Rapid Cycling and Exceptional Yield in a Metal-Organic Framework Water Harvester.

Sorbent-assisted water harvesting from air represents an attractive way to address water scarcity in arid climates. Hitherto, sorbents developed for this technology have exclusively been designed to perform one water harvesting cycle (WHC) per day, but the productivities attained with this approach cannot reasonably meet the rising demand for drinking water. This work shows that a microporous aluminum-based metal-organic framework, MOF-303, can perform an adsorption-desorption cycle within minutes under a mild temperature swing, which opens the way for high-productivity water harvesting through rapid, continuous WHCs. Additionally, the favorable dynamic water sorption properties of MOF-303 allow it to outperform other commercial sorbents displaying excellent steady-state characteristics under similar experimental conditions. Finally, these findings are implemented in a new water harvester capable of generating 1.3 L kgMOF -1 day-1 in an indoor arid environment (32% relative humidity, 27 °C) and 0.7 L kgMOF -1 day-1 in the Mojave Desert (in conditions as extreme as 10% RH, 27 °C), representing an improvement by 1 order of magnitude over previously reported devices. This study demonstrates that creating sorbents capable of rapid water sorption dynamics, rather than merely focusing on high water capacities, is crucial to reach water production on a scale matching human consumption

Constitutive regulation of mitochondrial morphology by Aurora A kinase depends on a predicted cryptic targeting sequence at the N-terminus.

Aurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here, we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE-1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, because an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.MRC CRU

TQM implementation: An empirical examination and proposed generic model

Total quality management (TQM) is considered by many as an important quality and business performance improvement tool. The popularity of the concept has led to an explosion of TQM related literature. A careful review of the literature suggests that most publications recount the experiences or perceptions of the authors or deal with single case organisations. Furthermore, there is a dearth of empirical research and literature dealing with TQM's implementation process. This paper reports the findings of a research project that empirically examined the process of TQM implementation in a sample of organisations widely regarded as leading exponents of TQM. The paper presents a non-prescriptive model of the TQM implementation process derived from the findings and proposes an "outcome driven" approach as an alternative to the more commonplace TQM implementation strategies

Nbs1 Flexibly Tethers Ctp1 and Mre11-Rad50 to Coordinate DNA Double-Strand Break Processing and Repair

SummaryThe Nijmegen breakage syndrome 1 (Nbs1) subunit of the Mre11-Rad50-Nbs1 (MRN) complex protects genome integrity by coordinating double-strand break (DSB) repair and checkpoint signaling through undefined interactions with ATM, MDC1, and Sae2/Ctp1/CtIP. Here, fission yeast and human Nbs1 structures defined by X-ray crystallography and small angle X-ray scattering (SAXS) reveal Nbs1 cardinal features: fused, extended, FHA-BRCT1-BRCT2 domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. Genetic, biochemical, and structural analyses of an Nbs1-Ctp1 complex show Nbs1 recruits phosphorylated Ctp1 to DSBs via binding of the Nbs1 FHA domain to a Ctp1 pThr-Asp motif. Nbs1 structures further identify an extensive FHA-BRCT interface, a bipartite MDC1-binding scaffold, an extended conformational switch, and the molecular consequences associated with cancer predisposing Nijmegen breakage syndrome mutations. Tethering of Ctp1 to a flexible Nbs1 arm suggests a mechanism for restricting DNA end processing and homologous recombination activities of Sae2/Ctp1/CtIP to the immediate vicinity of DSBs

The impact generated by public and charity-funded research in the UK: A systematic literature review

Objective: To identify, synthesize and critically assess the empirical evidence of the impact generated by public and charity funded health research in the United Kingdom. Methods: We conducted a systematic literature review of the empirical evidence published in English in peer-reviewed journals between 2006 and 2017. Studies meeting the inclusion criteria were selected and their findings were analysed using the Payback Framework into five main categories: knowledge, benefits to future research and research use, benefits from informing policy and product development, health and health sector benefits and broader economic benefits. We assessed the studies for risk of selection, reporting and funding bias. Results: Thirteen studies met the inclusion criteria. The majority of the studies (10 out of 13) assessed impact at multiple domains including the main 5 key themes of the Payback Framework. All of them showed a positive impact of funded research on outcomes. Of those studies, one presented low risk of bias (8%), 6 studies were classified as presenting moderate risk of bias (46%) and 6 studies presented high risk of bias (46%). Conclusions: Empirical evidence on the impact of public and charity funded research is still limited and subject to funding and selection bias. More work is needed to establish the causal effects of funded research on academic outcomes, policy, practice and the broader economy

A scoping review to understand the effectiveness of linking schemes from healthcare providers to community resources to improve the health and well-being of people with long-term conditions

The prevalence of people living with long-term conditions is increasing, accompanied by an increased expectation that patients will become more involved in self-management. Long-term conditions are associated with increased social isolation and poor physical and mental health. But there remains a gap in health provision between providing medical treatment and effectively addressing psychosocial well-being. One potential way of addressing this gap is by utilising social interventions which link patients from health services to community-based sources of support. However, the mechanisms involved in the delivery of interventions providing that link and their effectiveness remain unclear. This review adopted the methodological framework for conducting scoping studies, searching for both academic and grey literature on social interventions which link people from healthcare settings to a range of community and voluntary sector organisations. A literature search between May and June 2013, involving five electronic databases, hand searching of two journals and the use of Google search engine, identified seven studies relevant to the review question. In terms of key characteristics and mechanisms of the interventions, mental health conditions and social isolation were the most common reasons for referral to the interventions, and referrals were usually made through general practices. Almost all the interventions were facilitator-led, whereby the facilitator worked to identify and link participants to appropriate community-based resources. In regard to health and social outcomes and their cost-effectiveness, studies reported improvement to participants’ psychological and social well-being as well as their decreased use of health services, although there were limited measures of participants’ physical health outcomes. Interventions for linking patients from healthcare setting to community-based resources target and address psychosocial needs of participants. The review identified involvement of health professionals in aiding the referral of patients to the intervention and the role of the intervention facilitators as key components of the interventions

The Poggendorff illusion affects manual pointing as well as perceptual judgements

Pointing movements made to a target defined by the imaginary intersection of a pointer with a distant landing line were examined in healthy human observers in order to determine whether such motor responses are susceptible to the Poggendorff effect. In this well-known geometric illusion observers make systematic extrapolation errors when the pointer abuts a second line (the inducer). The kinematics of extrapolation movements, in which no explicit target was present, where similar to those made in response to a rapid-onset (explicit) dot target. The results unambiguously demonstrate that motor (pointing) responses are susceptible to the illusion. In fact, raw motor biases were greater than for perceptual responses: in the absence of an inducer (and hence also the acute angle of the Poggendorff stimulus) perceptual responses were near-veridical, whilst motor responses retained a bias. Therefore, the full Poggendorff stimulus contained two biases: one mediated by the acute angle formed between the oblique pointer and the inducing line (the classic Poggendorff effect), which affected both motor and perceptual responses equally, and another bias, which was independent of the inducer and primarily affected motor responses. We conjecture that this additional motor bias is associated with an undershoot in the unknown direction of movement and provide evidence to justify this claim. In conclusion, both manual pointing and perceptual judgements are susceptible to the well-known Poggendorff effect, supporting the notion of a unitary representation of space for action and perception or else an early locus for the effect, prior to the divergence of processing streams

Estimating the returns to UK publicly funded cancer-related research in terms of the net value of improved health outcomes

© 2014 Glover et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background - Building on an approach developed to assess the economic returns to cardiovascular research, we estimated the economic returns from UK public and charitable funded cancer-related research that arise from the net value of the improved health outcomes. Methods - To assess these economic returns from cancer-related research in the UK we estimated: 1) public and charitable expenditure on cancer-related research in the UK from 1970 to 2009; 2) net monetary benefit (NMB), that is, the health benefit measured in quality adjusted life years (QALYs) valued in monetary terms (using a base-case value of a QALY of GB£25,000) minus the cost of delivering that benefit, for a prioritised list of interventions from 1991 to 2010; 3) the proportion of NMB attributable to UK research; 4) the elapsed time between research funding and health gain; and 5) the internal rate of return (IRR) from cancer-related research investments on health benefits. We analysed the uncertainties in the IRR estimate using sensitivity analyses to illustrate the effect of some key parameters. Results - In 2011/12 prices, total expenditure on cancer-related research from 1970 to 2009 was £15 billion. The NMB of the 5.9 million QALYs gained from the prioritised interventions from 1991 to 2010 was £124 billion. Calculation of the IRR incorporated an estimated elapsed time of 15 years. We related 17% of the annual NMB estimated to be attributable to UK research (for each of the 20 years 1991 to 2010) to 20 years of research investment 15 years earlier (that is, for 1976 to 1995). This produced a best-estimate IRR of 10%, compared with 9% previously estimated for cardiovascular disease research. The sensitivity analysis demonstrated the importance of smoking reduction as a major source of improved cancer-related health outcomes. Conclusions - We have demonstrated a substantive IRR from net health gain to public and charitable funding of cancer-related research in the UK, and further validated the approach that we originally used in assessing the returns from cardiovascular research. In doing so, we have highlighted a number of weaknesses and key assumptions that need strengthening in further investigations. Nevertheless, these cautious estimates demonstrate that the returns from past cancer research have been substantial, and justify the investments made during the period 1976 to 1995.Wellcome Trust, Cancer Research UK, the National Institute of Health Research, and the Academy of Medical Sciences