qualitative interviews were conducted with 39 women who had previously had a breast cancer diagnosis and undergone BRCA1/2 testing, participated in the Variants in Practice (ViP) study and received personalized risk (SNP) profiles. Interviews explored their understanding and experiences of receiving this SNP information. Women reported feeling positive about receiving their personalized risk profile, because it: provided an explanation for their previous diagnosis of cancer, vindicated previous risk management decisions and clarified their own and other family members’ risks. A small group was initially shocked to learn of the increased risk of a second primary breast cancer. This study suggests that the provision of personalized risk information about breast cancer generated by SNP profiling is understood and well received. However, a model of genetic counseling that incorporates monogenic and polygenic genetic information will need to be developed prior to clinical implementation.
Sec61β facilitates the maintenance of endoplasmic reticulum homeostasis by associating microtubules
Authors: Zhu Yimeng , Zhang Gangming , Lin Shaoyu , Shi Juanming , Zhang Hong , Hu Junjie
Published: November 2017

Sec61β, a subunit of the Sec61 translocon complex, is not essential in yeast and commonly used as a marker of endoplasmic reticulum (ER). In higher eukaryotes, such as Drosophila, deletion of Sec61β causes lethality, but its physiological role is unclear. Here, we show that Sec61β interacts directly with microtubules. Overexpression of Sec61β containing small epitope tags, but not a RFP tag, induces dramatic bundling of the ER and microtubule. A basic region in the cytosolic domain of Sec61β is critical for microtubule association. Depletion of Sec61β induces ER stress in both mammalian cells and Caenorhabditis elegans, and subsequent restoration of ER homeostasis correlates with the microtubule binding ability of Sec61β. Loss of Sec61β causes increased mobility of translocon complexes and reduced level of membrane-bound ribosomes. These results suggest that Sec61β may stabilize protein translocation by linking translocon complex to microtubule and provide insight into the physiological function of ER-microtubule interaction.
Audit seasonality and pricing of audit services: Theory and evidence from a meta-analysis
Authors: Ng Hooi Ying , Tronnes Per Christen , Wong Leon
Published: November 2017

Auditing is seasonal, with the majority of U.S. public companies having a December fiscal year-end. This results in an audit “busy season” and “off-season” with a non-trivial seasonal impact on the pricing of audit services. We apply an economic framework that explains how audit seasonality affects both the magnitude and the price elasticity of audit demand and audit supply. We find that the audit busy season is associated with an audit fee premium of approximately 10% based on a meta-analysis of 97 analyses from 18 audit fee studies of U.S public companies. A meta-regression of the contextual differences in research design between studies reveals that examining only Big N attenuates the busy season effect size but does not eliminate it, and that the busy season effect size may be larger post-SOX.
Delirium symptoms are associated with decline in cognitive function between ages 53 and 69 years: Findings from a British birth cohort study
Authors: Tsui Alex , Kuh Diana , Richards Marcus , Davis Daniel
Published: November 2017

Introduction

Few population studies have investigated whether longitudinal decline after delirium in mid‐to‐late life might affect specific cognitive domains.

Methods

Participants from a birth cohort completing assessments of search speed, verbal memory, and the Addenbrooke's Cognitive Examination at age 69 were asked about delirium symptoms between ages 60 and 69 years. Linear regression models estimated associations between delirium symptoms and cognitive outcomes.

Results

Period prevalence of delirium between 60 and 69 years was 4% (95% confidence interval 3.2%–4.9%). Self‐reported symptoms of delirium over the seventh decade were associated with worse scores in the Addenbrooke's Cognitive Examination (−1.7 points; 95% confidence interval −3.2, −0.1; P = .04). In association with delirium symptoms, verbal memory scores were initially lower, with subsequent decline in search speed by the age of 69 years. These effects were independent of other Alzheimer's risk factors.

Discussion

Delirium symptoms may be common even at relatively younger ages, and their presence may herald cognitive decline, particularly in search speed, over this time period.
Improving home care: Knowledge creation through engagement and design
Authors: Groop Johan , Ketokivi Mikko , Gupta Mahesh , Holmström Jan
Published: November 2017

In this paper, we apply a design science approach to help a Northern European city improve the efficiency of its home care delivery system. Our proposed solution emerges as a synthesis of applying Goldratt's Theory of Constraints and the principles of variable‐demand inventory replenishment. The improved system exhibits both more level resource utilization and higher productivity due to more efficient capacity utilization. In addition to improving system efficiency, we gain insights into how authentic operations management problems can be addressed through design research. A crucial aspect of empirically‐rooted practical problems is that they always involve multiple stakeholders with only partially overlapping preferences. Consequently, one must not assume or ascribe an a priori system objective, instead, it must arise from explicit empirical analysis of the relevant stakeholders. Another characteristic of authentic problems is that they are always embedded in an institutional context that sets significant boundary conditions to the feasibility of solutions. These boundary conditions are an important reminder of the complexity of empirically‐rooted managerial problems.
A tabletop, ultrashort pulse photoneutron source driven by electrons from laser wakefield acceleration
Authors: Jiao X.J. , Shaw J.M. , Wang T. , Wang X.M. , Tsai H. , Poth P. , Pomerantz I. , Labun L.A. , Toncian T. , Downer M.C. , Hegelich B.M.
Published: November 2017

Relativistic electron beams driven by laser wakefield acceleration were utilized to produce ultrashort neutron sources. The experiment was carried out on the 38 fs, ∼0.5 J, 800 nm Ti:Sapphire laser in the 10 TW UT3 laser lab at University of Texas at Austin. The target gas was a high density pulsed gas jet composed of 90% He and 10% N2. The laser pulse with a peak intensity of 1.5 × 1018 W/cm2 interacted with the target to create a cylindrical plasma channel of 60 μm radius (FWHM) and 1.5 mm length (FWHM). Electron beams of ∼80 pC with the Gaussian energy distribution centered at 37 MeV and a width of 30 MeV (FWHM) were produced via laser wakefield acceleration. Neutron fluences of ∼2.4 × 106 per shot with hundreds of ps temporal length were generated through bremsstrahlung and subsequent photoneutron reactions in a 26.6 mm thick tungsten converter. Results were compared with those of simulations using EPOCH and GEANT4, showing agreement in electron spectrum, neutron fluence, neutron angular distribution and conversion rate.
A survey of practices for the use of electronic health records to support research recruitment
Authors: Obeid Jihad S. , Beskow Laura M. , Rape Marie , Gouripeddi Ramkiran , Black R. Anthony , Cimino James J. , Embi Peter J. , Weng Chunhua , Marnocha Rebecca , Buse John B. ,   for the Methods and Process and Informatics Domain Task Force Workgroup
Published: November 2017

Electronic health records (EHRs) provide great promise for identifying cohorts and enhancing research recruitment. Such approaches are sorely needed, but there are few descriptions in the literature of prevailing practices to guide their use. A multidisciplinary workgroup was formed to examine current practices in the use of EHRs in recruitment and to propose future directions. The group surveyed consortium members regarding current practices. Over 98% of the Clinical and Translational Science Award Consortium responded to the survey. Brokered and self-service data warehouse access are in early or full operation at 94% and 92% of institutions, respectively, whereas, EHR alerts to providers and to research teams are at 45% and 48%, respectively, and use of patient portals for research is at 20%. However, these percentages increase significantly to 88% and above if planning and exploratory work were considered cumulatively. For most approaches, implementation reflected perceived demand. Regulatory and workflow processes were similarly varied, and many respondents described substantive restrictions arising from logistical constraints and limitations on collaboration and data sharing. Survey results reflect wide variation in implementation and approach, and point to strong need for comparative research and development of best practices to protect patients and facilitate interinstitutional collaboration and multisite research.
MARRIAGE AND ECONOMIC DEVELOPMENT IN THE TWENTIETH CENTURY
Authors: Moro Alessio , Moslehi Solmaz , Tanaka Satoshi
Published: November 2017

There is an extensive literature discussing how individuals’ marriage behavior changes as a country develops. However, no existing data set allows an explicit investigation of the relationship between marriage and economic development. In this paper, we construct new cross-country panel data on marital statistics for 16 OECD countries from 1900 to 2000, in order to analyze such a relationship. We use this data set, together with cross-country data on real GDP per capita and the value added share of agriculture, manufacturing, and services sectors, to document two novel stylized facts. First, the fraction of a country’s population that is married displays a hump-shaped relationship with the level of real GDP per capita. Second, the fraction of the married correlates positively with the share of manufacturing in GDP. We conclude that the stage of economic development of a country is a key factor that affects individuals’ family formation decisions.
The Practice and Science Connection: Let's Not Obsess Over Minding the Gap
Authors: Avolio Bruce J.
Published: November 2017

Over the last 5 years, there has been a surge of interest and activity among large groups of practitioners and scientists in industrial and organizational (I-O) psychology, who have joined together with a broad range of agencies and organizations, in small to very large collaborative teams, to examine some of the grand challenges and problems facing our field. For example, a consortium of university professors and their counterparts in fiveFortune100 firms, two global human resources (HR) consultancies, and NASA have been working together to examine the practical and scientific challenges in determining how to optimize the selection and on-boarding of a new generation of workers charged with building the first colony on Mars. One I-O practitioner involved with this initiative said, “Our project represents one of the most seamless and productive integration efforts involving the practice and scientific community, perhaps in the history of our profession.”
THE JUDGMENT OF PONTIUS PILATE: A CRITIQUE OF GIORGIO AGAMBEN
Authors: Dusenbury D. L.
Published: November 2017

InPilate and Jesus, Giorgio Agamben argues that Pontius Pilate never formally condemned Jesus of Nazareth. “The traditional interpretation of Jesus’ trial … must be revised,” he urges, because “there has not been any judgment in a technical sense.” In Agamben's telling, Pilate's non-judgment is the original truth of Jesus's death that has been covered over by tradition. This is an intriguing hypothesis, but Agamben's use of sources in arguing it is highly irregular. This article offers a critique of the legal and philological argumentation ofPilate and Jesus. In the process, it revisits an ancient—and still actual—controversy surrounding the Roman trial of Jesus and demonstrates that Pilate did sentence Jesus,pro tribunali, to death on a cross.
Stress exposure and psychopathology alter methylation of the serotonin receptor 2A (HTR2A) gene in preschoolers
Authors: Parade Stephanie H. , Novick Andrew M. , Parent Justin , Seifer Ronald , Klaver Samantha J. , Marsit Carmen J. , Gobin Asi Polly , Yang Bao-Zhu , Tyrka Audrey R.
Published: November 2017

Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor 2A (HTR2A) gene in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semistructured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. TheHTR2Agenotype and methylation ofHTR2Awere measured at two CpG sites (–1420 and –1224) from saliva DNA.HTR2Agenotype was associated withHTR2Amethylation at both CpG sites.HTR2Agenotype also moderated associations of contextual stress exposure andHTR2Amethylation at site –1420. Contextual stress was positively associated with –1420 methylation among A homozygotes, but negatively associated with –1420 methylation among G homozygotes. Posttraumatic stress disorder and major depressive disorder symptoms were negatively associated with methylation at –1420, but positively associated with methylation at –1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, andHTR2Amethylation may be a mechanism by which early adversity is biologically encoded.
Change in FK506 binding protein 5 (FKBP5) methylation over time among preschoolers with adversity
Authors: Parade Stephanie H. , Parent Justin , Rabemananjara Kantoniony , Seifer Ronald , Marsit Carmen J. , Yang Bao-Zhu , Zhang Huiping , Tyrka Audrey R.
Published: November 2017

FK506 binding protein 5 (FKBP5) alters stress response system functioning, and childhood maltreatment is associated with methylation of the FKBP5 gene. Yet it is unknown if maltreatment contributes to change in FKBP5 methylation over time. The current study draws upon a sample of 231 preschoolers, including 123 with child welfare documentation of moderate to severe maltreatment in the past 6 months, to understand if maltreatment contributes to change in FKBP5 methylation over a 6-month period. Review of child protection records and semistructured interviews in the home were used to assess maltreatment and exposure to other contextual stressors, as well as service utilization. Methylation of FKBP5 at two CpG sites in intron 7 was measured from saliva DNA at the time of initial study enrollment, and 6 months following enrollment. Child maltreatment was associated with change in FKBP5 methylation over time, but only when children were exposed to high levels of other contextual stressors. Service utilization was associated with increases in methylation over time, but only among children with the FKPB5 rs1360780 protective CC genotype. Methylation of FKBP5 is sensitive to stress exposure and may be a mechanism linking early adversity to long-term health and developmental outcomes.
A neurocomputational investigation of reinforcement-based decision making as a candidate latent vulnerability mechanism in maltreated children
Authors: Gerin Mattia I. , Puetz Vanessa B. , Blair R. James R. , White Stuart , Sethi Arjun , Hoffmann Ferdinand , Palmer Amy L. , Viding Essi , McCrory Eamon J.
Published: November 2017

Alterations in reinforcement-based decision making may be associated with increased psychiatric vulnerability in children who have experienced maltreatment. A probabilistic passive avoidance task and a model-based functional magnetic resonance imaging analytic approach were implemented to assess the neurocomputational components underlying decision making: (a) reinforcement expectancies (the representation of the outcomes associated with a stimulus) and (b) prediction error signaling (the ability to detect the differences between expected and actual outcomes). There were three main findings. First, the maltreated group (n = 18; mean age = 13), relative to nonmaltreated peers (n = 19; mean age = 13), showed decreased activity during expected value processing in a widespread network commonly associated with reinforcement expectancies representation, including the striatum (especially the caudate), the orbitofrontal cortex, and medial temporal structures including the hippocampus and insula. Second, consistent with previously reported hyperresponsiveness to negative cues in the context of childhood abuse, the maltreated group showed increased prediction error signaling in the middle cingulate gyrus, somatosensory cortex, superior temporal gyrus, and thalamus. Third, the maltreated group showed increased activity in frontodorsal regions and in the putamen during expected value representation. These findings suggest that early adverse environments disrupt the development of decision-making processes, which in turn may compromise psychosocial functioning in ways that increase latent vulnerability to psychiatric disorder.
Threat vigilance and socioeconomic disparities in metabolic health
Authors: Hostinar Camelia E. , Ross Kharah M. , Chan Meanne , Chen Edith , Miller Gregory E.
Published: November 2017

A quarter of the global population meets diagnostic criteria for metabolic syndrome (MetS). MetS prevalence stratifies by socioeconomic status (SES), such that low SES is associated with higher MetS risk starting in childhood. Despite this trend, some low-SES children maintain good metabolic health across the life span, but the factors responsible for their resilience are not well understood. This study examined the role of threat vigilance as either a moderator or a mediator of the effects of low early life SES on adult metabolic risk. Three hundred twenty-five Canadians aged 15–55 participated (M= 36.4 years,SD= 10.7; 55.4% female). We coded parental occupational status between the ages of 0 and 5 to index early life SES. We used the International Diabetes Federation case definition for MetS based on waist circumference, blood pressure, triglyceride levels, HDL cholesterol, and glycosylated hemoglobin measures. Threat vigilance was assessed using the Weapons Identification Procedure, a visual discrimination paradigm that captures implicit perceptions of threat. Analyses supported the moderator hypothesis: low early life SES was associated with MetS diagnosis exclusively among those with high levels of threat vigilance. This suggests that low early life SES environments that heighten vigilance to threat might be particularly detrimental for metabolic health. Conversely, low threat vigilance may buffer against the metabolic risks associated with socioeconomic disadvantage.
Childhood quality influences genetic sensitivity to environmental influences across adulthood: A life-course Gene × Environment interaction study
Authors: Keers Robert , Pluess Michael
Published: November 2017

While environmental adversity has been shown to increase risk for psychopathology, individuals differ in their sensitivity to these effects. Both genes and childhood experiences are thought to influence sensitivity to the environment, and these factors may operate synergistically such that the effects of childhood experiences on later sensitivity are greater in individuals who are more genetically sensitive. In line with this hypothesis, several recent studies have reported a significant three-way interaction (Gene × Environment × Environment) between two candidate genes and childhood and adult environment on adult psychopathology. We aimed to replicate and extend these findings in a large, prospective multiwave longitudinal study using a polygenic score of environmental sensitivity and objectively measured childhood and adult material environmental quality. We found evidence for both Environment × Environment and Gene × Environment × Environment effects on psychological distress. Children with a poor-quality material environment were more sensitive to the negative effects of a poor environment as adults, reporting significantly higher psychological distress scores. These effects were further moderated by a polygenic score of environmental sensitivity. Genetically sensitive children were more vulnerable to adversity as adults, if they had experienced a poor childhood environment but were significantly less vulnerable if their childhood environment was positive. These findings are in line with the differential susceptibility hypothesis and suggest that a life course approach is necessary to elucidate the role of Gene × Environment in the development of mental illnesses.
When inflammation and depression go together: The longitudinal effects of parent–child relationships
Authors: Beach Steven R. H. , Lei Man Kit , Simons Ronald L. , Barr Ashley B. , Simons Leslie G. , Ehrlich Katherine , Brody Gene H. , Philibert Robert A.
Published: November 2017

Parent–child relationships have long-term effects on health, particularly later inflammation and depression. We hypothesized that these effects would be mediated by later romantic partner relationships and elevated stressors in young adulthood, helping promote chronic, low grade, inflammation as well as depressive symptoms, and driving their covariation. It has been proposed recently that youth experiencing harsher parenting may also develop a stronger association between inflammation and depressive symptoms in adulthood and altered effects of stressors on outcomes. In the current investigation, we test these ideas using an 18-year longitudinal study ofN= 413 African American youth that provides assessment of the parent–child relationship (at age 10), pro-inflammatory cytokine profile and depressive symptoms (at age 28), and potential mediators in early young adulthood (assessed at ages 21 and 24). As predicted, the effect of harsher parent–child relationships (age 10) on pro-inflammatory state and increased depressive symptoms at age 28 were fully mediated through young adult stress and romantic partner relationships. In addition, beyond these mediated effects, parent–child relationships at age 10 moderated the concurrent association between inflammation and depressive symptoms, as well as the prospective association between romantic partner relationships and inflammation, and resulted in substantially different patterns of indirect effects from young adult mediators to outcomes. The results support theorizing that the association of depression and inflammation in young adulthood is conditional on earlier parenting, and suggest incorporating this perspective into models predicting long-term health outcomes.
Vitamin D status is associated with underweight and stunting in children aged 6–36 months residing in the Ecuadorian Andes
Authors: Mokhtar Rana R , Holick Michael F , Sempértegui Fernando , Griffiths Jeffrey K , Estrella Bertha , Moore Lynn L , Fox Matthew P , Hamer Davidson H
Published: November 2017

Objective

There is limited knowledge on vitamin D status of children residing in the Andes and its association with undernutrition. We evaluated the vitamin D status of children residing in a low socio-economic status (SES) setting in the Ecuadorian Andes and assessed the association between vitamin D status, stunting and underweight. We hypothesized that children who were underweight would have lower serum 25-hydroxyvitamin D (25(OH)D) levels and lower 25(OH)D levels would be associated with a higher risk of stunting.

Design

We conducted a cross-sectional secondary analysis of a randomized controlled trial, the Vitamin A, Zinc and Pneumonia study. Children had serum 25(OH)D concentrations measured. A sensitivity analysis was undertaken to determine a vitamin D cut-off specific for our endpoints. Associations between serum 25(OH)D and underweight (defined as weight-for-ageZ-score≤−1) and stunting (defined as height-for-ageZ-score≤−2) were assessed using multivariate logistic regression.

Setting

Children residing in five low-SES peri-urban neighbourhoods near Quito, Ecuador.

Subjects

Children (n516) aged 6–36 months.

Results

Mean serum 25(OH)D concentration was 58·0 (sd17·7) nmol/l. Sensitivity analysis revealed an undernutrition-specific 25(OH)D cut-off of <42·5 nmol/l; 18·6 % of children had serum 25(OH)D<42·5 nmol/l. Children who were underweight were more likely to have serum 25(OH)D<42·5 nmol/l (adjusted OR (aOR)=2·0; 95 % CI 1·2, 3·3). Children with low serum 25(OH)D levels were more likely to be stunted (aOR=2·8; 95 % CI 1·6, 4·7).

Conclusions

Low serum 25(OH)D levels were more common in underweight and stunted Ecuadorian children.
Functional mapping and annotation of genetic associations with FUMA
Authors: Watanabe Kyoko , Taskesen Erdogan , van Bochoven Arjen , Posthuma Danielle
Published: November 2017

A main challenge in genome-wide association studies (GWAS) is to pinpoint possible causal variants. Results from GWAS typically do not directly translate into causal variants because the majority of hits are in non-coding or intergenic regions, and the presence of linkage disequilibrium leads to effects being statistically spread out across multiple variants. Post-GWAS annotation facilitates the selection of most likely causal variant(s). Multiple resources are available for post-GWAS annotation, yet these can be time consuming and do not provide integrated visual aids for data interpretation. We, therefore, develop FUMA: an integrative web-based platform using information from multiple biological resources to facilitate functional annotation of GWAS results, gene prioritization and interactive visualization. FUMA accommodates positional, expression quantitative trait loci (eQTL) and chromatin interaction mappings, and provides gene-based, pathway and tissue enrichment results. FUMA results directly aid in generating hypotheses that are testable in functional experiments aimed at proving causal relations.
Identification of a neural crest stem cell niche by Spatial Genomic Analysis
Authors: Lignell Antti , Kerosuo Laura , Streichan Sebastian J. , Cai Long , Bronner Marianne E.
Published: November 2017

The neural crest is an embryonic population of multipotent stem cells that form numerous defining features of vertebrates. Due to lack of reliable techniques to perform transcriptional profiling in intact tissues, it remains controversial whether the neural crest is a heterogeneous or homogeneous population. By coupling multiplex single molecule fluorescence in situ hybridization with machine learning algorithm based cell segmentation, we examine expression of 35 genes at single cell  resolution in vivo. Unbiased hierarchical clustering reveals five spatially distinct subpopulations within the chick dorsal neural tube. Here we identify a neural crest stem cell niche that centers around the dorsal midline with high expression of neural crest genes, pluripotency factors, and lineage markers. Interestingly, neural and neural crest stem cells express distinct pluripotency signatures. This Spatial Genomic Analysis toolkit provides a straightforward approach to study quantitative multiplex gene expression in numerous biological systems, while offering insights into gene regulatory networks via synexpression analysis.
Publisher Correction: Cortical dendritic activity correlates with spindle-rich oscillations during sleep in rodents
Authors: Seibt Julie , Richard Clément J. , Sigl-Glöckner Johanna , Takahashi Naoya , Kaplan David I. , Doron Guy , de Limoges Denis , Bocklisch Christina , Larkum Matthew E.
Published: November 2017

In the originally published version of this Article, incorrect references were cited on two occasions in the Results section. Under the subheading ‘Ca2+ activity in single dendrites and somata of L5 neurons’, the final sentence of the second paragraph incorrectly cited reference 29 instead of reference 31. Under the subheading ‘Spiking of L5 cell bodies is not influenced by spindles’, the first sentence cited reference 30 instead of reference 29. These errors have now been corrected in both the PDF and HTML versions of the Article.
Author Correction: Demonstration of sub-luminal propagation of single-cycle terahertz pulses for particle acceleration
Authors: Walsh D. A. , Lake D. S. , Snedden E. W. , Cliffe M. J. , Graham D. M. , Jamison S. P.
Published: November 2017

The original version of this Article contained an error in the abstract, referring to “multi-megawatt-per-metre” instead of “multi-megavolt-per-metre”. This has now been corrected in both the PDF and HTML versions of the Article.
Publisher Correction: Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice
Authors: Vincent Jessica , Adura Carolina , Gao Pu , Luz Antonio , Lama Lodoe , Asano Yasutomi , Okamoto Rei , Imaeda Toshihiro , Aida Jumpei , Rothamel Katherine , Gogakos Tasos , Steinberg Joshua , Reasoner Seth , Aso Kazuyoshi , Tuschl Thomas , Patel Dinshaw J. , Glickman J. Fraser , Ascano Manuel
Published: November 2017

The previously published version of this Article contained errors in Fig. 6. In panel h the units of the x axis were incorrectly given as mM and should have been given as µM. Also, the IC50s for RU.365, RU.332 and RU.521 within panel h were incorrectly given as mM and should have been given as µM. These errors have been corrected in both the PDF and HTML versions of the Article.
Simple spatial scaling rules behind complex cities
Authors: Li Ruiqi , Dong Lei , Zhang Jiang , Wang Xinran , Wang Wen-Xu , Di Zengru , Stanley H. Eugene
Published: November 2017

Although most of wealth and innovation have been the result of human interaction and cooperation, we are not yet able to quantitatively predict the spatial distributions of three main elements of cities: population, roads, and socioeconomic interactions. By a simple model mainly based on spatial attraction and matching growth mechanisms, we reveal that the spatial scaling rules of these three elements are in a consistent framework, which allows us to use any single observation to infer the others. All numerical and theoretical results are consistent with empirical data from ten representative cities. In addition, our model can also provide a general explanation of the origins of the universal super- and sub-linear aggregate scaling laws and accurately predict kilometre-level socioeconomic activity. Our work opens a new avenue for uncovering the evolution of cities in terms of the interplay among urban elements, and it has a broad range of applications.