Nonclassical paths in the recurrence spectrum of diamagnetic atoms

Using time-independent scattering matrices, we study how the effects of nonclassical paths on the recurrence spectra of diamagnetic atoms can be extracted from purely quantal calculations. This study reveals an intimate relationship between two types of nonclassical paths: exotic ghost orbits and diffractive orbits. This relationship proves to be a previously unrecognized reason for the success of semiclassical theories, like closed-orbit theory, and permits a comprehensive reformulation of the semiclassical theory that elucidates its convergence properties.Comment: 5 pages, 4 figure

Relative pavement performance for dual and wide-based tyre assemblies using a finite element method

There is a need to assess the realistic tire contact pressure created by a tire in contact with a pavement. The contact pressure is a function of tire type, axle loading, and tire inflation pressure (TiP). The research carried out considered dual tire and wide-based tire assemblies across a range of axle loading and TiP. These contact pressures were incorporated into a finite element package (CAPA-3D) and modelled on a simple pavement structure. The strains from this modelling were sorted to produce key strains associated with the mechanisms of surface distress, near surface distress, deep asphalt distress, and the subgrade. The main distress mechanisms were top down cracking, asphalt cracking/rutting, bottom-up fatigue cracking, and subgrade rutting. This gave a method to fairly compare the dual and wide-based tire assemblies with the same axle loading and TiP. The analysis gave interesting results for the different distress mechanisms of the pavement. The wide-based tire gives consistently higher shear strains for all the areas of distress investigated. There is great variation in surface and near surface shear strains due to the different combinations of axle loading and TiP. It is clear that the wide-based tire is a more damaging tire for all combinations of TiP and axle loading. It is also apparent that how these factors interact has a great influence on the damaging potential of a tire

The estrogen-induced miR-19 downregulates secretory leucoprotease inhibitor expression in monocytes

Compared to females, males are more susceptible to acute viral and other respiratory tract infections that display greater severity and higher mortality. In contrast, females tend to fare worse with chronic inflammatory diseases. Circulating 17β-estradiol (E2) is a female-specific factor that may influence the progression of human lung diseases. Here we hypothesize that E2 modulates the inflammatory response of monocytes through microRNA (miRNA)-based modulation of secretory leucoprotease inhibitor (SLPI), an antiprotease with immunomodulatory effects. Monocytic cells were treated ± E2, and differentially expressed miRNAs were identified using PCR profiling. Cells were transfected with miRNA mimics or antimiRs and SLPI mRNA and protein levels were quantified. Luciferase activity assay using wildtype and ΔmiR-19a/b-SLPI3'UTR reporter constructs and chromatin immunoprecipitation on E2-treated monocytes were performed. E2 downregulated SLPI and upregulated miR-19 expression in monocytes. Transfection with premiR-19b reduced SLPI mRNA and protein levels and this effect was abrogated using antimiRs against miR-19b. miR-19b directly binds the SLPI 3'UTR. The mechanism responsible for E2-mediated upregulation of miR-19 occurs via increased MIR17HG promoter activity mediated by c-MYC. Overall E2 decreases SLPI expression in human monocytic cells, via changes in miRNA expression and highlights the potential for estrogen to modulate the innate immune system

Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model

NOTICE: this is the author’s version of a work that was accepted for publication in Neurobiology of Disease. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication.Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder caused by GAA repeat expansion within the FXN gene, leading to epigenetic changes and heterochromatin-mediated gene silencing that result in a frataxin protein deficit. Histone deacetylase (HDAC) inhibitors, including pimelic o-aminobenzamide compounds 106, 109 and 136, have previously been shown to reverse FXN gene silencing in short-term studies of FRDA patient cells and a knock-in mouse model, but the functional consequences of such therapeutic intervention have thus far not been described. We have now investigated the long-term therapeutic effects of 106, 109 and 136 in our GAA repeat expansion mutation-containing YG8R FRDA mouse model. We show that there is no overt toxicity up to 5 months of treatment and there is amelioration of the FRDA-like disease phenotype. Thus, while the neurological deficits of this model are mild, 109 and 106 both produced an improvement of motor coordination, whereas 109 and 136 produced increased locomotor activity. All three compounds increased global histone H3 and H4 acetylation of brain tissue, but only 109 significantly increased acetylation of specific histone residues at the FXN locus. Effects on FXN mRNA expression in CNS tissues were modest, but 109 significantly increased frataxin protein expression in brain tissue. 109 also produced significant increases in brain aconitase enzyme activity, together with reduction of neuronal pathology of the dorsal root ganglia (DRG). Overall, these results support further assessment of HDAC inhibitors for treatment of Friedreich ataxia.This work was supported by Repligen Corporation; Muscular Dystrophy Association (MDA) USA; Ataxia UK; Friedreich's Ataxia Research Alliance (FARA); GoFAR; and the Wellcome Trust [089757]

Oral health status of rural-urban migrant children in South China

International Journal of Paediatric Dentistry 2011; 21: 58-67 Background. In China, there is a massive rural-urban migration and the children of migrants are often unregistered residents (a 'floating population').Aim. This pilot study aimed to profile the oral health of migrant children in South China's principal city of migration and identify its socio-demographic/behavioural determinants.Design. An epidemiological survey was conducted in an area of Guangzhou among 5-year-old migrant children (n = 138) who received oral examinations according to the World Health Organization criteria. Parents' oral health knowledge/attitude, child practices, and impact of children's oral health on their quality-of-life (QoL) were assessed.Results. The caries rate and mean (SD) dmft were 86% and 5.17 (4.16), respectively, higher than those national statistics for both rural and urban areas (P < 0.05). Oral hygiene was satisfactory (DI-S < 1.0) in 3% of children. Oral health impacts on QoL were considerable; 60% reported one or more impacts. 58% variance in 'dmft' was explained by 'non-local-born', 'low-educated parents', 'bedtime feeding', 'parental unawareness of fluoride's effect and importance of teeth', and 'poor oral hygiene' (all P < 0.05). 'Non-local-born' and 'dmft' indicated poor oral health-related QoL (both P < 0.05), accounting for 32% of variance.Conclusion. Oral health is poor among rural-urban migrant children and requires effective interventions in targeted sub-groups. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd.postprin

Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: Analysis of the Cardiac Arrhythmia Suppression Trial

Objectives.We studied the relations between heart failure, ejection fraction, arrhythmia suppression and mortality.Background.Both left ventricular ejection fraction and functional class of heart failure are strongly associated with mortality after acute myocardial infarction. Both are also related to the presence of ventricular arrhythmias and have been identified as factors related to the ability to suppress ventricular arrhythmias. Little has been reported about the relations between these two factors and arrhythmia suppression or mortality.Methods.Baseline data from the Cardiac Arrhythmia Suppression Trial were used to define several categories of heart failure and to relate both the resulting categories and ejection fraction to arrhythmia suppression and mortality using logistic and survival regression analytic methodologies.Results.Regardless of the prospective baseline definition of heart failure used, the data consistently showed that heart failure was a more powerful predictor of subsequent congestive heart failure events and arrhythmia suppression and was equally powerful in predicting death. However, each variable provided incremental information when included in the prediction model. Heart failure and ejection fraction appeared to be independent predictors of death. Interactions were observed: A low ejection fraction was more predictive of failure of arrhythmia suppression in patients with than without evidence of heart failure before or at baseline; a low ejection fraction was more predictive of subsequent congestive heart failure events in patients without than with evidence of heart failure before or at baseline.Conclusions.Although heart failure as a prognostic feature appears to be somewhat superior to ejection fraction, both are powerful predictors of arrhythmia suppression and cardiac events in patients with ventricular arrhythmia after myocardial infarction. Each provides incremental prediction

Distribution of nerve fibers and nerve-immune cell association in mouse spleen revealed by immunofluorescent staining

The central nervous system regulates the immune system through the secretion of hormones from the pituitary gland and other endocrine organs, while the peripheral nervous system (PNS) communicates with the immune system through local nerve-immune cell interactions, including sympathetic/parasympathetic (efferent) and sensory (afferent) innervation to lymphoid tissue/organs. However, the precise mechanisms of this bi-directional crosstalk of the PNS and immune system remain mysterious. To study this kind of bi-directional crosstalk, we performed immunofluorescent staining of neurofilament and confocal microscopy to reveal the distribution of nerve fibers and nerve-immune cell associations inside mouse spleen. Our study demonstrates (i) extensive nerve fibers in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath, marginal zones, trabeculae, and red pulp; (ii) close associations of nerve fibers with blood vessels (including central arteries, marginal sinuses, penicillar arterioles, and splenic sinuses); (iii) close associations of nerve fibers with various subsets of dendritic cells, macrophages (Mac1+ and F4/80+), and lymphocytes (B cells, T helper cells, and cytotoxic T cells). Our data concerning the extensive splenic innervation and nerve-immune cell communication will enrich our knowledge of the mechanisms through which the PNS affects the cellular- and humoral-mediated immune responses in healthy and infectious/non-infectious states

Why business angels reject investment opportunities: Is it personal?

A major focus of research on business angels has examined their decision-making processes and investment criteria. As business angels reject most of the opportunities that they receive, this article explores the reasons informing such decisions. In view of angel heterogeneity, investment opportunities might be expected to be rejected for differing reasons. Two sources of data are used to examine this issue. Face-to-face interviews with 30 business angels in Scotland and Northern Ireland provided information on typical ‘deal killers’. This was complemented by an Internet survey of United Kingdom that attracted responses from 238 UK business angels. The findings confirm that the main reason for rejection relates to the entrepreneur/management team. However, angel characteristics do not explain the number of reasons given for opportunity rejection nor do they predict the reasons for rejecting investment opportunities. This could be related to the increasing trend for business angels to join organised groups which, in turn, leads to the development of a shared repertoire of investment approaches. We suggest the concept of ‘communities-of-practice’ as an explanation for this finding

Dyclonine rescues frataxin deficiency in animal models and buccal cells of patients with Friedreich's ataxia.

Inherited deficiency in the mitochondrial protein frataxin (FXN) causes the rare disease Friedreich's ataxia (FA), for which there is no successful treatment. We identified a redox deficiency in FA cells and used this to model the disease. We screened a 1600-compound library to identify existing drugs, which could be of therapeutic benefit. We identified the topical anesthetic dyclonine as protective. Dyclonine increased FXN transcript and FXN protein dose-dependently in FA cells and brains of animal models. Dyclonine also rescued FXN-dependent enzyme deficiencies in the iron-sulfur enzymes, aconitase and succinate dehydrogenase. Dyclonine induces the Nrf2 [nuclear factor (erythroid-derived 2)-like 2] transcription factor, which we show binds an upstream response element in the FXN locus. Additionally, dyclonine also inhibited the activity of histone methyltransferase G9a, known to methylate histone H3K9 to silence FA chromatin. Chronic dosing in a FA mouse model prevented a performance decline in balance beam studies. A human clinical proof-of-concept study was completed in eight FA patients dosed twice daily using a 1% dyclonine rinse for 1 week. Six of the eight patients showed an increase in buccal cell FXN levels, and fold induction was significantly correlated with disease severity. Dyclonine represents a novel therapeutic strategy that can potentially be repurposed for the treatment of FA

The Molecular Clockwork of the Fire Ant Solenopsis invicta

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