2,534 research outputs found

    Derivatives of meromorphic functions of finite order

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    A result is proved concerning meromorphic functions of finite order in the plane such that all but finitely many zeros of the second derivative are zeros of the first derivative

    Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

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    Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

    Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

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    The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

    GP/GPN partner* perspectives on clinical placements for student nurses in general practice: can a community of practice help to change the prevailing culture within general practice?

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    Background: The UK Government document 5 year forward view describes the need to move chronic disease management from secondary to primary care, which will require a significant increase in the numbers of General Practice Nurses (GPNs). Until recently, there has been no specific recruitment strategy to address this increased need. In recent times, a number of solutions have been suggested to address this impending GPN recruitment crisis. For example, Health Education England (HEE) commission General Practitioners (GPs), who are members of the Advanced Training Practice Scheme (ATPS), to provide placements for student nurses within general practice. Methods: A descriptive qualitative study was undertaken, in which data were collected using semi-structured interviews with 16 GPs and 2 GPN partners∗. Qualitative analysis used a framework approach and themes were cross-checked within the team and member checking was undertaken with a convenience sample of GPs. The research had ethical approval and anonymity and confidentiality were maintained. Results: From the GP perspective, there were two key themes that emerged from the data. The first theme of 'fishing in the same small pond' included succession planning for the general practice workforce, the 'merry go round' of poaching staff from other practices, and the myths and misunderstandings that have grown up around general practice nursing. The second theme, 'growing your own', looked at the impact of the student nurse placements as a means to address the crisis in GPN recruitment. There was recognition of the need for cultural change in the way that GPNs are recruited, and that the ATPS was one way of helping to achieve that change. There were however a number of challenges to sustaining this cultural shift, such as the financial constrains placed upon the GP practice, and the need to function as a 'small business'. Conclusions: Despite all the challenges, the evidence is that, through the Community of Practice (CoP), the ATPS scheme is beginning to 'bear fruit', and there is a subtle but discernible move by GPs from a 'why would we?' to 'why wouldn't we?' invest in education and training for nurses in general practice. N.B. The term GPN partner∗denotes a GPN who is a 'full partner' in the practice business, holding the same NHS contracts and the same status as a GP. For the purposes of the paper itself, the term GP will be used to denote both types of partner

    Smart homes and their users:a systematic analysis and key challenges

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    Published research on smart homes and their users is growing exponentially, yet a clear understanding of who these users are and how they might use smart home technologies is missing from a field being overwhelmingly pushed by technology developers. Through a systematic analysis of peer-reviewed literature on smart homes and their users, this paper takes stock of the dominant research themes and the linkages and disconnects between them. Key findings within each of nine themes are analysed, grouped into three: (1) views of the smart home-functional, instrumental, socio-technical; (2) users and the use of the smart home-prospective users, interactions and decisions, using technologies in the home; and (3) challenges for realising the smart home-hardware and software, design, domestication. These themes are integrated into an organising framework for future research that identifies the presence or absence of cross-cutting relationships between different understandings of smart homes and their users. The usefulness of the organising framework is illustrated in relation to two major concerns-privacy and control-that have been narrowly interpreted to date, precluding deeper insights and potential solutions. Future research on smart homes and their users can benefit by exploring and developing cross-cutting relationships between the research themes identified
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