1,411 research outputs found

    OXPHOS Inhibition via LUC7L2 as a Target for SF3B1-Mutant Myelodysplastic Syndrome

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    SF3B1 gene mutations are the most common spliceosome mutations seen in myelodysplastic syndrome (MDS) patients. Though it is well known SF3B1 mutations cause downstream changes in erythroid differentiation and the cell cycle, which leads to malignancy, metabolic changes arising from this mutation are unknown. We conducted RNA sequencing from SF3B1-mutant MDS patient samples and found several genes related to metabolism were alternatively spliced. Of these, LUC7L2 was selected as our target as previous studies show its involvement in promoting oxidative phosphorylation (OXPHOS) via various downstream mechanisms when knocked down.We show that OXPHOS is increased in MOLM-13 myeloid malignant cells when LUC7L2 is inhibited. The results suggested that this gene, which is alternatively spliced and shows lower expression in SF3B1-mutant MDS, increases myeloid malignant dependence on OXPHOS

    2017 ASC Bidding Competition – Heavy Civil

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    We represent the 2017 Montana Tech Heavy Civil Team. Our senior design project consisted of competing in the Region 6 ASC (Associated Schools of Construction) Heavy Civil Bidding Competition in Sparks, Nevada. The competition required a full year of preparation. The fall semester was composed of planning, practicing, and gathering resources. The spring semester involved traveling to Sparks, Nevada, and performing in the competition. Preparing for the competition involved practice bids, where the team studied various aspects of heavy civil construction. Time was devoted to developing presentation skills, and different team bonding exercises encouraged unit cohesion. Finally, our preparation culminated with a simulated competition where we estimated a project and presented our solution to a mock panel of judges. The competition involved a 16-hour period where we developed our bid and solution for the given problem statement. We then were given an 8-hour time frame to prepare for a 20-minute presentation, which was followed by a 10-minute Q&A session

    Low-dose antibiotics: current status and outlook for the future

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    Antimicrobial therapy is a key factor in our success against pathogens poised to ravage at risk or infected individuals. However, we are currently at a watershed point as we face a growing crisis of antibiotic resistance among diverse pathogens. One area of intense interest is the impact of the application of antibiotics for uses other than the treatment of patients and the association with such utilization with emerging drug resistance. This Research Topic “Low- dose antibiotics: current status and outlook for the future” in Frontiers in Microbiology: Antimicrobials, Resistance and Chemotherapy details various aspects of the wide ranging effects of antimicrobial therapy from areas such as the regulation of host responses to modulation of bacterial virulence factors to acquisition of antibiotic resistance genes

    A bright radio HH object with large proper motions in the massive star-forming region W75N

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    We analyze radio continuum and line observations from the archives of the Very Large Array, as well as X-ray observations from the \emph{Chandra} archive of the region of massive star formation W75N. Five radio continuum sources are detected: VLA 1, VLA 2, VLA 3, Bc, and VLA 4. VLA 3 appears to be a radio jet; we detect J=1-0, v=0 SiO emission towards it, probably tracing the inner parts of a molecular outflow. The radio continuum source Bc, previously believed to be tracing an independent star, is found to exhibit important changes in total flux density, morphology, and position. These results suggest that source Bc is actually a radio Herbig-Haro object, one of the brightest known, powered by the VLA~3 jet source. VLA 4 is a new radio continuum component, located a few arcsec to the south of the group of previously known radio sources. Strong and broad (1,1) and (2,2) ammonia emission is detected from the region containing the radio sources VLA~1, VLA~2, and VLA~3. Finally, the 2-10 keV emission seen in the \emph{Chandra}/ACIS image shows two regions that could be the termination shocks of the outflows from the multiple sources observed in W75N.Comment: 26 pages, 7 figure

    Indirect Dark Matter Searches and Models

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    Indirect dark matter searches are briefly reviewed. Current experimental data from satellites and Cherenkov telescopes searching for antimatter and gamma rays in galactic and extragalactic regions, are compared with predictions from theoretical models of dark matter. The analysis is focused on WIMPs such as the neutralino and the sneutrino, and a superWIMP such as the gravitino, in several interesting supersymmetric models. In particular, the discussion is carried out in the context of R-parity conserving models such as the MSSM, the NMSSM, and an extended NMSSM, and the R-parity violating model ΌΜ\mu\nuSSM.Comment: Proceedings of RICAP 2011; 19 pages, 3 figures; Nuclear Instruments and Methods in Physics Research A (2012

    Bis-porphyrin tetragonal prisms assembled through Watson-Crick hydrogen bonding between complementary nucleobases

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    We report here on the self-Assembly of two components, a Zn(II) porphyrin substituted with four lipophilic cytidines and a linear linker substituted with two guanosines, into a Watson-Crick hydrogen-bonded tetragonal prism. The corresponding ensemble, comprising two cofacial porphyrin macrocycles, exhibited similar supramolecular behavior as a reference cyclic tetramer previously studied by us. The establishment of strong G:C interactions in apolar chlorinated solvents was demonstrated by the chemical shift recorded for the relevant H-bonded protons. Most importantly, the hexacomponent prism assembly, when partially dissociated by the addition of the competing DMSO solvent, exhibited a slow exchange on the NMR timescale with the individual constituents, which is characteristic of kinetically stabilized discrete assemblies. Absorption, emission, and CD spectroscopy experiments revealed that the spectral features of the tetragonal prism were totally different from the ones recorded for the porphyrin and linker components, which also showed strong self-Aggregation in apolar solvents. Temperature-dependent experiments, monitored by NMR and optical spectroscopy techniques, revealed remarkable thermodynamic stability for the prism assembl

    To green or not to green! That is the question. Does green infrastructure provide significant thermoregulation in a maritime temperate climate?

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    The ecosystem service delivery of urban green infrastructure (UGI) is now manifest. Types and level of service provision, however, can alter radically, based on factors such as location, species choice, planting design and vegetation management. The value of vegetation to provide a cooling service is generally understood in hot climates, but the merit in temperate climates remains ambiguous. Indeed, policy makers within cooler countries (e.g. UK) remain to be convinced that expenditure on UGI is justified, at least from the point of view of city cooling alone. Occasional warm days do occur of course, and climate change models predict that heat wave events will become more frequent within the UK, including those that pose a risk to human health. To help UK policy makers make better-informed decisions around UGI, a number of our research programmes have targeted the role vegetation plays in regulating temperature, but specifically within the context of a maritime-temperate climate. Two examples of ‘green interventions’ are discussed here. The first documents the role of green façades to cool a wall system and the second illustrates the cooling influence conferred by roadside trees. Both experiments used a replicated sampling approach to ensure statistical robustness, and hence convince policy makers that data is representative of UK scenarios and results are reproducible. In the first experiment, 10 separate wall sections are used to investigate the cooling influence of two different plant genotypes (Prunus and Phaseolus) on both exterior and interior wall spaces. In the second study, road surface temperatures are documented with respect to both built and green infrastructure, i.e. we compare the influence of buildings and street trees on the surface temperatures across a road profile. Again replicate data are used to provide a ‘generic’ summer temperature profile for the city of Sheffield, rather than just specific locations at one point in time. Results show that green facades can reduce exterior and interior (cavity) wall air temperature by 3oC and 5oC respectively. Likewise, large street trees have a mean cooling influence of 4.5oC on road surfaces near their base compared to comparable sections adjacent to buildings. To maximise cooling, the data suggests that trees need to be provided on both sides of a roadway, i.e. a single tree did not manage to cool the pavement at th
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