bluuebunny/crossref_metadata_2025 huggingface dataset:
BRG1 interacts with GLI2 and binds Mef2c gene in a hedgehog signalling dependent manner during in vitro cardiomyogenesis
Authors: Fair Joel Vincent , Voronova Anastassia , Bosiljcic Neven , Rajgara Rashida , Blais Alexandre , Skerjanc Ilona Sylvia
Published: August 2016

Background

The Hedgehog (HH) signalling pathway regulates cardiomyogenesis in vivo and in differentiating P19 embryonal carcinoma (EC) cells, a mouse embryonic stem (mES) cell model. To further assess the transcriptional role of HH signalling during cardiomyogenesis in stem cells, we studied the effects of overexpressing GLI2, a primary transducer of the HH signalling pathway, in mES cells.

Results

Stable GLI2 overexpression resulted in an enhancement of cardiac progenitor-enriched genes, Mef2c, Nkx2-5, and Tbx5 during mES cell differentiation. In contrast, pharmacological blockade of the HH pathway in mES cells resulted in lower expression of these genes. Mass spectrometric analysis identified the chromatin remodelling factor BRG1 as a protein which co-immunoprecipitates with GLI2 in differentiating mES cells. We then determined that BRG1 is recruited to a GLI2-specific Mef2c gene element in a HH signalling-dependent manner during cardiomyogenesis in P19 EC cells, a mES cell model.

Conclusions

Thus, we propose a mechanism where HH/GLI2 regulates the expression of Mef2c by recruiting BRG1 to the Mef2c gene, most probably via chromatin remodelling, to ultimately regulate in vitro cardiomyogenesis.
A pilot investigation of the prevalence of US‐detectable forefoot joint pathology and reported foot‐related disability in participants with systemic lupus erythematosus
Authors: Mukherjee Sandeep , Cherry Lindsey , Zarroug Jalaa , Culliford David , Bowen Catherine , Arden Nigel , Edwards Christopher
Published: August 2016

Background

The main aim of this study was to determine the prevalence of US‐detectable forefoot bursae, metatarsophalangeal (MTP) joint and metacarpophalangeal (MCP) joint synovial hypertrophy (SH), Power Doppler (PD) signal or erosion in participants with systemic lupus erythematosus (SLE). A secondary aim was to determine the strength of potential association between patient reported foot‐related disability and US‐detected forefoot bursae, MTP joint SH, PD signal or erosion in participants with SLE.

Method

A cross‐sectional observational study of 20 participants with SLE was completed to determine the prevalence of US‐detected forefoot bursal, MTP and MCP joint pathology. Patient‐reported foot‐related impairment and activity limitation (accumulatively referred to as disability) were also recorded. Spearmans' Rank Correlation analyses were completed to determine the potential strength of association between US‐detected pathology and patient report disability.

Results

The prevalence of MTP joint SH and PD was 80 % (16/20) and 10 % (2/20), respectively. The prevalence of MCP joint SH and PD was 60 % (12/20) and 30 % (6/20) respectively. A significant association was noted between PD scores for the MTP joints and MCP joints (r = 0.556; p = 0.011) although this was not demonstrated for SH scores (r = 0.176; p = 0.459). Significant associations between forefoot bursal prevalence and MTP joint PD were noted (r = 0.467; p = 0.038). The prevalence of bursae and bursal PD (grade 2 or above) was 100 % (20/20) and 10 % (2/20), respectively. Moderate foot‐related impairment and activity limitation was reported by 95 and 85 % of participants respectively.

Conclusion

This pilot study suggests that US‐detected MTP, MCP joint and forefoot bursal abnormalities may be prevalent in participants with SLE and they may experience a moderate level of foot‐related disability. Further research is required to substantiate these preliminary findings.
Study on chemotaxis and chemokinesis of bone marrow-derived mesenchymal stem cells in hydrogel-based 3D microfluidic devices
Authors: Yoon Dayoung , Kim Hyerim , Lee Eojin , Park Min Hee , Chung Seok , Jeon Hojeong , Ahn Cheol-Hee , Lee Kangwon
Published: August 2016

Background

Controlling the fate of mesenchymal stems cells (MSCs) including proliferation, migration and differentiation has recently been studied by many researchers in the tissue engineering field. Especially, recruitment of stem cells to injury sites is the first and crucial step in tissue regeneration. Although significant progress has been made in the chemotactic migration of MSCs, MSC migration in three dimensional environments remains largely unknown. We developed a 3D hydrogel-based microfluidic-device to study the migration behavior of human MSCs in the presence of stromal-cell derived factor-1α (SDF-1α), interleukin 8 (IL-8) and Substance P (SP) which have been utilized as chemoattractant candidates of human mesenchymal stem cells (hMSCs).

Results

We systematically investigated the chemotactic migration behaviors of hMSCs and their responses to SDF-1α, IL-8, and SP. SDF-1α was shown to be the most fascinating chemoattractant candidate among those factors at a certain time point. We also found that each chemokine showed different chemoattractant abilities according to their concentration. In the case of SP, this factor showed chemokinesis not chemotaxis. Especially at a 7–8 × 10
−8
M concentration range, the chemokinesis ability driven by SP was further increased. The data suggest that some factors at the optimal concentration exhibit chemokinesis or chemotaxis in a 3D hydrogel-based microfluidic device.

Conclusion

In this study on chemotaxis and chemokinesis of hMSCs, the system parameters such as chemokine concentration, system stability, and 2D or 3D microenvironment are critically important to obtain meaningful results.
SEG News
Authors: Sprunt Eve
Published: August 2016

The SEG Board of Directors during its May 2016 meeting unanimously approved a new antiharassment policy that covers the behavior of everyone who participates in Society meetings and activities. I worked with SEG President John Bradford, the SEG Women's Network Committee (WNC), and SEG Executive Director Dorsey Morrow to draft the policy.
Understanding the seismic disorder attribute and its applications
Authors: Chopra Satinder , Marfurt Kurt J.
Published: August 2016

While reflections associated with conformal sedimentary layers are usually coherent and continuous, other reflections, such as mass-transport complexes, karst collapse, and salt, may appear to be quite chaotic, without any specific orientation. We also may see chaotic events that have little to do with the target geology but rather are artifacts due to variations in the overburden and surface or budget limitations resulting in a suboptimum acquisition program. While some of these artifact issues can be handled at the time of processing, a certain level of randomness remains in most seismic data volumes. Geologic features of interpretational interest, such as fault damage zones, unconformities, and gas chimneys, often have randomness associated with them. The published work on randomness describes techniques such as cross correlation, which measures randomness associated with noise, the chaos attribute based on eigen-analysis of gradient covariance, and the seismic disorder attribute based on application of second derivative operators in the three axial directions in a 3D seismic volume. We apply the seismic disorder attribute to two different data sets and find that it is a useful attribute for assessing the signal-to-noise ratio and data quality, in addition to helping delineate damage zones associated with large faults and the interior of salt dome structures.
Reviews
Authors: Irvine Richard , Wood Ray , Liu Lanbo , Green William R. , Bartel David
Published: August 2016

Reflexive Cartography: A new perspective on mapping, by Emanuela Casti, ISBN 978-0-12-803509-2, 2015, Elsevier, Modern Cartography Series, Vol. 6, 288 p., $US120.
Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival
Authors: Partridge Ann H. , Hughes Melissa E. , Warner Erica T. , Ottesen Rebecca A. , Wong Yu-Ning , Edge Stephen B. , Theriault Richard L. , Blayney Douglas W. , Niland Joyce C. , Winer Eric P. , Weeks Jane C. , Tamimi Rulla M.
Published: August 2016

Purpose

Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes.

Methods

We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer–specific survival.

Results

A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors.

Conclusion

The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.
The BATTLE-2 Study: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Papadimitrakopoulou Vassiliki , Lee J. Jack , Wistuba Ignacio I. , Tsao Anne S. , Fossella Frank V. , Kalhor Neda , Gupta Sanjay , Byers Lauren Averett , Izzo Julie G. , Gettinger Scott N. , Goldberg Sarah B. , Tang Ximing , Miller Vincent A. , Skoulidis Ferdinandos , Gibbons Don L. , Shen Li , Wei Caimiao , Diao Lixia , Peng S. Andrew , Wang Jing , Tam Alda L. , Coombes Kevin R. , Koo Ja Seok , Mauro David J. , Rubin Eric H. , Heymach John V. , Hong Waun Ki , Herbst Roy S.
Published: August 2016

Purpose

By applying the principles of real-time biopsy, biomarker-based, adaptively randomized studies in non–small-cell lung cancer (NSCLC) established by the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, we conducted BATTLE-2 (BATTLE-2 Program: A Biomarker-Integrated Targeted Therapy Study in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer), an umbrella study to evaluate the effects of targeted therapies focusing on KRAS-mutated cancers.

Patients and Methods

Patients with advanced NSCLC (excluding sensitizing EGFR mutations and ALK gene fusions) refractory to more than one prior therapy were randomly assigned, stratified by KRAS status, to four arms: (1) erlotinib, (2) erlotinib plus MK-2206, (3) MK-2206 plus AZD6244, or (4) sorafenib. Tumor gene expression profiling–targeted next-generation sequencing was performed to evaluate predictive and prognostic biomarkers.

Results

Two hundred patients, 27% with KRAS-mutated (KRAS mut+) tumors, were adaptively randomly assigned to erlotinib (n = 22), erlotinib plus MK-2206 (n = 42), MK-2206 plus AZD6244 (n = 75), or sorafenib (n = 61). In all, 186 patients were evaluable, and the primary end point of an 8-week disease control rate (DCR) was 48% (arm 1, 32%; arm 2, 50%; arm 3, 53%; and arm 4, 46%). For KRAS mut+ patients, DCR was 20%, 25%, 62%, and 44% whereas for KRAS wild-type patients, DCR was 36%, 57%, 49%, and 47% for arms 1, 2, 3, and 4, respectively. Median progression-free survival was 2.0 months, not different by KRAS status, 1.8 months for arm 1, and 2.5 months for arms 2 versus arms 3 and 4 in KRAS mut+ patients (P = .04). Median overall survival was 6.5 months, 9.0 and 5.1 months for arms 1 and 2 versus arms 3 and 4 in KRAS wild-type patients (P = .03). Median overall survival was 7.5 months in mesenchymal versus 5 months in epithelial tumors (P = .02).

Conclusion

Despite improved progression-free survival on therapy that did not contain erlotinib for KRAS mut+ patients and improved prognosis for mesenchymal tumors, better biomarker-driven treatment strategies are still needed.
Blood vessel formation and function in bone
Authors: Sivaraj Kishor K. , Adams Ralf H.
Published: August 2016

In addition to their conventional role as a conduit system for gases, nutrients, waste products or cells, blood vessels in the skeletal system play active roles in controlling multiple aspects of bone formation and provide niches for hematopoietic stem cells that reside within the bone marrow. In addition, recent studies have highlighted roles for blood vessels during bone healing. Here, we provide an overview of the architecture of the bone vasculature and discuss how blood vessels form within bone, how their formation is modulated, and how they function during development and fracture repair.
Size regulation blossoms in Kobe
Authors: Hariharan Iswar K.
Published: August 2016

Coincident with the blossoming of the sakura was the 14th annual CDB Symposium hosted by the RIKEN Center for Developmental Biology in Kobe, Japan. This year's meeting, ‘Size in Development: Growth, Shape and Allometry' focused on the molecular and cellular mechanisms underlying differences in size and shape and how they have evolved. On display was the power of using diverse approaches ranging from the study of organoids to whole organisms.
Ontogeny of learning walks and the acquisition of landmark information in desert ants,Cataglyphis fortis
Authors: Fleischmann Pauline N. , Christian Marcelo , Müller Valentin L. , Rössler Wolfgang , Wehner Rüdiger
Published: August 2016

At the beginning of their foraging lives, desert ants (Cataglyphis fortis) are for the first time exposed to the visual world within which they henceforth must accomplish their navigational tasks. Their habitat, North African salt pans, are barren, and the nest entrance, a tiny hole in the ground, is almost invisible. Although natural landmarks are scarce and the ants mainly depend on path integration for returning to the starting point, they can also learn and use landmarks successfully to navigate through their largely featureless habitat. Here we study how the ants acquire this information at the beginning of their outdoor lives within a nest-surrounding array of three artificial black cylinders. Individually marked ‘newcomers’ exhibit a characteristic sequence of learning walks. The meandering learning walks covering all directions of the compass first occur only within a few centimeters distance from the nest entrance, but then increasingly widen, until after three to seven learning walks foraging starts. When displaced to a distant test field in which an identical array of landmarks has been installed, the ants shift their search density peaks the more closely to the fictive goal position, the more learning walks they have performed. These results suggest that learning of a visual landmark panorama around a goal is a gradual rather than an instantaneous process.
The Mechanics of Motivated Reasoning
Authors: Epley Nicholas , Gilovich Thomas
Published: August 2016

Whenever we see voters explain away their preferred candidate's weaknesses, dieters assert that a couple scoops of ice cream won't really hurt their weight loss goals, or parents maintain that their children are unusually gifted, we are reminded that people's preferences can affect their beliefs. This idea is captured in the common saying, “People believe what they want to believe.” But people don't simply believe what they want to believe. Psychological research makes it clear that “motivated beliefs” are guided by motivated reasoning—reasoning in the service of some self-interest, to be sure, but reasoning nonetheless. People generally reason their way to conclusions they favor, with their preferences influencing the way evidence is gathered, arguments are processed, and memories of past experience are recalled. Each of these processes can be affected in subtle ways by people's motivations, leading to biased beliefs that feel objective. In this symposium introduction, we set the stage for discussion of motivated beliefs in the papers that follow by providing more detail about the underlying psychological processes that guide motivated reasoning.
Can War Foster Cooperation?
Authors: Bauer Michal , Blattman Christopher , Chytilová Julie , Henrich Joseph , Miguel Edward , Mitts Tamar
Published: August 2016

In the past decade, nearly 20 studies have found a strong, persistent pattern in surveys and behavioral experiments from over 40 countries: individual exposure to war violence tends to increase social cooperation at the local level, including community participation and prosocial behavior. Thus while war has many negative legacies for individuals and societies, it appears to leave a positive legacy in terms of local cooperation and civic engagement. We discuss, synthesize, and reanalyze the emerging body of evidence and weigh alternative explanations. There is some indication that war violence enhances in-group or “parochial” norms and preferences especially, a finding that, if true, suggests that the rising social cohesion we document need not promote broader peace.
The Importance of School Systems: Evidence from International Differences in Student Achievement
Authors: Woessmann Ludger
Published: August 2016

Students in some countries do far better on international achievement tests than students in other countries. Is this all due to differences in what students bring with them to school—socioeconomic background, cultural factors, and the like? Or do school systems make a difference? This essay argues that differences in features of countries' school systems, and in particular their institutional structures, account for a substantial part of the cross-country variation in student achievement. It first documents the size and cross-test consistency of international differences in student achievement. Next, it uses the framework of an education production function to provide descriptive analysis of the extent to which different factors of the school system, as well as factors beyond the school system, account for cross-country achievement differences. Finally, it covers research that goes beyond descriptive associations by addressing leading concerns of bias in cross-country analysis. The available evidence suggests that differences in expenditures and class size play a limited role in explaining cross-country achievement differences, but that differences in teacher quality and instruction time do matter. This suggests that what matters is not so much the amount of inputs that school systems are endowed with, but rather how they use them. Correspondingly, international differences in institutional structures of school systems such as external exams, school autonomy, private competition, and tracking have been found to be important sources of international differences in student achievement.
Personal values influencing career path in academic medicine
Authors: Tsoi Marissa , Teitge Braden D. , Madan Christopher R. , Francescutti Louis H.
Published: August 2016

To pursue research, education, and health policy in one’s career, broadly defined as academic medicine, is one of the most important decisions of a trainee doctor’s career. Despite this, there is scant literature on which factors influence trainees’ choices towards clinical work or academic research. As the MD/PhD is a relatively young training path compared to the traditional PhD (Doctor of Philosophy) and MD (Doctor of Medicine) programs, it prompts the question: at the crossroads of a career, what sways the individual to select an MD, PhD, or MD/PhD program? This is a valuable question to be answered for trainees who are considering multiple career paths, for educators who want to guide undifferentiated students, and for policy makers who develop and coordinate research programs. “Intellectual stimulation” is the most consistently identified personal value which draws trainees to academic medicine. Mentorship is linked strongly to success in the field. Conversely, long training periods, a lack of autonomy, and financial considerations are deterrents from a career in academic medicine. Insight into the decision-making process is provided by recent trainees in these respective fields, as well as experienced academic clinicians.
Wealth Management: Art-banking
Authors: Саркисянц  , Sarkisyants A.
Published: August 2016

Th e article is devoted to art-banking, which is understood as the range of services in the financial and consulting

support of investments in physical assets with high intrinsic value, particularly in the works of art.
Innovative Approach to the Transformation of the Organizations Personnel Policy in Connection With Mental Values Changes of Young Employees
Authors: Ширшова  , Shirshova O. , Дементьева  , Dementeva D.
Published: August 2016

The article examines an innovative approach to change and correct the personnel policy of the company according to the young employees using the knowledge

of generational theory. In the last years the same category of employees is young generation Y, this is why we can see the obvious change of mental values and

attitudes of young people in the context of beliefs and expectations of the employer. The article analyzes the theoretical aspects of strategic human resource

management, and presents a program of development of young professionals. Realization of this program allows overcoming the differences of generations

of managers and subordinates within the company.
The Impact of Competing Ads on Click Performance in Sponsored Search
Authors: Agarwal Ashish , Mukhopadhyay Tridas
Published: August 2016

Our research examines the impact of competing ads on click performance of an ad in sponsored search. We use a unique data set of 1,267 advertiser keyword pairs with differing ad quality related to 360 keywords from a search engine to evaluate the click performance. We find that competing high-quality ads, appearing above the focal ad, have a lower negative effect on the click performance as compared to competing low-quality ads. We also find that this effect of competing ads varies with the ad position and the type of keyword. In general, the negative effect of competing high-quality ads decreases at low positions as compared to high positions. Furthermore, this decrease in the negative effect of competing high-quality ads is more substantial for specific keywords.

Our results reveal consumer behavior in evaluating different quality ads in sponsored search. More specifically, our results suggest that consumers use the presence of high-quality competing ads as a signal of higher quality of the focal ad. Our findings can help advertisers better evaluate their relative performance for different positions for various types of keywords. This can also help evaluate the efficacy of the auction design mechanism.
Impact Factors
Authors: Arruda J. Roberto F. , Champieux Robin , Cook Colleen , Davis Mary Ellen K. , Gedye Richard , Goodman Laurie , Jacobs Neil , Ross David , Taylor Stuart
Published: August 2016

Tracking the metrics of a more open publishing world will be key to selling “open” and encouraging broader adoption of open solutions. Will more openness mean lower impact, though (for whatever reason—less visibility, less readability, less press, etc.)? Why or why not? Perhaps more fundamentally, how useful are impact factors anyway? What are they really tracking, and what do they mean? What are the pros and cons of our current reliance on these measures? Would faculty be satisfied with an alternative system as long as it is recognized as reflecting meaningfully on the quality of their scholarship? What might such an alternative system look like?
Report from the Embargo Workgroup
Authors: Campbell Glenorchy , Gordon Gregg , Helmuth Laura , Kingsley Danny , Massant Eric , McCulloch Audrey , McMillan Gail , Peatfield Tony , Riley Ann , Schweitzer Will , Webster Keith
Published: August 2016

The Embargo Working Group began by defining “embargo,” encapsulating it into four main types and then focusing on the post-publication and subscription embargoes. Among other things, we discussed the dispersed nature of usage metrics and their possible impact on the duration of embargoes. This, in part, led us to recognize the lack of an evidence on which to base decisions surrounding the need for embargoes and their duration. Therefore, we focused on what it would take to address the key issue: ‘What are the impacts of embargoes on scholarly communication?’ We concluded by considering how to fund a global survey of key stakeholders and what data the survey should collect in order to provide data about the issues surrounding embargoes.OSI2016 Workshop QuestionIn an information system where so much information is destined for subscription journals, the assumption has been that embargos allow publishers time to recoup their investments, and also allow the press time to prepare news articles about research. Is this assumption warranted? Why or why not? Is the public interest being served by embargos? What about by embargos on federally-funded research? Are there any facts or options that haven’t yet been considered to address the concerns animating the embargo solution?
Report from the Information Overload and Underload Workgroup
Authors: Alexander Bryan , Barrett Kim , Cumming Sioux , Herron Patrick , Holland Claudia , Keane Kathleen , Ogburn Joyce , Orlowitz Jake , Thomas Mary Augusta , Tsao Jeff
Published: August 2016

The duality of information overload and underload is a defining issue of our age. Scholarly information is abundant but not universally accessible to all scholars and learners, thereby hindering or prohibiting equitable engagement in ongoing scholarly conversations. Access is a core aspect of the issue of overload and underload—both access to research materials and access to venues where one can contribute to the scholarly corpus—but it is not the only aspect. Our group agreed that the problem of overload is preferable to that of underload; however, the dual nature of the issue makes that conclusion more nuanced, dynamic, and situational. In this report we explore the many factors and causes of information overload and underload and also develop ideas for solutions. A summary of the issues is provided.OSI2016 Workgroup QuestionInformation underload occurs when we don’t have access to the information we need (for a variety of reasons, including cost)—researchers based at smaller institutions and in the global pe­riphery, policymakers, and the general public, particularly with regard to medical research. Overload occurs when we can access everything but are simply overwhelmed by the torrent of information available (not all of which is equally valuable). Are these issues two sides of the same coin? In both cases, how can we work together to figure out how to get people the information they need? Can we? How widespread are these issues? What are the economic and research consequences of information underload and overload?
Representações sobre a liderança da macroequipa e das microequipas em contextos de empreendedorismo social
Authors: Pais Celso , Parente Cristina
Published: August 2016

No presente artigo mostramos como é representada coletivamente a liderança em organizações socialmente empreendedoras. Partimos dos conceitos de macroequipa e microequipa. Foram estudadas sete organizações que apresentam características socialmente empreendedoras, dentro do panorama do terceiro setor. A investigação adotou uma metodologia de cariz qualitativo, recorrendo à realização de entrevistas semiestruturadas, individuais e coletivas, respetivamente junto de líderes de topo, de técnicos com funções de liderança, de técnicos sem funções de liderança, e de trabalhadores de base. A análise indutiva dos dados recolhidos permite realçar a importância dos comportamentos responsáveis, tanto da parte dos que possuem funções de liderança como dos que não exercem essas funções. Em geral, há uma representação indiciadora de perturbações no relacionamento com os subordinados, quando os líderes de topo se mostram distantes do terreno operacional das equipas (microequipas). Os líderes das microequipas, quando eficazes, são vistos como facilitadores, promovendo a autonomia responsável dos membros da equipa.
Transição e adaptação ao ensino superior e a demanda pelo sucesso nas instituições portuguesas
Authors: Soares Andreia Martins , Pinheiro Maria Do Rosário , Canavarro José Manuel Portocarrero
Published: August 2016

Não obstante as importantes transformações operadas nas instituições portuguesas de ensino terciário, desde os últimos anos do Estado Novo, e os esforços para cumprir a exigente missão de preparação dos seus estudantes para os desafios da Europa do Conhecimento, diversos indicadores colocam o ensino superior nacional por agora longe de um sistema de ensino que se pretende inclusivo, diferenciado e de grande qualidade. A investigação nacional sobre o sucesso académico e o processo de transição e adaptação ao ensino superior, centrada na compreensão destes fenómenos e subsequente planeamento/aplicação de intervenções neste âmbito, tem sido um bom auxílio à persecução das pretensões anteriores. Neste artigo de revisão abordar-se-ão estes complexos fenómenos, enfatizando as perspetivas adotadas e os resultados alcançados na investigação mais recente, bem como as respostas que as instituições nacionais de ensino terciário têm desenvolvido no sentido de promover o sucesso académico que, na sua aceção mais ampla, inclui um processo de transição e adaptação bem-sucedido.
5‐HT2B receptor antagonists attenuate myofibroblast differentiation and subsequent fibrotic responses in vitro and in vivo
Authors: Löfdahl Anna , Rydell‐Törmänen Kristina , Müller Catharina , Martina Holst C. , Thiman Lena , Ekström Gunilla , Wenglén Christina , Larsson‐Callerfelt Anna‐Karin , Westergren‐Thorsson Gunilla
Published: August 2016

Pulmonary fibrosis is characterized by excessive accumulation of connective tissue, along with activated extracellular matrix (ECM)‐producing cells, myofibroblasts. The pathological mechanisms are not well known, however serotonin (5‐HT) and 5‐HT class 2 (5‐HT2) receptors have been associated with fibrosis. The aim of the present study was to investigate the role of 5‐HT2B receptors in fibrosis, using small molecular 5‐HT2B receptor antagonists EXT5 and EXT9, with slightly different receptor affinity. Myofibroblast differentiation [production of alpha‐smooth muscle actin (α‐SMA)] and ECM synthesis were quantified in vitro, and the effects of the receptor antagonists were evaluated. Pulmonary fibrosis was also modeled in mice by subcutaneous bleomycin administrations (under light isoflurane anesthesia), and the effects of receptor antagonists on tissue density, collagen‐producing cells, myofibroblasts and decorin expression were investigated. In addition, cytokine expression was analyzed in serum. Lung fibroblasts displayed an increased α‐SMA (P < 0.05) and total proteoglycan production (P < 0.01) when cultured with TGF‐β1 together with 5‐HT, which were significantly reduced with both receptor antagonists. Following treatment with EXT5 or EXT9, tissue density, expression of decorin, number of collagen‐producing cells, and myofibroblasts were significantly decreased in vivo compared to bleomycin‐treated mice. Receptor antagonization also significantly reduced systemic levels of TNF‐α and IL‐1β, indicating a role in systemic inflammation. In conclusion, 5‐HT2B receptor antagonists have potential to prevent myofibroblast differentiation, in vitro and in vivo, with subsequent effect on matrix deposition. The attenuating effects of 5‐HT2B receptor antagonists on fibrotic tissue remodeling suggest these receptors as novel targets for the treatment of pulmonary fibrosis.
Hepatocyte Growth Factor Modulates MET Receptor Tyrosine Kinase and β-Catenin Functional Interactions to Enhance Synapse Formation
Authors: Xie Zhihui , Eagleson Kathie L. , Wu Hsiao-Huei , Levitt Pat
Published: August 2016

MET, a pleiotropic receptor tyrosine kinase implicated in autism risk, influences multiple neurodevelopmental processes. There is a knowledge gap, however, in the molecular mechanism through which MET mediates developmental events related to disorder risk. In the neocortex, MET is expressed transiently during periods of peak dendritic outgrowth and synaptogenesis, with expression enriched at developing synapses, consistent with demonstrated roles in dendritic morphogenesis, modulation of spine volume, and excitatory synapse development. In a recent coimmunoprecipitation/mass spectrometry screen, β-catenin was identified as part of the MET interactome in developing neocortical synaptosomes. Here, we investigated the influence of the MET/β-catenin complex in mouse neocortical synaptogenesis. Western blot analysis confirms that MET and β-catenin coimmunoprecipitate, but N-cadherin is not associated with the MET complex. Following stimulation with hepatocyte growth factor (HGF), β-catenin is phosphorylated at tyrosine142(Y142) and dissociates from MET, accompanied by an increase in β-catenin/N-cadherin and MET/synapsin 1 protein complexes. In neocortical neuronsin vitro, proximity ligation assays confirmed the close proximity of these proteins. Moreover, in neurons transfected with synaptophysin-GFP, HGF stimulation increases the density of synaptophysin/bassoon (a presynaptic marker) and synaptophysin/PSD-95 (a postsynaptic marker) clusters. Mutation of β-catenin at Y142 disrupts the dissociation of the MET/β-catenin complex and prevents the increase in clusters in response to HGF. The data demonstrate a new mechanism for the modulation of synapse formation, whereby MET activation induces an alignment of presynaptic and postsynaptic elements that are necessary for assembly and formation of functional synapses by subsets of neocortical neurons that express MET/β-catenin complex.
Parallel reverse genetic screening in mutant human cells using transcriptomics
Authors: Gapp Bianca V , Konopka Tomasz , Penz Thomas , Dalal Vineet , Bürckstümmer Tilmann , Bock Christoph , Nijman Sebastian MB
Published: August 2016

Reverse genetic screens have driven gene annotation and target discovery in model organisms. However, many disease‐relevant genotypes and phenotypes cannot be studied in lower organisms. It is therefore essential to overcome technical hurdles associated with large‐scale reverse genetics in human cells. Here, we establish a reverse genetic approach based on highly robust and sensitive multiplexed RNA sequencing of mutant human cells. We conduct 10 parallel screens using a collection of engineered haploid isogenic cell lines with knockouts covering tyrosine kinases and identify known and unexpected effects on signaling pathways. Our study provides proof of concept for a scalable approach to link genotype to phenotype in human cells, which has broad applications. In particular, it clears the way for systematic phenotyping of still poorly characterized human genes and for systematic study of uncharacterized genomic features associated with human disease.
Health Concept and Knowledge Management: Twenty-five Years of Evolution
Authors: Cornet R. , Chute C. G.
Published: August 2016

Objectives: The fields of health terminology, classification, ontology, and related information models have evolved dramatically over the past 25 years. Our objective was to review notable trends, described emerging or enabling technologies, and highlight major terminology systems during the interval.

Methods: We review the progression in health terminology systems informed by our own experiences as part of the community involved in this work, reinforced with literature review and citation.

Results: The transformation in size, scope, complexity, and adoption of health terminological systems and information models has been tremendous, on the scale of orders of magnitude.

Conclusion: The present “big science” era of inference and discovery in biomedicine would not have been possible or scalable absent the growth and maturation of health terminology systems and information models over the past 25 years.
Specialiojo Irako tribunolo funkcionavimas (materialiniai ir procesiniai aspektai)
Authors: Katarzyna Dróżdż Dominika
Published: August 2016

Straipsnyje analizuojamos Irako specialiojo tribu­nolo, įkurto 2003 m. gruodžio 10 d., statuto nuos­tatos, materialiniai ir procesiniai Tribunolo veiklos aspektai. Nurodoma, kad Statutu įdiegtas stebėtojų ir patarėjų tarptautinės teisės klausimais institutas – keliamas jų veiklos teisinio apibrėžtumo klausimas; apibūdinama Tribunolo jurisdikcija: nuo 1968 m. lie­pos 17 d. iki 2003 m. gegužės 1 d. padarytiems nusi­kaltimams, numatytiems Statuto 11–14 straipsniuo­se, už kuriuos gali būti traukiami tik Irako piliečiai ir nuolatiniai Irako gyventojai, nusikaltimus padarę Irake ir už jo ribų teisti. Nurodoma, kad nėra regla­mentuota asmenų, Tribunolo trauktinų baudžiamo­jon atsakomybėn, amžiaus riba; juridiniai asmenys (pvz., Baath partija) nėra teisiami. Taip pat, lyginant su Tarptautinio karinio tribunolo nuostatomis, Irako specialusis tribunolas negali paskelbti nė vienos gru­pės ar organizacijos kriminaline.Straipsnyje taip pat analizuojami nusikaltimai, už kuriuos gali teisti Irako specialusis tribunolas, lyginamas kitų ad hoc tribunolų veiklos teisinis re­glamentavimas. Autorė, be to, palyginusi Irako speci­aliojo tribunolo statuto ir Romos statuto bei 1949 m. Ženevos konvencijos papildomo protokolo nuostatas, daro išvadą, kad baudimas už kai kuriuos Irako spe­cialiojo tribunolo statute numatytus nusikaltimus būtų nesuderinamas su nullum crimen sine lege, nes tai nėra universaliai tarptautiniu lygiu pripažįstami nusikaltimai; terorizmo nusikaltimo Statute taip pat nenumatyta – tai būtų Irako nacionalinių teismų ju­risdikcijos klausimas.Taip pat teigiama, kad Statuto 11c) punktas turėtų būti traktuojamas kaip novela, nes numato agresiją kaip nusikalstamą veiką.Straipsnyje analizuojamos kaltinamųjų, liudytojų, nukentėjusiųjų teisės procese; pabrėžiama, kad Irako specialiojo tribunolo statute nenumatyta žalos atlygi­nimo instituto, kompensacijos už neteisėtą areštą ar sulaikymą; skiriama dėmesio reguliuojant procesą in absentia, Tribunolo sprendimo peržiūrai.The Iraqi Special Tribunal was established directly by the Iraqi Governing Council on December 10, 2003. The Tribunal has been mandated to try the accused for crimes under international law (genocide, crime against humanity and war crimes) and some violations of Stipulated Iraqi Laws.This article contains an analysis of the provisions of the Statute of the Iraqi Special Tribunal with regard to its material and procedural aspects. The Statute of this Tribunal was created taking for the pattern the Statute of International Criminal Court. However, the opinions of the Iraqis were also taken into account; the Iraqis wanted to have the solely power to exercise jurisdiction of this Tribunal.
Parent Experience With False-Positive Newborn Screening Results for Cystic Fibrosis
Authors: Hayeems Robin Z. , Miller Fiona A. , Barg Carolyn J. , Bombard Yvonne , Kerr Elizabeth , Tam Karen , Carroll June C. , Potter Beth K. , Chakraborty Pranesh , Davies Christine , Milburn Jennifer , Patton Sarah , Bytautas Jessica P. , Taylor Louise , Price April , Gonska Tanja , Keenan Katherine , Ratjen Felix , Guttmann Astrid
Published: August 2016

BACKGROUND:

The risk of psychosocial harm in families of infants with false-positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF) is a longstanding concern. Whether well designed retrieval and confirmatory testing systems can mitigate risks remains unknown.

METHODS:

Using a mixed-methods cohort design, we obtained prospective self-report data from mothers of infants with FP CF NBS results 2 to 3 months after confirmatory testing at Ontario’s largest follow-up center, and from a randomly selected control sample of mothers of screen negative infants from the same region. Mothers completed a questionnaire assessing experience and psychosocial response. A sample of mothers of FP infants completed qualitative interviews.

RESULTS:

One hundred thirty-four mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%) completed questionnaires; 54 mothers of FP infants were interviewed. Selected psychosocial response measures did not detect psychosocial distress in newborns or 1 year later (P > .05). Mothers recalled distress during notification of the positive result and in the follow-up testing period related to fear of chronic illness, but valued the screening system of care in mitigating concerns.

CONCLUSIONS:

Although immediate distress was reported among mothers of FP infants, selected psychometric tools did not detect these concerns. The NBS center from which mothers were recruited minimizes delay between notification and confirmatory testing and ensures trained professionals are communicating results and facilitating follow-up. These factors may explain the presence of minimal psychosocial burden. The screening system reflected herein may be a model for NBS programs working to minimize FP-related psychosocial harm.
The Doctrine of Discovery as a Doctrine of Domination
Authors: Greenberg Joy H.
Published: August 2016

Sheldon Wolfchild (dir.), The Doctrine of Discovery: Unmasking the Domination Code (38Plus2 Productions, 2014), DVD, $50US.  Steven T. Newcomb, Pagans in the Promised Land: Decoding the Doctrine of Christian Discovery (Golden, CO: Fulcrum Books, 2008), 216 pp., $19.95US (pbk). ISBN: 978-1-55591-642-8.
FONCTIONNEMENT ADVERBIAL ET SENS EN EMPLOI DE À UN POINT (QUE P)
Authors: BOUCHAREB Sonia
Published: August 2016

RÉSUMÉ. A un point que est présenté par les dictionnaires de langue, notamment le Trésor de la Langue Française (TLFi) comme une locution adverbiale « assimilable à un adverbe de degré, d’intensité » (article Point). Il s’agit là, en fait, non pas de sa nature mais de l’un de ses emplois. En emploi adverbial, cette séquence en point présente une latitude combinatoire conforme à celle des adverbes de degré. En dépit de ce comportement adverbial, à un point que P est identifié, dans le cadre de cet article, non pas comme une locution adverbiale mais comme une locution prépositionnelle à complément zéro. D’un point de vue sémantique, elle  constitue un adverbe de degré tout comme beaucoup, très, extrêmement et énormément toutefois à un point que P véhicule un degré bien plus intense. Ce sens émane, selon nous, de l’association du sens de chacun de ses éléments constitutifs.

 

Mots-clés: adverbe, degré, intensifieur, locution, modifieur, quantifieur, structure interne.

ABSTRACT. A un point que is defined by language dictionaries, especially by the Trésor de la Langue Française (TLFi), as an adverbial locution « comparable to an adverb of degree or intensity » (Point). In fact this is not a definition of its nature but of one of its uses. In its adverbial usage, this sequence in point presents combinatorial latitude in accordance with adverbs of degree. Despite this adverbial behavior, à un point que P is not identified, within the frame of this article, with an adverbial locution but with a prepositional locution with a zero complement. It is an adverb of degree as beaucoup, très, extrêmement and énormément. Yet, à un point que P conveys a more intense degree. According to us, this meaning comes from the combination of the meaning of each constitutive element.

 

Keywords: adverb, degree, intensifier, internal structure, locution, modifier, quantifier.
PAPEL HIDROSSENSÍVEL E ALTERNATIVO FOTOGRÁFICO EM ENSAIOS DE DEPOSIÇÃO DE GOTAS
Authors: Baio F. H. R. , Scarpin I. M. , Da Silva E. E.
Published: August 2016

Muitos ensaios fitotécnicos envolvendo tecnologia de aplicação de agrotóxicos utilizam como alvo artificial para caracterização do espectro de gotas o papel hidrossensível. O objetivo deste trabalho foi comparar os resultados do DMV (Diâmetro Mediano Volumétrico), índice Span (amplitude relativa) e da porcentagem de gotas menores que 100 µm obtidos pelo uso de um papel hidrossensível comercial e de um alternativo fotográfico em relação aos do analisador de partícula por difração laser. Foram utilizados três modelos de pontas: ponta tipo leque comum XR11001; ponta tipo leque com pré-orifício LBD11001; e a ponta tipo leque de grande ângulo com pré-orifício TT11001. A caracterização do espectro de gotas foi realizada por três métodos de mensuração (medidor de partícula a laser, papel hidrossensível comercial e papel fotográfico) e por dois volumes de aplicação (70 e 100 L ha-1). As metodologias pelo uso de papel hidrossensível comercial e pelo uso de papel fotográfico alternativo não conseguem detectar todas as gotas menores que 100 µm, gotas muito finas (ASAE, 2009), afetando a mensuração do DMV, índice Span e do percentual de gotas <100 µm, em ensaios de tecnologia de aplicação utilizando pontas TT, XR e LBD, segundo os volumes de aplicação de 70 e 100 L ha-1. O papel fotográfico alternativo caracteriza de forma semelhante o espectro de gotas em relação ao uso do papel hidrossensível comercial.
PREGNANCY RATES AND BODY MORPHOMETRY IN NELLORE COWS SUBMITTED TO PROGESTERONE AND TEMPORARY WEANING OF CALVES
Authors: Chacur M. G. M. , Vasconcelos F. F. , Dias H. S. , Aurélio P. T. F. , Gabriel Filho L. R. A. , Cremasco C. P. , Putti F. F.
Published: August 2016

Body morphometry and temporary weaning (TW) associated to two protocols of fixed-time artificial insemination (FTAI) with intravaginal progesterone releasing device (IPRD) upon pregnancy rates were evaluated. Cows, at 45-59 days post-partum, were randomly divided into group 1 (n=147) and group 2 (n=197). Group 1: received 1g progesterone (IPRD) and 2mg estradiol benzoate on day 0 (EB-D0); 150μg D-cloprostenol on day 7 (PGF-2α-D7); 0,5mg estradiol cypionate and (TW-48 hours) on day 9 (EC+TW-D9); FTAI on day 11 (D11); group 2: IPRD+EB (D0); PGF-2α+EC+TW (72 hours) on D8; FTAI (D11). The pregnancy rate was higher in cows submitted to TW (72 hours) than in cows with TW (48 hours), or rather, 49.74% vs 30.60% (p<0.05). There was a statistical difference (p<0.05) in groups 1 and 2 between pregnant or non-pregnant cows with regard to body weight (412kg vs 400kg and 419kg vs 390kg) and body condition score (BCS) (3.33 vs 3.08 and 3.53 vs 3/32) respectively. Further, 72-hour weaning associated to the applied protocol improved the pregnancy rate. The evaluation of BCS during post-partum may adjust the start of the breeding season.
A sedimentação em uma abordagem sistêmica
Authors: Zerfass Henrique , Zerfass Geise de Santana dos Anjos
Published: August 2016

A sedimentação pode ser vista como um sistema na superfície da Terra. A mesma apresenta um atributo fundamental de sistema, a equifinalidade, traduzida na busca da estabilidade entre erosão e deposição. O sistema sedimentar possui entrada e saída de massa e energia e transferência interna de massa. A energia adicionada é térmica e gravitacional. A massa é incorporada por meio de absorção de gases atmosféricos, chuva e neve, intemperismo e erosão, e fotossíntese. A energia sai como de perda de calor e acumulação de energia química nas rochas. A massa é perdida por intermédio da incorporação ao registro estratigráfico, decomposição da matéria orgânica e liberação de gases para a atmosfera. É possível ainda uma divisão em subsistemas, combase na energia motora: (i) inércia, (ii) gradientes de densidade, (iii) marés e (iv) ondas. Em termos didáticos, a visão sistêmica aproxima disciplinas como sedimentologia, paleontologia e geoquímica