Collaborative learning: a connected community approach

Collaborative Learning in group settings currently occurs across a substantial portion of the UK Higher Education curriculum. This style of learning has many roots including: Enterprise in Higher Education, Action Learning and Action Research, Problem Based Learning, and Practice Based Learning. As such our focus on Collaborative Learning development can be viewed as an evolutionary. This collaborative and active group learning provides the foundation for what can be collectively called connectivist ‘Learning Communities’. In this setting a primary feature of a ‘Learning Community’ is one that carries a responsibility to promote one another’s learning. This paper will outline a developmental collaborative learning approach and describe a supporting software environment, known as the Salford Personal Development Environment (SPDE), that has been developed and implemented to assist in delivering collaborative learning for post graduate and other provision. This is done against a background of much research evidence that group based activity can enhance learning. These findings cover many approaches to group based learning and over a significant period of time. This paper reports on work-in-progress and the features of the environment that are designed to help promote individual and group or community learning that have been influenced by the broad base of research findings in this area

Preclinical correction of human Fanconi anemia complementation group A bone marrow cells using a safety-modified lentiviral vector.

One of the major hurdles for the development of gene therapy for Fanconi anemia (FA) is the increased sensitivity of FA stem cells to free radical-induced DNA damage during ex vivo culture and manipulation. To minimize this damage, we have developed a brief transduction procedure for lentivirus vector-mediated transduction of hematopoietic progenitor cells from patients with Fanconi anemia complementation group A (FANCA). The lentiviral vector FancA-sW contains the phosphoglycerate kinase promoter, the FANCA cDNA, and a synthetic, safety-modified woodchuck post transcriptional regulatory element (sW). Bone marrow mononuclear cells or purified CD34(+) cells from patients with FANCA were transduced in an overnight culture on recombinant fibronectin peptide CH-296, in low (5%) oxygen, with the reducing agent, N-acetyl-L-cysteine (NAC), and a combination of growth factors, granulocyte colony-stimulating factor (G-CSF), Flt3 ligand, stem cell factor, and thrombopoietin. Transduced cells plated in methylcellulose in hypoxia with NAC showed increased colony formation compared with 21% oxygen without NAC (P<0.03), showed increased resistance to mitomycin C compared with green fluorescent protein (GFP) vector-transduced controls (P<0.007), and increased survival. Thus, combining short transduction and reducing oxidative stress may enhance the viability and engraftment of gene-corrected cells in patients with FANCA

Robust identification of dynamically distinct regions in stratified turbulence

We present a new robust method for identifying three dynamically distinct regions in a stratified turbulent flow, which we characterise as quiescent flow, intermittent layers and turbulent patches. The method uses the cumulative filtered distribution function of the local density gradient to identify each region. We apply it to data from direct numerical simulations of homogeneous stratified turbulence, with unity Prandtl number, resolved on up to $8192\times 8192\times 4096$ grid points. In addition to classifying regions consistently with contour plots of potential enstrophy, our method identifies quiescent regions as regions where \unicode[STIX]{x1D716}/\unicode[STIX]{x1D708}N^{2}\sim O(1), layers as regions where \unicode[STIX]{x1D716}/\unicode[STIX]{x1D708}N^{2}\sim O(10) and patches as regions where \unicode[STIX]{x1D716}/\unicode[STIX]{x1D708}N^{2}\sim O(100). Here, \unicode[STIX]{x1D716} is the dissipation rate of turbulence kinetic energy, \unicode[STIX]{x1D708} is the kinematic viscosity and $N$ is the (overall) buoyancy frequency. By far the highest local dissipation and mixing rates, and the majority of dissipation and mixing, occur in patch regions, even when patch regions occupy only 5 % of the flow volume. We conjecture that treating stratified turbulence as an instantaneous assemblage of these different regions in varying proportions may explain some of the apparently highly scattered flow dynamics and statistics previously reported in the literature.The research activities of G.D.P. and S.dB.K. were funded by the US Office of Naval Research via grant N00014-15-1-2248. Additional support to G.D.P. and S.dB.K. was provided from the UK Engineering and Physical Sciences Research Council grant EP/K034529/1 entitled ‘Mathematical Underpinnings of Stratified Turbulence’, which also funds the research activity of J.R.T. and C.P.C. H.S. gratefully acknowledges the award of a Crighton Fellowship at the Department of Applied Mathematics & Theoretical Physics, University of Cambridge. High-performance computing resources were provided through the US Department of Defense High Performance Computing Modernization Program by the Army Engineer Research and Development Center and the Army Research Laboratory under Frontier Project FP-CFD-FY14-007.This is the author accepted manuscript. The final version is available from Cambridge University Press via https://doi.org/10.1017/jfm.2016.61

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent

Identification of 2-Aminothiazole-4-Carboxylate Derivatives Active against Mycobacterium tuberculosis H37Rv and the β-Ketoacyl-ACP Synthase mtFabH

Background Tuberculosis (TB) is a disease which kills two million people every year and infects approximately over one-third of the world's population. The difficulty in managing tuberculosis is the prolonged treatment duration, the emergence of drug resistance and co-infection with HIV/AIDS. Tuberculosis control requires new drugs that act at novel drug targets to help combat resistant forms of Mycobacterium tuberculosis and reduce treatment duration. Methodology/Principal Findings Our approach was to modify the naturally occurring and synthetically challenging antibiotic thiolactomycin (TLM) to the more tractable 2-aminothiazole-4-carboxylate scaffold to generate compounds that mimic TLM's novel mode of action. We report here the identification of a series of compounds possessing excellent activity against M. tuberculosis H37Rv and, dissociatively, against the β-ketoacyl synthase enzyme mtFabH which is targeted by TLM. Specifically, methyl 2-amino-5-benzylthiazole-4-carboxylate was found to inhibit M. tuberculosis H37Rv with an MIC of 0.06 µg/ml (240 nM), but showed no activity against mtFabH, whereas methyl 2-(2-bromoacetamido)-5-(3-chlorophenyl)t​hiazole-4-carboxylateinhibited mtFabH with an IC50 of 0.95±0.05 µg/ml (2.43±0.13 µM) but was not active against the whole cell organism. Conclusions/Significance These findings clearly identify the 2-aminothiazole-4-carboxylate scaffold as a promising new template towards the discovery of a new class of anti-tubercular agents

Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure

Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown. We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium

Calcitization of aragonitic bryozoans in Cenozoic tropical carbonates from East Kalimantan, Indonesia

© The Author(s) 2016. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The file attached is the published version of the article