A point particle model of lightly bound skyrmions

A simple model of the dynamics of lightly bound skyrmions is developed in which skyrmions are replaced by point particles, each carrying an internal orientation. The model accounts well for the static energy minimizers of baryon number 1≤B≤8 obtained by numerical simulation of the full field theory. For 9≤B≤23, a large number of static solutions of the point particle model are found, all closely resembling size B subsets of a face centred cubic lattice, with the particle orientations dictated by a simple colouring rule. Rigid body quantization of these solutions is performed, and the spin and isospin of the corresponding ground states extracted. As part of the quantization scheme, an algorithm to compute the symmetry group of an oriented point cloud, and to determine its corresponding Finkelstein-Rubinstein constraints, is devised

Epigenetic control of the vasopressin promoter explains physiological ability to regulate vasopressin transcription in dehydration and salt loading states in the rat

The synthesis of arginine vasopressin (AVP) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus is sensitive to increased plasma osmolality and a decreased blood volume, and thus is robustly increased by both dehydration (increased plasma osmolality and decreased blood volume) and salt loading (increased plasma osmolality). Both stimuli result in functional remodelling of the SON and PVN, a process referred to as functional‐related plasticity. Such plastic changes in the brain have recently been associated with altered patterns of DNA methylation at CpG (cytosine‐phosphate‐guanine) residues, a process considered to be important for the regulation of gene transcription. In this regard, the proximal Avp promoter contains a number of CpG sites and is recognised as one of four CpG islands for the Avp gene, suggesting that methylation may be regulating Avp transcription. In the present study, we show that, in an immortalised hypothalamic cell line 4B, the proximal Avp promoter is highly methylated, and treatment of these cells with the DNA methyltransferase inhibitor 5‐Aza‐2′‐deoxycytidine to demethylate DNA dramatically increases basal and stimulated Avp biosynthesis. We report no changes in the expression of DNA methyltransferases, Dnmt1 and Dnmt3a, whereas there is decreased expression of the demethylating enzyme ten‐eleven‐translocation 2, Tet2, in the SON by dehydration and salt loading. We found higher methylation of the SON Avp promoter in dehydrated but not salt‐loaded rats. By analysis of individual CpG sites, we observed hypomethylation, hypermethylation and no change in methylation of specific CpGs in the SON Avp promoter of the dehydrated rat. Using reporter gene assays, we show that mutation of individual CpGs can result in altered Avp promoter activity. We propose that methylation of the SON Avp promoter is necessary to co‐ordinate the duel inputs of increased plasma osmolality and decreased blood volume on Avp transcription in the chronically dehydrated rat

Compromised Motor Dexterity Confounds Processing Speed Task Outcomes in Stroke Patients

Most conventional measures of information processing speed require motor responses to facilitate performance. However, although not often addressed clinically, motor impairment, whether due to age or acquired brain injury, would be expected to confound the outcome measure of such tasks. The current study recruited 29 patients (20 stroke and 9 transient ischemic attack) with documented reduction in dexterity of the dominant hand, and 29 controls, to investigate the extent to which 3 commonly used processing speed measures with varying motor demands (a Visuo-Motor Reaction Time task, and the Wechsler Adult Intelligence Scale-IV Symbol Search and Coding subtests) may be measuring motor-related speed more so than cognitive speed. Analyses include correlations between indices of cognitive and motor speed obtained from two other tasks (Inspection Time and Pegboard task, respectively) with the three speed measures, followed by hierarchical regressions to determine the relative contribution of cognitive and motor speed indices toward task performance. Results revealed that speed outcomes on tasks with relatively high motor demands, such as Coding, were largely reflecting motor speed in individuals with reduced dominant hand dexterity. Thus, findings indicate the importance of employing measures with minimal motor requirements, especially when the assessment of speed is aimed at understanding cognitive rather than physical function

Understanding the impact of heavy ions and tailoring the optical properties of large-area Monolayer WS2 using Focused Ion Beam

Focused ion beam (FIB) has been used as an effective tool for precise nanoscale fabrication. It has recently been employed to tailor defect engineering in functional nanomaterials such as two-dimensional transition metal dichalcogenides (TMDCs), providing desirable properties in TMDC-based optoelectronic devices. However, the damage caused by the FIB irradiation and milling process to these delicate atomically thin materials, especially in the extended area, has not yet been elaboratively characterised. Understanding the correlation between lateral ion beam effects and optical properties of 2D TMDCs is crucial in designing and fabricating high-performance optoelectronic devices. In this work, we investigate lateral damage in large-area monolayer WS2 caused by the gallium focused ion beam milling process. Three distinct zones away from the milling location are identified and characterised via steady-state photoluminescence (PL) and Raman spectroscopy. An unexpected bright ring-shaped emission around the milled location has been revealed by time-resolved PL spectroscopy with high spatial resolution. Our finding opens new avenues for tailoring the optical properties of TMDCs by charge and defect engineering via focused ion beam lithography. Furthermore, our study provides evidence that while some localised damage is inevitable, distant destruction can be eliminated by reducing the ion beam current. It paves the way for the use of FIB to create nanostructures in 2D TMDCs, as well as the design and realisation of optoelectrical devices on a wafer scale

Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication

publishedVersio

A novel LIPS assay for insulin autoantibodies

Insulin autoantibodies (IAA) are often the first marker of autoimmunity detected in children in the preclinical phase of type 1 diabetes (T1D). Currently, the vast majority of laboratories adopt the radiobinding micro-assay (RBA) for measuring IAA. Our aim was to replace RBA with a novel non-radioactive IAA Luciferase Immuno Precipitation System (LIPS) assay with improved performance. We developed (pro)insulin antigens with alternative placements of a NanoLuc (TM) luciferase reporter (NLuc). Performance in LIPS was evaluated by testing sera from new onset T1D (n = 80), blood donors (n = 123), schoolchildren (n = 186), first-degree relatives (FDRs) from the Bart's Oxford family study (n = 53) and from the Belgian Diabetes Registry (n = 136), coded sera from the Islet Autoantibody Standardization Program (IASP) (T1D n = 50, blood donors n = 90). IAA LIPS based on B chain-NLuc proinsulin or B chain-NLuc insulin, in which NLuc was fused at the C-terminus of the insulin B chain, required only 2 mu L of serum and a short incubation time, showed high concordance with RBA (Spearman r = 0.866 and 0.833, respectively), high assay performance (B chain-NLuc proinsulin ROC-AUC = 0.894 and B chain-NLuc insulin ROC-AUC = 0.916), and an adjusted sensitivity at 95% specificity ranking on par with the best assays submitted to the two most recent IASP workshops. In FDRs, the IAA LIPS showed improved discrimination of progressors to T1D compared to RBA. We established a novel high-performance non-radioactive IAA LIPS that might replace the current gold standard RBA and find wide application in the study of the IAA response in T1D

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment

Background and purpose An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren’s contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC’s impact on quality of life and the value of its treatments. Methods Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were deined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little ingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0–1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L proile most accurately relects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. Results Estimated utilities based on the responses of 1,745 qualiied respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little ingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little inger from 50 to 12 degrees would improve utility by 0.02. Interpretation DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and lexible framework to assess utility for varying degrees of DC severity

First Observation of CP Violation in B0->D(*)CP h0 Decays by a Combined Time-Dependent Analysis of BaBar and Belle Data

We report a measurement of the time-dependent CP asymmetry of B0->D(*)CP h0 decays, where the light neutral hadron h0 is a pi0, eta or omega meson, and the neutral D meson is reconstructed in the CP eigenstates K+ K-, K0S pi0 or K0S omega. The measurement is performed combining the final data samples collected at the Y(4S) resonance by the BaBar and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain ( 471 +/- 3 ) x 10^6 BB pairs recorded by the BaBar detector and ( 772 +/- 11 ) x 10^6, BB pairs recorded by the Belle detector. We measure the CP asymmetry parameters -eta_f S = +0.66 +/- 0.10 (stat.) +/- 0.06 (syst.) and C = -0.02 +/- 0.07 (stat.) +/- 0.03 (syst.). These results correspond to the first observation of CP violation in B0->D(*)CP h0 decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.Comment: 9 pages, 2 figures, submitted to Physical Review Letter

Study protocol: cross-national comparative case study of recovery-focused mental health care planning and coordination (COCAPP).

BACKGROUND: The collaborative care planning study (COCAPP) is a cross-national comparative study of care planning and coordination in community mental healthcare settings. The context and delivery of mental health care is diverging between the countries of England and Wales whilst retaining points of common interest, hence providing a rich geographical comparison for research. Across England the key vehicle for the provision of recovery-focused, personalised, collaborative mental health care is the care programme approach (CPA). The CPA is a form of case management introduced in England in 1991, then revised in 2008. In Wales the CPA was introduced in 2003 but has now been superseded by The Mental Health (Care Co-ordination and Care and Treatment Planning) (CTP) Regulations (Mental Health Measure), a new statutory framework. In both countries, the CPA/CTP requires providers to: comprehensively assess health/social care needs and risks; develop a written care plan (which may incorporate risk assessments, crisis and contingency plans, advanced directives, relapse prevention plans, etc.) in collaboration with the service user and carer(s); allocate a care coordinator; and regularly review care. The overarching aim of this study is to identify and describe the factors that ensure CPA/CTP care planning and coordination is personalised, recovery-focused and conducted collaboratively. METHODS/DESIGN: COCAPP will employ a concurrent transformative mixed methods approach with embedded case studies. Phase 1 (Macro-level) will consider the national context through a meta-narrative mapping (MNM) review of national policies and the relevant research literature. Phase 2 (Meso-level and Micro-level) will include in-depth micro-level case studies of everyday 'frontline' practice and experience with detailed qualitative data from interviews and reviews of individual care plans. This will be nested within larger meso-level survey datasets, senior-level interviews and policy reviews in order to provide potential explanations and understanding. DISCUSSION: COCAPP will help identify the key components that support and hinder the provision of personalised, recovery-focused care planning and provide an informed rationale for a future planned intervention and evaluation

Leukotriene biosynthesis inhibition ameliorates acute lung injury following hemorrhagic shock in rats

<p>Abstract</p> <p>Background</p> <p>Hemorrhagic shock followed by resuscitation is conceived as an insult frequently induces a systemic inflammatory response syndrome and oxidative stress that results in multiple-organ dysfunction syndrome including acute lung injury. MK-886 is a leukotriene biosynthesis inhibitor exerts an anti inflammatory and antioxidant activity.</p> <p>Objectives</p> <p>The objective of present study was to assess the possible protective effect of MK-886 against hemorrhagic shock-induced acute lung injury via interfering with inflammatory and oxidative pathways.</p> <p>Materials and methods</p> <p>Eighteen adult Albino rats were assigned to three groups each containing six rats: group I, sham group, rats underwent all surgical instrumentation but neither hemorrhagic shock nor resuscitation was done; group II, Rats underwent hemorrhagic shock (HS) for 1 hr then resuscitated with Ringer's lactate (1 hr) (induced untreated group, HS); group III, HS + MK-886 (0.6 mg/kg i.p. injection 30 min before the induction of HS, and the same dose was repeated just before reperfusion period). At the end of experiment (2 hr after completion of resuscitation), blood samples were collected for measurement of serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The trachea was then isolated and bronchoalveolar lavage fluid (BALF) was carried out for measurement of leukotriene B₄(LTB₄), leukotriene C₄(LTC₄) and total protein. The lungs were harvested, excised and the left lung was homogenized for measurement of malondialdehyde (MDA) and reduced glutathione (GSH) and the right lung was fixed in 10% formalin for histological examination.</p> <p>Results</p> <p>MK-886 treatment significantly reduced the total lung injury score compared with the HS group (<it>P </it>< 0.05). MK-886 also significantly decreased serum TNF-α & IL-6; lung MDA; BALF LTB₄, LTC₄& total protein compared with the HS group (<it>P </it>< 0.05). MK-886 treatment significantly prevented the decrease in the lung GSH levels compared with the HS group (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>The results of the present study reveal that MK-886 may ameliorate lung injury in shocked rats via interfering with inflammatory and oxidative pathways implicating the role of leukotrienes in the pathogenesis of hemorrhagic shock-induced lung inflammation.</p