Genetic separation of Sae2 nuclease activity from Mre11 nuclease functions in budding yeast

Sae2 promotes the repair of DNA double-strand breaks in Saccharomyces cerevisiae. The role of Sae2 is linked to the Mre11/Rad50/Xrs2 (MRX) complex, which is important for the processing of DNA ends into single-stranded substrates for homologous recombination. Sae2 has intrinsic endonuclease activity, but the role of this activity has not been assessed independently from its functions in promoting Mre11 nuclease activity. Here we identify and characterize separation-of-function mutants that lack intrinsic nuclease activity or the ability to promote Mre11 endonucleolytic activity. We find that the ability of Sae2 to promote MRX nuclease functions is important for DNA damage survival, particularly in the absence of Dna2 nuclease activity. In contrast, Sae2 nuclease activity is essential for DNA repair when Mre11 nuclease is compromised. Resection of DNA breaks is impaired when either Sae2 activity is blocked, suggesting roles for both Mre11 and Sae2 nuclease activities in promoting the processing of DNA ends in vivo. Finally, both activities of Sae2 are important for sporulation, indicating that the processing of meiotic breaks requires both Mre11 and Sae2 nuclease activities

Lessons from the evaluation of the UK's NHS R&D Implementation Methods Programme

Background: Concern about the effective use of research was a major factor behind the creation of the NHS R&D Programme in 1991. In 1994, an advisory group was established to identify research priorities in research implementation. The Implementation Methods Programme (IMP) flowed from this, and its commissioning group funded 36 projects. In 2000 responsibility for the programme passed to the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D, which asked the Health Economics Research Group (HERG), Brunel University, to conduct an evaluation in 2002. By then most projects had been completed. This evaluation was intended to cover: the quality of outputs, lessons to be learnt about the communication strategy and the commissioning process, and the benefits from the projects. Methods: We adopted a wide range of quantitative and qualitative methods. They included: documentary analysis, interviews with key actors, questionnaires to the funded lead researchers, questionnaires to potential users, and desk analysis. Results: Quantitative assessment of outputs and dissemination revealed that the IMP funded useful research projects, some of which had considerable impact against the various categories in the HERG payback model, such as publications, further research, research training, impact on health policy, and clinical practice. Qualitative findings from interviews with advisory and commissioning group members indicated that when the IMP was established, implementation research was a relatively unexplored field. This was reflected in the understanding brought to their roles by members of the advisory and commissioning groups, in the way priorities for research were chosen and developed, and in how the research projects were commissioned. The ideological and methodological debates associated with these decisions have continued among those working in this field. The need for an effective communication strategy for the programme as a whole was particularly important. However, such a strategy was never developed, making it difficult to establish the general influence of the IMP as a programme. Conclusion: Our findings about the impact of the work funded, and the difficulties faced by those developing the IMP, have implications for the development of strategic programmes of research in general, as well as for the development of more effective research in this field

Temperature-Dependent Battery Models for High-Power Lithium-Ion Batteries

In this study, two battery models for a high-power lithium ion (Li-Ion) cell were compared for their use in hybrid electric vehicle simulations in support of the U.S. Department of Energy's Hybrid Electric Vehicle Program. Saft America developed the high-power Li-Ion cells as part of the U.S. Advanced Battery Consortium/U.S. Partnership for a New Generation of Vehicles programs. Based on test data, the National Renewable Energy Laboratory (NREL) developed a resistive equivalent circuit battery model for comparison with a 2-capacitance battery model from Saft. The Advanced Vehicle Simulator (ADVISOR) was used to compare the predictions of the two models over two different power cycles. The two models were also compared to and validated with experimental data for a US06 driving cycle. The experimental voltages on the US06 power cycle fell between the NREL resistive model and Saft capacitance model predictions. Generally, the predictions of the two models were reasonably close to th e experimental results; the capacitance model showed slightly better performance. Both battery models of high-power Li-Ion cells could be used in ADVISOR with confidence as accurate battery behavior is maintained during vehicle simulations

Back to School Netball Style: An Emerging Highly Inclusive Game for Physical Education or Sport

This article describes netball, a fresh invasion game option to involve students of all ability levels. It is an inclusive and engaging team sport played globally that has the ability to keep students active and engaged in physical education

Digital Watchdogs? Data reporting and the traditional 'fourth estate' role for journalists

As governments throughout the world transition to storing and releasing vast amounts of numerical information digitally, journalists are increasingly using digital data reporting as an investigative tool to report on issues in the public interest and to hold government - elected officials and bureaucracy – to account. Through a series of qualitative interviews with data journalists in 17 countries, this article examines the impact that digital data reporting is having on the traditional role of journalism as a fourth estate. Findings suggest the emergence of digital data reporting as a key tool in accountability journalism and in informing and engaging the public. However, the failure of popular ‘tabloid’ journalism to engage with data journalism means that a new technologically adept and data-informed elite class is on the rise, with important implications for democratic processes in advanced societies

A decade of clinical negligence in ophthalmology

Abstract Background To present an overview of the clinical negligence claims for ophthalmology in the National Health Service (NHS) in England from 1995 to 2006. To compare ophthalmic subspecialties with respect to claim numbers and payments. Methods All the claims on the NHS Litigation Authority database for ophthalmology for the period 1995 to 2006 were analysed. Claims were categorised by ophthalmic subspecialty, and subspecialties were ranked according to numbers of claims, total damages paid, average level of damages and paid:closed ratio (a measure of the likelihood of a claim resulting in payment of damages). Results There were 848 claims, 651 of which were closed. 46% of closed claims resulted in payment of damages. The total cost of damages over the period was £11 million. The mean level of damages was £37,100. Cataract made up the largest share of claims (31%), paediatric ophthalmology had the highest mean damages (£170,000), and claims related to glaucoma were most likely to result in payment of damages (64%). Conclusion Clinical negligence claims in ophthalmology in England are infrequent, but most ophthalmologists will face at least one in their career. Ophthalmic subspecialties show marked differences with regard to their litigation profiles. From a medical protection perspective, these results suggest that indemnity premiums should be tailored according to the subspecialty areas an ophthalmologist is involved in.</p

Challenges of comprehensive taxon sampling in comparative biology: Wrestling with rosids

Using phylogenetic approaches to test hypotheses on a large scale, in terms of both species sampling and associated species traits and occurrence data—and doing this with rigor despite all the attendant challenges—is critical for addressing many broad questions in evolution and ecology. However, application of such approaches to empirical systems is hampered by a lingering series of theoretical and practical bottlenecks. The community is still wrestling with the challenges of how to develop species‐level, comprehensively sampled phylogenies and associated geographic and phenotypic resources that enable global‐scale analyses. We illustrate difficulties and opportunities using the rosids as a case study, arguing that assembly of biodiversity data that is scale‐appropriate—and therefore comprehensive and global in scope—is required to test global‐scale hypotheses. Synthesizing comprehensive biodiversity data sets in clades such as the rosids will be key to understanding the origin and present‐day evolutionary and ecological dynamics of the angiosperms.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143800/1/ajb21059.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143800/2/ajb21059_am.pd

Two randomized crossover multicenter studies investigating gastrointestinal symptoms after bread consumption in individuals with noncoeliac wheat sensitivity: do wheat species and fermentation type matter?

Background: Many individuals reduce their bread intake due to the belief that wheat is the cause of their gastrointestinal (GI) symptoms. Different grains and processing methods may impact tolerability. Objective: We investigated the effects of six different types of bread on GI symptoms in individuals with self-reported non-coeliac wheat sensitivity (NCWS). Methods: Two parallel randomised double-blind crossover multicentre studies were conducted. NCWS individuals, in whom coeliac disease and wheat allergy were ruled out, received five slices of (study A, n=20) yeast fermented (YF) or (study B, n=20) sourdough fermented (SF) bread made of bread wheat, spelt or emmer on three separate intervention days. Each test day was preceded by a run-in period of 3 days and separated by a wash-out period of at least 7 days. GI symptoms were evaluated by change in symptom score (test day minus average of the 3-day run-in period) on a 0-100mm visual analogue scale (delta VAS). Responders were defined as an increase in delta VAS of at least 15mm for overall GI symptoms, abdominal discomfort, abdominal pain, bloating and/or flatulence. Results: The overall change in GI symptoms did not differ between breads of different grains (YF p=0.267; SF p=0.144). The number of responders was also comparable for both YF (6 to wheat, 5 to spelt, and 7 to emmer, p=0.761) and SF breads (9 to wheat, 7 to spelt, and 8 to emmer, p=0.761). Conclusion: The majority of NCWS individuals experienced GI symptoms for at least one of the breads, but on a group level, no differences were found between different grain types for either YF or SF breads. Clinical Trial Registry: ClinicalTrials.gov, NCT0408447