854 research outputs found
Characterizing university students’ self-regulated learning behavior using dispositional learning analytics
[EN] Learning analytics can be used in conjunction with learner dispositions to identify at-risk students and provide personalized guidance on how to improve. Participants in the current study were students (n=192) studying a first year anatomy and physiology course. A two-step cluster analysis was performed using learning analytics data from the learning management system and self-regulated learning behavior from meta-learning assessment tasks. Three clusters of students were identified – high, medium and low self-regulated learners. High self-regulated learners were engaged with the meta-learning tasks, reported the most self-regulated learning strategies and used new strategies during semester. They also had the highest academic achievement. Compared to low self-regulated leaners, medium self-regulated learners were more engaged in the meta-learning tasks and used more learning strategies during semester, including new strategies; however, both medium and low self-regulated learners had similar levels of academic achievement. It is possible that the medium self-regulated learners represent students who were attempting to improve their learning, but had not yet found strategies that were right for them. Future evaluation of academic performance may determine whether the attempts to improve learning by medium self-regulated learners distinguishes them from low self-regulated learners in the later years of their study.Ainscough, L.; Leung, R.; Colthorpe, K.; Langfield, T. (2019). Characterizing university students’ self-regulated learning behavior using dispositional learning analytics. En HEAD'19. 5th International Conference on Higher Education Advances. Editorial Universitat Politècnica de València. 233-241. https://doi.org/10.4995/HEAD19.2019.9153OCS23324
Analysis of yeast resistance to lignocellulosic-derived inhibitors
The rapid depletion of fossil fuel reserves and concurrent increase in global temperatures has resulted in global demand for the production of alternative environmentally friendly fuels. First-generation biofuels that utilise cash crops for the extraction of fermentable sugars currently exist, but are highly controversial due to socioeconomic and environmental reasons such as diverting food production or deforestation. Therefore, second-generation biofuels that utilise lignocellulosic waste materials are a more attractive prospect. In Europe, lignocellulosic biomass wastes such as wheat straw, display great potential for the production of alternative energy sources such as bioethanol for transportation. Conversion to this biofuel requires microorganisms that will effectively utilise the constituent sugars to produce a high yield of product. Saccharomyces cerevisiae (S. cerevisiae) strains possess the most desirable phenotypes for this objective. However, the components of wheat straw are difficult to break down, therefore pretreatment is required. Pretreatment methods vary but often utilise various chemicals that produce compounds that are inhibitory to yeast. This affects the efficiency of fermentations. The focus of this work is on formic acid and a synthetic media containing the main inhibitor compounds released during pre-treatment of steam exploded wheat straw. Six pair-wise F1 crosses between four distinct parental S. cerevisiae clean lineage populations have been generated previously by Cubillos et al., 2009. The 96 F1 progeny from each cross have been assayed for tolerance phenotypes in order to determine QTLs (Quantitative Trait Loci), which will enable us to map genes contributing to the multi-genic trait of inhibitor tolerance. Overall, three QTLs were identified for formic acid and five QTLs were identified from the synthetic inhibitor mix. Candidate genes were selected from the QTL analysis and were tested by performing reciprocal hemizygosity assays to determine which genes are responsible for inhibitor resistance to enable the development of yeast strains suitable for second-generation biofuel production
Repurposing screen identifies mebendazole as a clinical candidate to synergise with docetaxel for prostate cancer treatment
BACKGROUND: Docetaxel chemotherapy in prostate cancer has a modest impact on survival. To date, efforts to develop
combination therapies have not translated into new treatments. We sought to develop a novel therapeutic strategy to tackle
chemoresistant prostate cancer by enhancing the efficacy of docetaxel.
METHODS: We performed a drug-repurposing screen by using murine-derived prostate cancer cell lines driven by clinically
relevant genotypes. Cells were treated with docetaxel alone, or in combination with drugs (n = 857) from repurposing libraries, with
cytotoxicity quantified using High Content Imaging Analysis.
RESULTS: Mebendazole (an anthelmintic drug that inhibits microtubule assembly) was selected as the lead drug and shown to
potently synergise docetaxel-mediated cell killing in vitro and in vivo. Dual targeting of the microtubule structure was associated
with increased G2/M mitotic block and enhanced cell death. Strikingly, following combined docetaxel and mebendazole treatment,
no cells divided correctly, forming multipolar spindles that resulted in aneuploid daughter cells. Liposomes entrapping docetaxel
and mebendazole suppressed in vivo prostate tumour growth and extended progression-free survival.
CONCLUSIONS: Docetaxel and mebendazole target distinct aspects of the microtubule dynamics, leading to increased apoptosis
and reduced tumour growth. Our data support a new concept of combined mebendazole/docetaxel treatment that warrants
further clinical evaluation
Analysis of yeast resistance to lignocellulosic-derived inhibitors
The rapid depletion of fossil fuel reserves and concurrent increase in global temperatures has resulted in global demand for the production of alternative environmentally friendly fuels. First-generation biofuels that utilise cash crops for the extraction of fermentable sugars currently exist, but are highly controversial due to socioeconomic and environmental reasons such as diverting food production or deforestation. Therefore, second-generation biofuels that utilise lignocellulosic waste materials are a more attractive prospect. In Europe, lignocellulosic biomass wastes such as wheat straw, display great potential for the production of alternative energy sources such as bioethanol for transportation. Conversion to this biofuel requires microorganisms that will effectively utilise the constituent sugars to produce a high yield of product. Saccharomyces cerevisiae (S. cerevisiae) strains possess the most desirable phenotypes for this objective. However, the components of wheat straw are difficult to break down, therefore pretreatment is required. Pretreatment methods vary but often utilise various chemicals that produce compounds that are inhibitory to yeast. This affects the efficiency of fermentations. The focus of this work is on formic acid and a synthetic media containing the main inhibitor compounds released during pre-treatment of steam exploded wheat straw. Six pair-wise F1 crosses between four distinct parental S. cerevisiae clean lineage populations have been generated previously by Cubillos et al., 2009. The 96 F1 progeny from each cross have been assayed for tolerance phenotypes in order to determine QTLs (Quantitative Trait Loci), which will enable us to map genes contributing to the multi-genic trait of inhibitor tolerance. Overall, three QTLs were identified for formic acid and five QTLs were identified from the synthetic inhibitor mix. Candidate genes were selected from the QTL analysis and were tested by performing reciprocal hemizygosity assays to determine which genes are responsible for inhibitor resistance to enable the development of yeast strains suitable for second-generation biofuel production
The signal transducer IL6ST (gp130) as a predictive and 2 prognostic biomarker in breast cancer
Novel biomarkers are needed to continue to improve breast cancer clinical management and outcome. IL6-like cytokines, whose pleiotropic functions include roles in many hallmarks of malignancy, rely on the signal transducer IL6ST (gp130) for all their signalling. To date, 10 separate independent studies based on the analysis of clinical breast cancer samples have identified IL6ST as a predictor. Consistent findings suggest that IL6ST is a positive prognostic factor and is associated with ER status. Interestingly, these studies include 4 multigene signatures (EndoPredict, EER4, IRSN-23 and 42GC) that incorporate IL6ST to predict risk of recurrence or outcome from endocrine or chemotherapy. Here we review the existing evidence on the promising predictive and prognostic value of IL6ST. We also discuss how this potential could be further translated into clinical practice beyond the EndoPredict tool, which is already available in the clinic. The most promising route to further exploit IL6ST’s promising predicting power will likely be through additional hybrid multifactor signatures that allow for more robust stratification of ER+ breast tumours into discrete groups with distinct outcomes, thus enabling greater refinement of the treatment-selection process
Detection of splicing events and multiread locations from RNA-seq data based on a geometric-tail (GT) distribution of intron length
Stripped of illusions? Exploring system justification processes in Capitalist and post-Communist societies
Sociologists and political scientists have often observed that citizens of Central and Eastern Europe express high levels of disillusionment with their social, economic and political systems, in comparison with citizens of Western capitalist societies. In this review, we analyze system legitimation and delegitimation in post-Communist societies from a social psychological perspective. We draw on system justification theory, which seeks to understand how, when and why people do (and do not) defend, bolster and justify existing social systems. We review some of the major tenets and findings of the theory and compare research on system-justifying beliefs and ideologies in traditionally Capitalist and post-Communist countries to determine: (1) whether there are robust differences in the degree of system justification in post-Communist and Capitalist societies, and (2) the extent to which hypotheses derived from system justification theory receive support in the post-Communist context. To this end, we summarize research findings from over 20 countries and cite previously unpublished data from a public opinion survey conducted in Poland. Our analysis confirms that there are lower levels of system justification in post-Communist countries. At the same time, we find that system justification possesses similar social and psychological antecedents, manifestations and consequences in the two types of societies. We offer potential explanations for these somewhat complicated patterns of results and conclude by addressing implications for theory and research on system justification and system change (or transition)
A functional genomics screen reveals a strong synergistic effect between docetaxel and the mitotic gene DLGAP5 that is mediated by the androgen receptor
Based on a molecular classification of prostate cancer using gene expression pathway signatures, we derived a set of 48 genes in critical pathways that significantly predicts clinical outcome in all tested patient cohorts. We tested these genes in a functional genomics screen in a panel of three prostate cancer cell lines (LNCaP, PC3, DU145), using RNA interference. The screen revealed several genes whose knockdown caused strong growth inhibition in all cell lines. Additionally, we tested the gene set in the presence of docetaxel to see whether any gene exhibited additive or synergistic effects with the drug. We observed a strong synergistic effect between DLGAP5 knockdown and docetaxel in the androgen-sensitive line LNCaP, but not in the two other androgen-independent lines. We then tested whether this effect was connected to androgen pathways and found that knockdown of the androgen receptor by si-RNA attenuated the synergy significantly. Similarly, androgen desensitized LNCaP-AI cells had a higher IC50 to docetaxel and did not exhibit the synergistic interaction. Short-term exposure to enzalutamide did not significantly alter the behaviour of parental LNCaP cells. An immunofluorescence analysis in LNCaP cells suggests that under the double insult of DLGAP5 knockdown and docetaxel, cells predominantly arrest in metaphase. In contrast, the knockdown of the androgen receptor by siRNA appears to assist cells to progress through metaphase in to anaphase, even in the presence of docetaxel. Our data suggest that DLGAP5 has a unique function in stabilizing spindle formation and surviving microtubule assault from docetaxel, in an androgen-regulated cell cycle system
Behavioral Health Service Use and Expenditures in Massachusetts Medicare and Medicaid Members Aged 55 and Over, 2005
Summary: This report describes behavioral health service use and expenditures for Massachusetts Medicare and Medicaid (MassHealth) members aged 55 and over with behavioral health disorders (BHDs) in calendar year 2005. With an expected increase in the number of elders with BHDs, a better and more comprehensive understanding of behavioral health service delivery is essential in order to identify opportunities for systematic changes that can improve behavioral health services for elders. However, older adults have not been the main focus of previous studies on behavioral health services and expenditures. Furthermore, although existing studies have examined behavioral health services and expenditures in broad geographic areas and at the national level, few studies have taken into account variations among health insurance coverage, particularly Medicare and Medicaid which are important resources for elders and for people with disabilities
- …