A Simple Model for the DNA Denaturation Transition

We study pairs of interacting self-avoiding walks on the 3d simple cubic lattice. They have a common origin and are allowed to overlap only at the same monomer position along the chain. The latter overlaps are indeed favored by an energetic gain. This is inspired by a model introduced long ago by Poland and Sheraga [J. Chem. Phys. {\bf 45}, 1464 (1966)] for the denaturation transition in DNA where, however, self avoidance was not fully taken into account. For both models, there exists a temperature T_m above which the entropic advantage to open up overcomes the energy gained by forming tightly bound two-stranded structures. Numerical simulations of our model indicate that the transition is of first order (the energy density is discontinuous), but the analog of the surface tension vanishes and the scaling laws near the transition point are exactly those of a second order transition with crossover exponent \phi=1. Numerical and exact analytic results show that the transition is second order in modified models where the self-avoidance is partially or completely neglected.Comment: 29 pages, LaTeX, 20 postscript figure

International perspective on healthcare provider gender bias in musculoskeletal pain management:a scoping review protocol

Introduction Chronic pain affects millions of individuals worldwide. Healthcare provider gender bias in the management of these individuals has societal and individual ramifications. Yet, a thorough and comprehensive literature summary on this topic is lacking. Therefore, this study aims to systematically: (1) identify and map the available scientific and grey literature as it relates to healthcare provider gender bias in the assessment, diagnosis and management of (chronic) musculoskeletal pain and (2) identify current gaps that necessitate further research. Methods and analysis This scoping review will be conducted in accordance with recent guidelines, and the results will be reported via the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The following databases will be searched: PubMed (National Library of Medicine), Embase (Elsevier), Scopus (Elsevier), CINAHL Complete (Ovid), Academic Search Complete (Ebscohost), Pre-Prints Database (National Library of Medicine) and Rehabilitation Reference Center from inception to August 2022. Additionally, relevant grey literature will be identified. All screening will be done by two independent reviewers during two stages: first title/abstract screening followed by full-text screening. Data will be extracted from the bibliometric, study characteristics, and pain science families of variables. Results will be descriptively mapped, and the frequency of concepts, population, characteristics and other details will be narratively reported. Additionally, results will be presented in tabular and graphical form. Ethics and dissemination As this study will neither involve human subject participation nor utilisation of protected data, ethical approval is not required. This study's methodological approach follows current recommendations. Study findings will be disseminated through conference presentations and international peer-review journal publication. In addition, infographics available in English, Spanish and German will be disseminated. Registration details This project will be registered in Open Science Framework prior to data collection

Unusual exanthema combined with cerebral vasculitis in pneumococcal meningitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bacterial meningitis is a complex, rapidly progressive disease in which neurological injury is caused in part by the causative organism and in part by the host's own inflammatory responses.</p> <p>Case presentation</p> <p>We present the case of a two-year-old Greek girl with pneumococcal meningitis and an atypical curvilinear-like skin eruption, chronologically associated with cerebral vasculitis. A diffusion-weighted MRI scan showed lesions with restricted diffusion, reflecting local areas of immunologically mediated necrotizing vasculitis.</p> <p>Conclusions</p> <p>Atypical presentations of bacterial meningitis may occur, and they can be accompanied by serious unexpected complications.</p

Comparative EPR and fluorescence conformational studies of fully active spin-labeled melanotropic peptides

Similar to melanocyte stimulating hormone (alpha -MSH), its potent and long-acting analogue, [Nle(4), D-Phe(7)]alpha -MSH, when labeled with the paramagnetic amino acid probe 2,2,6,6-tetramethylpiperidine-N-oxyl-4-amino-4-carboxylic acid (Toac), maintains its full biological potency, thus validating any comparative structural investigations between the two labeled peptides, Correlation times, calculated from tire electron paramagnetic resonance signal of Toac bound to the peptides, and Toac-Trp distances, estimated from the Toac fluorescence quenching of the Trp residue present in the peptides, indicate a more rigid and folded structure for the potent analogue as compared to the hormone, in aqueous medium. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.Universidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilUniv São Paulo, Inst Fis, BR-66318 São Paulo, BrazilUniv São Paulo, Inst Biociencias, Dept Fisiol, BR-11176 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, BR-04044020 São Paulo, BrazilWeb of Scienc

An examination of sex differences in associations between cord blood adipokines and childhood adiposity

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154308/1/ijpo12587.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154308/2/ijpo12587_am.pd

Local field theory for disordered itinerant quantum ferromagnets

An effective field theory is derived that describes the quantum critical behavior of itinerant ferromagnets in the presence of quenched disorder. In contrast to previous approaches, all soft modes are kept explicitly. The resulting effective theory is local and allows for an explicit perturbative treatment. It is shown that previous suggestions for the critical fixed point and the critical behavior are recovered under certain assumptions. The validity of these assumptions is discussed in the light of the existence of two different time scales. It is shown that, in contrast to previous suggestions, the correct fixed point action is not Gaussian, and that the previously proposed critical behavior was correct only up to logarithmic corrections. The connection with other theories of disordered interacting electrons, and in particular with the resolution of the runaway flow problem encountered in these theories, is also discussed.Comment: 17pp., REVTeX, 5 eps figs, final version as publishe

A brief introduction to mixed effects modelling and multi-model inference in ecology

Acknowledgements This paper is the result of a University of Exeter workshop on best practice for the application of mixed effects models and model selection in ecological studies Funding Xavier A. Harrison was funded by an Institute of Zoology Research Fellowship. David Fisher was funded by NERC studentship NE/H02249X/1. Lynda Donaldson was funded by NERC studentship NE/L501669/1. Beth S. Robinson was funded by the University of Exeter and the Animal and Plant Health Agency as part of ‘Wildlife Research Co-Operative’. Maria Correa-Cano was funded by CONACYT (The Mexican National Council for Science and Technology) and SEP (The Mexican Ministry of Education). Cecily Goodwin was funded by the Forestry Commission and NERC studentship NE/L501669/1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Perdeuterated GbpA Enables Neutron Scattering Experiments of a Lytic Polysaccharide Monooxygenase

publishedVersio

Mechanisms of photoreceptor death and survival in mammalian retina

The mammalian retina, like the rest of the central nervous system, is highly stable and can maintain its structure and function for the full life of the individual, in humans for many decades. Photoreceptor dystrophies are instances of retinal instability. Many are precipitated by genetic mutations and scores of photoreceptor-lethal mutations have now been identified at the codon level. This review explores the factors which make the photoreceptor more vulnerable to small mutations of its proteins than any other cell of the body, and more vulnerable to environmental factors than any other retinal neurone. These factors include the highly specialised structure and function of the photoreceptors, their high appetite for energy, their self-protective mechanisms and the architecture of their energy supply from the choroidal circulation. Particularly important are the properties of the choroidal circulation, especially its fast flow of near-arterial blood and its inability to autoregulate. Mechanisms which make the retina stable and unstable are then reviewed in three different models of retinal degeneration, retinal detachment, photoreceptor dystrophy and light damage. A two stage model of the genesis of photoreceptor dystrophies is proposed, comprising an initial "depletion" stage caused by genetic or environmental insult and a second "late" stage during which oxygen toxicity damages and eventually destroys any photoreceptors which survive the initial depletion. It is a feature of the model that the second "late" stage of retinal dystrophies is driven by oxygen toxicity. The implications of these ideas for therapy of retinal dystrophies are discussed

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse