986 resultados para Non-BMP character


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We study the stability and dynamics of non-Boussinesq convection in pure gases ?CO2 and SF6? with Prandtl numbers near Pr? 1 and in a H2-Xe mixture with Pr= 0.17. Focusing on the strongly nonlinear regime we employ Galerkin stability analyses and direct numerical simulations of the Navier-Stokes equations. For Pr ? 1 and intermediate non-Boussinesq effects we find reentrance of stable hexagons as the Rayleigh number is increased. For stronger non-Boussinesq effects the usual, transverse side-band instability is superseded by a longitudinal side-band instability. Moreover, the hexagons do not exhibit any amplitude instability to rolls. Seemingly, this result contradicts the experimentally observed transition from hexagons to rolls. We resolve this discrepancy by including the effect of the lateral walls. Non-Boussinesq effects modify the spiral defect chaos observed for larger Rayleigh numbers. For convection in SF6 we find that non-Boussinesq effects strongly increase the number of small, compact convection cells and with it enhance the cellular character of the patterns. In H2-Xe, closer to threshold, we find instead an enhanced tendency toward roll-like structures. In both cases the number of spirals and of targetlike components is reduced. We quantify these effects using recently developed diagnostics of the geometric properties of the patterns.

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This paper presents a preliminary study in which Machine Learning experiments applied to Opinion Mining in blogs have been carried out. We created and annotated a blog corpus in Spanish using EmotiBlog. We evaluated the utility of the features labelled firstly carrying out experiments with combinations of them and secondly using the feature selection techniques, we also deal with several problems, such as the noisy character of the input texts, the small size of the training set, the granularity of the annotation scheme and the language object of our study, Spanish, with less resource than English. We obtained promising results considering that it is a preliminary study.

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Purpose – This article aims to investigate whether intermediaries reduce loss aversion in the context of a high-involvement non-frequently purchased hedonic product (tourism packages). Design/methodology/approach – The study incorporates the reference-dependent model into a multinomial logit model with random parameters, which controls for heterogeneity and allows representation of different correlation patterns between non-independent alternatives. Findings – Differentiated loss aversion is found: consumers buying high-involvement non-frequently purchased hedonic products are less loss averse when using an intermediary than when dealing with each provider separately and booking their services independently. This result can be taken as identifying consumer-based added value provided by the intermediaries. Practical implications – Knowing the effect of an increase in their prices is crucial for tourism collective brands (e.g. “sun and sea”, “inland”, “green destinations”, “World Heritage destinations”). This is especially applicable nowadays on account of the fact that many destinations have lowered prices to attract tourists (although, in the future, they will have to put prices back up to their normal levels). The negative effect of raising prices can be absorbed more easily via indirect channels when compared to individual providers, as the influence of loss aversion is lower for the former than the latter. The key implication is that intermediaries can – and should – add value in competition with direct e-tailing. Originality/value – Research on loss aversion in retailing has been prolific, exclusively focused on low-involvement and frequently purchased products without distinguishing the direct or indirect character of the distribution channel. However, less is known about other types of products such as high-involvement non-frequently purchased hedonic products. This article focuses on the latter and analyzes different patterns of loss aversion in direct and indirect channels.

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Background. Low back pain is an increasing global health problem, which is associated with intervertebral disc (IVD) damage and degeneration. Major changes occur in the nucleus pulposus (NP), with the degradation of the extracellular matrix (ECM).1 Further studies showed that growth factors from transforming growth factor β (TGFβ) and bone morphogenic proteins (BMP) family may induce chondrogenic differentiation of mesenchymal stem cells (MSC).2 Focusing on non-viral gene therapies and their possible translation into the clinics, we investigated if GDF6 (syn. BMP13 or CDMP2) can induce regeneration of degraded NP. We hypothesized that IVD transfected with plasmid over-expressing GDF6 also up-regulates other NP- and chondrogenic cell markers and enhances ECM deposition. Methods. Bovine nucleus pulposus (bNPC) and annulus fibrosus cells (bAFC) were harvested from bovine coccygeal IVD. Primary cells were then electroporized with plasmid GDF6 (Origene, vector RG211366) by optimizing parameters using the Neon Transfection system (Life Technologies, Basel). After transfection, cells were cultured in 2D monolayer or 3D alginate beads for 7, 14 or 21 days. Transfection efficiency of pGDF6 was analyzed by immunohistochemistry and fluorescent microscopy. Cell phenotype was quantified by real-time RT-PCR. To test a non-viral gene therapy applied directly to 3D whole organ culture, coccygeal bovine IVDs were harvested as previously described. Bovine IVDs were transfected by injection of plasmid GDF6 into the center. Electroporation was performed with ECM830 Square Wave Electroporation System (Harvard Apparatus, MA) using 2-needle array electrode or tweezertrodes. 72 h after tranfection discs were fixed and cryosectioned and analyzed by immunofluorescence against GDF6. Results. RT-PCR and immunohistochemistry confirmed up-regulation of GFP and GDF6 in the primary bNPC/bAFC culture. The GFP-tagged GDF6 protein, however, was not visible, possibly due to failure of dimer formation as a result of fusion structure. Organ IVD culture transfection revealed GDF6 positive staining in the center of the disc using 2-needle array electrode. Results from tweezertrodes did not show any GDF6 positive cells. Conclusion. Non-viral transfection is an appealing approach for gene therapy as it fulfills the translational safety aspects of transiency and lacks the toxic effects of viral transduction. We identified novel parameters to successfully transfect primary bovine IVD cells. For transfection of whole IVD explants electroporation parameters need to be further optimized. Acknowledgements. This project was funded by the Lindenhof Foundation (Funds “Research & Teaching”) Project no. 13-02-F. The imaging part of this study was performed with the facility of the Microscopy Imaging Center (MIC), University of Bern. References. Roughly PJ (2004): Spine (Phila), 29:2691-2699 Clarke LE, McConell JC, Sherratt MJ, Derby B, Richardson SM, Hoyland JA (2014), Arthritis Research & Therapy, 16:R67

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We have investigated the microstructure and bonding of two biomass-based porous carbon chromatographic stationary phase materials (alginic acid-derived Starbon® and calcium alginate-derived mesoporous carbon spheres (AMCS) and a commercial porous graphitic carbon (PGC), using high resolution transmission electron microscopy, electron energy loss spectroscopy (EELS), N2 porosimetry and X-ray photoelectron spectroscopy (XPS). The planar carbon sp -content of all three material types is similar to that of traditional nongraphitizing carbon although, both biomass-based carbon types contain a greater percentage of fullerene character (i.e. curved graphene sheets) than a non-graphitizing carbon pyrolyzed at the same temperature. This is thought to arise during the pyrolytic breakdown of hexauronic acid residues into C5 intermediates. Energy dispersive X-ray and XPS analysis reveals a homogeneous distribution of calcium in the AMCS and a calcium catalysis mechanism is discussed. That both Starbon® and AMCS, with high-fullerene character, show chromatographic properties similar to those of a commercial PGC material with extended graphitic stacks, suggests that, for separations at the molecular level, curved fullerene- like and planar graphitic sheets are equivalent in PGC chromatography. In addition, variation in the number of graphitic layers suggests that stack depth has minimal effect on the retention mechanism in PGC chromatography. © 2013 Elsevier Ltd. All rights reserved.

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The study uses the value test developed by Shalom Schwartz to examine the value system of Hungarian entrepreneurs. First, the dataset of the last wave of the European Social Survey is used to define those value orientations which generally distinguish entrepreneurs from the rest of society in Europe. Second, the prevalence of these ‘entrepreneurial values’ in the general populations of various countries, and Hungary in particular, is explored. Third, using compatible data from a survey of 300 Hungarian small entrepreneurs, the value orientations that distinguish them from other European entrepreneurs and Hungarian non-entrepreneurs are examined. Multivariate regression analyses allow us to draw a nuanced value-portrait of the typical Hungarian entrepreneur. The main conclusion is that although Hungarian small entrepreneurs share the ’core values’ of entrepreneurs in Europe, they are less adventurous and less materialist, but held personal freedom and human relations especially dear.

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Character education has been viewed by many educators as having significant historical, academic, and social value. Many stakeholders in education argue for character development as a curricular experience. While understanding the degree to which character education is of worth to stakeholders of institutions is important, understanding students, teachers, and administrators perspectives from their lived experiences is likewise significant. The purpose of this phenomenological study was to gain a deeper understanding of character education within a Biblical framework environment by examining the lived experiences of students, administrators, and teachers of a Seventh-day Adventist School. Phenomenology describes individuals' daily experiences of phenomena, the manner in which these experiences are structured, and focuses analysis on the perspectives of the persons having the experience (Moustakas, 1994). This inquiry was undertaken to answer the question: What are the perceptions of students, teachers, and an administrator toward character education in a Seventh-day Adventist school setting? Ten participants (seven students and three adults) formed the homogeneous purposive sample, and the major data collection tool was semi-structured interviews (Patton, 1990; Seidman, 2006). Three 90-minute open-ended interviews were conducted with each of the participants. Data analysis included a three-phase process of description, reduction and interpretation. The findings from this study revealed that participants perceived that their involvement in the school's character education program decreased the tendency to violence, improved their conduct and ethical sensibility, enhanced their ability to engage in decision-making concerning social relationships and their impact on others, brought to their attention the emerging global awareness of moral deficiency, and fostered incremental progress from practice and recognition of vices to their acquisition of virtues. The findings, therefore, provide a model for teaching character education from a Seventh-day Adventist perspective. The model is also relevant for non-Seventh day Adventists who aspire to teach character education as a means to improving social and moral conditions in schools.

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Non-cognitive skills have caught the attention of current education policy writers in Canada. Within the last 10 years, almost every province has produced a document including the importance of supporting non-cognitive skills in K-12 students in the classroom. Although often called different names (such as learning skills, cross curricular competencies, and 20th Century Skills) and occasionally viewed through different lenses (such as emotional intelligence skills, character skills, and work habits), what unifies non-cognitive skills within the policy documents is the claim that students that are strong in these skills are more successful in academic achievement and are more successful in post-secondary endeavors. Though the interest from policy-makers and educators is clear, there are still many questions about non-cognitive skills that have yet to be answered. These include: What skills are the most important for teacher’s to support in the classroom? What are these skills’ exact contributions to student success? How can teachers best support these skills? Are there currently reliable and valid measures of these skills? These are very important questions worth answering if Canadian teachers are expected to support non-cognitive skills in their classrooms with an already burdened workload. As well, it can begin to untangle the plethora of research that exists within the non-cognitive realm. Without a critical look at the current literature, it is impossible to ensure that these policies are effective in Canadian classrooms, and to see an alignment between research and policy. Upon analysis of Canadian curriculum, five non-cognitive skills were found to be the most prevalent among many of the provinces: Self-Regulation, Collaboration, Initiative, Responsibility and Creativity. The available research literature was then examined to determine the utility of teaching these skills in the classroom (can students improve on these skills, do these skills impact other aspects of students’ lives, and are there methods to validly and reliably assess these skills). It was found that Self-Regulation and Initiative had the strongest basis for being implemented in the classroom. On the other hand, Creativity still requires a lot more justification in terms of its impact on students’ lives and ability to assess in the classroom.

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New materials for OLED applications with low singlet–triplet energy splitting have been recently synthesized in order to allow for the conversion of triplet into singlet excitons (emitting light) via a Thermally Activated Delayed Fluorescence (TADF) process, which involves excited-states with a non-negligible amount of Charge-Transfer (CT). The accurate modeling of these states with Time-Dependent Density Functional Theory (TD-DFT), the most used method so far because of the favorable trade-off between accuracy and computational cost, is however particularly challenging. We carefully address this issue here by considering materials with small (high) singlet–triplet gap acting as emitter (host) in OLEDs and by comparing the accuracy of TD-DFT and the corresponding Tamm-Dancoff Approximation (TDA), which is found to greatly reduce error bars with respect to experiments thanks to better estimates for the lowest singlet–triplet transition. Finally, we quantitatively correlate the singlet–triplet splitting values with the extent of CT, using for it a simple metric extracted from calculations with double-hybrid functionals, that might be applied in further molecular engineering studies.

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Character education has been viewed by many educators as having significant historical, academic, and social value. Many stakeholders in education argue for character development as a curricular experience. While understanding the degree to which character education is of worth to stakeholders of institutions is important, understanding students, teachers, and administrators perspectives from their lived experiences is likewise significant. The purpose of this phenomenological study was to gain a deeper understanding of character education within a Biblical framework environment by examining the lived experiences of students, administrators, and teachers of a Seventh-day Adventist School. Phenomenology describes individuals’ daily experiences of phenomena, the manner in which these experiences are structured, and focuses analysis on the perspectives of the persons having the experience (Moustakas, 1994). ). This inquiry was undertaken to answer the question: What are the perceptions of students, teachers, and an administrator toward character education in a Seventh-day Adventist school setting? Ten participants (seven students and three adults) formed the homogeneous purposive sample, and the major data collection tool was semi-structured interviews (Patton, 1990; Seidman, 2006). Three 90-minute open-ended interviews were conducted with each of the participants. Data analysis included a three-phase process of description, reduction and interpretation. The findings from this study revealed that participants perceived that their involvement in the school’s character education program decreased the tendency to violence, improved their conduct and ethical sensibility, enhanced their ability to engage in decision-making concerning social relationships and their impact on others, brought to their attention the emerging global awareness of moral deficiency, and fostered incremental progress from practice and recognition of vices to their acquisition of virtues. The findings, therefore, provide a model for teaching character education from a Seventh-day Adventist perspective. The model is also relevant for non-Seventh day Adventists who aspire to teach character education as a means to improving social and moral conditions in schools.

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The Positive Youth Development (PYD) perspective is a strength-based conceptualization of youth. It highlights the importance of mutually beneficial relationships between youth and their environment to develop the “Five Cs”, key assets that include character. Character has long been a subject of programming due to its focus on helping children lead moral, empathic, and prosocial lives. There are, however, many limitations in character research, including poorly operationalized definitions of character; a failure to examine the developmental and broader social context in which character exists; and a lack of evaluation of more practical character programming. The goal of this dissertation was to address these gaps in knowledge and inform the character education programming literature. The first study examined the relationships among age, gender, the school social context, and character. Moral character was negatively associated with grade, and being a girl was positively associated with moral character. The relationships between positive peer interactions at school and character (fairness, integrity) were stronger among students who reported low initial moral character when positive peer interactions was high. In the second study, the Build Character: Build Success Program, a character education program, was evaluated over six months to examine its effects on character behaviours, victimization, and school climate. No program effects were found for students in grades 1 to 3, but a slight decrease in victimization in one experimental school was found for students in grades 4 to 8. This lack of general program effects may be due to the short-term nature of the intervention, which may not have been long enough to result in measurable behaviour change. Implementation data indicated that teachers did not teach all program elements, which also may have influenced the results of the program evaluation. The present dissertation contributes to knowledge about character and its programming by: introducing new measures to operationalize character, discovering developmental patterns in character in school-aged children, highlighting gender differences in character, examining character within its broad social context, and evaluating short-term character education programming.

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With progressive climate change, the preservation of biodiversity is becoming increasingly important. Only if the gene pool is large enough and requirements of species are diverse, there will be species that can adapt to the changing circumstances. To maintain biodiversity, we must understand the consequences of the various strategies. Mathematical models of population dynamics could provide prognoses. However, a model that would reproduce and explain the mechanisms behind the diversity of species that we observe experimentally and in nature is still needed. A combination of theoretical models with detailed experiments is needed to test biological processes in models and compare predictions with outcomes in reality. In this thesis, several food webs are modeled and analyzed. Among others, models are formulated of laboratory experiments performed in the Zoological Institute of the University of Cologne. Numerical data of the simulations is in good agreement with the real experimental results. Via numerical simulations it can be demonstrated that few assumptions are necessary to reproduce in a model the sustained oscillations of the population size that experiments show. However, analysis indicates that species "thrown together by chance" are not very likely to survive together over long periods. Even larger food nets do not show significantly different outcomes and prove how extraordinary and complicated natural diversity is. In order to produce such a coexistence of randomly selected species—as the experiment does—models require additional information about biological processes or restrictions on the assumptions. Another explanation for the observed coexistence is a slow extinction that takes longer than the observation time. Simulated species survive a comparable period of time before they die out eventually. Interestingly, it can be stated that the same models allow the survival of several species in equilibrium and thus do not follow the so-called competitive exclusion principle. This state of equilibrium is more fragile, however, to changes in nutrient supply than the oscillating coexistence. Overall, the studies show, that having a diverse system means that population numbers are probably oscillating, and on the other hand oscillating population numbers stabilize a food web both against demographic noise as well as against changes of the habitat. Model predictions can certainly not be converted at their face value into policies for real ecosystems. But the stabilizing character of fluctuations should be considered in the regulations of animal populations.

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Pulmonary arterial hypertension (PAH) is a progressive disease of the small pulmonary arteries, characterised by pulmonary vascular remodelling due to excessive proliferation and resistance to apoptosis of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs). The increased pulmonary vascular resistance and elevated pulmonary artery pressures result in right heart failure and premature death. Germline mutations of the bone morphogenetic protein receptor-2 (bmpr2) gene, a receptor of the transforming growth factor beta (TGF-β) superfamily, account for approximately 75%-80% of the cases of heritable form of PAH (HPAH) and 20% of sporadic cases or idiopathic PAH (IPAH). IPAH patients without known bmpr2 mutations show reduced expression of BMPR2. However only ~ 20% of bmpr2-mutation carriers will develop the disease, due to an incomplete penetrance, thus the need for a ‘second hit’ including other genetic and/or environmental factors is accepted. Diagnosis of PAH occurs most frequently when patients have reached an advanced stage of disease. Although modern PAH therapies can markedly improve a patient’s symptoms and slow the rate of clinical deterioration, the mortality rate from PAH remains unacceptably high. Therefore, the development of novel therapeutic approaches is required for the treatment of this multifaceted disease. Noncoding RNAs (ncRNAs) include microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs are ~ 22 nucleotide long and act as negative regulators of gene ex-pression via degradation or translational inhibition of their target mRNAs. Previous studies showed extensive evidence for the role of miRNAs in the development of PAH. LncRNAs are transcribed RNA molecules greater than 200 nucleotides in length. Similar to classical mRNA, lncRNAs are translated by RNA polymerase II and are generally alternatively spliced and polyadenylated. LncRNAs are highly versatile and function to regulate gene expression by diverse mechanisms. Unlike miRNAs, which exhibit well-defined actions in negatively regulating gene expression via the 3’-UTR of mRNAs, lncRNAs play more diverse and unpredictable regulatory roles. Although a number of lncRNAs have been intensively investigated in the cancer field, studies of the role of lncRNAs in vascular diseases such as PAH are still at a very early stage. The aim of this study was to investigate the involvement of specific ncRNAs in the development of PAH using experimental animal models and cell culture. The first ncRNA we focused on was miR-143, which is up-regulated in the lung and right ventricle tissues of various animal models of PH, as well as in the lungs and PASMCs of PAH patients. We show that genetic ablation of miR-143 is protective against the development of chronic hypoxia induced PH in mice, assessed via measurement of right ventricular systolic pressure (RVSP), right ventricular hypertrophy (RVH) and pulmonary vascular remodelling. We further report that knockdown of miR-143-3p in WT mice via anti-miR-143-3p administration prior to exposure of mice to chronic hypoxia significantly decreases certain indices of PH (RVSP) although no significant changes in RVH and pulmo-nary vascular remodelling were observed. However, a reversal study using antimiR-143-3p treatment to modulate miR-143-3p demonstrated a protective effect on RVSP, RVH, and muscularisation of pulmonary arteries in the mouse chronic hypoxia induced PH model. In vitro experiments showed that miR-143-3p overexpression promotes PASMC migration and inhibits PASMC apoptosis, while knockdown miR-143-3p elicits the opposite effect, with no effects observed on cellular proliferation. Interestingly, miR-143-3p-enriched exosomes derived from PASMCs mediated cell-to-cell communication between PASMCs and PAECs, contributing to the pro-migratory and pro-angiogenic phenotype of PAECs that underlies the pathogenesis of PAH. Previous work has shown that miR-145-5p expression is upregulated in the chronic hypoxia induced mouse model of PH, as well as in PAH patients. Genetic ablation and pharmacological inhibition (subcutaneous injection) of miR-145-5p exert a protective against the de-velopment of PAH. In order to explore the potential for alternative, more lung targeted delivery strategies, miR-145-5p expression was inhibited in WT mice using intranasal-delivered antimiR-145-5p both prior to and post exposure to chronic hypoxia. The decreased expression of miR-145-5p in lung showed no beneficial effect on the development of PH compared with control antimiRNA treated mice exposed to chronic hypoxia. Thus, miR-143-3p modulated both cellular and exosome-mediated responses in pulmonary vascular cells, while the inhibition of miR-143-3p prevented the development of experimental pulmonary hypertension. We focused on two lncRNAs in this project: Myocardin-induced Smooth Muscle Long noncoding RNA, Inducer of Differentiation (MYOSLID) and non-annotated Myolnc16, which were identified from RNA sequencing studies in human coronary artery smooth muscle cells (HCASMCs) that overexpress myocardin. MYOSLID was significantly in-creased in PASMCs from patients with IPAH compared to healthy controls and increased in circulating endothelial progenitor cells (EPCs) from bmpr2 mutant PAH patients. Exposure of PASMCs to hypoxia in vitro led to a significant upregulation in MYOSLID expres-sion. MYOSLID expression was also induced by treatment of PASMC with BMP4, TGF-β and PDGF, which are known to be triggers of PAH in vitro. Small interfering RNA (siR-NA)-mediated knockdown MYOSLID inhibited migration and induced cell apoptosis without affecting cell proliferation and upregulated several genes in the BMP pathway in-cluding bmpr1α, bmpr2, id1, and id3. Modulation of MYOSLID also affected expression of BMPR2 at the protein level. In addition, MYOSLID knockdown affected the BMP-Smad and BMP-non-Smad signalling pathways in PASMCs assessed by phosphorylation of Smad1/5/9 and ERK1/2, respectively. In PAECs, MYOSLID expression was also induced by hypoxia exposure, VEGF and FGF2 treatment. In addition, MYOSLID knockdown sig-nificantly decreased the proliferation of PAECs. Thus, MYOSLID may be a novel modulator in pulmonary vascular cell functions, likely through the BMP-Smad and –non-Smad pathways. Treatment of PASMCs with inflammatory cytokines (IL-1 and TNF-α) significantly in-duced the expression of Myolnc16 at a very early time point. Knockdown of Myolnc16 in vitro decreased the expression of il-6, and upregulated the expression of il-1 and il-8 in PASMCs. Moreover, the expression levels of chemokines (cxcl1, cxcl6 and cxcl8) were sig-nificantly decreased with Myolnc16 knockdown. In addition, Myolnc16 knockdown decreased the MAP kinase signalling pathway assessed by phosphorylation of ERK1/2 and p38 MAPK and inhibited cell migration and proliferation in PASMCs. Thus, Myolnc16 may a novel modulator of PASMCs functions through anti-inflammatory signalling pathways. In summary, in this thesis we have demonstrated how miR-143-3p plays a protective role in the development of PH both in vivo animal models and patients, as well as in vitro cell cul-ture. Moreover, we have showed the role of two novel lncRNAs in pulmonary vascular cells. These ncRNAs represent potential novel therapeutic targets for the treatment of PAH with further work addressing to investigate the target genes, and the pathways modulated by these ncRNAs during the development of PAH.