Cosmic ray short burst observed with the Global Muon Detector Network (GMDN) on June 22, 2015

We analyze the short cosmic ray intensity increase ("cosmic ray burst": CRB) on June 22, 2015 utilizing a global network of muon detectors and derive the global anisotropy of cosmic ray intensity and the density (i.e. the omnidirectional intensity) with 10-minute time resolution. We find that the CRB was caused by a local density maximum and an enhanced anisotropy of cosmic rays both of which appeared in association with Earth's crossing of the heliospheric current sheet (HCS). This enhanced anisotropy was normal to the HCS and consistent with a diamagnetic drift arising from the spatial gradient of cosmic ray density, which indicates that cosmic rays were drifting along the HCS from the north of Earth. We also find a significant anisotropy along the HCS, lasting a few hours after the HCS crossing, indicating that cosmic rays penetrated into the inner heliosphere along the HCS. Based on the latest geomagnetic field model, we quantitatively evaluate the reduction of the geomagnetic cut-off rigidity and the variation of the asymptotic viewing direction of cosmic rays due to a major geomagnetic storm which occurred during the CRB and conclude that the CRB is not caused by the geomagnetic storm, but by a rapid change in the cosmic ray anisotropy and density outside the magnetosphere.Comment: accepted for the publication in the Astrophysical Journa

Verdier specialization via weak factorization

Let X in V be a closed embedding, with V - X nonsingular. We define a constructible function on X, agreeing with Verdier's specialization of the constant function 1 when X is the zero-locus of a function on V. Our definition is given in terms of an embedded resolution of X; the independence on the choice of resolution is obtained as a consequence of the weak factorization theorem of Abramovich et al. The main property of the specialization function is a compatibility with the specialization of the Chern class of the complement V-X. With the definition adopted here, this is an easy consequence of standard intersection theory. It recovers Verdier's result when X is the zero-locus of a function on V. Our definition has a straightforward counterpart in a motivic group. The specialization function and the corresponding Chern class and motivic aspect all have natural `monodromy' decompositions, for for any X in V as above. The definition also yields an expression for Kai Behrend's constructible function when applied to (the singularity subscheme of) the zero-locus of a function on V.Comment: Minor revision. To appear in Arkiv f\"or Matemati

Singularities and Topology of Meromorphic Functions

We present several aspects of the "topology of meromorphic functions", which we conceive as a general theory which includes the topology of holomorphic functions, the topology of pencils on quasi-projective spaces and the topology of polynomial functions.Comment: 21 pages, 1 figur

Target identification of Mycobacterium tuberculosis phenotypic\textit{Mycobacterium tuberculosis phenotypic} hits using a concerted chemogenomic, biophysical and structural approach

Mycobacterium phenotypic hits are a good reservoir for new chemotypes for the treatment of tuberculosis. However, the absence of defined molecular targets and modes of action could lead to failure in drug development. Therefore, a combination of ligand-based and structure-based chemogenomic approaches followed by biophysical and biochemical validation have been used to identify targets for Mycobacterium tuberculosis phenotypic hits. Our approach identified EthR and InhA as targets for several hits, with some showing dual activity against these proteins. From the 35 predicted EthR inhibitors, eight exhibited an IC50 below 50 μM against M. tuberculosis EthR and three were confirmed to be also simultaneously active against InhA. Further hit validation was performed using X-ray crystallography yielding eight new crystal structures of EthR inhibitors. Although the EthR inhibitors attain their activity against M. tuberculosis by hitting yet undefined targets, these results provide new lead compounds that could be further developed to be used to potentiate the effect of EthA activated pro-drugs, such as ethionamide, thus enhancing their bactericidal effect.GM is grateful to the European Molecular Biology Laboratory and Marie Sklodowska-Curie Actions for funding this work. VM and MB acknowledge Bill & Melinda Gates Foundation [subcontract by the Foundation for the National Institutes of Health (NIH)] (OPP1024021). VM and MS acknowledge the European Community’s Seventh Framework Programme [grant number 260872]. GP would like to acknowledge the Wellcome Trust and the European Molecular Biology Laboratory for funding. JPO was funded by the member nation states of the European Molecular Biology Laboratory. TLB acknowledges The Wellcome Trust for funding and support (grant number 200814/Z/16/Z)

Adjustment Methods for Planimetric Observations and Co-Ordinates in Survey Networks

Correction and adjustment of observed angles and sides in geodetic networks are necessary for the purpose of the correct location of coordinated points. Correction equations are usually in the form of linear overdetermined (observation) or underdetermined (condition) equations which are solved by the least squares theorem. The introduction of the electro-magnetic methods of linear measurement requires the adjustment of sides as well as the adjustment of angles necessary in classical triangulation nets. For the simultaneous adjustment of angles and sides two new sets of conditions have been introduced: (i) the area misfit condition, where the area obtained from distances and angles has to satisfy a special condition, and (ii) that the sum of the projections of the three sides of a triangle on the coordinate axes have to satisfy a zero condition. A special study has been made into the adjustment of the braced geodetic quadrilateral, as being one of the most favourable figures from the adjustment point of view. The different apices of this quadrilateral have been investigated to allow a choice to be made as to which of them shall be introduced in an angle misfit condition during adjustment. This gives rise to the conclusion that all apices will introduce the same corrections for all practical purposes. Since observed angles and sides are different physical quantities, the question of relative weighting has been given special attention and recommendations have been made in the light of various theoretical and practical investigations. The Systematic relaxation method for adjusting survey nets has been theoretically derived by Professors Southwell and Black based on the minimum strain-energy conserved in an elastic frame-work at the position of equilibrium. Using this theory mechanical analogues have been designed and constructed for the first time to carry out the adjustment of the triangulation net directly from field observations, without the necessity of forming and solving a set of linear equations. An analogue for the adjustment of angles was found to be excessively complicated mechanically and difficult to use in practice. Through the use of a direction adjustment method these limitations have been overcome. The final model constructed achieved comparable results to those obtained numerically by a least squares solution. Suggestions for a more highly developed version are made and the situations favourable to mechanical analogue computations are discussed. The use of an electrical analogue as suggested by Su using a D.C. circuit has been thoroughly investigated from both the theoretical and practical points of view, which showed that such a solution will be simple only for certain limited cases. As an alternative the possibilities of the more general purpose electronic analogue computer have been investigated via the solution of correction equations. Various examples have been solved on this computer which proved to have several advantages over other computation methods. Finally equivalent problems have been solved numerically on a digital computer for a comparison of the relative merits of analogue and digital methods for the particular case of adjustment of geodetic networks. The relative merits of these solutions are discussed in the light of different problems and circumstances

Systematic Review of Intervention Studies Aiming at Reducing Inequality in Dental Caries among Children.

(1) Background: The objective is to systematically review the evidence on intervention programs aiming at reducing inequality in dental caries among children. (2) Methods: Two independent investigators searched MEDLINE, Cochrane library, and Ovid up to December 2020 to identify intervention studies assessing the impact on socioeconomic inequalities in dental caries among children. The interventions included any health promotion/preventive intervention aiming at reducing caries among children across different socioeconomic groups. Comparison groups included children with alternative or no intervention. Cochrane criteria were used to assess interventional studies for risk of bias. (3) Results: After removal of duplicate studies, 1235 articles were retained. Out of 43 relevant papers, 13 articles were identified and used in qualitative synthesis, and reported quantifiable outcomes. The included studies varied in measurements of interventions, sample size, age groups, and follow-up time. Five studies assessed oral health promotion or health-education, four assessed topical fluorides, and four assessed water fluoridation. Interventions targeting the whole population showed a consistent reduction of socioeconomic inequalities in dental caries among children. (4) Conclusion: The quality of included papers was moderate. High heterogeneity did not allow aggregation of the findings. The overall findings suggest that whole population interventions such as water fluoridation are more likely to reduce inequalities in children's caries than target population and individual interventions

Allostatic load and depressive symptoms in older adults: An analysis of 12-year panel data

BACKGROUND: Whether changes in allostatic load (AL) and depressive symptoms relate over time has not been yet fully explored. This study evaluated the association between AL and depressive symptoms over 12 years among community-dwelling older adults. METHODS: Panel data from 8291 participants in the English Longitudinal Study of Ageing were analysed. Depressive symptoms were assessed with the 8-item Centre for Epidemiologic Studies Depression Scale (CES-D). The AL score was derived from nine metabolic, cardiovascular and immune biomarkers. The association between AL and depressive symptoms was modelled in a linear hybrid model adjusting for time-invariant (sex, ethnicity) and time-variant confounders (age, marital status, education, wealth, physical activity, smoking status, alcohol intake, limitations in daily living, comorbidities). RESULTS: The mean AL score was 3.1 (SD: 2.1), 3.5 (2.3), 3.2 (2.3) and 3.3 (2.5) whereas the mean CES-D score was 1.4 (SD: 1.8), 1.2 (1.8), 1.2 (1.8) and 1.2 (1.7) in waves 2, 4, 6 and 8, respectively. In the adjusted model, the between-person differences (coefficient: 0.02, 95% CI: 0.01, 0.04) but not the within-individual differences (0.01; 95% CI: −0.01, 0.03) in the AL score were associated with CES-D score. The between-person coefficient indicates that participants with greater AL scores also had slightly higher CES-D scores. The within-person coefficient indicates that changes in the AL score were not associated with changes in the CES-D score. CONCLUSION: AL was associated with depressive symptoms. However, most of the association was driven by differences in AL between individuals rather than changes in AL over time

Multiple-length-scale elastic instability mimics parametric resonance of nonlinear oscillators

Spatially confined rigid membranes reorganize their morphology in response to the imposed constraints. A crumpled elastic sheet presents a complex pattern of random folds focusing the deformation energy while compressing a membrane resting on a soft foundation creates a regular pattern of sinusoidal wrinkles with a broad distribution of energy. Here, we study the energy distribution for highly confined membranes and show the emergence of a new morphological instability triggered by a period-doubling bifurcation. A periodic self-organized focalization of the deformation energy is observed provided an up-down symmetry breaking, induced by the intrinsic nonlinearity of the elasticity equations, occurs. The physical model, exhibiting an analogy with parametric resonance in nonlinear oscillator, is a new theoretical toolkit to understand the morphology of various confined systems, such as coated materials or living tissues, e.g., wrinkled skin, internal structure of lungs, internal elastica of an artery, brain convolutions or formation of fingerprints. Moreover, it opens the way to new kind of microfabrication design of multiperiodic or chaotic (aperiodic) surface topography via self-organization.Comment: Submitted for publicatio

Systematic review and meta-analysis of randomised controlled trials on the effectiveness of school-based dental screening versus no screening on improving oral health in children

OBJECTIVES: The current study aimed to evaluate the effectiveness of school-based dental screening versus no screening on improving oral health in children aged 3-18 years by a systematic review and meta-analysis of randomised controlled trials. SOURCES AND STUDY SELECTION: Three sets of independent reviewers searched MEDLINE, EMBASE, Web of Science and other sources through April 2016 to identify published and nonpublished studies without language restrictions and extracted data. DATA: Primary outcomes included prevalence and mean number of teeth with caries, incidence of dental attendance and harms of screening. Cochrane's criteria for risk of bias assessment were used. RESULTS: A total of five cluster RCTs (of unclear or high risk of bias), including 28,442 children, were meta-analysed. For an intracluster correlation coefficient of 0.030, there was no statistically significant difference in dental attendance between children who received dental screening and those who did not receive dental screening (RR 1.11, 95% 0.97, 1.27). The Chi-square test for heterogeneity and the Higgin's I(2) value indicated a substantial heterogeneity. Only one study reported the prevalence and mean number of deciduous and permanent teeth with dental caries and found no significant differences between the screening and no screening groups. CONCLUSIONS: There is currently no evidence to support or refute the clinical benefits or harms of dental screening. Routine dental screening may not increase the dental attendance of school children, but there is a lot of uncertainty in this finding because of the quality of evidence. CLINICAL SIGNIFICANCE: Evidence from the reviewed trials suggests no clinical benefit from school-based screening in improving children's oral health. However, there is a lot of uncertainty in this finding because of the quality of evidence. There is a need to conduct a well-designed trial with an intensive follow-up arm and cost-effectiveness analysis

Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy

Inflammation in myocarditis induces cardiac injury and triggers disease progression to heart failure. NLRP3 inflammasome activation is a newly identified amplifying step in the pathogenesis of myocarditis. We previously have demonstrated that mesenchymal stromal cells (MSC) are cardioprotective in Coxsackievirus B3 (CVB3)-induced myocarditis. In this study, MSC markedly inhibited left ventricular (LV) NOD2, NLRP3, ASC, caspase-1, IL-1β, and IL-18 mRNA expression in CVB3-infected mice. ASC protein expression, essential for NLRP3 inflammasome assembly, increased upon CVB3 infection and was abrogated in MSC-treated mice. Concomitantly, CVB3 infection in vitro induced NOD2 expression, NLRP3 inflammasome activation and IL-1β secretion in HL-1 cells, which was abolished after MSC supplementation. The inhibitory effect of MSC on NLRP3 inflammasome activity in HL-1 cells was partly mediated via secretion of the anti-oxidative protein stanniocalcin-1. Furthermore, MSC application in CVB3-infected mice reduced the percentage of NOD2-, ASC-, p10- and/or IL-1β- positive splenic macrophages, natural killer cells, and dendritic cells. The suppressive effect of MSC on inflammasome activation was associated with normalized expression of prominent regulators of myocardial contractility and fibrosis to levels comparable to control mice. In conclusion, MSC treatment in myocarditis could be a promising strategy limiting the adverse consequences of cardiac and systemic NLRP3 inflammasome activation