bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau: From research to clinical development
Authors: Holtzman David M. , Carrillo Maria C. , Hendrix James A. , Bain Lisa J. , Catafau Ana M. , Gault Laura M. , Goedert Michel , Mandelkow Eckhard , Mandelkow Eva‐Maria , Miller David S. , Ostrowitzki Susanne , Polydoro Manuela , Smith Sean , Wittmann Marion , Hutton Michael 
Published: May 2016

AbstractAlzheimer's Association Research Roundtable Fall 2015—Tau: From research to clinical development. Tau pathology is recognized as the key driver of disease progression in Alzheimer's and other neurodegenerative diseases. Although this makes tau an attractive target for the development of novel diagnostic and therapeutic strategies, the mechanisms underlying the onset and progression of tau‐related neurotoxicity remain elusive. Recent strides in the development of sophisticated preclinical models and the emergence of tau PET imaging and fluid biomarkers provide new opportunities to increase our understanding of tau biology, overcome translational challenges, and accelerate the advancement of tau therapeutics from bench to bedside. With this in mind, the Alzheimer's Association convened a Research Roundtable in October 2015, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of tau pathogenic pathways and review the evolution of tau therapeutics and biomarkers currently in development. The meeting provided a forum to share experience and expertise with the common goal of advancing the discovery and development of new treatment strategies and expediting the design and implementation of efficient clinical trials.
Relación entre rasgos y tipos de personalidad con la especialidad médica elegida por un grupo de médicos residentes
Authors: Ruiz Zavala Jorge Humberto , Enríquez Sandoval Matilde Loreto , Gómez Sánchez Enrique Alfonso , León Hernández Saúl Renán 
Published: May 2016

Introducción: El estudio de los rasgos y tipos de personalidad de los médicos se inició en los Estados Unidos en 1960 bajo la hipótesis de que la personalidad induce la elección del tipo de especialidad médica que se decide realizar. En Chile y España es donde más se ha estudiado esta relación. En México hay pocos estudios que han servido para comprender las formas en las que afrontan los problemas que se presentan durante su formación. Este es el primer estudio que se realiza con los médicos residentes de las diferentes especialidades que se imparten en el Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra con la hipótesis de que existe relación entre los tipos de personalidad con la especialidad elegida.
Objetivo: Determinas si los tipos de personalidad de los médicos residentes del Instituto Nacional de Rehabilitación difieren significativamente entre las distintas especialidades.
Método: Se realizó un estudio transversal aplicando el cuestionario factorial de la personalidad 16PF-5 a 50 médicos residentes de cinco de las siete especialidades que se cursan en el Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra. El cuestionario explora 16 rasgos primarios con los cuales se integran 5 dimensiones generales de personalidad. Los datos obtenidos se analizaron con SPSS 17. Para la comparación de dos proporciones se aplicó chi cuadrado, la forma de la distribución de las puntuaciones del cuestionario factorial de personalidad se corroboraron con el estadístico Kolmogorov Smirnov. Las comparaciones de medias por sexo se efectuaron con t de Student para muestras independientes o en su caso con U de Mann Whitney. Las comparaciones de medias por especialidad se hicieron con el análisis de varianza o con Kruskal- Wallis, los análisis multivariados se realizaron con el modelo de análisis iscriminante y análisis de varianza de dos factores.
Resultados: De los 16 rasgos destacan: razonamiento, tensión y autosuficiencia; más bajas: afabilidad y vigilancia; de las 5 dimensiones sobresalieron independencia y ansiedad y más bajas extraversión y dureza. Por género se diferenciaron M vs. F: estabilidad 6.20 ± 1.3 vs.5.17 ± 1.5 (p = 0.018) y atrevimiento 6.45 ± 1.4 vs.4.70 ± 1.4 (p = 0.0001).
Conclusiones: Existen diferencias sobresalientes entre los rasgos y dimensiones de la personalidad.
Attenuation of wind-induced pressure perturbations in alpine snow
Authors: DRAKE STEPHEN A. , HUWALD HENDRIK , PARLANGE MARC B. , SELKER JOHN S. , NOLIN ANNE W. , HIGGINS CHAD W. 
Published: May 2016

ABSTRACTWindpumping has been identified as a process that could potentially enhance sublimation of surface snow at high forcing frequency and spawn air movement deeper in firn at lower frequencies. We performed an experiment to examine the relationship between high-frequency wind and pressure measurements within the top meter of an alpine snowpack and compared experimental results with two theoretical predictions. We find that both theoretical predictions underestimate high-frequency perturbation pressure attenuation with depth in the near-surface snowpack and the discrepancy between theory and measurement increases with perturbation pressure frequency. The impact of this result for near-surface snow is that potential enhanced sublimation will occur over a shallower snow depth than these two theories predict. Correspondingly, interstitial air mixing at depth in firn will be driven by lower frequencies than these two theories predict. While direct measurement of these energy-rich lower frequencies is beyond the scope of this paper, stationary pressure measurements validate the presence of a pressure field that could drive near-surface circulation.
Lake ice formation processes and thickness evolution at Lake Abashiri, Hokkaido, Japan
Authors: OHATA YU , TOYOTA TAKENOBU , SHIRAIWA TAKAYUKI 
Published: May 2016

AbstractLake-ice properties at Lake Abashiri, Hokkaido, Japan, were examined using field observations and a 1-D thermodynamic model to clarify formation processes at mid-latitudes subject to significant snowfall as well as moderate air temperature. At all lake sites examined, the ice comprised two distinct layers: a snow ice (SI) layer on top and a congelation ice (CI) layer below. The SI layer occupied as much as 29–73% of the total ice thickness, a much greater fraction than that reported for lakes at Arctic high latitudes. In the model, the CI growth rate was estimated using the traditional heat budget method, while the SI growth rate was calculated assuming the excessive snowfall from the isostatic balance is converted to SI by a snow compression rate (β) with the surface melting rate added when the surface heat budget becomes positive. By tuning the value ofβto the observational results of SI thickness, the model outcome successfully reproduced the observational thicknesses of CI and SI, and the break-up date of the lake. Essentially, the model findings show how snow and its formation into SI reduce, by about half, the seasonal variability of total ice thickness.
“This guy says I should talk like that all the time”: Challenging intersecting ideologies of language and gender in an American Stuttering English comedienne's stand-up routine
Authors: Dumas Nathaniel W. 
Published: May 2016

AbstractAmerican Stuttering English (ASE) speakers (or ‘persons who stutter’ in pathological perspectives) have historically had tense relationships with comedic representations of their speech. Mainstream representations pathologize and ridicule stuttering, rather than appreciate it as a legitimate language variety. These depictions also increase non-ASE speakers' ‘possessive investment’ (Lipsitz 1995) in Standard American Fluent English as the dominant language variety. Recently, some ASE speakers have reinterpreted ASE and comedic portrayals of their speech using stand-up comedy. This article analyzes the comedic work of Rona B, an ASE comedienne. Using data on her YouTube channel, I argue that Rona B draws on her intersectional experiences as a female ASE speaker to construct a voice that critiques both the political agendas of anti-linguistic discrimination, which downplays gender, and of antisexism, which minimizes sociolinguistic differences. This study expands on contemporary calls in sociolinguistics that position intracategorical intersectionality as key for analyzing performances on language variation. (Gender, variation, American Stuttering English, performance, stand-up comedy, language ideologies)*
MAKING HISTORY ONLINE
Authors: Hitchcock Tim , Shoemaker Robert 
Published: May 2016

ABSTRACTThis article considers the implications of recent innovations in digital history for the relationship between the academy and the public. It argues that while digitisation and the internet have attracted large new audiences, academic historians have been reluctant to engage with this new public. We suggest that recent innovations in academic digital history, such as the highly technocratic ‘Culturomics’ movement, have had the unintended effect of driving a wedge between higher education and the wider public. Similarly, academic history writing has been slow to embrace the possibilities of the internet as a means of dissemination and engagement; and academic publishing has moved even more reluctantly. Despite these issues, this article argues that the internet offers real opportunities for bridging the divide between the academy and a wider audience. Through non-traditional forms of publication such as blogging; through Open Access policies; and through new forms of visualisation of complex data, the digital and online allow us to present complex history to a wider audience. We conclude that historians need to embrace the ‘affordances’ and ‘disruptions’ posed by the internet to render the discipline more open and democratically accessible.
On the Richter–Thomassen Conjecture about Pairwise Intersecting Closed Curves
Authors: PACH JÁNOS , RUBIN NATAN , TARDOS GÁBOR 
Published: May 2016

A long-standing conjecture of Richter and Thomassen states that the total number of intersection points between any n simple closed Jordan curves in the plane, so that any pair of them intersect and no three curves pass through the same point, is at least (1−o(1))n2.We confirm the above conjecture in several important cases, including the case (1) when all curves are convex, and (2) when the family of curves can be partitioned into two equal classes such that each curve from the first class touches every curve from the second class. (Two closed or open curves are said to be touching if they have precisely one point in common and at this point the two curves do not properly cross.)An important ingredient of our proofs is the following statement. Let S be a family of n open curves in ℝ2, so that each curve is the graph of a continuous real function defined on ℝ, and no three of them pass through the same point. If there are nt pairs of touching curves in S, then the number of crossing points is $\Omega(nt\sqrt{\log t/\log\log t})$.
Revisiting the Regime of Trademark Protection in Bangladesh: TRIPS Compatibility and Ramifications
Authors: SAYEED Muhammad A. 
Published: May 2016

AbstractBangladesh recently established a new trademark regime in 2009, repealing the seventy-year-old statute that was enacted as a response of the colonial government to comply with the requirements of the Paris Convention. This newly established regime governing the protection of trademarks was particularly important in discharging Bangladesh’s obligations under the WTO Agreement on TRIPS. The present study is an attempt to examine the compatibility of Bangladeshi law with the TRIPS regime of trademarks. The major focus of this study is, however, confined to the TRIPS compatibility of the Trademarks Act in relation to the aspects of acquisition and cancellation of trademark rights in particular, and the nature and scope of these rights in general. In so doing, this paper thus speaks of the success and ramifications of the present regime in exploiting the TRIPS flexibilities—the challenge that Bangladesh is supposed to encounter as a member of LDCs.
Learning to Read: the Case of Moroccan Students who Learn Spanish
Authors: Aguilera-Jiménez Antonio , Delgado Carmen , Luque Alfonso , Moreno-Pérez Francisco J. , Rodríguez-Ortiz Isabel. R. , Saldaña David 
Published: May 2016

AbstractThe aims of this study are to assess L1 and L2 variables that influence the reading acquisition of students of Moroccan origin in the South of Spain and compare their reading ability with native Spanish-speaking children. Participants were 38 students of Moroccan origin and 37 native Spanish-speaking students from the same classes. We used an oral vocabulary test and a reading comprehension test, which taps lexical, semantic, and syntactic reading processes, and reading fluency. The results indicated that immigrant students differed from native Spanish-speaking students in word reading, reading fluency, and the use of punctuation marks, but there were no significant differences in reading comprehension. In native Spanish-speaking students, reading comprehension correlated significantly with oral vocabulary and the other reading processes, but in the students of Moroccan origin, only receptive oral vocabulary in L2 correlated with the use of punctuation marks. Being in schools with educational resources specifically aimed at helping the Moroccan pupils was associated with a higher level of word reading in immigrant students.
TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis
Authors: Aizawa Sayaka , Okamoto Toru , Sugiyama Yukari , Kouwaki Takahisa , Ito Ayano , Suzuki Tatsuya , Ono Chikako , Fukuhara Takasuke , Yamamoto Masahiro , Okochi Masayasu , Hiraga Nobuhiko , Imamura Michio , Chayama Kazuaki , Suzuki Ryosuke , Shoji Ikuo , Moriishi Kohji , Moriya Kyoji , Koike Kazuhiko , Matsuura Yoshiharu 
Published: May 2016

AbstractSignal-peptide peptidase (SPP) is an intramembrane protease that participates in the production of the mature core protein of hepatitis C virus (HCV). Here we show that SPP inhibition reduces the production of infectious HCV particles and pathogenesis. The immature core protein produced in SPP-knockout cells or by treatment with an SPP inhibitor is quickly degraded by the ubiquitin–proteasome pathway. Oral administration of the SPP inhibitor to transgenic mice expressing HCV core protein (CoreTg) reduces the expression of core protein and ameliorates insulin resistance and liver steatosis. Moreover, the haploinsufficiency of SPP in CoreTg has similar effects. TRC8, an E3 ubiquitin ligase, is required for the degradation of the immature core protein. The expression of the HCV core protein alters endoplasmic reticulum (ER) distribution and induces ER stress in SPP/TRC8 double-knockout cells. These data suggest that HCV utilizes SPP cleavage to circumvent the induction of ER stress in host cells.
The gut microbiota: a major player in the toxicity of environmental pollutants?
Authors: Claus Sandrine P , Guillou Hervé , Ellero-Simatos Sandrine 
Published: May 2016

AbstractExposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants.
Analysis of four scales for global severity evaluation in Parkinson’s disease
Authors: Martínez-Martín Pablo , Rojo-Abuin Jose Manuel , Rodríguez-Violante Mayela , Serrano-Dueñas Marcos , Garretto Nélida , Martínez-Castrillo Juan Carlos , Arillo Víctor Campos , Fernández William , Chaná-Cuevas Pedro , Arakaki Tomoko , Alvarez Mario , Ibañez Ivonne Pedroso , Rodríguez-Blázquez Carmen , Chaudhuri Kallol Ray , Merello Marcelo 
Published: May 2016

AbstractGlobal evaluations of Parkinson’s disease (PD) severity are available, but their concordance and accuracy have not been previously tested. The present international, cross-sectional study was aimed at determining the agreement level among four global scales for PD (Hoehn and Yahr, HY; Clinical Global Impression of Severity, CGIS; Clinical Impression of Severity Index, CISI-PD; and Patient Global Impression of Severity, PGIS) and identifying which of them better correlates with itemized PD assessments. Assessments included additional scales for evaluation of the movement impairment, disability, affective disorders, and quality of life. Spearman correlation coefficients, weighted and generalized kappa, and Kendall’s concordance coefficient were used. Four hundred thirty three PD patients, 66% in HY stages 2 or 3, mean disease duration 8.8 years, were analyzed. Correlation between the global scales ranged from 0.60 (HY with PGIS) to 0.91 (CGIS with CISI-PD). Kendall’s coefficient of concordance resulted 0.76 (P<0.0001). HY and CISI-PD showed the highest association with age, disease duration, and levodopa-equivalent daily dose, and CISI-PD with measures of PD manifestations, disability, and quality of life. PGIS and CISI-PD correlated similarly with anxiety and depression scores. The lowest agreement in classifying patients as mild, moderate, or severe was observed between PGIS and HY or CISI-PD (58%) and the highest between CGIS and CISI-PD (84.3%). The four PD global severity scales agree moderately to strongly among them; clinician-based ratings estimate PD severity, as established by other measures, better than PGIS; and the CISI-PD showed the highest association with measures of impairment, disability, and quality of life.
Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome
Authors: Agrawal S. , Chanley M. A. , Westbrook D. , Nie X. , Kitao T. , Guess A. J. , Benndorf R. , Hidalgo G. , Smoyer W. E. 
Published: May 2016

AbstractGlucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20–50% of patients. Thiazolidinediones have recently been suggested to be renoprotective and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment.
Near-Infrared Quantum Cutting Long Persistent Luminescence
Authors: Zou Zehua , Feng Lin , Cao Cheng , Zhang Jiachi , Wang Yuhua 
Published: May 2016

AbstractBy combining the unique features of the quantum cutting luminescence and long persistent luminescence, we design a new concept called “near-infrared quantum cutting long persistent luminescence (NQPL)”, which makes it possible for us to obtain highly efficient (>100%) near-infrared long persistent luminescence in theory. Guided by the NQPL concept, we fabricate the first NQPL phosphor Ca2Ga2GeO7:Pr3+,Yb3+. It reveals that both the two-step energy transfer of model (I) and the one-step energy transfer of model (IV) occur in 3P0 levels of Pr3+. Although the actual efficiency is not sufficient for the practical application at this primitive stage, this discovery and the associated materials are still expected to have important implications for several fields such as crystalline Si solar cells and bio-medical imaging.
Functional differences in hepatitis C virus nonstructural (NS) 3/4A- and 5A-specific T cell responses
Authors: Holmström Fredrik , Chen Margaret , Balasiddaiah Anangi , Sällberg Matti , Ahlén Gustaf , Frelin Lars 
Published: May 2016

AbstractThe hepatitis C virus nonstructural (NS) 3/4A and NS5A proteins are major targets for the new direct-acting antiviral compounds. Both viral proteins have been suggested as modulators of the response to the host cell. We have shown that NS3/4A- and NS5A-specific T cell receptors confer different effector functions and that killing of NS3/4A-expressing hepatocytes is highly dependent on IFN-γ. We here characterize the functional differences in the T cell responses to NS3/4A and NS5A. NS3/4A- and NS5A-specific T cells could be induced at various frequencies in wild-type-, NS3/4A- and NS5A-transgenic mice. Priming of NS5A-specific T cells required a high DNA dose and was unlike NS3/4A dependent on both CD4+ and CD8+ T cells, but less influenced by CD25+/GITR+ regulatory T cells. The presence of IL-12 greatly improved specific CD8+ T cell priming by NS3/4A but not by NS5A, suggesting a less dependence of IFN-γ for NS5A. This notion was supported by the observation that NS5A-specific T cells could eliminate NS5A-expressing hepatocytes also in the absence of IFN-γ-receptor-2. This supports that NS3/4A- and NS5A-specific T cells become activated and eliminate antigen expressing, or infected hepatocytes, by distinct mechanisms and that NS5A-specific T cells show an overall less dependence of IFN-γ.