143 research outputs found
Cardiovascular risk in high-hazard occupations: the role of occupational cardiology
Abstract
Work is beneficial for health, but many individuals develop cardiovascular disease (CVD) during their working lives. Occupational cardiology is an emerging field that combines traditional cardiology sub-specialisms with prevention and risk management unique to specific employment characteristics and conditions. In some occupational settings incapacitation through CVD has the potential to be catastrophic due to the nature of work and/or the working environment. These are often termed 'hazardous' or 'high-hazard' occupations. Consequently, many organizations that employ individuals in high-hazard roles undertake pre-employment medicals and periodic medical examinations to screen for CVD. The identification of CVD that exceeds predefined employer (or regulatory body) risk thresholds can result in occupational restriction, or disqualification, which may be temporary or permanent. This article will review the evidence related to occupational cardiology for several high-hazard occupations related to aviation and space, diving, high altitude, emergency workers, commercial transportation, and the military. The article will focus on environmental risk, screening, surveillance, and risk management for the prevention of events precipitated by CVD. Occupational cardiology is a challenging field that requires a broad understanding of general cardiology, environmental, and occupational medicine principles. There is a current lack of consensus and contemporary evidence which requires further research. Provision of evidence-based, but individualized, risk stratification and treatment plans is required from specialists that understand the complex interaction between work and the cardiovascular system. There is a current lack of consensus and contemporary evidence in occupational cardiology and further research is required
Electron and Hole Spin Splitting and Photogalvanic Effect in Quantum Wells
A theory of the circular photogalvanic effect caused by spin splitting in
quantum wells is developed. Direct interband transitions between the hole and
electron size-quantized subbands are considered. It is shown that the
photocurrent value and direction depend strongly on the form of the spin-orbit
interaction. The currents induced by structure-, bulk-, and interface-inversion
asymmetry are investigated. The photocurrent excitation spectra caused by spin
splittings in both conduction and valence bands are calculated.Comment: 7 pages, 3 figure
Scapinin, the Protein Phosphatase 1 Binding Protein, Enhances Cell Spreading and Motility by Interacting with the Actin Cytoskeleton
Copyright (c) 2009 Sagara et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Scapinin, also named phactr3, is an actin and protein phosphatase 1 (PP1) binding protein, which is expressed in the adult brain and some tumor cells. At present, the role(s) of scapinin in the brain and tumors are poorly understood. We show that the RPEL-repeat domain of scapinin, which is responsible for its direct interaction with actin, inhibits actin polymerization in vitro. Next, we established a Hela cell line, where scapinin expression was induced by tetracycline. In these cells, expression of scapinin stimulated cell spreading and motility. Scapinin was colocalized with actin at the edge of spreading cells. To explore the roles of the RPEL-repeat and PP1-binding domains, we expressed wild-type and mutant scapinins as fusion proteins with green fluorescence protein (GFP) in Cos7 cells. Expression of GFP-scapinin (wild type) also stimulated cell spreading, but mutation in the RPEL-repeat domain abolished both the actin binding and the cell spreading activity. PP1-binding deficient mutants strongly induced cell retraction. Long and branched cytoplasmic processes were developed during the cell retraction. These results suggest that scapinin enhances cell spreading and motility through direct interaction with actin and that PP1 plays a regulatory role in scapinin-induced morphological changes.ArticlePLOS ONE. 4(1):e4247 (2009)journal articl
Spintronics: Fundamentals and applications
Spintronics, or spin electronics, involves the study of active control and
manipulation of spin degrees of freedom in solid-state systems. This article
reviews the current status of this subject, including both recent advances and
well-established results. The primary focus is on the basic physical principles
underlying the generation of carrier spin polarization, spin dynamics, and
spin-polarized transport in semiconductors and metals. Spin transport differs
from charge transport in that spin is a nonconserved quantity in solids due to
spin-orbit and hyperfine coupling. The authors discuss in detail spin
decoherence mechanisms in metals and semiconductors. Various theories of spin
injection and spin-polarized transport are applied to hybrid structures
relevant to spin-based devices and fundamental studies of materials properties.
Experimental work is reviewed with the emphasis on projected applications, in
which external electric and magnetic fields and illumination by light will be
used to control spin and charge dynamics to create new functionalities not
feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes
from the published versio
Genetic and immune landscape evolution in MMR-deficient colorectal cancer.
Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) have high mutation burdens, which make these tumours immunogenic and many respond to immune checkpoint inhibitors. The MMRd hypermutator phenotype may also promote intratumour heterogeneity (ITH) and cancer evolution. We applied multiregion sequencing and CD8 and programmed death ligand 1 (PD-L1) immunostaining to systematically investigate ITH and how genetic and immune landscapes coevolve. All cases had high truncal mutation burdens. Despite pervasive ITH, driver aberrations showed a clear hierarchy. Those in WNT/ÎČ-catenin, mitogen-activated protein kinase, and TGF-ÎČ receptor family genes were almost always truncal. Immune evasion (IE) drivers, such as inactivation of genes involved in antigen presentation or IFN-Îł signalling, were predominantly subclonal and showed parallel evolution. These IE drivers have been implicated in immune checkpoint inhibitor resistance or sensitivity. Clonality assessments are therefore important for the development of predictive immunotherapy biomarkers in MMRd CRCs. Phylogenetic analysis identified three distinct patterns of IE driver evolution: pan-tumour evolution, subclonal evolution, and evolutionary stasis. These, but neither mutation burdens nor heterogeneity metrics, significantly correlated with T-cell densities, which were used as a surrogate marker of tumour immunogenicity. Furthermore, this revealed that genetic and T-cell infiltrates coevolve in MMRd CRCs. Low T-cell densities in the subgroup without any known IE drivers may indicate an, as yet unknown, IE mechanism. PD-L1 was expressed in the tumour microenvironment in most samples and correlated with T-cell densities. However, PD-L1 expression in cancer cells was independent of T-cell densities but strongly associated with loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and may contribute to a higher recurrence risk of MMRd CRCs with impaired CDX2 expression. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland
Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY
© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding WiskottâAldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin ÎČ. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes
of Health, an American Heart Association Predoctoral Fellowship
(J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a
National Science Foundation Predoctoral Fellowship (B.B.)
The mechanism of macroautophagy: The movie
This animated movie presents the mechanism of macroautophagy, hereafter autophagy, by showing the molecular features of the formation of autophagosomes, the hallmark organelle of this intracellular catabolic pathway. It is based on our current knowledge and it also illustrates how autophagosomes can recognize and eliminate selected cargoes.</p
Spin dynamics in semiconductors
This article reviews the current status of spin dynamics in semiconductors
which has achieved a lot of progress in the past years due to the fast growing
field of semiconductor spintronics. The primary focus is the theoretical and
experimental developments of spin relaxation and dephasing in both spin
precession in time domain and spin diffusion and transport in spacial domain. A
fully microscopic many-body investigation on spin dynamics based on the kinetic
spin Bloch equation approach is reviewed comprehensively.Comment: a review article with 193 pages and 1103 references. To be published
in Physics Reports
Rapidity dependence of antiproton to proton ratios in Au+Au collisions at sqrt{s_{NN}}=130 GeV
Measurements, with the BRAHMS detector, of the antiproton to proton ratio at
central and forward rapidities are presented for Au+Au reactions at
sqrt{s_{NN}}=130 GeV, and for three different collision centralities. For
collisions in the 0-40% centrality range we find $N(\bar{{\rm p}})/N({\rm p}) =
0.64 +- 0.04 (stat.) +- 0.06 (syst.) at y ~0, 0.66 +- 0.03 +- 0.06 at y ~ 0.7,
and 0.41 +- 0.04 +- 0.06 at y ~ 2. The ratios are found to be nearly
independent of collision centrality and transverse momentum. The measurements
demonstrate that the antiproton and proton rapidity densities vary differently
with rapidity, and indicate that a net-baryon free midrapidity plateau (Bjorken
limit) is not reached at this RHIC energy.Comment: 8 pages, 3 figure
Osteochondral Grafting: Effect of Graft Alignment, Material Properties, and Articular Geometry
Osteochondral grafting for cartilage lesions is an attractive surgical procedure; however, the clinical results have not always been successful. Surgical recommendations differ with respect to donor site and graft placement technique. No clear biomechanical analysis of these surgical options has been reported. We hypothesized that differences in graft placement, graft biomechanical properties, and graft topography affect cartilage stresses and strains. A finite element model of articular cartilage and meniscus in a normal knee was constructed. The model was used to analyze the magnitude and the distribution of contact stresses, von Mises stresses, and compressive strains in the intact knee, after creation of an 8-mm diameter osteochondral defect, and after osteochondral grafting of the defect. The effects of graft placement, articular surface topography, and biomechanical properties were evaluated. The osteochondral defect generated minimal changes in peak contact stress (3.6 MPa) relative to the intact condition (3.4 MPa) but significantly increased peak von Mises stress (by 110%) and peak compressive strain (by 63%). A perfectly matched graft restored stresses and strains to near intact conditions. Leaving the graft proud by 0.5 mm generated the greatest increase in local stresses (peak contact stresses = 6.7 MPa). Reducing graft stiffness and curvature of articular surface had lesser effects on local stresses. Graft alignment, graft biomechanical properties, and graft topography all affected cartilage stresses and strains. Contact stresses, von Mises stresses, and compressive strains are biomechanical markers for potential tissue damage and cell death. Leaving the graft proud tends to jeopardize the graft by increasing the stresses and strains on the graft. From a biomechanical perspective, the ideal surgical procedure is a perfectly aligned graft with reasonably matched articular cartilage surface from a lower load-bearing region of the knee
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