1,609 research outputs found

    Transforming Epistemologies in the Postcolonial African University? the Challenge of the Politics of Knowledge

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    The process of knowledge production, dissemination and consumption has captured much scholarly attention from a political viewpoint in recent times. Discourses on development, empowerment, transformation and democracy have revolved around knowledge and power and more precisely on the politics of knowledge. Institutions of higher learning, especially universities, globally, as nerve centres of knowledge production and distribution, have not been spared from the challenges of the politics of knowledge. In this conceptual paper, we theorise the dynamics of the challenges and opportunities of the politics of knowledge in the context of the postcolonial African university's endeavour to transform epistemologies in higher education in the 21st century Africa. Our case is premised on three claims, namely that 1) the production and mediation of knowledge is a genuinely political process(Weiler, 2011b) 2) universities can be considered among the most political institutions in society (Ordorika, 1999) and 3) recontextualisation and transformation of university epistemologies (Weiler, 2011a) is a prerequisite for an authentic postcolonial African university

    Beyond Goldwater-Nichols

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    This report culminated almost two years of effort at CSIS, which began by developing an approach for both revisiting the Goldwater-Nichols Department of Defense Reorganization Act of 1986 and for addressing issues that were beyond the scope of that landmark legislation

    Detection of siRNA induced mRNA silencing by RT-qPCR: considerations for experimental design

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    <p>Abstract</p> <p>Background</p> <p>RNA interference (RNAi) has been one of the most rapidly expanding areas of biological research in the past decade, revolutionizing the ability to analyze gene function. Thorough validation of siRNA duplexes is required prior to use in experimental systems, ideally by western blotting to show a reduction in protein levels. However, in many cases good antibodies are not available, and researchers must rely on RT-qPCR to detect knockdown of the mRNA species.</p> <p>Findings</p> <p>We have observed a phenomenon that gives a disparity between analyzing small interfering RNA (siRNA) efficacy by western blotting of the protein levels and real-time quantitative PCR (RT-qPCR) measurement of mRNA levels. Detection of this phenomenon was dependent upon the location of the target amplicon for PCR primers within the mRNA.</p> <p>Conclusions</p> <p>Our data suggests that for certain mRNAs, degradation of the 3' mRNA fragment resulting from siRNA mediated cleavage is blocked, leaving an mRNA fragment that can act as a template for cDNA synthesis, giving rise to false negative results and the rejection of a valid siRNA duplex. We show that this phenomenon may be avoided by the careful design of RT-qPCR primers for each individual siRNA experiment.</p

    "Making Safety Happen" Through Probabilistic Risk Assessment at NASA

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    NASA is using Probabilistic Risk Assessment (PRA) as one of the tools in its Safety & Mission Assurance (S&MA) tool belt to identify and quantify risks associated with human spaceflight. This paper discusses some of the challenges and benefits associated with developing and using PRA for NASA human space programs. Some programs have entered operation prior to developing a PRA, while some have implemented PRA from the start of the program. It has been observed that the earlier a design change is made in the concept or design phase, the less impact it has on cost and schedule. Not finding risks until the operation phase yields much costlier design changes and major delays, which can result in discussions of just accepting the risk. Risk contributors identified by PRA are not just associated with hardware failures. They include but are not limited to crew fatality due to medical causes, the environment the vehicle and crew are exposed to, the software being used, and the reliability of the crew performing required actions. Some programs have entered operation prior to developing a PRA, and while PRA can still provide a benefit for operations and future design trades, the benefit of implementing PRA from the start of the program provides the added benefit of informing design and reducing risk early in program development. Currently, NASAs International Space Station (ISS) program is in its 20th year of on-orbit operations around the Earth and has several new programs in the design phase preparing to enter the operation phase all of which have active (or living) PRAs. These programs incorporate PRA as part of their Risk-Informed, Decision-Making (RIDM) process. For new NASA human spaceflight programs discussion begins with mission concept, establishing requirements, forming the PRA team, and continues through the design cycles into the operational phase. Several examples of PRA related applications and observed lessons are included

    Sex-Biased Gene Flow Among Elk in the Greater Yellowstone Ecosystem

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    We quantified patterns of population genetic structure to help understand gene flow among elk populations across the Greater Yellowstone Ecosystem. We sequenced 596 base pairs of the mitochondrial control region of 380 elk from eight populations. Analysis revealed high mitochondrial DNA variation within populations, averaging 13.0 haplotypes with high mean gene diversity (0.85). The genetic differentiation among populations for mitochondrial DNA was relatively high (FST = 0.161; P = 0.001) compared to genetic differentiation for nuclear microsatellite data (FST = 0.002; P = 0.332), which suggested relatively low female gene flow among populations. The estimated ratio of male to female gene flow (mm/mf = 46) was among the highest we have seen reported for large mammals. Genetic distance (for mitochondrial DNA pairwise FST) was not significantly correlated with geographic (Euclidean) distance between populations (Mantel’s r = 0.274, P = 0.168). Large mitochondrial DNA genetic distances (e.g., FST . 0.2) between some of the geographically closest populations (,65 km) suggested behavioral factors and/or landscape features might shape female gene flow patterns. Given the strong sex-biased gene flow, future research and conservation efforts should consider the sexes separately when modeling corridors of gene flow or predicting spread of maternally transmitted diseases. The growing availability of genetic data to compare male vs. female gene flow provides many exciting opportunities to explore the magnitude, causes, and implications of sex-biased gene flow likely to occur in many species

    Convective Fingering of an Autocatalytic Reaction Front

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    We report experimental observations of the convection-driven fingering instability of an iodate-arsenous acid chemical reaction front. The front propagated upward in a vertical slab; the thickness of the slab was varied to control the degree of instability. We observed the onset and subsequent nonlinear evolution of the fingers, which were made visible by a {\it p}H indicator. We measured the spacing of the fingers during their initial stages and compared this to the wavelength of the fastest growing linear mode predicted by the stability analysis of Huang {\it et. al.} [{\it Phys. Rev. E}, {\bf 48}, 4378 (1993), and unpublished]. We find agreement with the thickness dependence predicted by the theory.Comment: 11 pages, RevTex with 3 eps figures. To be published in Phys Rev E, [email protected], [email protected], [email protected]

    Identification and functional characterization of a highly divergent N-acetylglucosaminyltransferase I (TbGnTI) in <em>Trypanosoma brucei</em>

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    Trypanosoma brucei expresses a diverse repertoire of N-glycans, ranging from oligomannose and paucimannose structures to exceptionally large complex N-glycans. Despite the presence of the latter, no obvious homologues of known β1–4-galactosyltransferase or β1–2- or β1–6-N-acetylglucosaminyltransferase genes have been found in the parasite genome. However, we previously reported a family of putative UDP-sugar-dependent glycosyltransferases with similarity to the mammalian β1–3-glycosyltransferase family. Here we characterize one of these genes, TbGT11, and show that it encodes a Golgi apparatus resident UDP-GlcNAc:α3-d-mannoside β1–2-N-acetylglucosaminyltransferase I activity (TbGnTI). The bloodstream-form TbGT11 null mutant exhibited significantly modified protein N-glycans but normal growth in vitro and infectivity to rodents. In contrast to multicellular organisms, where the GnTI reaction is essential for biosynthesis of both complex and hybrid N-glycans, T. brucei TbGT11 null mutants expressed atypical “pseudohybrid” glycans, indicating that TbGnTII activity is not dependent on prior TbGnTI action. Using a functional in vitro assay, we showed that TbGnTI transfers UDP-GlcNAc to biantennary Man(3)GlcNAc(2), but not to triantennary Man(5)GlcNAc(2), which is the preferred substrate for metazoan GnTIs. Sequence alignment reveals that the T. brucei enzyme is far removed from the metazoan GnTI family and suggests that the parasite has adapted the β3-glycosyltransferase family to catalyze β1–2 linkages

    Class 3 semaphorins expression and association with innervation and angiogenesis within the degenerate human intervertebral disc

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    Nerve and blood vessel ingrowth during intervertebral disc degeneration, is thought to be a major cause of low back pain, however the regulation of this process is poorly understood. Here, we investigated the expression and regulation of a subclass of axonal guidance molecules known as the class 3 semaphorins, and their receptors; plexins and neuropilins within human NP tissue and their regulation by pro-inflammatory cytokines. Importantly this determined whether semaphorin expression was associated with the presence of nerves and blood vessels in tissues from human intervertebral discs. The study demonstrated that semaphorin3A, 3C, 3D, 3E and 3F and their receptors were expressed by native NP cells and further demonstrated their expression was regulated by IL-1β but to a lesser extent by IL-6 and TNFα. This is the first study to identify sema3C, sema3D and their receptors within the nucleus pulposus of intervertebral discs. Immunopositivity shows significant increases in semaphorin3C, 3D and their receptor neuropilin-2 in degenerate samples which were shown to contain nerves and blood vessels, compared to non-degenerate samples without nerves and blood vessels. Therefore data presented here suggests that semaphorin3C may have a role in promoting innervation and vascularisation during degeneration, which may go on to cause low back pain

    Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration

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    Introduction : The degenerate intervertebral disc (IVD) becomes innervated by sensory nerve fibres, and vascularised by blood vessels. This study aimed to identify neurotrophins, neuropeptides and angiogenic factors within native IVD tissue and to further investigate whether pro-inflammatory cytokines are involved in the regulation of expression levels within nucleus pulposus (NP) cells, nerve and endothelial cells. Methods : Quantitative real-time PCR (qRT-PCR) was performed on 53 human IVDs from 52 individuals to investigate native gene expression of neurotrophic factors and their receptors, neuropeptides and angiogenic factors. The regulation of these factors by cytokines was investigated in NP cells in alginate culture, and nerve and endothelial cells in monolayer using RT-PCR and substance P (SP) protein expression in interleukin-1 (IL-1ß) stimulated NP cells. Results : Initial investigation on uncultured NP cells identified expression of all neurotrophins by native NP cells, whilst the nerve growth factor (NGF) receptor was only identified in severely degenerate and infiltrated discs, and brain derived neurotrophic factor (BDNF) receptor expressed by more degenerate discs. BDNF expression was significantly increased in infiltrated and degenerate samples. SP and vascular endothelial growth factor (VEGF) were higher in infiltrated samples. In vitro stimulation by IL-1ß induced NGF in NP cells. Neurotropin-3 was induced by tumour necrosis factor alpha in human dermal microvascular endothelial cells (HDMECs). SP gene and protein expression was increased in NP cells by IL-1ß. Calcitonin gene related peptide was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by IL-1ß and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1ß. VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but were not modulated by cytokines. Conclusions : The release of cytokines, in particular IL-1ß during IVD degeneration, induced significant increases in NGF and VEGF which could promote neuronal and vascular ingrowth. SP which is released into the matrix could potentially up regulate the production of matrix degrading enzymes and also sensitise nerves, resulting in nociceptive transmission and chronic low back pain. This suggests that IL-1ß is a key regulatory cytokine, involved in the up regulation of factors involved in innervation and vascularisation of tissues.</p

    Keratinocyte growth factor for the treatment of the acute respiratory distress syndrome (KARE): a randomised, double-blind, placebo-controlled phase 2 trial

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    <p>(<b>A</b>) Immunofluorescence signal for dystrophin is significantly reduced in the SSI heart (bottom left panel) compared with the immunofluorescent signal in the SHAM heart (upper left panel), and the SHAM+ALLN (upper right panel) and SSI+ALLN (bottom right panel) myocardium. (<b>B</b>) Protein levels of dystrophin in the SHAM, SSI, SHAM+ALLN and SSI+ALLN hearts were measured 24 h after the CLP procedure and were expressed in arbitrary units (AUs). α-Tubulin was used to determine equivalent loading conditions. The results (n = 6 per group) are representative of three different experiments. Scale bars indicate 50 μm.</p
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