bluuebunny/crossref_metadata_2025 huggingface dataset:
Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy
Authors: Eshleman Nichole , Liu Guangbo , McGrath Kaitlyn , Parker Roy , Buchan J. Ross
Published: June 2016

The nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3′ end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci (“TT foci”) are not stress granules but instead are a mRNP granule containing poly(A)+ mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3′ end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus.
Molecular studies of exercise, skeletal muscle, and ageing
Authors: Timmons James A. , Gallagher Iain J.
Published: June 2016

The purpose of an F1000 review is to reflect on the bigger picture, exploring controversies and new concepts as well as providing opinion as to what is limiting progress in a particular field. We reviewed about 200 titles published in 2015 that included reference to ‘skeletal muscle, exercise, and ageing’ with the aim of identifying key articles that help progress our understanding or research capacity while identifying methodological issues which represent, in our opinion, major barriers to progress. Loss of neuromuscular function with chronological age impacts on both health and quality of life. We prioritised articles that studied human skeletal muscle within the context of age or exercise and identified new molecular observations that may explain how muscle responds to exercise or age. An important aspect of this short review is perspective: providing a view on the likely ‘size effect’ of a potential mechanism on physiological capacity or ageing.
Complex mechanisms linking neurocognitive dysfunction to insulin resistance and other metabolic dysfunction
Authors: Stoeckel Luke E. , Arvanitakis Zoe , Gandy Sam , Small Dana , Kahn C. Ronald , Pascual-Leone Alvaro , Pawlyk Aaron , Sherwin Robert , Smith Philip
Published: June 2016

Scientific evidence has established several links between metabolic and neurocognitive dysfunction, and epidemiologic evidence has revealed an increased risk of Alzheimer’s disease and vascular dementia in patients with diabetes. In July 2015, the National Institute of Diabetes, Digestive, and Kidney Diseases gathered experts from multiple clinical and scientific disciplines, in a workshop entitled “The Intersection of Metabolic and Neurocognitive Dysfunction”, to clarify the state-of-the-science on the mechanisms linking metabolic dysfunction, and insulin resistance and diabetes in particular, to neurocognitive impairment and dementia. This perspective is intended to serve as a summary of the opinions expressed at this meeting, which focused on identifying gaps and opportunities to advance research in this emerging area with important public health relevance.
Business Cycles and Their International Transmission – the Introduction to the Problem
Authors: Szymanik Ewa
Published: June 2016

The article presents the problem of business cycle transmission and the role of canals of transmission in the contemporary world. Because of the theoretical character of the problem the used methodology is a presentation of the results of the researches and theoretical works about the problem of crisis sources and their transmission.
Rational And Methods Of Research Into Consumer Market Behaviour
Authors: Zalega Tomasz
Published: June 2016

The issue of rationality of consumption and consumer behavior becomes more and more relevant in today’s economy. The objective of this article is to analyze the rationality of consumer behaviors in the market from the point of view of various economic schools, using classical methods as well as the concept of ecological rationality which is more akin to an institutional approach. The article also addresses important, selected aspects concerning certain approaches and methods used in research on rationality of consumer behaviors in the market. Particular attention is paid to the problem of rationality in methodology of empirical studies. The analysis of selected research approaches (i.e. predictive and postdictive approach) to the problem of rational choice and consumer behavior, considered from the point of view of both those approaches, makes for a summing-up of the article.
Optimized Financial Systems Helps Customers Meet Their Personal Finance Goals with Optimization
Authors: Woodruff Joshua , Haskell William B. , Toriello Alejandro
Published: June 2016

We consider the retirement planning question that a single taxpayer or couple faces when determining an amount to save for retirement and the type of retirement account in which to allocate the assets. Additionally, taxpayers can choose to convert savings from one account type, such as a traditional individual retirement arrangement (IRA), into another, such as a Roth IRA; all such choices have both immediate and long-term tax consequences. We give the rationale for applying stochastic optimization in this setting and explain how such an optimization model can be constructed as a multiple-stage stochastic linear or mixed-integer program. Optimized Financial Systems implements such a model and uses it to advise clients; we demonstrate the approach’s benefits by examining its recommendations both for test data and in a case study based on an actual customer.
Extending Nonmarket Strategy: Political Economy and the Radical Flank Effect in Private Politics
Authors: Baron David P. , Neale Margaret , Rao Hayagreeva
Published: June 2016

This paper examines a private politics environment in which a confrontational activist and a cooperative activist face a profit-maximizing firm and a self-regulating firm. The environment is studied from a perspective that combines the radical flank effect from sociology and the political economy approach to private politics and nonmarket strategy. We present a formal model in which behavior depends upon favoritism, awareness of a positive externality, and own or aggregate objectives of the activists, and we calibrate these factors through an online experiment. From the experiment, the greater the harm from the confrontational activist, the higher are the offers to work with the cooperative activist and avoid targeting by the confrontational activist. The self-regulator is favored by the activists and offers less than the profit-maximizer. The confrontational activist also favors the self-regulator by threatening a less aggressive campaign. The intensity of the threat results in a positive externality, and to exploit the externality, donors shift resources from the cooperative activist to the confrontational activist. The transfer is greater if the activists’ objectives are the accomplishments of both activists rather than their own accomplishments. Strategy implications are drawn from the model and the results of the experiment.
Pre-conception care for women with diabetes: A public health issue
Authors: Hughes Clare , Spence Dale , Alderice Fiona , Gormley Kevin
Published: June 2016

Pre-conception care is recognised to be an effective strategy for addressing many health behaviours, particularly for women with diabetes, who carry a higher risk of morbidity and mortality. However, there is a lack of evidence of the most effective approaches for promoting pre-conception health and encouraging women to access services. This article explores this challenging issue and suggests a number of strategies that health professionals may consider in relation to promoting health in this area.
Train together to work together: Reviewing feedback of community-based skills drills training for midwives and paramedics
Authors: Pauley Tara , Dale Ailsa
Published: June 2016

Homebirth is recommended in the UK for women considered low-risk, but homebirth rates remain low. With the aim of enabling women to safely achieve the birth they want, and enabling midwives to support them in this, a community-based skills drills training session was organised by midwives at Hinchingbrooke Health Care NHS Trust, and attended by midwives, student midwives, maternity care assistants and paramedics. A questionnaire was given to participants to evaluate the training. A 100% response rate was achieved (n = 36). Results show a positive response from all parties in relation to the setting, which was deemed a more realistic environment for this workforce than that offered by hospital-based training. More funding and research to support this type of training may aid in raising homebirth rates, as well as developing midwives' and paramedics' confidence in dealing with emergencies in such settings.
Clinicians in the classroom: The matron
Authors: Power Alison , Briody Paula
Published: June 2016

The role of matron was introduced to give senior midwives and nurses the authority to get the basics right. Midwifery matrons' responsibilities include providing professional leadership; ensuring that care provided on wards, in antenatal clinics and the delivery suite is high-quality and woman-centred; and handling any complaints that arise. Given the nature of this demanding role, matrons are not able to commit to facilitating student learning in the hospital environment; however, at the University of Northampton, pre-registration midwifery students in the third year of their programme have the privilege of attending sessions with a matron. Paula Briody, matron for intrapartum care at Northampton General Hospital NHS Trust, facilitates two sessions which give students the opportunity to learn about this key role in midwifery.
Anaesthesia of the patient with cardiovascular disease part 2: anaesthesia for specific disorders
Authors: Scarabelli Stefania , Bradbrook Carl
Published: June 2016

In the first part of the article, risk assessment of the patient with cardiovascular disease (CVD) was discussed. In this second part, basic pathophysiology of the most commonly encountered CVD in dogs and cats are reviewed, together with haemodynamic goals during anaesthesia in these patients along with choice of the most suitable anaesthetic technique. Aspects of monitoring of anaesthesia for the patient with CVD are briefly reviewed.
Toileting troubles part 1: factors influencing house soiling in cats and dogs
Authors: Tomlinson Catherine
Published: June 2016

The discovery of faeces and urine in the home is a common annoyance for owners of cats and dogs and is often perceived, incorrectly, as an inevitable part of pet ownership. Lack of early intervention can lead to long-term house soiling; this can be exasperating and put strain on the human-animal bond, as well as requiring the investment of time and money in cleaning, repairing and sometimes even replacing soiled possessions. In extreme cases, house soiling can lead to a breakdown in the relationship to such a degree that the owner may relinquish their pet or have the animal euthanased. An understanding of the factors influencing house soiling issues, and the concomitant design of management programmes for individual cases, is pivotal for owners to maintain a good relationship with their animal. This article identifies the main types of house soiling issues and examines the factors influencing these; part 2 will provide ways of managing house soiling issues.
“The Lord Struck Him Down by the Hand of a Female!” Baroque Artists Depicting Judith in the Renaissance
Authors: Delis Tina M
Published: June 2016

Gender themed Research Project, using the biblical story of Judith and Holofernes to examine how Baroque artists tackled representing Judith as a female figure who openly subverts the Renaissance gender norms by defeating a male.  Focusing on the artists, Michelangelo Merisi da Caravaggio, Orazio Gentileschi and Artemisia Gentileschi, the paper explores through visual analysis how each artist approached representing the gender issue within the biblical narrative in their artwork.  The biblical narrative is discussed and two well-disseminated published articles about gender roles are reviewed.  Additionally, how the Counter-Reformation and the Catholic Church’s assertive stance for the purpose of art effects how images of Judith are painted.
A Study of Hypermethylated Circulating Tumor DNA as a Universal Colorectal Cancer Biomarker
Authors: Garrigou Sonia , Perkins Geraldine , Garlan Fanny , Normand Corinne , Didelot Audrey , Le Corre Delphine , Peyvandi Sanam , Mulot Claire , Niarra Ralph , Aucouturier Pascaline , Chatellier Gilles , Nizard Philippe , Perez-Toralla Karla , Zonta Eleonora , Charpy Cecile , Pujals Anais , Barau Caroline , Bouché Olivier , Emile Jean-François , Pezet Denis , Bibeau Frederic , Hutchison J Brian , Link Darren R , Zaanan Aziz , Laurent-Puig Pierre , Sobhani Iradj , Taly Valerie
Published: June 2016

BACKGROUND

Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored.

METHODS

We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up.

RESULTS

Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution.

CONCLUSIONS

These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.
TURISMO DE AVENTURA EM TAQUARUÇU – TO: ATIVIDADES E RISCOS
Authors: Melo Stella Maria Carvalho de , Aguiar Eveline Porto Sales
Published: June 2016

Este trabalho buscou analisar de que forma as atividades de aventura estão sendo desenvolvidas em Taquaruçu – TO, no que diz respeito aos riscos para seus praticantes. A pesquisa foi realizada durante os meses de agosto a novembro de 2015 e teve como referência Normas Técnicas da ABNT de certificação de atividades de aventura, considerando-se a classificação, a orientação e o inventário de perigos e riscos. Foram realizadas visitas em quatro cachoeiras, bem como nas suas trilhas de acesso e no mirante da região. Constatou-se que as trilhas de três delas devem ser guiadas, por conta do grau de severidade do meio, restando apenas uma a ser autoguiada. Porém nenhuma das trilhas atende a todas as regras determinadas pelas normas. A prática do cachoeirismo e da tirolesa também não cumpre todas as determinações. Com isso, percebeu-se que estas atividades não estão sendo desenvolvidas de forma mais segura, o que é um risco para os praticantes. Assim, este trabalho comprovou as fragilidades do turismo de aventura quanto aos riscos detectados, sendo proposta a construção de parcerias que visem a mais estudos na região e capacitação dos profissionais do setor, estimulando a prática da atividade, levando-se em consideração a qualidade e a confiabilidade dos serviços executados.
A PERCEPÇÃO DOS HÓSPEDES DE NEGÓCIOS QUANTO AO DESEMPENHO DA QUALIDADE DOS SERVIÇOS PRESTADOS NOS HOTÉIS DE FLORIANÓPOLIS: UMA ANÁLISE A PARTIR DO CONTEÚDO GERADO NO WEBSITE BOOKING.COM
Authors: Petry Tânia Regina Egert , Pickler Cibelli De Medeiros , Tomelin Carlos Alberto
Published: June 2016

A fim de melhorar sua participação nacional no segmento de turismo de negócios e eventos, os empreendedores da cidade de Florianópolis devem primar pela qualidade dos serviços oferecidos. Para tanto, com os consumidores cada vez mais exigentes e apoiados em sites de avaliações de serviços para auxiliar nas suas escolhas, uma maior atenção das empresas neste sentido denota-se necessária. No turismo, o chamado Conteúdo Gerado pelo Usuário (CGU) se populariza à medida que serve como fonte de informação. Por esta razão, o presente artigo teve como objetivo avaliar a percepção dos hóspedes de negócios quanto ao desempenho da qualidade dos serviços prestados em seis hotéis da cidade de Florianópolis. Para tal, utilizou-se um estudo do tipo exploratório-descritivo, tendo como método analítico o qualitativo. Foram avaliados 1.133 comentários postados pelos usuários no site de viagens Booking.com de acordo com as dimensões da qualidade do Modelo SERVPERF. A escolha do site se deu por sua penetração de escala junto ao público investigado. Os elementos de maior destaque apontados pelos hóspedes foram aferidos em escala de prioridade, utilizando-se para a análise de textos o Software NVIVO. Diante dos resultados, observou-se que os aspectos tangíveis tiveram maior grau de prioridade nas avaliações dos hóspedes, com destaque para a localização, o café da manhã e o conforto do quarto, como os principais pontos fortes, o que pode auxiliar os hotéis na formulação de estratégias para maximizar ainda mais estes aspectos. Em contrapartida, os equipamentos e as instalações foram mal avaliados, o que denota oportunidades de melhoria nas evidências físicas assinaladas. Ao se pensar nas categorias serviços e infraestrutura, percebe-se a inter-relação sobre atributos de qualidade nos aspectos tangíveis avaliados pelos hóspedes.
Is Prophethood Superfluous?Conflicting Outlook on the Necessity of Prophethood between Badiuzzaman Said Nursi and Some Muslim Philosophers
Authors: Saleh Fauzan
Published: June 2016

As early as tenth century, Abū Bakr al-Rāzī (d. 925), a notable figure in Islamic philosophy, claimed that prophethood is entirely superfluous, since God imparted the gift of reason to humankind, and reason is enough to guide them. Al-Rāzī’s skeptical view sounds provocative, and thus worthy of further study. However, some other philosophers, like al-Farābī, Ibn Sīnā and Ibn Maskawaih, acknowledge the necessity of prophethood for the guidance of human life. Their idea, though formulated in different reasoning from the one held by Muslim theologians, indicates their acceptance of the authority of divine revelation. On the other hand, Said Nursi, one of the greatest Muslim reformers in the modern time, maintains that since “divine power does not leave the ant without leader, or bees without a queen, it surely would not leave mankind without prophet or code of law.” After all, the order of the world necessitates the existence of the prophets to preserve its solidity. This article will scrutinize more critically Nursi’s idea on the necessity of divine revelation that would enlighten human path to truth, to be compared with some ideas held by Muslim philosophers in discussing the relationship between reason and revelation, and its corollaries.[Filsuf besar dari abad ke-10, Abū Bakr al-Rāzī (w. 925), menyatakan bahwa diutusnya seorang nabi sebenarnya tidak perlu lagi, karena Tuhan telah menganugerahkan akal pada manusia yang akan mampu membimbing mereka. Pandangan skeptis dari al-Rāzī ini terdengar provokatif dan perlu dieksplorasi lebih lanjut. Namun, beberapa filsuf seperti al-Farabi, Ibnu Sina, dan Ibn Maskawaih mengakui perlunya nabi untuk membimbing manusia. Pandangan para filsuf ini, meski dengan nalar yang berbeda dengan para ahli teologi, mengindikasikan penerimaan terhadap otoritas wahyu ketuhanan. Di sisi lain, Said Nursi, seorang pemikir-reformis modern, menyatakan bahwa karena “kuasa Tuhan tidak pernah membiarkan sekawanan semut tanpa pemimpin, atau sekelompok lebah tanpa ratunya, maka pastilah manusia juga tidak akan dibiarkan tanpa seorang nabi atau syariat.” Lebih dari itu, tata dunia juga memerlukan kehadiran seorang nabi untuk menjaga soliditasnya. Tulisan ini akan melihat secara lebih dalam dan kritis mengenai pemikiran Said Nursi tentang pentingnya wahyu ketuhanan untuk menerangi langkah manusia menemukan kebenaran; kemudian dibandingkan dengan pandangan filsuf-filsuf muslim lainnya dalam membincang keterkaitan nalar dan wahyu dengan segala konsekuensinya.]
A Role for Legitimacy in Sovereign Debt: A Review Essay on Odette Lienau, Rethinking Sovereign Debt, 2014
Authors: Herman Barry
Published: June 2016

The book under review seems especially relevant to the intergovernmental policy dialogues that have recently focused on how creditors and a borrowing government should vet sovereign borrowing, and how to hold the lender and borrower accountable for their decisions. The book seeks to specify under what circumstances, if any, there are limits to the legal obligation to repay a sovereign loan. While repayment is always required except in cases of sovereign insolvency when it is just not possible, there have been exceptions to absolute repayment obligation in practice and in legal theory. This review builds on the author’s analysis of determinants of illegitimacy (which would remove the obligation to repay) in order to examine why governments in fact repay their loans, why the loss of access to credit makes repudiation of odious loans rare, and how if enforcing the obligation to repay were restricted to “responsible” lending and borrowing under internationally agreed terms, it could advance socially and environmentally sustainable development, while maintaining normal financial market activity of sovereigns. Finally, complementing a loan-by-loan approach, this paper calls for an internationally concerted process for more effectively and fairly resolving sovereign insolvencies.
Improved impregnation efficiency and pulp yield of softwood kraft pulp by high effective alkali charge in the impregnation stage
Authors: Brännvall Elisabet , Bäckström Marie
Published: June 2016

A pulp yield increase up to 2% can be achieved by impregnation with a liquor containing 2 M effective alkali (EA) concentration instead of 1 M. The yield increase is due to higher cellulose and glucomannan contents in the pulp, which can be rationalized by less yield loss by peeling, as impregnation is more effective at an elevated EA level. A rapid loading of chips with alkali can be realized due to a high diffusion rate. When the temperature becomes higher in the cooking stage, enough alkali is available for delignification reactions without the risk of alkali depletion in the chip core, so that the delignification is more homogeneous.
Modeling the Transient VOC (toluene) Oxidation in a Packed-Bed Catalytic Reactor
Authors: Esparza-Isunza Tristán , López-Isunza Felipe
Published: June 2016

A model is developed to study the transient behavior of a non-isothermal, non-adiabatic packed-bed reactor during VOC (toluene) oxidation with air on a mixed-oxide catalyst via Mars-van Krevelen kinetic scheme. The aim is to find a safe reactor design and operating conditions for VOC elimination, which has been collected in a battery of adsorption units from dilute VOC streams. Once each adsorption column is saturated, a non-isothermal desorption takes place, and the gas stream exiting the sequence of VOC desorption columns feeds continuously the catalytic reactor for VOC elimination. The reactor model describes a 2D two-phase system interacting through the gas-solid interphase, including convection and axial and radial dispersions of mass and heat. The simulations show that the gas flow velocity, and reactor and particle diameters, are key parameters to achieve a safe design, and that traveling reaction fronts in the packed-bed exist when a series of reversible stepwise changes are performed in the concentration and temperature at the feed, as a result of the transient balance between heat generation and heat elimination along the packed-bed. When comparing the perturbation in VOC concentration at the feed versus those in temperature, a large parametric sensitivity is observed for the latter case without the presence of multiple steady states. Due to the uncertainty in the values of the effective heat transport parameters, transient responses of different magnitude are observed for the same operating conditions when using heat transport parameter of different magnitude.
A Study of the Soft-Sphere Model in Eulerian-Lagrangian Simulation of Gas-Liquid Flow
Authors: Xue Jing , Chen Feiguo , Yang Ning , Ge Wei
Published: June 2016

Eulerian-Lagrangian method is becoming more and more popular for the simulation of dispersed multiphase flow as the computational ability grows. An important issue in this method is the handle of collisions. Until now, both hard-sphere and soft-sphere models have been used extensively in the simulation of gas-solid systems while in gas-liquid systems only the hard-sphere model is used. This study presents an investigation of the performance of the soft-sphere model in gas-liquid systems. The open source software OpenFOAM is utilized to complete our simulations. We simulated the 2D Becker case to give a preliminary study of the suitability of the soft-sphere model in gas-liquid systems. We tested the normal stiffness coefficient from 50 N/m to 0.01 N/m and found that the coefficient 1 N/m predicted sufficiently accurate flow field. In the simulation of 3D Deen case, we tried more stiffness coefficients and found that the soft-sphere model successfully predicted the fluid velocity, and the result at a normal stiffness coefficient of 1 N/m is the optimum. It can be expected that the soft-sphere model is also suitable in gas-liquid systems.
A 6-year longitudinal study of self-efficacy in Chinese secondary school students in Hong Kong
Authors: Shek Daniel T.L. , Liang Lu-Yin
Published: June 2016

This study examined the development of self-efficacy in the high school years and the related socio-demographic and family correlates. A longitudinal research design was used to collect data from students in Grade 7 to Grade 12. At each wave, students responded to measures of socio-demographic characteristics (gender, economic disadvantage and non-intactness), family processes (family functioning and parent-child relational quality), academic and school competence and self-efficacy. Results showed that self-efficacy increased in the adolescent years. Regarding socio-demographic predictors, economic disadvantage and family non-intactness were related to adolescent self-efficacy. Findings also showed that family processes (family functioning and parent-child subsystem quality) and academic and school competence were related to adolescent self-efficacy but the nature of relationships was more complex than expected.
On the complexity of binary floating point pseudorandom generation
Authors: Nekrutkin Vladimir
Published: June 2016

The paper is devoted to the complexity analysis of binary floating point pseudorandom generators. We start with a stochastic model of a “usual”
pseudorandom generator (PRNG). Then integer outputs
of this generator are transformed into i.i.d. random variables,
agreed with
an abstract binary floating point system. Additionally, these random variables
are approximately uniformly distributed on the interval [0,1]. Therefore, they can interpreted as (random) outputs of a binary floating point pseudorandom generator
(flPRNG).
The simulation complexity of such a transformation is defined as the average number of PRNG's outputs
necessary to produce the unique
output of flPRNG.
Several transformations with minimal or approximately minimal complexities are presented and discussed.
Competing Rather than Collaborating: Egyptian Nongovernmental Organizations in Turbulence
Authors: Herrold Catherine , Atia Mona
Published: June 2016

This article examines how the Egyptian government produced a legal, regulatory, and operational environment designed to “divide and throttle” the country’s NGO sector. We identify a two-pronged government strategy toward the NGO sector – namely, flooding the field and bureaucratic overload – the effect of which was to fragment and weaken the sector and prevent it from forming an effective oppositional bloc. We furthermore argue that this government strategy promoted competition rather than cooperation among NGOs. Organizations espoused competing strategic visions for the sector that divided organizations into camps of “charity,” “development,” and “advocacy.” The ultimate consequence of this competition was a sector of NGOs that, instead of valuing pluralism and building upon diverse comparative advantages to create sector-wide strength, belittled each other and failed to coalesce. Egypt’s NGO sector became a tool of the state rather than a force for collective empowerment or a voice for societal change.
Impact of Handling Errors for Chemical Cross-contamination Risk for the Preparation of Parenteral Cytotoxic Drugs
Authors: Vazquez Raphael , Boubet Kevin , Guerrault-Moro Marie-Noelle , Crauste-Manciet Sylvie
Published: June 2016

The aim of the study was to evaluate the risk of chemical cross-contamination between preparations of cytotoxic drugs performed in hospital pharmacy. Simulation of handling process errors was performed with two selected tracers, thiamine and retinol to mimic hydrophilic and lipophilic cytotoxic drugs. Four types of handling errors were simulated: errors associated with the re-use of a disposable transfer device: syringe, spike and needle and errors associated with surface contamination such as the use of a contaminated pad. The results show rates of contamination above the limit of quantification with the re-use of a syringe, a needle or a spike. For example, with the thiamine solution at 50 mg/ml final concentration, the re-use of a spike led to a contamination of approximately 100 µl equivalent to 5 mg. By contrast, the use of a surface contaminated pad failed to detect a cross-contamination. Cross-contamination related to a contamination of surface by a cytotoxic drug represents a low risk. However, the re-use of a single medical device due to handling human error led to quantifiable risk of cross-contamination. Furthermore, this type of error is very difficult to detect and may be frequent enough to have potential impact on patient.
Probabilistic pragmatics, or why Bayes’ rule is probably important for pragmatics
Authors: Franke Michael , Jäger Gerhard
Published: June 2016

Probabilistic pragmatics aspires to explain certain regularities of language use and interpretation as behavior of speakers and listeners
who want to satisfy their conversational interests in a context that may contain a substantial amount of uncertainty. This approach differs
substantially from more familiar approaches in theoretical pragmatics. To set it apart, we here work out some of its key distinguishing
features and show, by way of some simple examples, how probabilistic pragmatics instantiates these.
Pragmatisms and Logical Empiricisms: Response to Misak and Klein
Authors: Uebel Thomas
Published: June 2016

This paper responds to the generous comments by Alexander Klein and Cheryl Misak on my “American Pragmatism and the Vienna Circle: The Early Years”. First, besides offering some clarification of my original thesis, I argue that Jerusalem was not liable to the anti-Spencerian criticisms by James that Klein adduces in the course of defending James against the charge of psychologism. Then I investigate the impact of Wittgenstein’s Ramsey-derived pragmatism, importantly foregrounded by Misak, on the Vienna Circle and argue that it was mainly limited to Schlick but not recognized as pragmatist, also leaving unaffected the impact of James’s pragmatism on Frank, Hahn and Neurath specified in my original paper. That said, Klein’s and Misak’s comments add significantly to our understanding of long-neglected transatlantic philosophical connections in the early twentieth century.
Influence of Strength Level on the Rest Interval Required During an Upper-Body Power Training Session
Authors: Hernández Davó Jose Luis , Botella Ruiz Javier , Sabido Rafael
Published: June 2016

Hernández Davó, JL, Botella Ruiz, J, and Sabido, R. Influence of strength level on the rest interval required during an upper-body power training session. J Strength Cond Res 31(2): 339–347, 2017—The present study aimed to investigate the influence of subjects' strength level on both the ability to maintain power output performance and the physiological and perceived exertion responses during a power training session when different rest intervals (RI) are used. Thirty-eight (18 men and 20 women) subjects were divided into a stronger or weaker group based on their ability to produce peak power output. Testing was performed using the same protocol (5 sets of 8 repetitions with 40% of 1 repetition maximum) in the bench press throw exercise, but differing the RI between sets (1, 2, and 3 minutes). During the sessions, mechanical (peak power), physiological ([La−]) and perceptual (RPE) variables were measured. In addition, delayed onset muscular soreness (DOMS) 24 and 48 hours after the training session was reported. Both stronger and weaker (men and women) groups showed significant impairments in mechanical, physiological, and perceptual data when resting 1 minute. Nevertheless, although stronger groups were able to sustain power output over the sets when using the 2-minute RI, weaker groups needed at least 3 minutes to maintain power output performance. Therefore, strength level heavily influences the rest interval required during a power training session and should be taken into account when prescribing such training sessions.
GABA Receptors on Orexin and Melanin-Concentrating Hormone Neurons Are Differentially Homeostatically Regulated Following Sleep Deprivation
Authors: Toossi Hanieh , del Cid-Pellitero Esther , Jones Barbara E.
Published: June 2016

Though overlapping in distribution through the hypothalamus, orexin (Orx) and melanin-concentrating hormone (MCH) neurons play opposite roles in the regulation of sleep–wake states. Orx neurons discharge during waking, whereas MCH neurons discharge during sleep. In the present study, we examined in mice whether GABAAand GABABreceptors (Rs) are present on Orx and MCH neurons and might undergo differential changes as a function of their different activities following sleep deprivation (SD) and sleep recovery (SR). Applying quantitative stereological image analysis to dual-immunofluorescent stained sections, we determined that the proportion of Orx neurons positively immunostained for GABAARs was significantly higher following SD (∼48%) compared with sleep control (SC; ∼24%) and SR (∼27%), and that the luminance of the GABAARs was significantly greater. In contrast, the average proportion of the MCH neurons immunostained for GABAARs was insignificantly lower following SD (∼43%) compared with SC (∼54%) and SR (56%), and the luminance of the GABAARs was significantly less. Although, GABABRs were observed in all Orx and MCH neurons (100%), the luminance of these receptors was differentially altered following SD. The intensity of GABABRs in the Orx neurons was significantly greater after SD than after SC and SR, whereas that in the MCH neurons was significantly less. The present results indicate that GABA receptors undergo dynamic and differential changes in the wake-active Orx neurons and the sleep-active MCH neurons as a function of and homeostatic adjustment to their preceding activity and sleep–wake state.
Neural Representation of Odor-Guided Behavior in the Rat Olfactory Thalamus
Authors: Courtiol Emmanuelle , Wilson Donald A.
Published: June 2016

The mediodorsal thalamus (MDT) is a higher-order corticocortical thalamic nucleus involved in cognition and memory. However, anatomically, the MDT is also the primary site of olfactory representation in the thalamus, receiving strong inputs from olfactory cortex and having reciprocal connections with orbitofrontal cortex (OFC). Nonetheless, its role in olfaction remains unclear. Here, we recorded single units in the MDT, as well as local field potentials in the MDT, piriform cortex (PCX), and OFC in rats performing a two-alternative odor discrimination task. We show that subsets of MDT units display odorant selectivity during sampling, as well as encoding of spatio-motor aspects of the task. Furthermore, the olfactory trans-thalamic network rapidly switches functional connectivity between MDT and cortical areas depending on current task demands, with, for example, MDT-PCX coupling enhanced during odor sampling and MDT-OFC coupling enhanced during the decision/goal approach compared with baseline and presampling. These results demonstrate MDT representation of diverse sensorimotor components of an olfactory task.

SIGNIFICANCE STATEMENTThe mediodorsal thalamus (MDT) is the major olfactory thalamic nucleus and links the olfactory archicortex with the prefrontal neocortex. The MDT is well known to be involved in higher-order cognitive and memory functions, but its role in olfaction is poorly understood. Here, using single-unit and local field potential analyses, we explored MDT function during an odor-guided decision task in rats. We describe MDT odor and multisensory coding and demonstrate behavior-dependent functional connectivity within the MDT/sensory cortex/prefrontal cortex network. Our results suggest a rich representation of olfactory and other information within MDT required to perform this odor-guided task. Our work opens a new model system for understanding MDT function and exploring the important role of MDT in cortical–cortical communication.
Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain
Authors: Goeden Nick , Velasquez Juan , Arnold Kathryn A. , Chan Yen , Lund Brett T. , Anderson George M. , Bonnin Alexandre
Published: June 2016

Maternal inflammation during pregnancy affects placental function and is associated with increased risk of neurodevelopmental disorders in the offspring. The molecular mechanisms linking placental dysfunction to abnormal fetal neurodevelopment remain unclear. During typical development, serotonin (5-HT) synthesized in the placenta from maternall-tryptophan (TRP) reaches the fetal brain. There, 5-HT modulates critical neurodevelopmental processes. We investigated the effects of maternal inflammation triggered in midpregnancy in mice by the immunostimulant polyriboinosinic-polyribocytidylic acid [poly(I:C)] on TRP metabolism in the placenta and its impact on fetal neurodevelopment. We show that a moderate maternal immune challenge upregulates placental TRP conversion rapidly to 5-HT through successively transient increases in substrate availability and TRP hydroxylase (TPH) enzymatic activity, leading to accumulation of exogenous 5-HT and blunting of endogenous 5-HT axonal outgrowth specifically within the fetal forebrain. The pharmacological inhibition of TPH activity blocked these effects. These results establish altered placental TRP conversion to 5-HT as a new mechanism by which maternal inflammation disrupts 5-HT-dependent neurogenic processes during fetal neurodevelopment.

SIGNIFICANCE STATEMENTThe mechanisms linking maternal inflammation during pregnancy with increased risk of neurodevelopmental disorders in the offspring are poorly understood. In this study, we show that maternal inflammation in midpregnancy results in an upregulation of tryptophan conversion to serotonin (5-HT) within the placenta. Remarkably, this leads to exposure of the fetal forebrain to increased concentrations of this biogenic amine and to specific alterations of crucially important 5-HT-dependent neurogenic processes. More specifically, we found altered serotonergic axon growth resulting from increased 5-HT in the fetal forebrain. The data provide a new understanding of placental function playing a key role in fetal brain development and how this process is altered by adverse prenatal events such as maternal inflammation. The results uncover important future directions for understanding the early developmental origins of mental disorders.
An Optogenetic Approach for Investigation of Excitatory and Inhibitory Network GABA Actions in Mice Expressing Channelrhodopsin-2 in GABAergic Neurons
Authors: Valeeva Guzel , Tressard Thomas , Mukhtarov Marat , Baude Agnes , Khazipov Rustem
Published: June 2016

To investigate excitatory and inhibitory GABA actions in cortical neuronal networks, we present a novel optogenetic approach using a mouse knock-in line with conditional expression of channelrhodopsin-2 (ChR2) in GABAergic interneurons. During whole-cell recordings from hippocampal and neocortical slices from postnatal day (P) 2–P15 mice, photostimulation caused depolarization and excitation of interneurons and evoked barrages of postsynaptic GABAergic currents. Excitatory/inhibitory GABA actions on pyramidal cells were assessed by monitoring the alteration in the frequency of EPSCs during photostimulation of interneurons. We found that in slices from P2–P8 mice, photostimulation evoked an increase in EPSC frequency, whereas in P9–P15 mice the response switched to a reduction in EPSC frequency, indicating a developmental excitatory-to-inhibitory switch in GABA actions on glutamatergic neurons. Using a similar approach in urethane-anesthetized animalsin vivo, we found that photostimulation of interneurons reduces EPSC frequency at ages P3–P9. Thus, expression of ChR2 in GABAergic interneurons of mice enables selective photostimulation of interneurons during the early postnatal period, and these mice display a developmental excitatory-to-inhibitory switch in GABA action in cortical slicesin vitro, but so far show mainly inhibitory GABA actions on spontaneous EPSCs in the immature hippocampus and neocortexin vivo.

SIGNIFICANCE STATEMENTWe report a novel optogenetic approach for investigating excitatory and inhibitory GABA actions in mice with conditional expression of channelrhodopsin-2 in GABAergic interneurons. This approach shows a developmental excitatory-to-inhibitory switch in the actions of GABA on glutamatergic neurons in neocortical and hippocampal slices from neonatal mouse pupsin vitro, but also reveals inhibitory GABA actions in the neonatal mouse neocortex and hippocampusin vivo.
Transient P2X7 Receptor Antagonism Produces Lasting Reductions in Spontaneous Seizures and Gliosis in Experimental Temporal Lobe Epilepsy
Authors: Jimenez-Pacheco Alba , Diaz-Hernandez Miguel , Arribas-Blázquez Marina , Sanz-Rodriguez Amaya , Olivos-Oré Luis A. , Artalejo Antonio R. , Alves Mariana , Letavic Michael , Miras-Portugal M. Teresa , Conroy Ronan M. , Delanty Norman , Farrell Michael A. , O'Brien Donncha F. , Bhattacharya Anindya , Engel Tobias , Henshall David C.
Published: June 2016

Neuroinflammation is thought to contribute to the pathogenesis and maintenance of temporal lobe epilepsy, but the underlying cell and molecular mechanisms are not fully understood. The P2X7 receptor is an ionotropic receptor predominantly expressed on the surface of microglia, although neuronal expression has also been reported. The receptor is activated by the release of ATP from intracellular sources that occurs during neurodegeneration, leading to microglial activation and inflammasome-mediated interleukin 1β release that contributes to neuroinflammation. Using a reporter mouse in which green fluorescent protein is induced in response to the transcription ofP2rx7, we show that expression of the receptor is selectively increased in CA1 pyramidal and dentate granule neurons, as well as in microglia in mice that developed epilepsy after intra-amygdala kainic acid-induced status epilepticus. P2X7 receptor levels were increased in hippocampal subfields in the mice and in resected hippocampus from patients with pharmacoresistant temporal lobe epilepsy. Cells transcribingP2rx7in hippocampal slices from epileptic mice displayed enhanced agonist-evoked P2X7 receptor currents, and synaptosomes from these animals showed increased P2X7 receptor levels and altered calcium responses. A 5 d treatment of epileptic mice with systemic injections of the centrally available, potent, and specific P2X7 receptor antagonist JNJ-47965567 (30 mg/kg) significantly reduced spontaneous seizures during continuous video-EEG monitoring that persisted beyond the time of drug presence in the brain. Hippocampal sections from JNJ-47965567-treated animals obtained >5 d after treatment ceased displayed strongly reduced microgliosis and astrogliosis. The present study suggests that targeting the P2X7 receptor has anticonvulsant and possibly disease-modifying effects in experimental epilepsy.

SIGNIFICANCE STATEMENTTemporal lobe epilepsy is the most common and drug-resistant form of epilepsy in adults. Neuroinflammation is implicated as a pathomechanism, but the upstream mechanisms driving gliosis and how important this is for seizures remain unclear. In our study, we show that the ATP-gated P2X7 receptor is upregulated in experimental epilepsy and resected hippocampus from epilepsy patients. Targeting the receptor with a new centrally available antagonist, JNJ-47965567, suppressed epileptic seizures well beyond the time of treatment and reduced underlying gliosis in the hippocampus. The findings suggest a potential disease-modifying treatment for epilepsy based on targeting the P2X7 receptor.