1,920 research outputs found

    Role of Schizosaccharomyces pombe RecQ homolog recombination and checkpoint genes in UV Damage tolerance

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    The cellular responses to DNA damage are complex and include direct DNA repair pathways that remove the damage and indirect damage responses which allow cells to survive DNA damage that has not been, or cannot be, removed. We have identified the gene mutated in the rad12.502 strain as a Schizosaccharomyces pombe recQ homolog. The same gene (designated rqh1) is also mutated in the hus2.22 mutant. We show that Rqh1 is involved in a DNA damage survival mechanism which prevents cell death when UV-induced DNA damage cannot be removed. This pathway also requires the correct functioning of the recombination machinery and the six checkpoint tad gene products plus the Cds1 kinase. Our data suggest that Rqh1 operates during S phase as part of a mechanism which prevents DNA damage causing cell lethality. This process may involve the bypass of DNA damage sites by the replication fork. Finally, in contrast with the reported literature, we do not find that rqh1 (rad12) mutant cells are defective in UV dimer endonuclease activity

    Towards an optimized all lattice-matched InAlAs/InGaAsP/InGaAs multijunction solar cell with efficiency >50%

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    An approach for an all lattice-matched multijunction solar cell optimized design is presented with 5.807 Å lattice constant, together with a detailed analysis of its performance by means of full device modeling. The simulations show that a (1.93 eV)In_(0.37)Al_(0.63)As/(1.39 eV)In_(0.38)Ga_(0.62)As_(0.57)P_(0.43)/(0.94 eV)In_(0.38)Ga_(0.62)As 3-junction solar cell can achieve efficiencies >51% under 100-suns illumination (with V_(oc) = 3.34 V). As a key proof of concept, an equivalent 3-junction solar cell lattice-matched to InP was fabricated and tested. The independently connected single junction solar cells were also tested in a spectrum splitting configuration, showing similar performance to a monolithic tandem device, with V_(oc) = 1.8 V

    Learning to work together - lessons from a reflective analysis of a research project on public involvement

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    Abstract Background Patient and public involvement (PPI) is now an expectation of research funders, in the UK, but there is relatively little published literature on what this means in practice – nor is there much evaluative research about implementation and outputs. Policy literature endorses the need to include PPI representation at all stages of planning, performing and research dissemination, and recommends resource allocation to these roles; but details of how to make such inputs effective in practice are less common. While literature on power and participation informs the debate, there are relatively few published case studies of how this can play out through the lived experience of PPI in research; early findings highlight key issues around access to knowledge, resources, and interpersonal respect. This article describes the findings of a case study of PPI within a study about PPI in research. Methods The aim of the study was to look at how the PPI representatives’ inputs had developed over time, key challenges and changes, and lessons learned. We used realist evaluation and normalisation process theory to frame and analyse the data, which was drawn from project documentation, minutes of meetings and workshops, field notes and observations made by PPI representatives and researchers; documented feedback after meetings and activities; and the structured feedback from two formal reflective meetings. Findings Key findings included the need for named contacts who support, integrate and work with PPI contributors and researchers, to ensure partnership working is encouraged and supported to be as effective as possible. A structure for partnership working enabled this to be enacted systematically across all settings. Some individual tensions were nonetheless identified around different roles, with possible implications for clarifying expectations and deepening understandings of the different types of PPI contribution and of their importance. Even in a team with research expertise in PPI, the data showed that there were different phases and challenges to ‘normalising’ the PPI input to the project. Mutual commitment and flexibility, embedded through relationships across the team, led to inclusion and collaboration. Conclusion Work on developing relationships and teambuilding are as important for enabling partnership between PPI representatives and researchers as more practical components such as funding and information sharing. Early explicit exploration of the different roles and their contributions may assist effective participation and satisfaction

    Trypanosoma brucei aquaglyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the main genetic determinant of resistance to these drugs.

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    OBJECTIVES: Trypanosoma brucei drug transporters include the TbAT1/P2 aminopurine transporter and the high-affinity pentamidine transporter (HAPT1), but the genetic identity of HAPT1 is unknown. We recently reported that loss of T. brucei aquaglyceroporin 2 (TbAQP2) caused melarsoprol/pentamidine cross-resistance (MPXR) in these parasites and the current study aims to delineate the mechanism by which this occurs. METHODS: The TbAQP2 loci of isogenic pairs of drug-susceptible and MPXR strains of T. brucei subspecies were sequenced. Drug susceptibility profiles of trypanosome strains were correlated with expression of mutated TbAQP2 alleles. Pentamidine transport was studied in T. brucei subspecies expressing TbAQP2 variants. RESULTS: All MPXR strains examined contained TbAQP2 deletions or rearrangements, regardless of whether the strains were originally adapted in vitro or in vivo to arsenicals or to pentamidine. The MPXR strains and AQP2 knockout strains had lost HAPT1 activity. Reintroduction of TbAQP2 in MPXR trypanosomes restored susceptibility to the drugs and reinstated HAPT1 activity, but did not change the activity of TbAT1/P2. Expression of TbAQP2 sensitized Leishmania mexicana promastigotes 40-fold to pentamidine and >1000-fold to melaminophenyl arsenicals and induced a high-affinity pentamidine transport activity indistinguishable from HAPT1 by Km and inhibitor profile. Grafting the TbAQP2 selectivity filter amino acid residues onto a chimeric allele of AQP2 and AQP3 partly restored susceptibility to pentamidine and an arsenical. CONCLUSIONS: TbAQP2 mediates high-affinity uptake of pentamidine and melaminophenyl arsenicals in trypanosomes and TbAQP2 encodes the previously reported HAPT1 activity. This finding establishes TbAQP2 as an important drug transporter

    A Scheme for Solving the Plane–Plane Challenge in Force Measurements at the Nanoscale

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    Non-contact interaction between two parallel flat surfaces is a central paradigm in sciences. This situation is the starting point for a wealth of different models: the capacitor description in electrostatics, hydrodynamic flow, thermal exchange, the Casimir force, direct contact study, third body confinement such as liquids or films of soft condensed matter. The control of parallelism is so demanding that no versatile single force machine in this geometry has been proposed so far. Using a combination of nanopositioning based on inertial motors, of microcrystal shaping with a focused-ion beam (FIB) and of accurate in situ and real-time control of surface parallelism with X-ray diffraction, we propose here a “gedanken” surface-force machine that should enable one to measure interactions between movable surfaces separated by gaps in the micrometer and nanometer ranges

    Plant geography and water quality data for Chesapeake Bay waters of Virginia\u27s Eastern Shore

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    Plant geography and water quality data were collected in shallow water near Cape Charles and Occohannock Creek, Virginia on two occasions. Data from April, 1978 included hydrography, distribution and abundance of -submerged aquatic vegetation, phytoplankton census, and water clarity data. Data from May, 1978 included hydrography, phytoplankton census, water clarity, and primary productivity data. The May data collection was coincident with an overflight of the NASA JSC C-130 aircraft (6600 m) acquiring color infrared photography and multispectral scanner data; cell concentrations reached 105/ml, chlorophyll~ 72 pg/1, and suspended sediment 94 mg/1.
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