1,702 research outputs found

    The Duffin-Schaeffer Conjecture with extra divergence II

    Get PDF
    This paper takes a new step in the direction of proving the Duffin-Schaeffer Conjecture for measures arbitrarily close to Lebesgue. The main result is that under a mild `extra divergence' hypothesis, the conjecture is true.Comment: 7 page

    Exploring the Levinthal limit in protein folding

    Get PDF
    According to the thermodynamic hypothesis, the native state of proteins is uniquely defined by their amino acid sequence. On the other hand, according to Levinthal, the native state is just a local minimum of the free energy and a given amino acid sequence, in the same thermodynamic conditions, can assume many, very different structures that are as thermodynamically stable as the native state. This is the Levinthal limit explored in this work. Using computer simulations, we compare the interactions that stabilize the native state of four different proteins with those that stabilize three non-native states of each protein and find that the nature of the interactions is very similar for all such 16 conformers. Furthermore, an enhancement of the degree of fluctuation of the non-native conformers can be explained by an insufficient relaxation to their local free energy minimum. These results favor Levinthal's hypothesis that protein folding is a kinetic non-equilibrium process.FCT - Foundation for Science and Technology, Portugal [UID/Multi/04326/2013]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Conselho Nacional de Desenvolvimento Cientia co e Tecnologico (CNPq

    Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

    Get PDF
    Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

    Marginalization of end-use technologies in energy innovation for climate protection

    Get PDF
    Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

    Gregarious immunisation in the mealworm beetle, Tenebrio molitor

    Get PDF
    Investment in immunity is costly: one way in which hosts can ameliorate these costs is through immune priming, whereby hosts develop increased protection to future infection following previous exposure to a parasite or immune elicitor. Priming offers hosts a more efficient way of managing immune insult by allowing for a stronger and faster response to an immune insult. As well as investing in physiological immune defences, hosts can also leverage behavioural responses to reduce the costs of infection. Group-living in insects offers several benefits, such as predator avoidance. However, it can be costly in terms of increasing the risks of exposure to parasites. Group facilitation of disease resistance through a variety of processes collectively known as 'social immunity' is well established in the eusocial insects. Many gregarious insects share several features of their ecology with eusocial species, and should thus be predisposed to many of the same risks of infection, and the same evolved processes that mitigate these risks. A form of immune priming known 'social immunisation' has recently been described in eusocial insects, whereby immunologically naïve individuals exhibit enhanced immunity against infection after being housed with infected nestmates. Whether similar mechanisms exist in gregarious but non-social insects is unknown, and it is this premise that forms the conceptual basis of this thesis. I investigated whether a non-social but gregarious insect, the mealworm beetle (Tenebrio molitor), altered its immune investment following cohabitation with an immunestimulated conspecific. I examined the potential role of both physiological and behavioural defences in offering prophylactic protection against perceived pathogenic threat. I also investigated the potential mechanisms of such an form of immunisation by examining immune responses induced by cohabitation with conspecifics challenged by a live (and transmissible) bacterial infection and those challenged by either heat-killed bacteria or an artificial antigen (both non-transmissible). Finally, I examined the role of host behaviour in affecting immunisation, quantifying behavioural changes in immune-stimulated hosts (referred to as 'sickness behaviours') to try and identify visual or behavioural cues which may be utilised by naïve hosts to stimulate prophylactic defences, There was no robust evidence for a parsimonious process of gregarious immunisation. However, there were differences between the sexes in their immune responses to infection threat, as well as in their induction of sickness behaviours following infection. Whilst there was little evidence for an upregulation of immunity in naïve females, females appeared to exhibit enhanced tolerance of infection following cohabitation with a 'sick' conspecific, as they suffered no decrease in longevity despite the presence of relatively high parasite loads. Males showed the opposite pattern to that predicted by gregarious immunisation, decreasing their investment in physiological defence following exposure to 'sick' conspecifics. Despite finding no clear evidence for enhanced resistance through a straightforward process of gregarious immunisation, these data suggest that naïve T. mollitor may be able detect social cues of infection produced by parasitised conspecifics. I propose that the immune responses displayed by both males and females constitute tolerance strategies which help hosts to minimise the costs of parasitism. Due to intrinsic differences in the life-history trajectories of the sexes, females are predicted to invest in immunological tolerance mechanisms aimed at self-preservation in order to preserve their capacity for future reproduction, whereas males are predicted to terminally invest in reproduction in order to maximise their fitness

    Single pulse enhanced coherent diffraction imaging of bacteria with an X-ray free electron laser

    Get PDF
    High-resolution imaging offers one of the most promising approaches for exploring and understanding the structure and function of biomaterials and biological systems. X-ray free-electron lasers (XFELs) combined with coherent diffraction imaging can theoretically provide high-resolution spatial information regarding biological materials using a single XFEL pulse. Currently, the application of this method suffers from the low scattering cross-section of biomaterials and X-ray damage to the sample. However, XFELs can provide pulses of such short duration that the data can be collected using the "diffract and destroy" approach before the effects of radiation damage on the data become significant. These experiments combine the use of enhanced coherent diffraction imaging with single-shot XFEL radiation to investigate the cellular architecture of Staphylococcus aureus with and without labeling by gold (Au) nanoclusters. The resolution of the images reconstructed from these diffraction patterns were twice as high or more for gold-labeled samples, demonstrating that this enhancement method provides a promising approach for the high-resolution imaging of biomaterials and biological systems.1134Ysciescopu

    Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

    Get PDF
    Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

    Search for sterile neutrino mixing in the MINOS long-baseline experiment

    Get PDF
    A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿µ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿µ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles ¿24 and ¿34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1×10-12¿¿s/eV at 90% C.L

    Validation and Use of 22Na Turnover to Measure Food Intake in Free-Ranging Lizards

    Get PDF
    As the food intake of free-ranging animals has proved to be difficult to measure by traditional means, the feasibility of using radioactive Na to measure food consumption in a small scincid lizard (Lampropholis guichenoti) was assessed. This technique has previously been used only for several species of mammal. A significant relationship between food intake and Na turnover was found in the laboratory, with Na turnover underestimating intake by 7.6%. The food intake of free-ranging members of a field population was estimated by 22Na turnover to be 9.55, 0.65, 9.39 and 13.75 mg dry weight (day)-1 during autumn, winter, spring and summer respectively. Estimates of assimilated and expended energy from these food intake values agree closely with data reported for other lizards using alternative techniques. This study also describes the technical innovations which were necessary to study lizards weighing less than 1 g; and it suggests that 22Na can provide an easy, reliable and inexpensive means of studying the energetics of many free-living animals

    A survey of undergraduate orthodontic teaching and factors affecting pursuit of postgraduate training

    Get PDF
    Background: Undergraduate orthodontic teaching has been focused on developing an understanding of occlusal development in an effort to equip practitioners to make appropriate referrals for specialist-delivered care. However, there is a growing interest among general dentists in delivering more specialised treatments, including short-term orthodontic alignment. This study aimed to assess the levels of knowledge of occlusal problems among final year undergraduate dental students, as well as their interest in various orthodontics techniques and training.Methods: A 36-item electronic questionnaire was sent to all final year undergraduate students in four dental institutes in the UK (Barts and the London, Kings College London, Cardiff and Dundee). The questionnaire explored satisfaction with undergraduate orthodontic teaching; students’ perception of knowledge, based on General Dental Council learning outcomes; perceptions of the need for specialist involvement in the management of dental problems; interest in further training in orthodontics; and potential barriers to undertaking specialist training.Results: The overall response rate was 66% (239/362). The majority of students (84.1%) were aware of GDC guidance in terms of undergraduate teaching. Students reported a preference for case-based and practical teaching sessions in orthodontics, with less interest in lectures or problem-based learning approaches. A high percentage were interested in further teaching in interceptive orthodontics (60.3%) and fixed appliance therapy (55.7%). Further training including specialist orthodontic training (36.4%), Invisalign (59%) and Six Month Smiles (41%) courses appealed to undergraduates. Levels of student debt, course fees and geographical issues were seen as potential barriers to formal, specialist training pathways.Conclusions: Satisfaction with undergraduate orthodontic teaching is high and interest in further training, including specialist training pathways, continues to be high. While short-term orthodontics is not taught at undergraduate level, there appears to be an appetite to undertake alternatives to conventional orthodontics among dental students
    corecore