461 research outputs found

    Building nonparametric nn-body force fields using Gaussian process regression

    Full text link
    Constructing a classical potential suited to simulate a given atomic system is a remarkably difficult task. This chapter presents a framework under which this problem can be tackled, based on the Bayesian construction of nonparametric force fields of a given order using Gaussian process (GP) priors. The formalism of GP regression is first reviewed, particularly in relation to its application in learning local atomic energies and forces. For accurate regression it is fundamental to incorporate prior knowledge into the GP kernel function. To this end, this chapter details how properties of smoothness, invariance and interaction order of a force field can be encoded into corresponding kernel properties. A range of kernels is then proposed, possessing all the required properties and an adjustable parameter nn governing the interaction order modelled. The order nn best suited to describe a given system can be found automatically within the Bayesian framework by maximisation of the marginal likelihood. The procedure is first tested on a toy model of known interaction and later applied to two real materials described at the DFT level of accuracy. The models automatically selected for the two materials were found to be in agreement with physical intuition. More in general, it was found that lower order (simpler) models should be chosen when the data are not sufficient to resolve more complex interactions. Low nn GPs can be further sped up by orders of magnitude by constructing the corresponding tabulated force field, here named "MFF".Comment: 31 pages, 11 figures, book chapte

    Showing Israel the red card. Activists engaged in pro-Palestinian sport-related campaigns

    Get PDF
    © 2017 Informa UK Limited, trading as Taylor & Francis Group. This article explores the motivations of activists involved in pro-Palestinian sports-based campaigns. The activists’ intention is to bring pressure to bear upon Israel until it complies with international law and supports the rights of Palestinian people under the universal principles of human rights. In response to expressions of pro-Palestinian solidarity, the Israeli state and its supporters are interpreting such activity as a ‘new’ manifestation of ‘old’ antisemitism. In seeking to assess whether such activity is informed by antisemitism, 10 semi-structured interviews were conducted with activists to examine their motives. Their political biographies were explored as were their views on the use of sport as platform to express support for the Palestinian people and/or their displeasure at Israeli participation in international sport. One central theme was the activists’ responses to the suggestion that they were motivated by antisemitism. A qualitative content analysis of the interview transcripts revealed a shared observation that the accusation of antisemitism was a ‘shameless tactic’ employed by those seeking to cover up the ongoing injustices experienced by the Palestinian people. Sport was seen as a legitimate platform for political activity, to raise public awareness and to put pressure on the Israeli state. The findings contribute to a better understanding of activist motivations, the use of sport as a political platform and the challenges facing sport and its governing bodies

    From DNA sequence to application: possibilities and complications

    Get PDF
    The development of sophisticated genetic tools during the past 15 years have facilitated a tremendous increase of fundamental and application-oriented knowledge of lactic acid bacteria (LAB) and their bacteriophages. This knowledge relates both to the assignments of open reading frames (ORF’s) and the function of non-coding DNA sequences. Comparison of the complete nucleotide sequences of several LAB bacteriophages has revealed that their chromosomes have a fixed, modular structure, each module having a set of genes involved in a specific phase of the bacteriophage life cycle. LAB bacteriophage genes and DNA sequences have been used for the construction of temperature-inducible gene expression systems, gene-integration systems, and bacteriophage defence systems. The function of several LAB open reading frames and transcriptional units have been identified and characterized in detail. Many of these could find practical applications, such as induced lysis of LAB to enhance cheese ripening and re-routing of carbon fluxes for the production of a specific amino acid enantiomer. More knowledge has also become available concerning the function and structure of non-coding DNA positioned at or in the vicinity of promoters. In several cases the mRNA produced from this DNA contains a transcriptional terminator-antiterminator pair, in which the antiterminator can be stabilized either by uncharged tRNA or by interaction with a regulatory protein, thus preventing formation of the terminator so that mRNA elongation can proceed. Evidence has accumulated showing that also in LAB carbon catabolite repression in LAB is mediated by specific DNA elements in the vicinity of promoters governing the transcription of catabolic operons. Although some biological barriers have yet to be solved, the vast body of scientific information presently available allows the construction of tailor-made genetically modified LAB. Today, it appears that societal constraints rather than biological hurdles impede the use of genetically modified LAB.

    Inter-observer variability of visual analysis of “stress”-only adenosine first-pass myocardial perfusion imaging in relation to clinical experience and reading criteria

    Get PDF
    To assess the inter-observer agreement of adenosine “stress”-only visual analysis of perfusion MR images in relation to experience and reading criteria. 106 adenosine perfusion MR examinations out of 350, 46 consecutive positive examinations and 60 randomly selected negative examinations were visually analysed by three individual readers (two residents and a technician) with different levels of experience. Readings (blinded for any information) were compared with the reading of an expert radiologist. After a month the examinations were presented again (randomly) without knowledge regarding the first readings. This time readings were performed with the systematical use of reading criteria. Agreement with the expert reading was good for the most experienced resident (k = 0.88). Kappa was 0.48 for the least experienced, and 0.57 for the technician. After the second systematical reading inter-observer agreement increased to 0.9, 0.68 and 0.77 respectively. Overall kappa increased from 0.59 to 0.71. The use of reading criteria significantly improved the performance of the least experienced reader (P = 0.01). Visual analysis of adenosine “stress”-only first-pass perfusion MR images has moderate to very good agreement. Performance is experience related, but the systematic use of reading criteria significantly increased performance for the least experienced observer

    Performance of adenosine “stress-only” perfusion MRI in patients without a history of myocardial infarction: a clinical outcome study

    Get PDF
    To assess the diagnostic value of adenosine “stress-only” myocardial perfusion MR for ischemia detection as an indicator for coronary angiography in patients without a prior myocardial infarction and a necessity to exclude ischemia. Adenosine perfusion MRI was performed at 1.5 T in 139 patients with a suspicion of ischemia and no prior myocardial infarction. After 3 min of adenosine infusion a perfusion sequence was started. Patients with a perfusion defect were referred to coronary angiography (CAG). Patients with a normal perfusion were enrolled in follow-up. Fourteen out of 139 patients (10.1%) had a perfusion defect indicative of ischemia. These patients underwent a coronary angiogram, which showed complete agreement with the perfusion images. 125 patients with a normal myocardial perfusion entered follow-up (median 672 days, range 333–1287 days). In the first year of follow-up one Major Adverse Coronary Event (MACE) occurred and one patient had new onset chest pain with a confirmed coronary stenosis. Reaching a negative predictive value for MACE of 99.2% and for any coronary event of 98.4%. At 2 year follow-up no additional MACE occurred. Sensitivity of adenosine perfusion MR for MACE is 93.3% and specificity and positive predictive value are 100%. Adenosine myocardial perfusion MR for the detection of myocardial ischemia in a “stress-only” protocol in patients without prior myocardial infarctions, has a high diagnostic accuracy. This fast examination can play an important role in the evaluation of patients without prior myocardial infarctions and a necessity to exclude ischemia

    The additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress cardiac MRI for the detection of myocardial ischemia

    Get PDF
    Purpose of this study was to assess the additional value of first pass myocardial perfusion imaging during peak dose of dobutamine stress Cardiac-MR (CMR). Dobutamine Stress CMR was performed in 115 patients with an inconclusive diagnosis of myocardial ischemia on a 1.5 T system (Magnetom Avanto, Siemens Medical Systems). Three short-axis cine and grid series were acquired during rest and at increasing doses of dobutamine (maximum 40 μg/kg/min). On peak dose dobutamine followed immediately by a first pass myocardial perfusion imaging sequence. Images were graded according to the sixteen-segment model, on a four point scale. Ninety-seven patients showed no New (Induced) Wall Motion Abnormalities (NWMA). Perfusion imaging showed absence of perfusion deficits in 67 of these patients (69%). Perfusion deficits attributable to known previous myocardial infarction were found in 30 patients (31%). Eighteen patients had NWMA, indicative for myocardial ischemia, of which 14 (78%) could be confirmed by a corresponding perfusion deficit. Four patients (22%) with NWMA did not have perfusion deficits. In these four patients NWMA were caused by a Left Bundle Branch Block (LBBB). They were free from cardiac events during the follow-up period (median 13.5 months; range 6–20). Addition of first-pass myocardial perfusion imaging during peak-dose dobutamine stress CMR can help to decide whether a NWMA is caused by myocardial ischemia or is due to an (inducible) LBBB, hereby preventing a false positive wall motion interpretation

    Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy

    Get PDF
    Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal \u3b2-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and \u3b2-catenin. A pharmacological activator of the WNT/\u3b2-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and \u3b2-catenin, and evidence for targeted activation of the WNT/\u3b2-catenin pathway as a potential treatment for this disease

    Evaluation of multi-exponential curve fitting analysis of oxygen-quenched phosphorescence decay traces for recovering microvascular oxygen tension histograms

    Get PDF
    Although it is generally accepted that oxygen-quenched phosphorescence decay traces can be analyzed using the exponential series method (ESM), its application until now has been limited to a few (patho)physiological studies, probably because the reliability of the recovered oxygen tension (pO2) histograms has never been extensively evaluated and lacks documentation. The aim of this study was, therefore, to evaluate the use of the ESM to adequately determine pO2 histograms from phosphorescence decay traces. For this purpose we simulated decay traces corresponding to uni- and bimodal pO2 distributions and recovered the pO2 histograms at different signal-to-noise ratios (SNRs). Ultimately, we recovered microvascular pO2 histograms measured in the rat kidney in a model of endotoxemic shock and fluid resuscitation and showed that the mean microvascular oxygen tension, 〈pO2〉, decreased after induction of endotoxemia and that after 2 h of fluid resuscitation, 〈pO2〉 remained low, but the hypoxic peak that had arisen during endotoxemia was reduced. This finding illustrates the importance of recovering pO2 histograms under (patho)physiological conditions. In conclusion, this study has characterized how noise affects the recovery of pO2 histograms using the ESM and documented the reliability of the ESM for recovering both low- and high-pO2 distributions for SNRs typically found in experiments. This study might therefore serve as a frame of reference for investigations focused on oxygen (re)distribution during health and disease and encourage researchers to (re-)analyze data obtained in (earlier) studies possibly revealing new insights into complex disease states and treatment strategies

    Better the devil you know:Threat effects and attachment to the European Union

    Get PDF
    The EU is facing unprecedented challenges and significant threats to its economic and political security. Austerity, the Eurozone crisis, rising immigration and heightened fear of terrorism all present serious challenges to the process of integration. How does this context of insecurity impact on what the EU means to its citizens? Will the public become increasingly Eurosceptic or will they discover a hitherto unrecognised attachment to the EU as the prospect of its collapse becomes real? Psychological research has demonstrated that individual exposure to threat decreases cognitive capacity, inducing a tendency towards rigidity or conservatism - a tendency to cling to the ‘devil you know’. So what might this mean for the European integration process? Using experimental techniques drawn from political psychology, the authors find a dual threat effect. The EU symbol has a negative (anti-EU) effect on EU-related attitudes when presented in neutral context. This is consonant with conceptualisations of the EU as a threat to national cultural and political norms. In contrast, however, visual priming of participants with EU symbols has a positive (pro-EU) effect on related attitudes when these are presented in a context that implies a subtle but imminent threat to the benefits of EU membership
    corecore