bluuebunny/crossref_metadata_2025 huggingface dataset:
A population of gap junction-coupled neurons drives recurrent network activity in a developing visual circuit
Authors: Liu Zhenyu , Ciarleglio Christopher M. , Hamodi Ali S. , Aizenman Carlos D. , Pratt Kara G.
Published: January 2016

In many regions of the vertebrate brain, microcircuits generate local recurrent activity that aids in the processing and encoding of incoming afferent inputs. Local recurrent activity can amplify, filter, and temporally and spatially parse out incoming input. Determining how these microcircuits function is of great interest because it provides glimpses into fundamental processes underlying brain computation. Within the Xenopus tadpole optic tectum, deep layer neurons display robust recurrent activity. Although the development and plasticity of this local recurrent activity has been well described, the underlying microcircuitry is not well understood. Here, using a whole brain preparation that allows for whole cell recording from neurons of the superficial tectal layers, we identified a physiologically distinct population of excitatory neurons that are gap junctionally coupled and through this coupling gate local recurrent network activity. Our findings provide a novel role for neuronal coupling among excitatory interneurons in the temporal processing of visual stimuli.
Multilevel Deficiency of White Matter Connectivity Networks in Alzheimer’s Disease: A Diffusion MRI Study with DTI and HARDI Models
Authors: Wang Tao , Shi Feng , Jin Yan , Yap Pew-Thian , Wee Chong-Yaw , Zhang Jianye , Yang Cece , Li Xia , Xiao Shifu , Shen Dinggang
Published: January 2016

Alzheimer’s disease (AD) is the most common form of dementia in elderly people. It is an irreversible and progressive brain disease. In this paper, we utilized diffusion-weighted imaging (DWI) to detect abnormal topological organization of white matter (WM) structural networks. We compared the differences between WM connectivity characteristics at global, regional, and local levels in 26 patients with probable AD and 16 normal control (NC) elderly subjects, using connectivity networks constructed with the diffusion tensor imaging (DTI) model and the high angular resolution diffusion imaging (HARDI) model, respectively. At the global level, we found that the WM structural networks of both AD and NC groups had a small-world topology; however, the AD group showed a significant decrease in both global and local efficiency, but an increase in clustering coefficient and the average shortest path length. We further found that the AD patients had significantly decreased nodal efficiency at the regional level, as well as weaker connections in multiple local cortical and subcortical regions, such as precuneus, temporal lobe, hippocampus, and thalamus. The HARDI model was found to be more advantageous than the DTI model, as it was more sensitive to the deficiencies in AD at all of the three levels.
Preparation of MicroencapsulatedBacillus subtilisSL-13 Seed Coating Agents and Their Effects on the Growth of Cotton Seedlings
Authors: Tu Liang , He Yanhui , Shan Chunhui , Wu Zhansheng
Published: January 2016

Inoculation of the bacterial cells of microbial seed coating agents (SCAs) into the environment may result in limited survival and colonization. Therefore, the application efficacy of an encapsulated microbial seed coating agent (ESCA) was investigated on potted cotton plants; the agent was prepared with polyvinyl alcohol, sodium dodecyl sulfate, bentonite, and microencapsulatedBacillus subtilisSL-13. Scanning electron micrography revealed that the microcapsules were attached to ESCA membranes. The ESCA film was uniform, bubble-free, and easy to peel. The bacterial contents of seeds coated with each ESCA treatment reached 106 cfu/seed. Results indicated that the germination rate of cotton seeds treated with ESCA4(1.0% (w/v) sodium alginate, 4.0% polyvinyl alcohol, 1.0% sodium dodecyl sulfate, 0.6% acacia, 0.5% bentonite, and 10% (v/v) microcapsules) increased by 28.74%. Other growth factors of the cotton seedlings, such as plant height, root length, whole plant fresh weight, and whole plant dry weight, increased by 52.70%, 25.13%, 46.47%, and 33.21%, respectively. Further analysis demonstrated that the peroxidase and superoxide dismutase activities of cotton seedlings improved, whereas their malondialdehyde contents decreased. Therefore, the ESCA can efficiently improve seed germination, root length, and growth. The proposed ESCA exhibits great potential as an alternative to traditional SCA in future agricultural applications.
Game-Theory-Based Approach for Energy Routing in a Smart Grid Network
Authors: Hong June S. , Kim Mihui
Published: January 2016

Small power plants and buildings with renewable power generation capability have recently been added to traditional central power plants. Through these facilities, prosumers appear to have a concurrent role in both energy production and consumption. Based on bidirectional power transfers by large numbers of prosumers, a smart microgrid has become an important factor in efficiently controlling the microgrids used in power markets and in conducting effective power trades among grids. In this paper, we present an approach utilizing the game theory for effective and efficient energy routing, which is a novel and challenging procedure for a smart microgrid network. First, we propose strategies for choosing the desired transaction price for both electricity surpluses and shortages to maximize profits through energy transactions. An optimization scheme is utilized to search for an energy route with minimum cost using the solving method used in a traditional transportation problem by treating the sale and purchase quantities as transportation supply and demand, respectively. To evaluate the effect of the proposed decision strategies, we simulated our mechanism, and the results proved that our mechanism yields results pursued by each strategy. Our proposed strategies will contribute to spreading a smart microgrid for enhancing the utilization of microgrids.
Novel Distributed PZT Active Vibration Control Based on Characteristic Model for the Space Frame Structure
Authors: Zhong Hua , Wang Yong , Ran Hanzheng , Wang Qing , Shao Changxing
Published: January 2016

A novel distributed PZT control strategy based on characteristic model is presented for space frame structure in this paper. It is a challenge to obtain the exact mechanical model for space structure, since it is a coupling MIMO plant with unknown parameters and disturbances. Thus the characteristic modeling theory is adopted to establish the needed model, which can accurately describe the dynamic characteristics of the space frame structure in real time. On basis of this model, a keep tracking controller is designed to suppress the vibration actively. It is shown that the proposed model-free method is very robust and easy to implement. To solve the complex and difficulty problem on PZT location optimization, an efficient method with modal strain energy and maximum vibration amplitude is proposed. Finally, a simulation study is conducted to investigate the effectiveness of the proposed active vibration control scheme.
Comparison of Two Botulinum Neurotoxin A Injection Patterns with or without the Medial Lower Eyelid in the Treatment of Blepharospasm
Authors: Yang Hui , Lu Jing , Zhao Xiujuan , Ding Xiaohu , Wang Zhonghao , Cai Xiaoyu , Luo Yan , Lu Lin
Published: January 2016

The aim of this study was to evaluate the efficacy of two botulinum toxin A (BoNT-A) injection patterns with or without the medial lower eyelid (MLE) in treating benign essential blepharospasm (BEB) and influencing lacrimal drainage. Two different injection patterns of BoNT-A were randomly applied to 98 eyes of 49 BEB patients: MLE Group received a full injection pattern of 5 sites and non-MLE Group received a MLE waived injection pattern of 4 sites. Tear breakup time (BUT), Schirmer I test, lagophthalmos height, and lower lid tear meniscus height (TMH) were measured and Jankovic Rating Scale (JRS) was surveyed before injection and at 1 week, 1 month, and 3 months after injection. The symptom of BEB was relieved in both groups as suggested by JRS scores at all time points after injection, and MLE Group came up with a better JRS score at 3 months. The increases of Schirmer I test value and TMH in MLE Group were higher than those in non-MLE Group at 1 week after injection. This study shows that the MLE-involved full injection pattern is a better choice for patients with BEB. It has longer-lasting effects in relieving BEB symptoms and better efficacy in reducing lacrimal drainage. Clinical Trials registration number isNCT02327728.
Differences in Ventilatory Threshold for Exercise Prescription in Outpatient Diabetic and Sarcopenic Obese Subjects
Authors: Emerenziani Gian Pietro , Gallotta Maria Chiara , Migliaccio Silvia , Greco Emanuela A. , Marocco Chiara , di Lazzaro Luca , Fornari Rachele , Lenzi Andrea , Baldari Carlo , Guidetti Laura
Published: January 2016

Aim of the study was to examine cardiorespiratory parameters at individual ventilatory threshold (IVT) and peak exercise capacity (V˙O2peak) in outpatient diabetic and sarcopenic obese subjects. Seventeen obese subjects (BMI:36.6±4.1 kg·m−1) and sixteen SO subjects (BMI:37.0±7.3 kg·m−1) were compared with sixteen T2DM subjects (BMI:37.7±5.6 kg·m−1). All groups performed an incremental exercise test on a treadmill according to their physical ability.V˙O2peak, %HRmax, and maximal metabolic equivalent (METmax) were evaluated at maximal effort. Moreover,V˙O2ivt, %V˙O2peak, %HRmax, %HRR, ΔHR, and METivt were assessed at IVT. No significant differences were found in any physiological parameters at maximal effort (V˙O2peak, %HRmax, andMETmax) in all groups. On the contrary,V˙O2ivt, %V˙O2peak, %HRmax, %HRR, ΔHR, andMETivtwere significantly lower in T2DM subjects as compared to OB and SO subjects at IVT (p<0.05). Our results show that while at maximal effort there are no differences among groups, at IVT the physiological parameters are lower in T2DM subjects than in OB and SO subjects. Therefore, due to the differences observed in the groups, we suggest usng the IVT as a useful parameter to prescribe aerobic exercise in obese with sarcopenia or diabetes mellitus conditions.
Modeling and Simulation of the Hydrogenation ofα-Methylstyrene on Catalytically Active Metal Foams as Tubular Reactor Packing
Authors: Lali Farzad , Pahner Felix-Aron , Lange Rüdiger
Published: January 2016

This work presents a one-dimensional reactor model for a tubular reactor packed with a catalytically active foam packing with a pore density of 30 PPI in cocurrent upward flow in the example of hydrogenation reaction ofα-methylstyrene to cumene. This model includes material, enthalpy, and momentum balances as well as continuity equations. The model was solved within the parameter space applied for experimental studies under assumption of a bubbly flow. The method of orthogonal collocation on finite elements was applied. For isothermal and polytropic processes and steady state conditions, axial profiles for concentration, temperature, fluid velocities, pressure, and liquid holdup were computed and the conversions for various gas and liquid flow rates were validated with experimental results. The obtained results were also compared in terms of space time yield and catalytic activity with experimental results and stirred tank and also with random packed bed reactor. The comparison shows that the application of solid foams as reactor packing is advantageous compared to the monolithic honeycombs and random packed beds.
Review and Outcome of Prolonged Cardiopulmonary Resuscitation
Authors: Youness Houssein , Al Halabi Tarek , Hussein Hussein , Awab Ahmed , Jones Kellie , Keddissi Jean
Published: January 2016

The maximal duration of cardiopulmonary resuscitation (CPR) is unknown. We report a case of prolonged CPR. We have then reviewed all published cases with CPR duration equal to or more than 20 minutes. The objective was to determine the survival rate, the neurological outcome, and the characteristics of the survivors.Measurements and Main Results. The CPR data for 82 patients was reviewed. The median duration of CPR was 75 minutes. Patients mean age was 43 ± 21 years with no significant comorbidities. The main causes of the cardiac arrests were myocardial infarction (29%), hypothermia (21%), and pulmonary emboli (12%). 74% of the arrests were witnessed, with a mean latency to CPR of 2 ± 6 minutes and good quality chest compression provided in 96% of the cases. Adjunct therapy included extracorporeal membrane oxygenation (18%), thrombolysis (15.8%), and rewarming for hypothermia (19.5%). 83% were alive at 1 year, with full neurological recovery reported in 63 patients.Conclusion. Patients undergoing prolonged CPR can survive with good outcome. Young age, myocardial infarction, and potentially reversible causes of cardiac arrest such as hypothermia and pulmonary emboli predict a favorable result, especially when the arrest is witnessed and followed by prompt and good resuscitative efforts.
Stem Cell Modeling of Core Binding Factor Acute Myeloid Leukemia
Authors: Mosna Federico , Gottardi Michele
Published: January 2016

Even though clonally originated from a single cell, acute leukemia loses its homogeneity soon and presents at clinical diagnosis as a hierarchy of cells endowed with different functions, of which only a minority possesses the ability to recapitulate the disease. Due to their analogy to hematopoietic stem cells, these cells have been named “leukemia stem cells,” and are thought to be chiefly responsible for disease relapse and ultimate survival after chemotherapy. Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) is cytogenetically characterized by either the t(8;21) or the inv(16)/t(16;16) chromosomal abnormalities, which, although being pathognomonic, are not sufficient per se to induce overt leukemia but rather determine a preclinical phase of disease when preleukemic subclones compete until the acquisition of clonal dominance by one of them. In this review we summarize the concepts regarding the application of the “leukemia stem cell” theory to the development of CBF AML; we will analyze the studies investigating the leukemogenetic role of t(8;21) and inv(16)/t(16;16), the proposed theories of its clonal evolution, and the role played by the hematopoietic niches in preserving the disease. Finally, we will discuss the clinical implications of stem cell modeling of CBF AML for the therapy of the disease.
Assessing the Added Value of Dynamical Downscaling Using the Standardized Precipitation Index
Authors: Bowden Jared H. , Talgo Kevin D. , Spero Tanya L. , Nolte Christopher G.
Published: January 2016

In this study, the Standardized Precipitation Index (SPI) is used to ascertain the added value of dynamical downscaling over the contiguous United States. WRF is used as a regional climate model (RCM) to dynamically downscale reanalysis fields to compare values of SPI over drought timescales that have implications for agriculture and water resources planning. The regional climate generated by WRF has the largest improvement over reanalysis for SPI correlation with observations as the drought timescale increases. This suggests that dynamically downscaled fields may be more reliable than larger-scale fields for water resource applications (e.g., water storage within reservoirs). WRF improves the timing and intensity of moderate to extreme wet and dry periods, even in regions with homogenous terrain. This study also examines changes in SPI from the extreme drought of 1988 and three “drought busting” tropical storms. Each of those events illustrates the importance of using downscaling to resolve the spatial extent of droughts. The analysis of the “drought busting” tropical storms demonstrates that while the impact of these storms on ending prolonged droughts is improved by the RCM relative to the reanalysis, it remains underestimated. These results illustrate the importance and some limitations of using RCMs to project drought.
Deconstructing Complex Multimorbidity in the Very Old: Findings from the Newcastle 85+ Study
Authors: Collerton Joanna , Jagger Carol , Yadegarfar Mohammad E. , Davies Karen , Parker Stuart G. , Robinson Louise , Kirkwood Thomas B. L.
Published: January 2016

Objectives. To examine the extent and complexity of the morbidity burden in 85-year-olds; identify patterns within multimorbidity; and explore associations with medication and healthcare use.Participants. 710 men and women; mean (SD) age 85.5 (0.4) years.Methods. Data on 20 chronic conditions (diseases and geriatric conditions) ascertained from general practice records and participant assessment. Cluster analysis within the multimorbid sample identified subgroups sharing morbidity profiles. Clusters were compared on medication and healthcare use.Results. 92.7% (658/710) of participants had multimorbidity; median number of conditions: 4 (IQR 3–6). Cluster analysis (multimorbid sample) identified five subgroups sharing similar morbidity profiles; 60.0% (395/658) of participants belonged to one of two high morbidity clusters, with only 4.9% (32/658) in the healthiest cluster. Healthcare use was high, with polypharmacy (≥5 medications) in 69.8% (459/658). Between-cluster differences were found in medication count (p=0.0001); hospital admissions (p=0.022); and general practitioner (p=0.034) and practice nurse consultations (p=0.011). Morbidity load was related to medication burden and use of some, but not all, healthcare services.Conclusions. The majority of 85-year-olds had extensive and complex morbidity. Elaborating participant clusters sharing similar morbidity profiles will help inform future healthcare provision and the identification of common underlying biological mechanisms.
Adaptation to AI Therapy in Breast Cancer Can Induce Dynamic Alterations in ER Activity Resulting in Estrogen-Independent Metastatic Tumors
Authors: Varešlija Damir , McBryan Jean , Fagan Ailís , Redmond Aisling M. , Hao Yuan , Sims Andrew H. , Turnbull Arran , Dixon J.M. , Ó Gaora Peadar , Hudson Lance , Purcell Siobhan , Hill Arnold D.K. , Young Leonie S.
Published: January 2016

Purpose: Acquired resistance to aromatase inhibitor (AI) therapy is a major clinical problem in the treatment of breast cancer. The detailed mechanisms of how tumor cells develop this resistance remain unclear. Here, the adapted function of estrogen receptor (ER) to an estrogen-depleted environment following AI treatment is reported.

Experimental Design: Global ER chromatin immuno-precipitation (ChIP)-seq analysis of AI-resistant cells identified steroid-independent ER target genes. Matched patient tumor samples, collected before and after AI treatment, were used to assess ER activity.

Results: Maintained ER activity was observed in patient tumors following neoadjuvant AI therapy. Genome-wide ER–DNA-binding analysis in AI-resistant cell lines identified a subset of classic ligand-dependent ER target genes that develop steroid independence. The Kaplan–Meier analysis revealed a significant association between tumors, which fail to decrease this steroid-independent ER target gene set in response to neoadjuvant AI therapy, and poor disease-free survival and overall survival (n = 72 matched patient tumor samples, P = 0.00339 and 0.00155, respectively). The adaptive ER response to AI treatment was highlighted by the ER/AIB1 target gene, early growth response 3 (EGR3). Elevated levels of EGR3 were detected in endocrine-resistant local disease recurrent patient tumors in comparison with matched primary tissue. However, evidence from distant metastatic tumors demonstrates that the ER signaling network may undergo further adaptations with disease progression as estrogen-independent ER target gene expression is routinely lost in established metastatic tumors.

Conclusions: Overall, these data provide evidence of a dynamic ER response to endocrine treatment that may provide vital clues for overcoming the clinical issue of therapy resistance. Clin Cancer Res; 22(11); 2765–77. ©2016 AACR.
Epigenetic Regulation of the Homeobox GeneMSX1Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer
Authors: Bonito Nair A. , Borley Jane , Wilhelm-Benartzi Charlotte S. , Ghaem-Maghami Sadaf , Brown Robert
Published: January 2016

Purpose: Although high-grade serous ovarian cancer (HGSOC) is frequently chemoresponsive, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival (PFS) of less than 6 months. Validated predictive biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of intrinsic resistance. Our aim was to identify DNA methylation biomarkers of poor response to chemotherapy and demonstrate involvement of the associated gene in platinum drug cell sensitivity.

Experimental Design: DNA methylation was investigated in independent tumor cohorts using Illumina HumanMethylation arrays and gene expression by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction and siRNA knockdown of ovarian cancer cell lines.

Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in independent cohorts of HGSOC patients, which recur by 6 months compared with after 12 months (P < 0.05, q < 0.05, n = 78), have poor RECIST response (P < 0.05, q < 0.05, n = 61), and are associated with PFS in an independent cohort (n = 146). A decrease in methylation at these CpG sites correlates with decreased MSX1 gene expression. MSX1 expression is associated with PFS (HR, 0.92; 95% CI, 0.85–0.99; P = 0.029; n = 309). Cisplatin-resistant ovarian cancer cell lines have reduced MSX1 expression, and MSX1 overexpression leads to cisplatin sensitization, increased apoptosis, and increased cisplatin-induced p21 expression.

Conclusions: Hypomethylation of CpG sites within the MSX1 gene is associated with resistant HGSOC disease at presentation and identifies expression of MSX1 as conferring platinum drug sensitivity. Clin Cancer Res; 22(12); 3097–104. ©2016 AACR.
Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques
Authors: Shalhoub Joseph , Viiri Leena E. , Cross Amanda J. , Gregan Scott M. , Allin David M. , Astola Nagore , Franklin Ian J. , Davies Alun H. , Monaco Claudia
Published: January 2016

Molecular characterisation of vulnerable atherosclerosis is necessary for targeting functional imaging and plaque-stabilising therapeutics. Inflammation has been linked to atherogenesis and the development of high-risk plaques. We set to quantify cytokine, chemokine and matrix metalloproteinase (MMP) protein production in cells derived from carotid plaques to map the inflammatory milieu responsible for instability. Carotid endarterectomies from carefully characterised symptomatic (n=35) and asymptomatic (n=32) patients were enzymatically dissociated producing mixed cell type atheroma cell suspensions which were cultured for 24 hours. Supernatants were interrogated for 45 analytes using the Luminex 100 platform. Twenty-nine of the 45 analytes were reproducibly detectable in the majority of donors. The in vitro production of a specific network of mediators was found to be significantly higher in symptomatic than asymptomatic plaques, including: tumour necrosis factor α, interleukin (IL) 1β, IL-6, granulocytemacrophage colony-stimulating factor (GM-CSF), macrophage colonystimulating factor (M-CSF), CCL5, CCL20, CXCL9, matrix metalloproteinase (MMP)-3 and MMP-9. Ingenuity pathway analysis of differentially expressed analytes between symptomatic and asymptomatic patients identified a number of key biological pathways (p > 10–25). In conclusion, the carotid artery plaque culprit of ischaemic neurological symptoms is characterised by an inflammatory milieu favouring inflammatory cell recruitment and pro-inflammatory macrophage polarisation.

Supplementary Material to this article is available online at www.thrombosis-online.com.
Narrativas transmídias e uma cosm(o)ética ativista e jornalística na “Copa do Brasil”
Authors: Sousa Gisella Meneguelli
Published: January 2016

Este artigo busca refletir sobre a narrativa transmídia como recurso de criação e de divulgação das manifestações ocorridas no Brasil durante a Copa do Mundo de 2014. Na tentativa de compreendermos os processos narrativos em alguns meios de comunicação e redes sociais, analisamos o componente transmídia como organizador dos discursos de opinião pública, seja no jornalismo tradicional, seja no jornalismo anárquico.
A copa em tweets: análise comparativa do uso das hashtags #EstadaonaCopa e #BairristanaCopa
Authors: Zago Gabriela Da Silva
Published: January 2016

Neste trabalho, procuramos analisar e comparar a utilização de hashtags de cobertura no Twitter por um site jornalístico e outro humorístico durante a Copa do Mundo de 2014: o jornal O Estado de S. Paulo, que utilizou a hashtag #EstadaonaCopa para sua cobertura em sites de rede social, e o site satírico O Bairrista, que adotou a hashtag #BairristanaCopa. O estudo foi operacionalizado a partir da combinação de observação com análise de redes sociais como métodos para compreender a estrutura e a dinâmica das redes em torno das respectivas hashtags. Resultados apontam para estruturas de rede semelhantes, porém com dinâmicas diferentes observadas em cada um dos casos estudados.
The artwork of Claudia Andujar analyzed from a history of photography engendered by institutional discursive intricacies
Authors: Soares Carolina
Published: January 2016

This text captures the photographic production of Claudia Andujar of the late 1950s and early 1960s - even before the work developed with the Yanomami - for an analysis that takes into account the dimension of the chosen subject; its visual representation and the ways of its circulation. By emphasizing these aspects, the goal is to understand how the aesthetic developed by the artist in question is contaminated and thus constituted by discursive criteria aligned with a history of photography forged by institutional mechanisms.
Evidence of multiple paternal contribution in Podocnemis sextuberculata (Testudines: Podocnemididae) detected by microsatellite markers.
Authors: Fantin Cleiton , Pereira Dorothy Ivila Melo , Ferreira Jorge Frank , Machado Paulo Cesar Andrade , Hrbek Tomas , Monjeló Luiz Alberto Santos , Farias Izeni Pires
Published: January 2016

Evidência de contribuição paterna múltipla em Podocnemis sextuberculata (Chelonia: Podocnemididae) por meio de marcadores microssatélites. Encontramos evidências de paternidade múltipla em uma amostra de 80 recém-eclodidos de sete ninhos de Podocnemis sextuberculata situados ao longo do rio Amazonas, no município de Barreirinha, AM, Brasil, e 54 indivíduos recém-eclodidos de cinco ninhos na Reserva Biológica Abufari, Tapauá, AM, Brasil. Como observado em outras espécies do gênero, P. sextuberculata apresentou comportamento poliândrico. Por meio da frequência alélica e variação em seis locos microssatélite para cada localidade, a ocorrência de paternidade múltipla em ninhos amostrados dessa espécie foi inferida, mesmo o genótipo da mãe sendo desconhecido. Para um dos ninhos, um mínimo de quatro machos contribuíram para a prole, enquanto que para quase todos os outros ninhos, pelo menos dois machos contribuíram. Apenas um dos 12 ninhos não mostrou evidência clara de contribuição de mais de um macho. Esta é a primeira evidência genética de paternidade múltipla em P. sextuberculata.
Genetic diversity and structure of two species of Enyalius (Squamata: Leiosauridae) from neotropical biodiversity hotspots
Authors: Vargas Sarah M. , Santos Marcelo de Oliveira , Novelli Iara Alves , Varela-Rios Celso Henrique , Lima Lúcio Moreira Campos , Lucas Priscila da Silva , Cozendey Pilar , Paiva Raquel Morais , Gomides Samuel Campos , Malaguti Sara , Sousa Bernadete Maria de
Published: January 2016

Diversidade e estrutura genética de duas espécies de Enyalius (Squamata: Leiosauridae) em hotspots neotropicais de biodiversidade. Os lagartos do gênero Enyalius são endêmicos da América do Sul, sendo predominantemente encontrados no Cerrado e em fragmentos da Floresta Atlântica. Este é um gênero pouco estudado, e não foram encontrados dados relacionados à diversidade e à estrutura genética das espécies do gênero. Neste trabalho, investigamos a diversidade genética de populações de E. bilineatus (N = 20) e E. perditus (N = 28), usando um fragmento de 234-pb do citocromo b, e comparamos as sequências geradas com outras publicadas. Dezenove haplótipos distintos foram encontrados (11 de E. perditus e oito de E. bilineatus), sendo oito deles novos registros. Os valores de diversidade haplotípica foram muito similares para as duas espécies (0.684 para E. perditus e 0.647 para E. bilineatus). A distância genética entre as duas espécies foi de 20.3%, e as distâncias intraespecíficas foram 2.0% para E. perditus e 5.6% para E. bilineatus. Nossos dados sugerem que as populações de E. bilineatus são altamente divergentes e que a espécie deve apresentar diversidade críptica. Este é o primeiro estudo medindo a diversidade genética de espécies do gênero Enyalius oriundas de regiões consideradas hotspots da biodiversidade neotropical e apresenta dados relevantes para um melhor entendimento das relações inter e intrapopulacionais, assim como a distribuição das linhagens genéticas desse gênero endêmico.
Impact of Complete Versus Incomplete Circumferential Lines Around the Pulmonary Veins During Catheter Ablation of Paroxysmal Atrial Fibrillation
Authors: Kuck Karl-Heinz , Hoffmann Boris A. , Ernst Sabine , Wegscheider Karl , Treszl Andras , Metzner Andreas , Eckardt Lars , Lewalter Thorsten , Breithardt Günter , Willems Stephan
Published: January 2016

Background—

Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients. It is not known whether complete pulmonary vein isolation (PVI) is superior to incomplete PVI with regard to the patients’ clinical outcome.

Methods and Results—

Patients with drug-refractory, symptomatic paroxysmal AF were randomly assigned to either incomplete (group A) or complete PVI (group B). In group A, a persistent gap was intentionally left within the circumferential ablation line, whereas in group B, complete PVI without any gaps was intended. At 3 months, all patients underwent invasive reevaluation to assess the rate of persistent PVI. Clinical follow-up was based on daily 30-s transtelephonic ECG transmissions. Primary study end point was the time to first recurrence of (symptomatic or asymptomatic) AF. A total of 233 patients were enrolled (116 in group A and 117 in group B). AF recurrence within 3 months was observed in a total of 161 patients (136 [84.5%] with symptomatic and 25 [15.5%] with asymptomatic AF); AF recurred in 62.2% of group B patients and 79.2% of group A patients (
P
<0.001), for a difference in favor of complete PVI of 17.1% (95% confidence interval, 5.3%–28.9%). Invasive restudy in 103 group A patients and 93 group B patients revealed conduction gaps in 92 (89.3%) and 65 (69.9%) patients, respectively.

Conclusions—

This study proves the superiority of complete PVI over incomplete PVI with respect to AF recurrence within 3 months. However, the rate of electric reconduction 3 months after PVI is high in patients with initially isolated PVs.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
; Unique identifier: NCT00293943.
Chronic Co-Administration of Sepiapterin and
l
-Citrulline Ameliorates Diabetic Cardiomyopathy and Myocardial Ischemia/Reperfusion Injury in Obese Type 2 Diabetic Mice
Authors: Baumgardt Shelley L. , Paterson Mark , Leucker Thorsten M. , Fang Juan , Zhang David X. , Bosnjak Zeljko J. , Warltier David C. , Kersten Judy R. , Ge Zhi-Dong
Published: January 2016

Background—

Diabetic heart disease is associated with tetrahydrobiopterin oxidation and high arginase activity, leading to endothelial nitric oxide synthase dysfunction. Sepiapterin (SEP) is a tetrahydrobiopterin precursor, and
l
-citrulline (
l
-Cit) is converted to endothelial nitric oxide synthase substrate,
l
-arginine. Whether SEP and
l
-Cit are effective at reducing diabetic heart disease is not known. The present study examined the effects of SEP and
l
-Cit on diabetic cardiomyopathy and ischemia/reperfusion injury in obese type 2 diabetic mice.

Methods and Results—

Db/db and C57BLKS/J mice at 6 to 8 weeks of age received vehicle, SEP, or
l
-Cit orally alone or in combination for 8 weeks. Cardiac function was evaluated with echocardiography. Db/db mice displayed hyperglycemia, obesity, and normal blood pressure and cardiac function compared with C57BLKS/J mice at 6 to 8 weeks of age. After vehicle treatment for 8 weeks, db/db mice had reduced ejection fraction, mitral
E
/
A
ratio, endothelium-dependent relaxation of coronary arteries, tetrahydrobiopterin concentrations, ratio of endothelial nitric oxide synthase dimers/monomers, and nitric oxide levels compared with vehicle-treated C57BLKS/J mice. These detrimental effects of diabetes mellitus were abrogated by co-administration of SEP and
l
-Cit. Myocardial infarct size was increased, and coronary flow rate and ±d
P
/d
t
were decreased during reperfusion in vehicle-treated db/db mice subjected to ischemia/reperfusion injury compared with control mice. Co-administration of SEP and
l
-Cit decreased infarct size and improved coronary flow rate and cardiac function in both C57BLKS/J and db/db mice.

Conclusions—

Co-administration of SEP and
l
-Cit limits diabetic cardiomyopathy and ischemia/reperfusion injury in db/db mice through a tetrahydrobiopterin/endothelial nitric oxide synthase/nitric oxide pathway.
Novel Molecular Imaging Approaches to Abdominal Aortic Aneurysm Risk Stratification
Authors: Toczek Jakub , Meadows Judith L. , Sadeghi Mehran M.
Published: January 2016

Selection of patients for abdominal aortic aneurysm repair is currently based on aneurysm size, growth rate, and symptoms. Molecular imaging of biological processes associated with aneurysm growth and rupture, for example, inflammation and matrix remodeling, could improve patient risk stratification and lead to a reduction in abdominal aortic aneurysm morbidity and mortality.
18
F-fluorodeoxyglucose-positron emission tomography and ultrasmall superparamagnetic particles of iron oxide magnetic resonance imaging are 2 novel approaches to abdominal aortic aneurysm imaging evaluated in clinical trials. A variety of other tracers, including those that target inflammatory cells and proteolytic enzymes (eg, integrin α
v
β
3
and matrix metalloproteinases), have proven effective in preclinical models of abdominal aortic aneurysm and show great potential for clinical translation.
Efficacy and Safety of Cangrelor in Women Versus Men During Percutaneous Coronary Intervention
Authors: O’Donoghue Michelle L. , Bhatt Deepak L. , Stone Gregg W. , Steg Ph. Gabriel , Gibson C. Michael , Hamm Christian W. , Price Matthew J. , Prats Jayne , Liu Tiepu , Deliargyris Efthymios N. , Mahaffey Kenneth W. , White Harvey D. , Harrington Robert A.
Published: January 2016

Background—

Cangrelor is an intravenous ADP receptor antagonist that leads to potent and reversible inhibition of platelet aggregation. The relative safety and efficacy of some antiplatelet drugs in women has been disputed.

Methods and Results—

The Cangrelor versus Standard Therapy to Achieve Optimal Management of Platelet Inhibition (CHAMPION PHOENIX) trial randomized 11 145 patients undergoing elective or urgent percutaneous coronary intervention to cangrelor or clopidogrel. The primary efficacy end point was the composite of death, myocardial infarction, ischemia-driven revascularization, or stent thrombosis at 48 hours; the key secondary end point was stent thrombosis at 48 hours. The primary safety end point was GUSTO severe bleeding at 48 hours. Of subjects analyzed, 3051 (28%) were female. Cangrelor reduced the odds of the primary end point by 35% in women (adjusted odds ratio [OR], 0.65; 95% confidence interval [CI], 0.48–0.89) and by 14% in men (OR, 0.86; 95% CI, 0.70–1.05;
P
interaction=0.23) compared with clopidogrel. Cangrelor reduced the odds of stent thrombosis by 61% in women (OR, 0.39; 95% CI, 0.20–0.77) and 16% in men (OR, 0.84; 95% CI, 0.53–1.33;
P
interaction=0.11). The odds of severe bleeding were similar in both women and men treated with cangrelor (0.3% versus 0.2%,
P
=0.30 [women]; 0.1% versus 0.1%,
P
=0.41 [men];
P
interaction=0.88) versus clopidogrel. Cangrelor increased the odds of moderate bleeding in women (0.9% versus 0.3%,
P
=0.02), but not in men (0.2% versus 0.2%,
P
=0.68;
P
interaction=0.040). The net clinical benefit (primary efficacy and safety end point) favored cangrelor in both women (OR, 0.68; 95% CI, 0.50–0.92) and men (OR, 0.87; 95% CI, 0.71–1.06;
P
interaction=0.26).

Conclusions—

In CHAMPION PHOENIX, cangrelor reduced the odds of major adverse cardiovascular events and stent thrombosis in women and men and appeared to offer greater net clinical benefit than clopidogrel.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01156571.
Preserved Autonomic Cardiovascular Regulation With Cardiac Pacemaker Inhibition: A Crossover Trial Using High‐Fidelity Cardiovascular Phenotyping
Authors: Heusser Karsten , Tank Jens , Brinkmann Julia , Schroeder Christoph , May Marcus , Großhennig Anika , Wenzel Daniela , Diedrich André , Sweep Fred C. G. J. , Mehling Heidrun , Luft Friedrich C. , Jordan Jens
Published: January 2016

Background

Sympathetic and parasympathetic influences on heart rate (HR), which are governed by baroreflex mechanisms, are integrated at the cardiac sinus node through hyperpolarization‐activated cyclic nucleotide–gated channels (HCN4). We hypothesized that HCN4 blockade with ivabradine selectively attenuates HR and baroreflex HR regulation, leaving baroreflex control of muscle sympathetic nerve activity intact.

Methods and Results

We treated 21 healthy men with 2×7.5 mg ivabradine or placebo in a randomized crossover fashion. We recorded electrocardiogram, blood pressure, and muscle sympathetic nerve activity at rest and during pharmacological baroreflex testing. Ivabradine reduced normalized HR from 65.9±8.1 to 58.4±6.2 beats per minute (
P
<0.001) with unaffected blood pressure and muscle sympathetic nerve activity. On ivabradine, cardiac and sympathetic baroreflex gains and blood pressure responses to vasoactive drugs were unchanged. Ivabradine aggravated bradycardia during baroreflex loading.

Conclusions

HCN4 blockade with ivabradine reduced HR, leaving physiological regulation of HR and muscle sympathetic nerve activity as well as baroreflex blood pressure buffering intact. Ivabradine could aggravate bradycardia during parasympathetic activation.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00865917.
Blood Pressure Reactivity to Psychological Stress in Young Adults and Cognition in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Yano Yuichiro , Ning Hongyan , Reis Jared P. , Lewis Cora E. , Launer Lenore J. , Bryan R. Nick , Yaffe Kristine , Sidney Stephen , Albanese Emiliano , Greenland Philip , Lloyd‐Jones Donald , Liu Kiang
Published: January 2016

Background

The classic view of blood pressure (
BP
) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress‐induced
BP
reactivity in young adults is associated with midlife cognitive function is sparse.

Methods and Results

We assessed
BP
reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty‐three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow‐up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow‐up resting
BP
, lower systolic
BP
(
SBP
) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [
SE
]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [
SE
]: −0.06 [0.02] and −0.05 [0.02]; all
P
<0.01).
SBP
reactivity was more consistently associated than diastolic
BP
reactivity with cognitive function scores. The associations between
SBP
reactivity and cognitive function were mostly similar between blacks and whites.

Conclusions

Lower psychological stress‐induced
SBP
reactivity in younger adults was associated with lower cognitive function in midlife.
BP
reactivity to psychological stressors may have different associations with target organs in hypertension.
From Positivity to Negativity Bias: Ambiguity Affects the Neurophysiological Signatures of Feedback Processing
Authors: Gibbons Henning , Schnuerch Robert , Stahl Jutta
Published: January 2016

Previous studies on the neurophysiological underpinnings of feedback processing almost exclusively used low-ambiguity feedback, which does not fully address the diversity of situations in everyday life. We therefore used a pseudo trial-and-error learning task to investigate ERPs of low- versus high-ambiguity feedback. Twenty-eight participants tried to deduce the rule governing visual feedback to their button presses in response to visual stimuli. In the blocked condition, the same two feedback words were presented across several consecutive trials, whereas in the random condition feedback was randomly drawn on each trial from sets of five positive and five negative words. The feedback-related negativity (FRN-D), a frontocentral ERP difference between negative and positive feedback, was significantly larger in the blocked condition, whereas the centroparietal late positive complex indicating controlled attention was enhanced for negative feedback irrespective of condition. Moreover, FRN-D in the blocked condition was due to increased reward positivity (Rew-P) for positive feedback, rather than increased (raw) FRN for negative feedback. Our findings strongly support recent lines of evidence that the FRN-D, one of the most widely studied signatures of reinforcement learning in the human brain, critically depends on feedback discriminability and is primarily driven by the Rew-P. A novel finding concerned larger frontocentral P2 for negative feedback in the random but not the blocked condition. Although Rew-P points to a positivity bias in feedback processing under conditions of low feedback ambiguity, P2 suggests a specific adaptation of information processing in case of highly ambiguous feedback, involving an early negativity bias. Generalizability of the P2 findings was demonstrated in a second experiment using explicit valence categorization of highly emotional positive and negative adjectives.
HOW TO WATCH TELEVISION?: Pedagogy and Paedocracy in Beckett's Television Plays
Authors: Bignell Jonathan
Published: January 2016

This article responds to scholarship on Beckett's television plays that regards them as positive interventions which encourage the viewer to reconsider the conventions of the medium, and that raise the cultural standards of television drama. In making claims about how the plays address and educate their viewers, critical approaches shift between conceptions of audience. This analysis of Beckett's plays on British television reconsiders their aesthetic strategies, their relationship with television culture, and the dominant assumptions of critical writing about them by examining the parallel between conceptions of the audience and conceptions of the child in writing about television and Beckett's television plays.
ANNIHILATING ALL THAT'S MADE: Beckett's and The Pastoral Tradition
Authors: Hamilton Geoff
Published: January 2016

This article focuses on the importance of pastoral parody in . Conceptions of a rejuvenating natural world persist in the novel, but are vigorously and decisively undercut. Pastoral's representative characters, who traditionally cope with their weakness and exposure to hostile elements by constructing consoling narratives, often in song, emerge in as unconsoled wanderers, speaking at length and with great longing of speaking no more. Pastoral is exposed for its contemporary impotence, but the tradition carries on, employed and eschewed within a characteristically self-effacing rhetoric.
An "Other Object of Note": Circle and Point in Samuel Beckett's
Authors: Ackerley Chris
Published: January 2016

Although the picture of a circle and centre is present in the earliest drafts of , the painting itself underwent several significant changes before obtaining its final form (, 128-31). A curiosity arises concerning the words "right" and "left" used to define the relationship of point to circle, for these finally assume the perspective of the object perceived, rather than that of the subject perceiving. Tracing this detail through the various notebooks, manuscripts and typescript (particularly those at the Harry Ransom Humanities Center, Austin) offers unexpected insights into Beckett's wider artistic practice, as well as into the evolution of .
Samuel Beckett's 'J.M. Mime': Generic Mutations of a Dramatic Fragment
Authors: McMullan Anna
Published: January 2016

'J.M. Mime' is an abandoned dramatic fragment, written by Samuel Beckett in 1963 for the Irish actor Jack MacGowran. Although the fragment has been published in its entirety in facsimile and elements of it have been cited, to my knowledge it has not been analysed in detail. This article sets out to give an overview of the different sections of the manuscript, and draws on S.E. Gontarski's concept of "textual biography" in order to place the mime in relation to preoccupations that recur in later work, as textual motifs and experiments mutate into narrative or televisual media.
Dante, Pétrarque, Leopardi, Beckett Une Divine Perspective
Authors: Ferrini Jean-Pierre
Published: January 2016

This paper proposes to examine the "disjunctive conjunction" that links Dante Beckett in establishing a line ("a divine perspective") that starts with Dante, but that passes by the works of Petrarca (the ) and a poem by Leopardi (). We are presenting for instance the annotations that can be found in the exemplary of the that Beckett owned (Avigdor Arikha fund).
Mercier Et/and Camier : Un voyage de découverte linguistique est-il traduisible?
Authors: Astbury Helen
Published: January 2016

This articles studies the English translation of Beckett's first French-language novel, in order to ascertain whether the linguistic discovery it represents was translatable into English. A close analysis of how Beckett translated his very markedly oral French reveals how Beckett uses for the first time, Hibemo-English structures and words, as if the use of a foreign language had allowed him to rediscover his mother tongue as he has never used it before.
For to End Yet Again with Sacrificial Rituals"
Authors: Cousineau Tom
Published: January 2016

This paper analyzes against the background of Greek tragedy. I interpret Beckett's professed aim of creating "form in movement" in his own production of the play in relation to the rhythmical movements of a chorus that were a central feature of tragedy. Drawing upon René Girard's non-sacrificial interpretation of the Crucifixion of Christ, I further argue that "nothing happens" in Godot because, unlike a tragedy in which the plague that has descended on Thebes can be blamed on a designated scapegoat, it is a play in which human suffering cannot be alleviated by recourse to magical solutions.