bluuebunny/crossref_metadata_2025 huggingface dataset:
From Enlightenment to Risk
Authors: Clarke Simon
Published: July 2017

This original new book offers a comprehensive introduction to social theories and how they are applied to contemporary social problems. It charts a critical path from Max Weber, the early Frankfurt School, through to the work of Michel Foucault, the concept of Postmodernism and current debates surrounding globalization, risk and network society. Exploring all the key ideas and thinkers, in addition to the most recent debates in the field, this book will be an engaging and lucid read for all those seeking to understand contemporary social theory today.
A Matched Case–Control Study on Early and Late Results of Carotid Endarterectomy Performed in Young Patients
Authors: Dorigo Walter , Fargion Aaron , Giacomelli Elena , Bassoli Giulia , Pulli Raffaele , Pratesi Giovanni , Piffaretti Gabriele , Pratesi Carlo
Published: July 2017

Objective

The aim of the study was to describe the perioperative and long‐term results of carotid endarterectomy (CEA) in patients aged 60 or less and compare them to patients of more advanced age in a retrospective single‐centre case–control study.

Methods

From January 1996 to December 2014, 5893 consecutive CEAs were performed in our institution. Data concerning these interventions were prospectively inserted in a dedicated database. A retrospective analysis of that database was performed and 457 interventions performed in patients aged 60 or less were found (group 1). The control group was represented by 457 interventions selected from the remaining 5436 by a one‐to‐one coarsened exact matching on the basis of all the baseline demographic and clinical covariates significantly different in the two groups (group 2). The two groups were compared in terms of intraoperative technical features and perioperative (<30 days) results of interventions (transient ischaemic attack‐TIA, stroke and death rates) with χ2 test. Follow‐up data were analysed by life‐table analysis (Kaplan–Meier test) in terms of survival, stroke‐free and neurological symptom‐free survival, freedom from severe restenosis and occlusion and freedom from reintervention, and the results in the two groups were compared by means of log rank test.

Results

There were no differences between the two groups in terms of clinical presentation and of degree of carotid stenosis on operated side. Anaesthesiological and surgical details were also similar between the two groups. Thirty‐day stroke and death rate was 0.6% in both groups (p = 0.9). Follow‐up was available for 877 patients (96% of the study group) with a mean duration of 50 months. Estimated 10‐year survival rates were 85% in group 1 (SE 0.03) and 76% in group 2 (SE 0.04, p = 0.003, log rank 8.9). At the same time interval, stroke‐free survival was also significantly better in group 1 (85%, SE 0.035) than in group 2 (72.5%, SE 0.03; p = 0.002, log rank 10.1). The corresponding figures in terms of any neurological symptom‐free survival were 82.8% in group 1 (SE 0.04) and 70.3% in group 2 (SE 0.04, p = 0.002, log rank 9.7). Estimated freedom from severe restenosis and occlusion was 76.5% in group 1 (SE 0.04) and 88.5% in group 2 (SE 0.035, p = 0.001, log rank 11.9). Disease recurrence was symptomatic in six cases, three in each group. Estimated freedom from reintervention rates at 10 years was 87% in group 1 (SE 0.035) and 91.5% in group 2 (SE 0.03; p = 0.2, log rank 1.1).

Conclusions

CEA in patents aged 60 or less is safe and provides significantly better long‐term results than those obtained in patients over 60 in terms of survival and stroke‐free survival. Younger patients appear to have higher rates of recurrent carotid stenosis compared to the older cohort; however, these rarely require a secondary intervention.
Current Strategy of Fetal Therapy I: Principles of In-utero Treatment, Pharmacologic Intervention, Stem Cell Transplantation and Gene Therapy
Authors: Phithakwatchara Nisarat , Nawapun Katika , Panchalee Tacharee , Viboonchart Sommai , Mongkolchat Nadda , Wataganara Tuangsit
Published: July 2017

Fetal conditions with high morbidity are amenable for prenatal intervention. It is important that the selective and investigative nature of most procedures needs to be clarified with the family during counseling session. Fetal therapy is fostered by accurate prenatal diagnosis with advanced fetal imaging, and molecular genetics technology. The treatments can be categorized into medical treatment, stem cell transplantation and gene therapy, minimally invasive intervention, endoscopic surgery, and open hysterotomy approach. Scientific validation of their genuine benefits has been a subject of ongoing researches. Prenatal administrations of pharmaceutical agents, for prophylactic or therapeutic purposes, have been broadly adopted. Transplacental administration of betamethasone to enhance the function of pneumocytes type II in premature fetus has been widely practiced for decades, and it might be the most common ‘fetal therapy’ being performed. However, the optimal dosage and interval of prenatal steroids administration was validated only recently. More invasive route of fetal administration, such as transamniotic, direct intramuscular, and intravenous injection, may be required for other pharmacologic agents. In this article, the authors selected to review common fetal conditions whose proposed prenatal pharmacologic treatments have undergone scientific validations. In-utero stem cell transplantation and gene therapy remain highly experimental. Informed choice and clinical experiment need to be balanced when prenatal treatment is offered.
Dementia prevalence and incidence in a federation of European Electronic Health Record databases: The European Medical Informatics Framework resource
Authors: Perera Gayan , Pedersen Lars , Ansel David , Alexander Myriam , Arrighi H. Michael , Avillach Paul , Foskett Nadia , Gini Rosa , Gordon Mark F. , Gungabissoon Usha , Mayer Miguel‐Angel , Novak Gerald , Rijnbeek Peter , Trifirò Gianluca , van der Lei Johan , Visser Pieter J. , Stewart Robert
Published: July 2017

Introduction

The European Medical Information Framework consortium has assembled electronic health record (EHR) databases for dementia research. We calculated dementia prevalence and incidence in 25 million persons from 2004 to 2012.

Methods

Six EHR databases (three primary care and three secondary care) from five countries were interrogated. Dementia was ascertained by consensus harmonization of clinical/diagnostic codes. Annual period prevalences and incidences by age and gender were calculated and meta‐analyzed.

Results

The six databases contained 138,625 dementia cases. Age‐specific prevalences were around 30% of published estimates from community samples and incidences were around 50%. Pooled prevalences had increased from 2004 to 2012 in all age groups but pooled incidences only after age 75 years. Associations with age and gender were stable over time.

Discussion

The European Medical Information Framework initiative supports EHR data on unprecedented number of people with dementia. Age‐specific prevalences and incidences mirror estimates from community samples in pattern at levels that are lower but increasing over time.
Fundamentals of Nonparametric Bayesian Inference
Authors: Ghosal Subhashis , van der Vaart Aad
Published: July 2017

Explosive growth in computing power has made Bayesian methods for infinite-dimensional models - Bayesian nonparametrics - a nearly universal framework for inference, finding practical use in numerous subject areas. Written by leading researchers, this authoritative text draws on theoretical advances of the past twenty years to synthesize all aspects of Bayesian nonparametrics, from prior construction to computation and large sample behavior of posteriors. Because understanding the behavior of posteriors is critical to selecting priors that work, the large sample theory is developed systematically, illustrated by various examples of model and prior combinations. Precise sufficient conditions are given, with complete proofs, that ensure desirable posterior properties and behavior. Each chapter ends with historical notes and numerous exercises to deepen and consolidate the reader's understanding, making the book valuable for both graduate students and researchers in statistics and machine learning, as well as in application areas such as econometrics and biostatistics.
Meaningful Resistance
Authors: Simmons Erica S.
Published: July 2017

Meaningful Resistance explores the origins and dynamics of resistance to markets through an examination of two social movements that emerged to voice and channel opposition to market reforms. Protests against water privatization in Cochabamba, Bolivia, and rising corn prices in Mexico City, Mexico, offer a lens to analyze the mechanisms by which perceived, market-driven threats to material livelihood can prompt resistance. By exploring connections among marketization, local practices, and political protest, the book shows how the material and the ideational are inextricably linked in resistance to subsistence threats. When people perceive that markets have put subsistence at risk, material and symbolic worlds are both at stake; citizens take to the streets not only to defend their pocketbooks, but also their conceptions of community. The book advances contemporary scholarship by showing how attention to grievances in general, and subsistence resources in particular, can add explanatory leverage to analyses of contentious politics.
Men and Sex
Authors: Graham Philip
Published: July 2017

Men and Sex provides a comprehensive yet accessible account of male sexuality by using the theoretical concept of the 'sexual script' to illuminate different aspects of men's sexual behaviour. Graham begins by discussing different theories of sexuality, before providing a more detailed description of sexual script theory. This proposes how male sexual behaviour can be explained as a result of cultural influences modified by individual experience and personality as well as by interaction with others. Individual chapters detail the development of sexual scripts in childhood and adolescence, masturbation, cultural influences on sexuality, heterosexual behaviour, variations and problems in sexual functioning, homosexual behaviour, transsexualism, procreative sex, coercive sexual behaviour, the impact of physical and mental health problems on sexuality, and sexuality and pornography. The concluding chapter looks at the future of male sexuality. The book makes a valuable contribution to the burgeoning literature on masculinity studies.
WTO Analytical Index
Authors: Legal Affairs Division, World Trade Organization
Published: July 2017

The WTO Analytical Index is a comprehensive guide to the interpretation and application of the WTO Agreements by the Appellate Body, dispute settlement panels and other WTO bodies. It contains extracts of key pronouncements and findings from tens of thousands of pages of WTO jurisprudence, including panel reports, Appellate Body reports, Article 21.3(c) awards and Article 22.6 decisions. This unique work will be of assistance to anyone working in the field of WTO law, including lawyers, economists, academics and students. It is produced by the Legal Affairs Division of the WTO Secretariat with contributions from other divisions of the Secretariat and the Appellate Body Secretariat. The third edition of the WTO Analytical Index covers developments in WTO law and practice over the period January 1995 to September 2011.
The “Likeness” of E-Vapour Products and Cigarettes in the World Trade Organization
Authors: FOLTEA Marina , MARKITANOVA Anna
Published: July 2017

The regulation of e-vapour products is a relatively new topic. While the e-vapour product sector is fast evolving, the optimal regulation of these products is yet to be fully understood. Some wisdom may be borrowed from the regulation of cigarettes, but many tobacco-relevant policies may not be applied to these new products. Evaluations are underway on many aspects of e-vapour products, for example: their safety, potential health risks, illicit trade, taxation and advertising. This paper examines yet another dimension – one which arises at the intersection of international health and trade law – namely whether e-vapour products and cigarettes may be found “like” in a WTO dispute challenging trade restrictive measures applying to e-vapour products.

In particular, the analysis focuses on a hypothetical ban on the importation, distribution, sale and offering for sale of e-vapour products (referred to as a general ban) – a measure that is either being contemplated or already implemented in some domestic jurisdictions. It finds that e-vapour products and cigarettes may be “like” under WTO law. In the event that a positive finding is made on other remaining tests necessary to determine discrimination (importantly the “less favourable treatment”) and provided the regulating member finds no solid evidence to justify the ban under GATT Article XX, a general ban on e-vapour products risks being found WTO inconsistent.
Qui Exanimis Nascitur? Can “Better Regulation” in the European Union really be a Servant of Technocracy?
Authors: JARLBÆK PEDERSEN Morten
Published: July 2017

Better regulation is of grave importance to the European Union, as it is seen as a way of obtaining output legitimacy. To achieve this, the European Commission has established a so-called REFIT Stakeholder Platform where stakeholders’ proposals for more effective and efficient EU law are discussed. The central premise for this meta-regulatory instrument is depoliticisation of the REFIT program and the whole better regulation agenda. To ensure this, the European Commission plays a crucial gatekeeping role by only granting access for proposals that echo that premise and by securing depoliticised deliberation afterwards. Utilising a novel typology linking regulatory reform proposals to the risk of politicisation, the argument advanced in this article is that only a minority of the proposals to be considered by Platform members have a low risk of depoliticisation. This, it is argued, is due to the Commission not having a sufficiently well-developed understanding of the premises for REFIT it has itself established.
Changes in the boundary-layer structure at the edge of the ultimate regime in vertical natural convection
Authors: Ng Chong Shen , Ooi Andrew , Lohse Detlef , Chung Daniel
Published: July 2017

In thermal convection for very large Rayleigh numbers ($Ra$), the thermal and viscous boundary layers are expected to undergo a transition from a classical state to an ultimate state. In the former state, the boundary-layer thicknesses follow a laminar-like Prandtl–Blasius–Polhausen scaling, whereas in the latter, the boundary layers are turbulent with logarithmic corrections in the sense of Prandtl and von Kármán. Here, we report evidence of this transition via changes in the boundary-layer structure of vertical natural convection (VC), which is a buoyancy-driven flow between differentially heated vertical walls. The numerical dataset spans $Ra$ values from $10^{5}$ to $10^{9}$ and a constant Prandtl number value of $0.709$. For this $Ra$ range, the VC flow has been previously found to exhibit classical state behaviour in a global sense. Yet, with increasing $Ra$, we observe that near-wall higher-shear patches occupy increasingly larger fractions of the wall areas, which suggest that the boundary layers are undergoing a transition from the classical state to the ultimate shear-dominated state. The presence of streaky structures – reminiscent of the near-wall streaks in canonical wall-bounded turbulence – further supports the notion of this transition. Within the higher-shear patches, conditionally averaged statistics yield a logarithmic variation in the local mean temperature profiles, in agreement with the log law of the wall for mean temperature, and an $Ra^{0.37}$ effective power-law scaling of the local Nusselt number. The scaling of the latter is consistent with the logarithmically corrected $1/2$ power-law scaling predicted for ultimate thermal convection for very large $Ra$. Collectively, the results from this study indicate that turbulent and laminar-like boundary layer coexist in VC at moderate to high $Ra$ and this transition from the classical state to the ultimate state manifests as increasingly larger shear-dominated patches, consistent with the findings reported for Rayleigh–Bénard convection and Taylor–Couette flows.
EXPLOTACIÓN DE PECES E INTENSIFICACIÓN EN AMBIENTES ÁRIDOS: COMPARANDO EL REGISTRO EN HUMEDALES DEL CENTRO-OCCIDENTE DE ARGENTINA
Authors: Corbat Mercedes , Zangrando A. Francisco J. , Gil Adolfo F. , Chiavazza Horacio
Published: July 2017

Este trabajo tiene por objetivo contribuir al conocimiento existente sobre la explotación de peces continentales en las zonas áridas de Sudamérica. El aprovechamiento de los peces para la subsistencia humana se aborda a partir de la evidencia zooarqueológica disponible en dos ambientes de humedales del centro-occidente de Argentina: las lagunas de Guanacache y Llancanelo. La explotación de este recurso permite discutir el proceso de intensificación propuesto para los últimos 2000 años en la región. La integración y comparación de la información ictioarqueológica con la arqueofaunística en general revela que la explotación de peces más antigua (ca. 3000 años a.P.) se registra en Llancanelo. En ambos humedales, el consumo de peces parece haber sido una estrategia que acompañó los primeros momentos de ocupación de las lagunas y estaría representando una adaptación al medio. Las tendencias temporales en los índices de abundancia y diversidad analizados no muestran evidencias de procesos de intensificación diferentes en ambos sectores. Finalmente, los peces representaron un recurso privilegiado tanto en Guanacache como en Llancanelo, cuyo consumo se vio complementado en ambos casos con el de otra fauna pequeña.
Embodying values and socio-religious difference: new markets of moral learning in Christian and Muslim schools in urban Tanzania
Authors: Dilger Hansjörg
Published: July 2017

Schools are institutionalized spaces of learning where children and young people are trained to become morally and ethically responsible members of society. Cultural ideas and values relating to friendship, social status and the nation, but also regarding one's own body, dress and emotional, verbal or gestural expression, are learned and performed by young people on an everyday basis. In this article, I build on ethnographic research on the ‘new’ generation of Christian and Muslim schools in Dar es Salaam, Tanzania (2008–10), and I show that particular ways of learning and performing values can be understood as a form of embodied morality that orients students and teachers in relation to their educational and socio-urban environments. I argue that schools do not represent monolithic ethical or moral frameworks or that the actors in these educational settings learn or embody those frameworks in uniform ways. Rather, the processes of ethical and moral (self-)formation are often highly fragmented due to the diverse (social, religious and economic) backgrounds of students and teachers as well as the logics of class formation in the neoliberal market, which causes a high degree of fluctuation across the (equally fragmented) educational landscape of Dar es Salaam. I therefore define ‘embodied morality’ as a partial and discontinuous practice whose specific forms and experience are inseparably entwined with the specific ideological, social and institutional environments of particular educational settings.
Ethics of life in the context of death: the emergence of ethical fields in HIV prevention
Authors: Bochow Astrid
Published: July 2017

Discussing the ethical positions of politicians and public intellectuals, mostly Christians, the article analyses the emergence of ethical fields through HIV prevention in the context of Botswana's proactive HIV politics since the turn of the millennium. I discuss the interaction between everyday experiences of death and suffering, activist engagements on the part of some leading figures in prevention, and various publics. All of these voices agree that people and institutions, such as the church, need to fulfil their responsibilities. In all these situations and among the public, kinship becomes a source of identity and of positive ethics of virtue to support behavioural changes. The virtue of responsibility becomes consensual, making it possible to bridge the apparent contestation between the imperative of safe sex, launched by public health discourses, and everyday practices, highlighting childbirth and the continuity of kinship as a way to connect to life and transcend death. These various public and private ethics feed into a political imaginary, drawing on ideas of kinship as guaranteeing social stability.
Antarctic Microbes Shape Nutrient Content of Snowmelt
Authors: Stanley Sarah
Published: July 2017

As temperatures continue to rise, snow-dwelling microbes could accelerate melting and influence downstream ecosystems.
2017 AGU Union Medal, Award, and Prize Recipients Announced
Authors: Davidson Eric , Mukasa Samuel
Published: July 2017

The world’s largest organization of Earth and space scientists honors 29 exceptional scientists and journalists.
Volcano’s Toxic Plume Returns as Stealth Hazard
Authors: Wendel JoAnna
Published: July 2017

During a closely watched eruption, plumes of harmful sulfur dioxide gas morphed into “plumerangs” of sulfuric-acid-rich aerosols that descended on populated parts of Iceland.
Investigation of sphingosine kinase 1 in interferon responses during dengue virus infection
Authors: Aloia Amanda L , Calvert Julie K , Clarke Jennifer N , Davies Lorena T , Helbig Karla J , Pitson Stuart M , Carr Jillian M
Published: July 2017

Dengue virus (DENV) regulates sphingosine kinase (SK)‐1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN‐β) but reduced levels of IFN‐stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell‐surface IFN‐alpha receptor (IFNAR)1 in both wild‐type (WT) and SK1−/− pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)‐STAT1 and key IFN regulatory factors (IRF)1 and −7 in SK1−/− pMEF. Direct IFN stimulation induced ISGs (viperin, IFIT1), CXCL10, IRF1 and −7 and p‐STAT1. Responses, however, were significantly reduced in SK1−/− pMEF, except for IFN‐stimulated CXCL10 and IRF7. Poor IFN responses in SK1−/− pMEF were associated with a small reduction in basal cell‐surface IFNAR1 and IRF1 mRNA in uninfected SK1−/− compared with WT pMEF. In contrast, treatment of cells with the SK1 inhibitor, SK1‐I or expression of an inhibitory SK1 short hairpin RNA (shRNA), both of which reduce DENV infection, does not alter basal IRF1 mRNA or affect type I IFN stimulation of p‐STAT1. Thus, cells genetically lacking SK1 can induce many responses normally following DENV infection, but have adaptive changes in IFNAR1 and IRF1 that compromise DENV‐induced type I IFN responses. This suggests a biological link between SK1 and IFN‐stimulated pathways. Other approaches to reduce SK1 activity, however, do not influence these important antiviral pathways but reduce infection and may be useful antiviral strategies.
Cohesion: a method for quantifying the connectivity of microbial communities
Authors: Herren Cristina M , McMahon Katherine D
Published: July 2017

The ability to predict microbial community dynamics lags behind the quantity of data available in these systems. Most predictive models use only environmental parameters, although a long history of ecological literature suggests that community complexity should also be an informative parameter. Thus, we hypothesize that incorporating information about a community’s complexity might improve predictive power in microbial models. Here, we present a new metric, called community ‘cohesion,’ that quantifies the degree of connectivity of a microbial community. We analyze six long-term (10+ years) microbial data sets using the cohesion metrics and validate our approach using data sets where absolute abundances of taxa are available. As a case study of our metrics’ utility, we show that community cohesion is a strong predictor of Bray–Curtis dissimilarity (R2=0.47) between phytoplankton communities in Lake Mendota, WI, USA. Our cohesion metrics outperform a model built using all available environmental data collected during a long-term sampling program. The result that cohesion corresponds strongly to Bray–Curtis dissimilarity is consistent across the six long-term time series, including five phytoplankton data sets and one bacterial 16S rRNA gene sequencing data set. We explain here the calculation of our cohesion metrics and their potential uses in microbial ecology.
Aurora-B kinase pathway controls the lateral to end-on conversion of kinetochore-microtubule attachments in human cells
Authors: Shrestha Roshan L. , Conti Duccio , Tamura Naoka , Braun Dominique , Ramalingam Revathy A. , Cieslinski Konstanty , Ries Jonas , Draviam Viji M.
Published: July 2017

Human chromosomes are captured along microtubule walls (lateral attachment) and then tethered to microtubule-ends (end-on attachment) through a multi-step end-on conversion process. Upstream regulators that orchestrate this remarkable change in the plane of kinetochore-microtubule attachment in human cells are not known. By tracking kinetochore movements and using kinetochore markers specific to attachment status, we reveal a spatially defined role for Aurora-B kinase in retarding the end-on conversion process. To understand how Aurora-B activity is counteracted, we compare the roles of two outer-kinetochore bound phosphatases and find that BubR1-associated PP2A, unlike KNL1-associated PP1, plays a significant role in end-on conversion. Finally, we uncover a novel role for Aurora-B regulated Astrin-SKAP complex in ensuring the correct plane of kinetochore-microtubule attachment. Thus, we identify Aurora-B as a key upstream regulator of end-on conversion in human cells and establish a late role for Astrin-SKAP complex in the end-on conversion process.
Two mouse models reveal an actionable PARP1 dependence in aggressive chronic lymphocytic leukemia
Authors: Knittel Gero , Rehkämper Tim , Korovkina Darya , Liedgens Paul , Fritz Christian , Torgovnick Alessandro , Al-Baldawi Yussor , Al-Maarri Mona , Cun Yupeng , Fedorchenko Oleg , Riabinska Arina , Beleggia Filippo , Nguyen Phuong-Hien , Wunderlich F. Thomas , Ortmann Monika , Montesinos-Rongen Manuel , Tausch Eugen , Stilgenbauer Stephan , P. Frenzel Lukas , Herling Marco , Herling Carmen , Bahlo Jasmin , Hallek Michael , Peifer Martin , Buettner Reinhard , Persigehl Thorsten , Reinhardt H. Christian
Published: July 2017

Chronic lymphocytic leukemia (CLL) remains an incurable disease. Two recurrent cytogenetic aberrations, namely del(17p), affecting TP53, and del(11q), affecting ATM, are associated with resistance against genotoxic chemotherapy (del17p) and poor outcome (del11q and del17p). Both del(17p) and del(11q) are also associated with inferior outcome to the novel targeted agents, such as the BTK inhibitor ibrutinib. Thus, even in the era of targeted therapies, CLL with alterations in the ATM/p53 pathway remains a clinical challenge. Here we generated two mouse models of Atm- and Trp53-deficient CLL. These animals display a significantly earlier disease onset and reduced overall survival, compared to controls. We employed these models in conjunction with transcriptome analyses following cyclophosphamide treatment to reveal that Atm deficiency is associated with an exquisite and genotype-specific sensitivity against PARP inhibition. Thus, we generate two aggressive CLL models and provide a preclinical rational for the use of PARP inhibitors in ATM-affected human CLL.
Heart regeneration in the salamander relies on macrophage-mediated control of fibroblast activation and the extracellular landscape
Authors: Godwin J. W. , Debuque R. , Salimova E. , Rosenthal N. A.
Published: July 2017

In dramatic contrast to the poor repair outcomes for humans and rodent models such as mice, salamanders and some fish species are able to completely regenerate heart tissue following tissue injury, at any life stage. This capacity for complete cardiac repair provides a template for understanding the process of regeneration and for developing strategies to improve human cardiac repair outcomes. Using a cardiac cryo-injury model we show that heart regeneration is dependent on the innate immune system, as macrophage depletion during early time points post-injury results in regeneration failure. In contrast to the transient extracellular matrix that normally accompanies regeneration, this intervention resulted in a permanent, highly cross-linked extracellular matrix scar derived from alternative fibroblast activation and lysyl-oxidase enzyme synthesis. The activation of cardiomyocyte proliferation was not affected by macrophage depletion, indicating that cardiomyocyte replacement is an independent feature of the regenerative process, and is not sufficient to prevent fibrotic progression. These findings highlight the interplay between macrophages and fibroblasts as an important component of cardiac regeneration, and the prevention of fibrosis as a key therapeutic target in the promotion of cardiac repair in mammals.
Caregiver burden in schizophrenia following paliperidone palmitate long acting injectables treatment: pooled analysis of two double-blind randomized phase three studies
Authors: Gopal Srihari , Xu Haiyan , McQuarrie Kelly , Savitz Adam , Nuamah Isaac , Woodruff Kimberly , Mathews Maju
Published: July 2017

The pooled analysis of two double-blind, randomized, multicenter, phase-3 studies evaluated predictors of improvement or worsening of schizophrenia-related caregiver burden following paliperidone palmitate long-acting injectables (1-monthly [PP1M] and 3-monthly [PP3M]) treatment. Caregivers were offered to complete the involvement evaluation questionnaire (involvement evaluation questionnaire; 31-item scale). Total, 1498 caregivers (intent-to-treat open-label analysis set, n = 1497; mean [SD] age: 51.5 [13.02] years, 27 countries) were included: 49% were parents and >50% caregivers spent >32 hours/week in caregiving. Majority of caregivers with considerable burden (n = 1405; mean [SD] baseline involvement evaluation questionnaire scores: 28.4 [15.07]) improved significantly from baseline to end-of-study (n = 756; mean [SD] change from open-label baseline to double-blind endpoint in long-acting injectable scores:−8.9 [14.73]); most improvements were seen in urging followed by worrying, tension, and supervision domains (mean [SD] change from open-label baseline to double-blind endpoint in involvement evaluation questionnaire scores, urging: −3.7 [6.45]; worrying:−2.6 [5.11]; tension:−2.3 [4.84]; supervision: −1.3 [3.69]). Improvements significantly correlated with relapse status, patient age, and age of diagnosis (p < 0.001) while long-acting injectable use at baseline, number, and duration of prior psychiatric hospitalizations (<24 months) had no significant correlation. Caregiver burden was significantly improved for patients on prior oral antipsychotics post-switching to long-acting injectable, with less impact on leisure days and hours spent in caregiving (p < 0.001). Family members of patients with schizophrenia experience considerable caregiver burden. Switching from oral antipsychotic to long-acting injectable can provide meaningful and significant improvement in caregiver burden.
Foragers of sympatric Asian honey bee species intercept competitor signals by avoiding benzyl acetate from Apis cerana alarm pheromone
Authors: Wen Ping , Cheng Yanan , Qu Yufeng , Zhang Hongxia , Li Jianjun , Bell Heather , Tan Ken , Nieh James
Published: July 2017

While foraging, animals can form inter- and intraspecific social signalling networks to avoid similar predators. We report here that foragers of different native Asian honey bee species can detect and use a specialized alarm pheromone component, benzyl acetate (BA), to avoid danger. We analysed the volatile alarm pheromone produced by attacked workers of the most abundant native Asian honey bee, Apis cerana and tested the responses of other bee species to these alarm signals. As compared to nest guards, A. cerana foragers produced 3.38 fold higher levels of BA. In foragers, BA and (E)-dec-2-en-1-yl acetate (DA) generated the strongest antennal electrophysiological responses. BA was also the only compound that alerted flying foragers and inhibited A. cerana foraging. BA thereby decreased A. cerana foraging for risky sites. Interestingly, although BA occurs only in trace amounts and is nearly absent in sympatric honeybee species (respectively only 0.07% and 0.44% as much in A. dorsata and A. florea), these floral generalists detected and avoided BA as strongly as they did to their own alarm pheromone on natural inflorescences. These results demonstrate that competing pollinators can take advantage of alarm signal information provided by other species.
Distinct brain responses to different inhibitions: Evidence from a modified Flanker Task
Authors: Xie Liufang , Ren Maofan , Cao Bihua , Li Fuhong
Published: July 2017

Whether inhibition is a unitary or multifaceted construct is still an open question. To clarify the electrophysiological distinction among the different types of inhibition, we used a modified flanker paradigm, in which interference inhibition, rule inhibition, and response inhibition were compared to non-inhibition condition. The results indicated that, compared to the non-inhibition condition (1) the interference inhibition condition induced larger negativities during N2 epoch at the frontal region, (2) the rule inhibition condition elicited a larger N1 at the posterior region, followed by a larger P3a at the frontal region, reflecting the function of proactive cognitive control in the new stimulus-reaction (S-R) association, and (3) the response inhibition condition evoked a larger P3b at the posterior region, reflecting the process of suppressing the old response and reprogramming the new action. These findings provide new evidence that distinct neural mechanisms underlie different types of inhibition.
Extreme Quantum Advantage when Simulating Classical Systems with Long-Range Interaction
Authors: Aghamohammadi Cina , Mahoney John R. , Crutchfield James P.
Published: July 2017

Classical stochastic processes can be generated by quantum simulators instead of the more standard classical ones, such as hidden Markov models. One reason for using quantum simulators has recently come to the fore: they generally require less memory than their classical counterparts. Here, we examine this quantum advantage for strongly coupled spin systems—in particular, the Dyson one-dimensional Ising spin chain with variable interaction length. We find that the advantage scales with both interaction range and temperature, growing without bound as interaction range increases. In particular, simulating Dyson’s original spin chain with the most memory-efficient classical algorithm known requires infinite memory, while a quantum simulator requires only finite memory. Thus, quantum systems can very efficiently simulate strongly coupled one-dimensional classical spin systems.
“High-Throughput Characterization of Region-Specific Mitochondrial Function and Morphology”
Authors: Daniele Joseph R. , Esping Daniel J. , Garcia Gilbert , Parsons Lee S. , Arriaga Edgar A. , Dillin Andrew
Published: July 2017

The tissue-specific etiology of aging and stress has been elusive due to limitations in data processing of current techniques. Despite that many techniques are high-throughput, they usually use singular features of the data (e.g. whole fluorescence). One technology at the nexus of fluorescence-based screens is large particle flow cytometry (“biosorter”), capable of recording positional fluorescence and object granularity information from many individual live animals. Current processing of biosorter data, however, do not integrate positional information into their analysis and data visualization. Here, we present a bioanalytical platform for the quantification of positional information (“longitudinal profiling”) of C. elegans, which we posit embodies the benefits of both high-throughput screening and high-resolution microscopy. We show the use of these techniques in (1) characterizing distinct responses of a transcriptional reporter to various stresses in defined anatomical regions, (2) identifying regions of high mitochondrial membrane potential in live animals, (3) monitoring regional mitochondrial activity in aging models and during development, and (4) screening for regulators of muscle mitochondrial dynamics in a high-throughput format. This platform offers a significant improvement in the quality of high-throughput biosorter data analysis and visualization, opening new options for region-specific phenotypic screening of complex physiological phenomena and mitochondrial biology.
Effects of ultrashort laser pulses on angular distributions of photoionization spectra
Authors: Ooi C. H. Raymond , Ho W. L. , Bandrauk A. D.
Published: July 2017

We study the photoelectron spectra by intense laser pulses with arbitrary time dependence and phase within the Keldysh framework. An efficient semianalytical approach using analytical transition matrix elements for hydrogenic atoms in any initial state enables efficient and accurate computation of the photoionization probability at any observation point without saddle point approximation, providing comprehensive three dimensional photoelectron angular distribution for linear and elliptical polarizations, that reveal the intricate features and provide insights on the photoionization characteristics such as angular dispersions, shift and splitting of photoelectron peaks from the tunneling or above threshold ionization(ATI) regime to non-adiabatic(intermediate) and multiphoton ionization(MPI) regimes. This facilitates the study of the effects of various laser pulse parameters on the photoelectron spectra and their angular distributions. The photoelectron peaks occur at multiples of 2ħω for linear polarization while  odd-ordered peaks are suppressed in the direction perpendicular to the electric field. Short pulses create splitting and angular dispersion where the peaks are strongly correlated to the angles. For MPI and elliptical polarization with shorter pulse﻿s﻿ the peaks split into doublets and the first peak vanishes. The carrier envelope phase(CEP) significantly affects the ATI spectra while the Stark effect shifts the spectra of intermediate regime to higher energies due to interference.
Comparison of commercial ELISA assays for quantification of corticosterone in serum
Authors: Kinn Rød Anne Marie , Harkestad Nina , Jellestad Finn Konow , Murison Robert
Published: July 2017

Enzyme-linked immunosorbent assay (ELISA) kits are widely used to quantify corticosterone levels for the assessment of stress in laboratory animals. The aim of this experiment was simply to evaluate if four different and widely used commercial ELISA assays would yield the same or similar values of corticosterone in serum samples taken from laboratory rats after the mild stress of being held for sampling blood from the saphenous vein. Trunk blood was sampled from 32 male Wistar rats 30 minutes after this mild stress exposure and analysed with each of four commercial ELISA kits. Both the Arbor Assays and the DRG-4164 kits were significantly higher than the DRG-5186 and the Enzo kits. There were no significant differences between the DRG-5186 and Enzo kits. Overall the correlations between kits were high. In conclusion, the commercial ELISA kits tested in the present experiment yielded different values of total corticosterone in the same serum samples. The precision in determining true values of the corticosterone level is low for these commercial ELISA kits, although they may be used to determine relative differences within studies.
Anti-AMPA GluA3 antibodies in Frontotemporal dementia: a new molecular target
Authors: Borroni B. , Stanic J. , Verpelli C. , Mellone M. , Bonomi E. , Alberici A. , Bernasconi P. , Culotta L. , Zianni E. , Archetti S. , Manes M. , Gazzina S. , Ghidoni R. , Benussi L. , Stuani C. , Di Luca M. , Sala C. , Buratti E. , Padovani A. , Gardoni F.
Published: July 2017

Frontotemporal Dementia (FTD) is a neurodegenerative disorder mainly characterised by Tau or TDP43 inclusions. A co-autoimmune aetiology has been hypothesised. In this study, we aimed at defining the pathogenetic role of anti-AMPA GluA3 antibodies in FTD. Serum and cerebrospinal fluid (CSF) anti-GluA3 antibody dosage was carried out and the effect of CSF with and without anti-GluA3 antibodies was tested in rat hippocampal neuronal primary cultures and in differentiated neurons from human induced pluripotent stem cells (hiPSCs). TDP43 and Tau expression in hiPSCs exposed to CSF was assayed. Forty-one out of 175 screened FTD sera were positive for the presence of anti-GluA3 antibodies (23.4%). FTD patients with anti-GluA3 antibodies more often presented presenile onset, behavioural variant FTD with bitemporal atrophy. Incubation of rat hippocampal neuronal primary cultures with CSF with anti-GluA3 antibodies led to a decrease of GluA3 subunit synaptic localization of the AMPA receptor (AMPAR) and loss of dendritic spines. These results were confirmed in differentiated neurons from hiPSCs, with a significant reduction of the GluA3 subunit in the postsynaptic fraction along with increased levels of neuronal Tau. In conclusion, autoimmune mechanism might represent a new potentially treatable target in FTD and might open new lights in the disease underpinnings.
Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma
Authors: Casagrande Viviana , Mauriello Alessandro , Bischetti Simone , Mavilio Maria , Federici Massimo , Menghini Rossella
Published: July 2017

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to hepatocarcinoma. Tissue inhibitor of metalloproteinase 3 (Timp3) has a role in the pathogenesis of fatty liver disease associated with obesity and is silenced during metabolic disorders and liver cancer. We generated an hepatocyte-specific TIMP3 ‘gain-of-function’ mouse model under the control of the Albumin promoter (AlbT3) and investigated its effects during high-fat diet (HFD). After 16 weeks of HFD, TIMP3 overexpression significantly improved glucose metabolism, hepatic fatty acid oxidation and cholesterol homeostasis. In AlbT3 mice CYP7A1, MDR3 and MRP2 gene expressions were observed, consistent with higher bile acid synthesis and export. Next, to evaluate the role of A Disintegrin and Metalloproteinase 17 (ADAM17), a crucial target of TIMP3, in these processes, we created mice deficient in Adam17 specifically in hepatocyte (A17LKO) or in myeloid lineage (A17MKO), founding that only A17LKO showed improvement in liver steatosis induced by HFD. Moreover, both, AlbT3 and A17LKO significantly reduced diethylnitrosamine-initiated, HFD-promoted hepatic tumorigenesis assessed by tumor multiplicity and total tumor area. Taken together, these data indicate that hepatic TIMP3 can slow progression of NAFLD, and tumorigenesis, at least in part, through the regulation of ADAM17 activity.
Multidimensional integrative analysis uncovers driver candidates and biomarkers in penile carcinoma
Authors: Marchi Fabio Albuquerque , Martins David Correa , Barros-Filho Mateus Camargo , Kuasne Hellen , Busso Lopes Ariane Fidelis , Brentani Helena , Trindade Filho Jose Carlos Souza , Guimarães Gustavo Cardoso , Faria Eliney F. , Scapulatempo-Neto Cristovam , Lopes Ademar , Rogatto Silvia Regina
Published: July 2017

Molecular data generation and their combination in penile carcinomas (PeCa), a significant public health problem in poor and underdeveloped countries, remain virtually unexplored. An integrativemethodology combin ing genome-wide copy number alteration, DNA methylation, miRNA and mRNA expression analysis was performed in a set of 20 usual PeCa. The well-ranked 16 driver candidates harboring genomic alterations and regulated by a set of miRNAs, including hsa-miR-31, hsa-miR-34a and hsa-miR-130b, were significantly associated with over-represented pathways in cancer, such as immune-inflammatory system, apoptosis and cell cycle. Modules of co-expressed genes generated from expression matrix were associated with driver candidates and classified according to the over-representation of passengers, thus suggesting an alteration of the pathway dynamics during the carcinogenesis. This association resulted in 10 top driver candidates (AR, BIRC5, DNMT3B, ERBB4, FGFR1, PML, PPARG, RB1, TNFSF10 and STAT1) selected and confirmed as altered in an independent set of 33 PeCa samples. In addition to the potential driver genes herein described, shorter overall survival was associated with BIRC5 and DNMT3B overexpression (log-rank test, P = 0.026 and P = 0.002, respectively) highlighting its potential as novel prognostic marker for penile cancer.
Fractal Electrodes as a Generic Interface for Stimulating Neurons
Authors: Watterson W. J. , Montgomery R. D. , Taylor R. P.
Published: July 2017

The prospect of replacing damaged body parts with artificial implants is being transformed from science fiction to science fact through the increasing application of electronics to interface with human neurons in the limbs, the brain, and the retina. We propose bio-inspired electronics which adopt the fractal geometry of the neurons they interface with. Our focus is on retinal implants, although performance improvements will be generic to many neuronal types. The key component is a multifunctional electrode; light passes through this electrode into a photodiode which charges the electrode. Its electric field then stimulates the neurons. A fractal electrode might increase both light transmission and neuron proximity compared to conventional Euclidean electrodes. These advantages are negated if the fractal’s field is less effective at stimulating neurons. We present simulations demonstrating how an interplay of fractal properties generates enhanced stimulation; the electrode voltage necessary to stimulate all neighboring neurons is over 50% less for fractal than Euclidean electrodes. This smaller voltage can be achieved by a single diode compared to three diodes required for the Euclidean electrode’s higher voltage. This will allow patients, for the first time, to see with the visual acuity necessary for navigating rooms and streets.
Image based modeling of bleb site selection
Authors: Collier Sharon , Paschke Peggy , Kay Robert R. , Bretschneider Till
Published: July 2017

Cells often employ fast, pressure-driven blebs to move through tissues or against mechanical resistance, but how bleb sites are selected and directed to the cell front remains an open question. Previously, we found that chemotaxingDictyosteliumcells preferentially bleb from concave regions, where membrane tension facilitates membrane-cortex detachment. Now, through a novel modeling approach based on actual cell contours, we use cell geometry to predict where blebs will form in migrating cells. We find that cell geometry alone, and by implication, physical forces in the membrane, is sufficient to predict the location of blebs in rounded cells moving in a highly resistive environment. The model is less successful with more polarized cells moving against less resistance, but can be greatly improved by positing a front-to-back gradient in membrane-cortex adhesion. In accord with this prediction, we find that Talin, which links membrane and cortex, forms such a front-to-back gradient. Thus our model provides a means of dissecting out the role of physical forces in controlling where blebs form, and shows that in certain circumstances they could be the major determining factor.