The role of social networks in students’ learning experiences

The aim of this research is to investigate the role of social networks in computer science education. The Internet shows great potential for enhancing collaboration between people and the role of social software has become increasingly relevant in recent years. This research focuses on analyzing the role that social networks play in students’ learning experiences. The construction of students’ social networks, the evolution of these networks, and their effects on the students’ learning experience in a university environment are examined

The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles

Caspases provide vital links in non-apoptotic regulatory networks controlling inflammation, compensatory proliferation, morphology and cell migration. How caspases are activated under non-apoptotic conditions and process a selective set of substrates without killing the cell remain enigmatic. Here we find that the Drosophila unconventional myosin CRINKLED (CK) selectively interacts with the initiator caspase DRONC and regulates some of its non-apoptotic functions. Loss of CK in the arista, border cells or proneural clusters of the wing imaginal discs affects DRONC-dependent patterning. Our data indicate that CK acts as substrate adaptor, recruiting SHAGGY46/GSK3-β to DRONC, thereby facilitating caspase-mediated cleavage and localized modulation of kinase activity. Similarly, the mammalian CK counterpart, MYO7A, binds to and impinges on CASPASE-8, revealing a new regulatory axis affecting receptor interacting protein kinase-1 (RIPK1)>CASPASE-8 signalling. Together, our results expose a conserved role for unconventional myosins in transducing caspase-dependent regulation of kinases, allowing them to take part in specific signalling events

Abiraterone shows alternate activity in models of endocrine resistant and sensitive disease.

Background Resistance to endocrine therapy remains a major clinical problem in the treatment of oestrogen-receptor positive (ER+) breast cancer. Studies show androgen-receptor (AR) remains present in 80-90% of metastatic breast cancers providing support for blockade of AR-signalling. However, clinical studies with abiraterone, which blocks cytochrome P450 17A1 (CYP17A1) showed limited benefit.Methods In order to address this, we assessed the impact of abiraterone on cell-viability, cell-death, ER-mediated transactivation and recruitment to target promoters. together with ligand-binding assays in a panel of ER+ breast cancer cell lines that were either oestrogen-dependent, modelling endocrine-sensitive disease, or oestrogen-independent modelling relapse on an aromatase inhibitor. The latter, harboured wild-type (wt) or naturally occurring ESR1 mutations.Results Similar to oestrogen, abiraterone showed paradoxical impact on proliferation by stimulating cell growth or death, depending on whether the cells are hormone-dependent or have undergone prolonged oestrogen-deprivation, respectively. Abiraterone increased ER-turnover, induced ER-mediated transactivation and ER-degradation via the proteasome.Conclusions Our study confirms the oestrogenic activity of abiraterone and highlights its differential impact on cells dependent on oestrogen for their proliferation vs. those that are ligand-independent and harbour wt or mutant ESR1. These properties could impact the clinical efficacy of abiraterone in breast cancer

Undulator design for Laser Plasma Based Free electron laser

The fourth generation of synchrotron radiation sources, commonly referred to as the Free Electron Laser (FEL), provides an intense source of brilliant X-ray beams enabling the investigation of matter at the atomic scale with unprecedented time resolution. These sources require the use of conventional linear accelerators providing high electron beam performance. The achievement of chirped pulse amplification allowing lasers to be operated at the Terawatt range, opened the way for the Laser Plasma Acceleration (LPA) technique where high energy electron bunches with high current can be produced within a very short centimeter-scale distance. Such an advanced acceleration concept is of great interest to be qualified by an FEL application for compact X-ray light sources. We explore in this paper what the LPA specificities imply on the design of the undulator, part of the gain medium. First, the LPA concept and state-of-art are presented showing the different operation regimes and what electron beam parameters are likely to be achieved. The LPA scaling laws are discussed afterwards to better understand what laser or plasma parameters have to be adjusted in order to improve electron beam quality. The FEL is secondly discussed starting with the spontaneous emission, followed by the different FEL configurations, the electron beam transport to the undulator and finally the scaling laws and correction terms in the high gain case. Then, the different types of compact undulators that can be implemented for an LPA based FEL application are analyzed. Finally, examples of relevant experiments are reported by describing the transport beamline, presenting the spontaneous emission characteristics achieved so far and the future prospects

DRP1 levels determine the apoptotic threshold during embryonic differentiation through a mitophagy-dependent mechanism.

The changes that drive differentiation facilitate the emergence of abnormal cells that need to be removed before they contribute to further development or the germline. Consequently, in mice in the lead-up to gastrulation, ∼35% of embryonic cells are eliminated. This elimination is caused by hypersensitivity to apoptosis, but how it is regulated is poorly understood. Here, we show that upon exit of naive pluripotency, mouse embryonic stem cells lower their mitochondrial apoptotic threshold, and this increases their sensitivity to cell death. We demonstrate that this enhanced apoptotic response is induced by a decrease in mitochondrial fission due to a reduction in the activity of dynamin-related protein 1 (DRP1). Furthermore, we show that in naive pluripotent cells, DRP1 prevents apoptosis by promoting mitophagy. In contrast, during differentiation, reduced mitophagy levels facilitate apoptosis. Together, these results indicate that during early mammalian development, DRP1 regulation of mitophagy determines the apoptotic response

Analysing the correlation between social network analysis measures and performance of students in social network-based engineering education

Social network-based engineering education (SNEE) is designed and implemented as a model of Education 3.0 paradigm. SNEE represents a new learning methodology, which is based on the concept of social networks and represents an extended model of project-led education. The concept of social networks was applied in the real-life experiment, considering two different dimensions: (1) to organize the education process as a social network-based process; and (2) to analyze the students' interactions in the context of evaluation of the students learning performance. The objective of this paper is to present a new model for students evaluation based on their behavior during the course and its validation in comparison with the traditional model of students' evaluation. The validation of the new evaluation model is made through an analysis of the correlation between social network analysis measures (degree centrality, closeness centrality, betweenness centrality, eigenvector centrality, and average tie strength) and the grades obtained by students (grades for quality of work, grades for volume of work, grades for diversity of work, and final grades) in a social network-based engineering education. The main finding is that the obtained correlation results can be used to make the process of the students' performance evaluation based on students interactions (behavior) analysis, to make the evaluation partially automatic, increasing the objectivity and productivity of teachers and allowing a more scalable process of evaluation. The results also contribute to the behavioural theory of learning performance evaluation. More specific findings related to the correlation analysis are: (1) the more different interactions a student had (degree centrality) and the more frequently the student was between the interaction paths of other students (betweenness centrality), the better was the quality of the work; (2) all five social network measures had a positive and strong correlation with the grade for volume of work and with the final graThe authors wish to acknowledge the support of the Fundacao para a Ciencia e Tecnologia (FCT), Portugal, through the Grants "Projeto Estrategico-UI 252-2011-2012'' reference PEst-OE/EME/UI0252/2011, "Ph.D. Scholarship Grant'' reference SFRH/BD/85672/2012, and the support of Parallel Planes Lda.info:eu-repo/semantics/publishedVersio

Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature

Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966–2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966–2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous

Potent pro-apoptotic combination therapy is highly effective in a broad range of cancers

Primary or acquired therapy resistance is a major obstacle to the effective treatment of cancer. Resistance to apoptosis has long been thought to contribute to therapy resistance. We show here that recombinant TRAIL and CDK9 inhibition cooperate in killing cells derived from a broad range of cancers, importantly without inducing detectable adverse events. Remarkably, the combination of TRAIL with CDK9 inhibition was also highly effective on cancers resistant to both, standard-of-care chemotherapy and various targeted therapeutic approaches. Dynamic BH3 profiling revealed that, mechanistically, combining TRAIL with CDK9 inhibition induced a drastic increase in the mitochondrial priming of cancer cells. Intriguingly, this increase occurred irrespective of whether the cancer cells were sensitive or resistant to chemo- or targeted therapy. We conclude that this pro-apoptotic combination therapy has the potential to serve as a highly effective new treatment option for a variety of different cancers. Notably, this includes cancers that are resistant to currently available treatment modalities