582 research outputs found
The limits of inter-religious dialogue and the form of football rituals: The case of Bosnia-Herzegovina
The difficulties with interfaith dialogue are linked, at least in part, to the lack of ritual forms (consisting of rules, ceremonial idioms, liturgy, and repertoires of action) designed to unite and integrate the "meta-group "formed by the various religious communities. By means of ethnographic research conducted in Bosnia-Herzegovina, the author studied the mechanisms with which, under particular conditions, some forms of collective ritual were able to create opportunities for the re-integration of the Bosnian population, which had been profoundly divided after the terrible war of 199295. Comparing the forms of religious rituals and those of sports ritualsin particular, of football ritualsthe author develops some considerations that can be applied to the general debate about inter-religious dialogue. The comparison brings to light some of the limits and difficulties that religious institutions encounter in giving life to an interfaith dialogue that directly and concretely involves the members of different communities. © 2007 Social Compass
Embracing additive manufacture: implications for foot and ankle orthosis design
<p>Abstract</p> <p>Background</p> <p>The design of foot and ankle orthoses is currently limited by the methods used to fabricate the devices, particularly in terms of geometric freedom and potential to include innovative new features. Additive manufacturing (AM) technologies, where objects are constructed via a series of sub-millimetre layers of a substrate material, may present the opportunity to overcome these limitations and allow novel devices to be produced that are highly personalised for the individual, both in terms of fit and functionality.</p> <p>Two novel devices, a foot orthosis (FO) designed to include adjustable elements to relieve pressure at the metatarsal heads, and an ankle foot orthosis (AFO) designed to have adjustable stiffness levels in the sagittal plane, were developed and fabricated using AM. The devices were then tested on a healthy participant to determine if the intended biomechanical modes of action were achieved.</p> <p>Results</p> <p>The adjustable, pressure relieving FO was found to be able to significantly reduce pressure under the targeted metatarsal heads. The AFO was shown to have distinct effects on ankle kinematics which could be varied by adjusting the stiffness level of the device.</p> <p>Conclusions</p> <p>The results presented here demonstrate the potential design freedom made available by AM, and suggest that it may allow novel personalised orthotic devices to be produced which are beyond the current state of the art.</p
Mathematical stories: Why do more boys than girls choose to study mathematics at AS-level in England?
Copyright @ 2005 Taylor & FrancisIn this paper I address the question: How is it that people come to choose mathematics and in what ways is this process gendered? I draw on the findings of a qualitative research study involving interviews with 43 young people all studying mathematics in post-compulsory education in England. Working within a post-structuralist framework, I argue that gender is a project and one that is achieved in interaction with others. Through a detailed reading of Toni and Claudiaâs stories I explore the tensions for young women who are engaging in mathematics, something that is discursively inscribed as masculine, while (understandably) being invested in producing themselves as female. I conclude by arguing that seeing âdoing mathematicsâ as âdoing masculinityâ is a productive way of understanding why mathematics is so male dominated and by looking at the implications of this understanding for gender and mathematics reform work.This work is funded by the ESR
The Potential of MLN3651 in Combination with Selumetinib as a Treatment for Merlin-Deficient Meningioma
Meningioma is the most common primary intracranial tumour, and surgical resection is the main therapeutic option. Merlin is a tumour suppressor protein that is frequently mutated in meningioma. The activity of the E3 ubiquitin ligase complex, CRL4-DCAF1, and the Raf/MEK/ERK scaffold protein Kinase suppressor of Ras 1 (KSR1) are upregulated in Merlin-deficient tumours, which drives tumour growth. Identifying small molecules that inhibit these key pathways may provide an effective treatment option for patients with meningioma. We used meningioma tissue and primary cells derived from meningioma tumours to investigate the expression of DDB1 and Cullin 4-associated factor 1 (DCAF1) and KSR1, and confirmed these proteins were overexpressed. We then used primary cells to assess the therapeutic potential of MLN3651, a neddylation inhibitor which impacts the activity of the CRL family of E3 ubiquitin ligases and the MAPK/ERK kinase (MEK1/2) inhibitor selumetinib. MLN3651 treatment reduced proliferation and activated apoptosis, whilst increasing Raf/MEK/ERK pathway activation. The combination of MLN3651 and the MEK1/2 inhibitor selumetinib prevented the increase in Raf/MEK/ERK activity, and had an additive effect compared with either treatment alone. Therefore, the combined targeting of CRL4-DCAF1 and Raf/MEK/ERK activity represents an attractive novel strategy in the treatment of Merlin-deficient meningioma.</jats:p
A Novel Inhibitor of Human La Protein with Anti-HBV Activity Discovered by Structure-Based Virtual Screening and In Vitro Evaluation
Background: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. Aims: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. Methods: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. Results: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50 % with P,0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression
Quantifying myosin light chain phosphorylation in single adherent cells with automated fluorescence microscopy
<p>Abstract</p> <p>Background</p> <p>In anchorage dependent cells, myosin generated contractile forces affect events closely associated with adhesion such as the formation of stress fibers and focal adhesions, and temporally distal events such as entry of the cell into S-phase. As occurs in many signaling pathways, a phosphorylation reaction (in this case, phosphorylation of myosin light chain) is directly responsible for cell response. Western blotting has been useful in measuring intracellular phosphorylation events, but cells are lysed in the process of sample preparation for western blotting, and spatial information such as morphology, localization of the phosphorylated species, and the distribution of individual cell responses across the population is lost. We report here a reliable automated microscopy method for quantitative measurement of myosin light chain phosphorylation in adherent cells. This method allows us to concurrently examine cell morphology, cell-cell contact, and myosin light chain diphosphorylation in vascular smooth muscle cells.</p> <p>Results</p> <p>Paraformaldehyde fixation and Triton X-100 permeabilization preserved cell morphology and myosin light chain phosphorylation better than the alternative fixation/permeabilization methods tested. We utilized automated microscopy methods to acquire three color images, determine cell spread area, and quantify the intensity of staining within each cell with anti-phospho-MLC antibody. Our results indicate that A10 rat aortic smooth muscle cells exhibit a re producible non-Gaussian distribution of MLC phosphorylation across a population of unsynchronized genetically identical cells. Adding an inhibitor of Rho kinase, Y27632, or plating cells on a low density of fibronectin, reduced phospho-myosin light chain signal as expected. On the other hand, adding calyculin A, an activator of contractility, increased myosin light chain phosphorylation. The IC<sub>50 </sub>for myosin light chain phosphorylation using Y27632 was determined to be 2.1 ± 0.6 micrometers. We observed a positive linear relationship between cell area and myosin light chain diphosphorylation, which is consistent with what has been reported in the literature using other methods.</p> <p>Conclusion</p> <p>Our results show that using proper specimen fixation techniques and background subtraction methods, imaging cytometry can be used to reliably measure relative myosin light chain phosphorylation in individual adherent cells. Importantly, the ability to make this measurement in adherent cells allows for simultaneous measurement of and correlation with other parameters of cellular topography such as morphology and cell-cell proximity. This assay has potential application in screening for drug development.</p
Demographic uncertainty and disease risk influence climate-informed management of an alpine species
Climate change is expected to disproportionately affect species occupying ecosystems with relatively hard boundaries, such as alpine ecosystems. Wildlife managers must identify actions to conserve and manage alpine species into the future, while considering other issues and uncertainties. Climate change and respiratory pathogens associated with widespread pneumonia epidemics in bighorn sheep (Ovis canadensis) may negatively affect mountain goat (Oreamnos americanus) populations. Mountain goat demographic and population data are challenging to collect and sparsely available, making population management decisions difficult. We developed predictive models incorporating these uncertainties and analyzed results within a structured decision making framework to make management recommendations and identify priority information needs in Montana, USA. We built resource selection models to forecast occupied mountain goat habitat and account for uncertainty in effects of climate change, and a Leslie matrix projection model to predict population trends while accounting for uncertainty in population demographics and dynamics. We predicted disease risks while accounting for uncertainty about presence of pneumonia pathogens and risk tolerance for mixing populations during translocations. Our analysis predicted that new introductions would produce more area occupied by mountain goats at mid-century, regardless of the effects of climate change. Population augmentations, carnivore management, and harvest management may improve population trends, although this was associated with considerable uncertainty. Tolerance for risk of disease transmission affected optimal management choices because translocations are expected to increase disease risks for mountain goats and sympatric bighorn sheep. Expected value of information analyses revealed that reducing uncertainty related to population dynamics would affect the optimal choice among management strategies to improve mountain goat trends. Reducing uncertainty related to the presence of pneumonia-associated pathogens and consequences of mixing microbial communities should reduce disease risks if translocations are included in future management strategies. We recommend managers determine tolerance for disease risks associated with translocations that they and constituents are willing to accept. From this, an adaptive management program can be constructed wherein a portfolio of management actions are chosen based on risk tolerance in each population range, combined with the amount that uncertainty is reduced when paired with monitoring, to ultimately improve achievement of fundamental objectives
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