5,942 research outputs found
Battle of the Blockbusters: Joss Whedon as Public Pedagogue
No full textThis article discusses the concept of public pedagogy and the reasons for considering it relevant to the work of the writer/ director/ producer Joss Whedon, creator of numberous TV programmes, such as Buffy the Vampire Slayer, Angel and Firefly, and Films Serenity, Marvel's The Avengers and The Age of Ultron. It analyzes Marvel’s The Avengers (Whedon, 2012) and Christopher Nolan’s (2012b) The Dark Knight Rises as competing public pedagogies.It suggests that popular films can be seen as important educational projects; filmmakers have tremendous resources at their disposal and their creations have a global reach that cannot be matched by individual teachers or national education systems. Whedon can be seen as a radical educator; he enables his audiences to experience ways of looking at the world that challenge aspects of neo-liberal hegemony, and also encourages them to become critical thinkers who have to reflect on their own feelings and perspectives and resist simplistic perspectives on morality and the difficult political choices facing global society
WAXSiS: a web server for the calculation of SAXS/WAXS curves based on explicit-solvent molecular dynamics
No full textSmall- and wide-angle X-ray scattering (SWAXS) has evolved into a powerful tool to study biological macromolecules in solution. The interpretation of SWAXS curves requires their accurate predictions from structural models. Such predictions are complicated by scattering contributions from the hydration layer and by effects from thermal fluctuations. Here, we describe the new web server WAXSiS (WAXS in solvent) that computes SWAXS curves based on explicit-solvent all-atom molecular dynamics (MD) simulations (http://waxsis.uni-goettingen.de/). The MD simulations provide a realistic model for both the hydration layer and the excluded solvent, thereby avoiding any solvent-related fitting parameters, while naturally accounting for thermal fluctuations.Open Access Publikationsfonds 201
MemGen: a general web server for the setup of lipid membrane simulation systems
No full textMotivation: Molecular dynamics simulations provide atomic insight into the physicochemical characteristics of lipid membranes and hence, a wide range of force field families capable of modelling various lipid types have been developed in recent years. To model membranes in a biologically realistic lipid composition, simulation systems containing multiple different lipids must be assembled. Results: We present a new web service called MemGen that is capable of setting up simulation systems of heterogenous lipid membranes. MemGen is not restricted to certain lipid force fields or lipid types, but instead builds membranes from uploaded structure files which may contain any kind of amphiphilic molecule. MemGen works with any all-atom or united-atom lipid representation.Deutsche Forschungsgemeinschaft [HU 1971/1-1
Stella Knight
No full textBlack-and-white photograph of a young girl, probably Stella Knight, later the wife of Christopher Ruess
Grove Farm, Nottingham: modelling the alluvial sequence of the Middle Trent Valley
No full textA proposed wind turbine development on the floodplain of the River Trent on the western outskirts of Nottingham required the construction of a deposit model prior to further archaeological evaluation and the development of an appropriate mitigation strategy. A series of 54 purposive boreholes was drilled and recorded with the aim of creating a deposit model that would guide future archaeological investigations. Another 6 boreholes and 22 test pits were subsequently excavated for geotechnical ground investigations, permitting refinement of the initial deposit model. These surveys permitted identification of several macro-stratigraphic units across the development area, allowing archaeological potential to be defined through geomorphological zonation of the site; landform elements included a palaeochannel, river terrace and alluvial floodplain, with the Holocene sequences extending from between c 0.4 and 7m below the modern ground level (BGL). A subsequent gradiometer survey refined the zonation of the site and allowed the identification of archaeological features cut into river terraces and the upper deposits of the deep Holocene alluvial sequence. No further archaeological works were conducted after the gradiometer survey which, together with the preceding ground investigations, provided sufficient evidence for the developer, consultant and archaeological curators to determine the potential archaeological impact of the proposed construction work and the likely scale of further evaluation and mitigation work. In this respect, the project provides a model for best practice in alluvial environments impacted by construction activity
Grove Farm, Nottingham: modelling the alluvial sequence of the Middle Trent Valley
No full textA proposed wind turbine development on the floodplain of the River Trent on the western outskirts of Nottingham required the construction of a deposit model prior to further archaeological evaluation and the development of an appropriate mitigation strategy. A series of 54 purposive boreholes was drilled and recorded with the aim of creating a deposit model that would guide future archaeological investigations. Another 6 boreholes and 22 test pits were subsequently excavated for geotechnical ground investigations, permitting refinement of the initial deposit model. These surveys permitted identification of several macro-stratigraphic units across the development area, allowing archaeological potential to be defined through geomorphological zonation of the site; landform elements included a palaeochannel, river terrace and alluvial floodplain, with the Holocene sequences extending from between c 0.4 and 7m below the modern ground level (BGL). A subsequent gradiometer survey refined the zonation of the site and allowed the identification of archaeological features cut into river terraces and the upper deposits of the deep Holocene alluvial sequence. No further archaeological works were conducted after the gradiometer survey which, together with the preceding ground investigations, provided sufficient evidence for the developer, consultant and archaeological curators to determine the potential archaeological impact of the proposed construction work and the likely scale of further evaluation and mitigation work. In this respect, the project provides a model for best practice in alluvial environments impacted by construction activity
Effects of the basic multicellular unit and lamellar thickness on osteonal fatigue life
No full textA remodeling cycle sets the size of the osteon and associated lamellae in the basic multicellular unit. Treatments and aging affect these micro-structural features. We previously demonstrated decreased fatigue life with an unexplained mechanism and decreased osteon size in cortical bone treated with high-dose bisphosphonate. Here, three finite element models were examined: type-1: a single osteon, as a homogeneous unit and with heterogeneous lamellae and interlamellae, type-2: a control, interstitial-only tissue and type-3: the osteon with cement line, set within the interstitial tissue. Models were loaded in simulated, sinusoidal bending fatigue. As osteon size was decreased, lamellar number and lamellar thickness were incrementally adjusted for each model. As hypothesized, lamellae within the larger type-1 models attained greater cycles to failure and the addition of an osteon to type-2 models (generating a type-3 model set) yielded increased fatigue life. However, as the osteon size was decreased, the potential for compressive damage nucleation was increased within the lamellae of the osteons versus the interstitium. Also, osteons with fewer, thicker lamellae displayed increased fatigue life. Osteonal microstructure plays a role in damage initiation location, especially when BMU size is smaller. Previous findings by us and others could partially be explained by this further understanding of increased probability for damage nucleation in smaller osteons.Peer reviewe
Knight-C4 is not associated with genetic or neuropathological effects.
No full text(A) The distribution of the APOE ℇ4 allele across 4 clusters shows no association with Knight-C4. (B) The distribution of Braak scores for tau across 4 clusters shows no significant correlation between Knight-C4 and Braak staging for tau. However, Knight-C4 exhibited more stage VI cases exceeding the mean distribution of Braak stage VI (dashed line) across all clusters. (C) The distribution of Braak scores for amyloid-β across 4 clusters showing no association with Knight-C4. The data underlying this figure can be found in S1 Data. (TIF)</p
Chronic High Fructose Intake Reduces Serum 1,25(OH)<sub>2</sub>D<sub>3</sub>Levels in Calcium-Sufficient Rodents
No full textExcessive fructose consumption inhibits adaptive increases in intestinal Ca2+transport in lactating and weanling rats with increased Ca2+requirements by preventing the increase in serum levels of 1,25(OH)2D3. Here we tested the hypothesis that chronic fructose intake decreases 1,25(OH)2D3 levels independent of increases in Ca2+ requirements. Adult mice fed for five wk a high glucose-low Ca2+ diet displayed expected compensatory increases in intestinal and renal Ca2+ transporter expression and activity, in renal CYP27B1 (coding for 1α-hydroxylase) expression as well as in serum 1,25(OH)2D3 levels, compared with mice fed isocaloric glucose- or fructose-normal Ca2+ diets. Replacing glucose with fructose prevented these increases in Ca2+ transporter, CYP27B1, and 1,25(OH)2D3 levels induced by a low Ca2+ diet. In adult mice fed for three mo a normal Ca2+ diet, renal expression of CYP27B1 and of CYP24A1 (24-hydroxylase) decreased and increased, respectively, when the carbohydrate source was fructose instead of glucose or starch. Intestinal and renal Ca2+ transporter activity and expression did not vary with dietary carbohydrate. To determine the time course of fructose effects, a high fructose or glucose diet with normal Ca2+ levels was fed to adult rats for three mo. Serum levels of 1,25(OH)2 D3 decreased and of FGF23 increased significantly over time. Renal expression of CYP27B1 and serum levels of 1,25(OH)2D3 still decreased in fructose- compared to those in glucose-fed rats after three mo. Serum parathyroid hormone, Ca2+ and phosphate levels were normal and independent of dietary sugar as well as time of feeding. Thus, chronically high fructose intakes can decrease serum levels of 1,25(OH)2D3 in adult rodents experiencing no Ca2+ stress and fed sufficient levels of dietary Ca2+. This finding is highly significant because fructose constitutes a substantial portion of the average diet of Americans already deficient in vitamin D.Peer reviewe
Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes
No full textOsteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-kB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X7R in ATP release; thus, we examined P2X7R-deficient mice and WT mice treated with P2X7R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X7RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1 KO and P2X7RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X7R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process.Peer reviewe
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