1,383 research outputs found

    Promoting and Supporting English Language Study in the USA

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    EnglishUSA has officially kicked off its project “Promoting and Supporting English Language Study in the U.S.A” (PASELS-USA). The 3-year project, funded by the Department of Commerce Market Development Cooperator Program (MDCP), is intended to generate exports and support high quality U.S. jobs through funding and cooperation with several stakeholders worldwide. EnglishUSA’s initiatives will help increase the visibility of U.S.-based English language programs in targeted markets and highlight the importance of the industry within the larger field of international education and exports

    Regulation of atypical PKCs

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    Protein phosphorylation plays an essential role in a diverse array of signalling cascades and regulates many cellular processes. Protein kinase Cs (PKCs) constitute one of the families of kinases involved in phosphorylating substrates on serine or threonine residues. These kinases were initially identified as being receptors for tumour promoters (phorbol esters) and the conditions required to activate different isoforms determine the subgroup classification of the 10 isoforms. Classical PKCs (α,ÎČ1, ÎČII and Îł) depend upon Ca2+ and lipids (DAG, PS- phospholipids.) Novel PKCs (ÎŽ, Ï”, η, ÎŒ and Ξ) are insensitive to Ca2+ but are activated by lipids, DAG and phospholipids. The atypical PKCs (ζ, i and λ) differ greatly. These proteins are insensitive to Ca2+ and phorbol ester binding. The lack of knowledge on the control of the atypical PKCs has made the role of the atypical PKCs more elusive. Nevertheless, PKC ζ has been implicated in cell growth and differentiation. Moreover, PKC ζ is thought to be involved in a plethora of signal transduction pathways, including the Ras and MEK/MAPK pathways. The related atypical PKC i may be involved in UV induced apoptosis and insulin signalling. The aims of this thesis are to define the control and biological role of the atypical PKCs - primarily focusing on PKC ζ. As one approach, the project attempted to create a knockout mouse. This would help define a biological end point and therefore permit elucidation of the inputs. This study led to the identification of a pseudogene and its origin is described. As a second approach to investigate PKC ζ control, various direct paths were followed - ranging from searching for potential binding proteins and cellular localisation, to analysis of activation by lipids and phosphorylation. These studies have provided evidence for the dynamic control of PKC ζ (and PKC i) through a kinase cascade involving the lipid kinase PI3-kinase, the lipid responsive PDK1 and finally phosphorylation of PKC ζ at a site defined as threonine 410. The operation of this pathway and its influence on PKC ζ autophosphorylation (in vivo) and activity (in vitro) are presented

    Interview with Cheryl Delk-le Good

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    An investigation of aerodynamic effects of body morphing for passenger cars in close-proximity

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    The potential energy-saving benefit for vehicles when travelling in a ‘platoon’ formation results from the reduction in total aerodynamic drag which may result from the interaction of bluff bodies in close-proximity. Early investigations of platooning, prompted by problems of congestion, had shown the potential for drag reduction but was not pursued. More recently, technologies developed for connected-autonomous vehicle control have provided a renewed interest in platooning particularly within the commercial vehicle industry. To date, most aerodynamics-based considerations of platooning have been conducted to assess the sensitivity of drag-saving to vehicle spacing and were based on formations of identically shaped constituents. In this study, the interest was the sensitivity of drag-saving to the shape of the individual platoon constituents. A new reference car, the Resnick model, was specially designed to include front and rear-end add-on sections to make distinct changes in profile form and simulate large-scale body morphing. The results of wind tunnel tests on small-scale models suggested that current trends in low-drag styling may not provide the ideal shape for platoon constituent members and that optimised forms are likely to be dependent upon position in the platoon

    A comparison of on-road aerodynamic drag measurements with wind tunnel data from Pininfarina and MIRA

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    The principal development tool for the vehicle aerodynamicist continues to be the full-scale wind tunnel. It is expected that this will continue for many years in the absence of a reliable alternative. As a true simulation of conditions on the road, the conventional full-scale wind tunnel has limitations. For example, the ground is fixed relative to the vehicle, allowing an unrepresentative boundary layer to develop, and the wheels of the test vehicle do not rotate. These limitations are known to influence measured aerodynamic data. In order to improve the representation of road conditions in the wind tunnel, most of the techniques used have attempted to control the ground plane boundary layer. Only at model scale has the introduction of a moving ground plane and rotating wheels been widely adopted. The Pininfarina full-scale wind tunnel now incorporates the Ground Effect Simulation System which allows testing with a moving belt and rotating wheels. A major feature of this facility is that test vehicles can be easily installed with only minor modifications. This paper compares aerodynamic drag measurements for a large saloon, in various configurations, obtained both in the wind tunnel and on the road. The wind tunnel results are presented for various ground simulations. These are: moving belt with rotating wheels and stationary belt with fixed wheels at Pininfarina, and the conventional fixed ground in the MIRA full-scale wind tunnel. The on-road data is derived from coastdown tests

    Leptonic contribution to the bulk viscosity of nuclear matter

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    For beta-equilibrated nuclear matter we estimate the contribution to the bulk viscosity from purely leptonic processes, namely the conversion of electrons to and from muons. For oscillation frequencies in the kiloHertz range, we find that this process provides the dominant contribution to the bulk viscosity when the temperature is well below the critical temperature for superconductivity or superfluidity of the nuclear matter.Comment: 15 pages, LaTeX, new appendix and general clarifications in response to referee comment

    Cripto promotes A–P axis specification independently of its stimulatory effect on Nodal autoinduction

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    The EGF-CFC gene cripto governs anterior–posterior (A–P) axis specification in the vertebrate embryo. Existing models suggest that Cripto facilitates binding of Nodal to an ActRII–activin-like kinase (ALK) 4 receptor complex. Cripto also has a crucial function in cellular transformation that is independent of Nodal and ALK4. However, how ALK4-independent Cripto pathways function in vivo has remained unclear. We have generated cripto mutants carrying the amino acid substitution F78A, which blocks the Nodal–ALK4–Smad2 signaling both in embryonic stem cells and cell-based assays. In criptoF78A/F78A mouse embryos, Nodal fails to expand its own expression domain and that of cripto, indicating that F78 is essential in vivo to stimulate Smad-dependent Nodal autoinduction. In sharp contrast to cripto-null mutants, criptoF78A/F78A embryos establish an A–P axis and initiate gastrulation movements. Our findings provide in vivo evidence that Cripto is required in the Nodal–Smad2 pathway to activate an autoinductive feedback loop, whereas it can promote A–P axis formation and initiate gastrulation movements independently of its stimulatory effect on the canonical Nodal–ALK4–Smad2 signaling pathway

    The Transcriptome of the Intraerythrocytic Developmental Cycle of Plasmodium falciparum

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    Plasmodium falciparum is the causative agent of the most burdensome form of human malaria, affecting 200–300 million individuals per year worldwide. The recently sequenced genome of P. falciparum revealed over 5,400 genes, of which 60% encode proteins of unknown function. Insights into the biochemical function and regulation of these genes will provide the foundation for future drug and vaccine development efforts toward eradication of this disease. By analyzing the complete asexual intraerythrocytic developmental cycle (IDC) transcriptome of the HB3 strain of P. falciparum, we demonstrate that at least 60% of the genome is transcriptionally active during this stage. Our data demonstrate that this parasite has evolved an extremely specialized mode of transcriptional regulation that produces a continuous cascade of gene expression, beginning with genes corresponding to general cellular processes, such as protein synthesis, and ending with Plasmodium-specific functionalities, such as genes involved in erythrocyte invasion. The data reveal that genes contiguous along the chromosomes are rarely coregulated, while transcription from the plastid genome is highly coregulated and likely polycistronic. Comparative genomic hybridization between HB3 and the reference genome strain (3D7) was used to distinguish between genes not expressed during the IDC and genes not detected because of possible sequence variations. Genomic differences between these strains were found almost exclusively in the highly antigenic subtelomeric regions of chromosomes. The simple cascade of gene regulation that directs the asexual development of P. falciparum is unprecedented in eukaryotic biology. The transcriptome of the IDC resembles a “just-in-time” manufacturing process whereby induction of any given gene occurs once per cycle and only at a time when it is required. These data provide to our knowledge the first comprehensive view of the timing of transcription throughout the intraerythrocytic development of P. falciparum and provide a resource for the identification of new chemotherapeutic and vaccine candidates
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