20 research outputs found

    Polθ promotes the repair of 5\u27-DNA-protein crosslinks by microhomology-mediated end-joining

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    DNA polymerase θ (Polθ) confers resistance to chemotherapy agents that cause DNA-protein crosslinks (DPCs) at double-strand breaks (DSBs), such as topoisomerase inhibitors. This suggests Polθ might facilitate DPC repair by microhomology-mediated end-joining (MMEJ). Here, we investigate Polθ repair of DSBs carrying DPCs by monitoring MMEJ in Xenopus egg extracts. MMEJ in extracts is dependent on Polθ, exhibits the MMEJ repair signature, and efficiently repairs 5\u27 terminal DPCs independently of non-homologous end-joining and the replisome. We demonstrate that Polθ promotes the repair of 5\u27 terminal DPCs in mammalian cells by using an MMEJ reporter and find that Polθ confers resistance to formaldehyde in addition to topoisomerase inhibitors. Dual deficiency in Polθ and tyrosyl-DNA phosphodiesterase 2 (TDP2) causes severe cellular sensitivity to etoposide, which demonstrates MMEJ as an independent DPC repair pathway. These studies recapitulate MMEJ in vitro and elucidate how Polθ confers resistance to etoposide

    Gate driver circuit with all-magnetic isolation for cascode-connected SiC JFETs in a three-level T-type bridge-leg

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    This article presents a gate driver circuit with all-magnetic isolation for driving SiC power devices in a three-level T-type bridge-leg. The gate driver circuitry used with SiC devices has to be tolerant of rapid common-mode voltage changes. With respect to the resultant potentially problematic common-mode current paths, an arrangement of transformers is proposed for supplying the power devices with drive signals and power for their local floating gate driver circuits. The high-frequency carrier phase-switching technique is used to reduce the number of transformers. Signal timing and other implementation issues are addressed when using this arrangement with the T-type converter. The circuit is demonstrated in a 540 V bridge-leg constructed around 650 V and 1200 V cascode-connected normally-on SiC JFETs

    ‘Can you recommend any good STI apps?’ A review of content, accuracy and comprehensiveness of current mobile medical applications for STIs and related genital infections

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    Objective Seeking sexual health information online is common, and provision of mobile medical applications (apps) for STIs is increasing. Young people, inherently at higher risk of STIs, are avid users of technology, and apps could be appealing sources of information. We undertook a comprehensive review of content and accuracy of apps for people seeking information about STIs. Methods Search of Google Play and iTunes stores using general and specific search terms for apps regarding STIs and genital infections (except HIV), testing, diagnosis and management, 10 September 2014 to 16 September 2014. We assessed eligible apps against (1) 19 modified Health on The Net (HON) Foundation principles; and (2) comprehensiveness and accuracy of information on STIs/genital infections, and their diagnosis and management, compared with corresponding National Health Service STI information webpage content. Results 144/6642 apps were eligible. 57 were excluded after downloading. 87 were analysed. Only 29% of apps met ≥6 HON criteria. Content was highly variable: 34/87 (39%) covered one or two infections; 40 (46%) covered multiple STIs; 5 (6%) focused on accessing STI testing. 13 (15%) were fully, 46 (53%) mostly and 28 (32%) partially accurate. 25 (29%) contained ≥1 piece of potentially harmful information. Apps available on both iOS and Android were more accurate than single-platform apps. Only one app provided fully accurate and comprehensive information on chlamydia. Conclusions Marked variation in content, quality and accuracy of available apps combined with the nearly one-third containing potentially harmful information risks undermining potential benefits of an e-Health approach to sexual health and well-being.The Electronic Self-Testing Instruments for Sexually Transmitted Infection (eSTI2) Consortium is funded under the UKCRC Translational Infection Research (TIR) Initiative supported by the Medical Research Council (Grant Number G0901608) with contributions to the Grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, the Chief Scientist Office of the Scottish Government Health Directorates and the Wellcome Trust

    The Economics of Rapid Multiplication of Hybrid Poplar Biomass Varieties

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    Background: Poplar (Populus spp.) hybridization is key to advancing biomass yields and conversion efficiency. Once superior varieties are selected, there is a lag in commercial use while they are multiplied to scale. Objective: The purpose of this study was to assess the influence of gains in biomass yield and quality on investment in rapid propagation techniques that speed the time to commercial deployment. Material and Methods: A factorial experiment of propagation method and hybrid variety was conducted to quantify the scale-up rate of in vitro and greenhouse clonal multiplication. These data were used in modeling the internal rate of return (IRR) on investment into rapid propagation as a function of genetic gains in biomass yield and quality and compared to a base case that assumed the standard method of supplying operational varieties in commercial quantities from nurseries as hardwood cuttings, capable of yields of 16.5 Mg ha−1 year−1. Results: Analysis of variance in macro-cutting yield showed that propagation method and varietal effects as well as their interaction were highly significant, with hedge propagation exceeding serial propagation in macro-cutting productivity by a factor of nearly 1.8. The Populus deltoides × P. maximowiczii and the Populus trichocarpa × P. maximowiczii varieties greatly exceeded the multiplication rate of the P. × generosa varieties due to their exceptional response to repeated hedging required to initiate multiple tracks of serial propagation. Analyses of investment into rapid propagation to introduce new material into plantation establishment followed by a 20-year rotation of six coppice harvests showed that gains in biomass yield and quality are warranted for a commitment to rapid propagation systems. The base case analysis was generally favored at yields up to 18 Mg−1 year−1 dependent on pricing. The rapid multiplication analysis proved superior to the base case analysis at the two highest yield levels (27.0 and 31.5 Mg ha−1 year−1,) at all price levels and at yields of 22.5 Mg−1 year−1, dependent on price and farm location. Conclusion: Rapid multiplication is a reliable method to move improved plant material directly into operations when valued appropriately in the marketplace

    The professional practice and training of neurology in the Asian and Oceanian Region: A cross-sectional survey by the Asian and Oceanian Association of Neurology (AOAN)

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    Objective: To survey AOAN member countries regarding their organizational structure, postgraduate neurology training program, and resources for neurological care provision. Methodology: A cross-sectional survey using a 36-item questionnaire was conducted among country representatives to AOAN from August 2015 to August 2016. Results: A total of 18/20 AOAN member countries participated in the survey. All the countries have organized association with regular meetings, election of officers and neurology training program. In 9/18 countries, professionals other than neurologists were eligible for affiliation. In 11/18 countries, prior Internal medicine training (or equivalent postgraduate housemanship) is prerequisite to neurology program. Recertification examination is not a practice, but submission of CME is required in 7/18 countries to maintain membership. 12/18 countries publish peer-reviewed journals with at least 1 issue per year. Subspecialty training is offered in 14/18 countries. The ratio of neurologist to population ranges from 1:14,000 to as low as 1:32 million with 9/18 having \u3c1 neurologist per 100,000 population. 6/18 countries have at least 1 specialized center solely for neurological diseases. In government-funded hospitals, the lag time to be seen by a neurologist and/or obtain neuroimaging scan ranges from 1day to 3months. All except one country have several medical- and lay- advocacy or support groups for different neurological conditions. Implications: The data generated can be used for benchmarking to improve neurological care, training, collaborative work and research in the field of neurosciences among the AOAN member countries. The paper presented several strategies used by the different organizations to increase their number of neurologists and improve the quality of training. Sharing of best practices, academic networking, exchange programs and use of telemedicine have been suggested
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