On chains in HH-closed topological pospaces

We study chains in an $H$-closed topological partially ordered space. We give sufficient conditions for a maximal chain $L$ in an $H$-closed topological partially ordered space such that $L$ contains a maximal (minimal) element. Also we give sufficient conditions for a linearly ordered topological partially ordered space to be $H$-closed. We prove that any $H$-closed topological semilattice contains a zero. We show that a linearly ordered $H$-closed topological semilattice is an $H$-closed topological pospace and show that in the general case this is not true. We construct an example an $H$-closed topological pospace with a non-$H$-closed maximal chain and give sufficient conditions that a maximal chain of an $H$-closed topological pospace is an $H$-closed topological pospace.Comment: We have rewritten and substantially expanded the manuscrip

Interstitial cell migration: integrin-dependent and alternative adhesion mechanisms

Adhesion and migration are integrated cell functions that build, maintain and remodel the multicellular organism. In migrating cells, integrins are the main transmembrane receptors that provide dynamic interactions between extracellular ligands and actin cytoskeleton and signalling machineries. In parallel to integrins, other adhesion systems mediate adhesion and cytoskeletal coupling to the extracellular matrix (ECM). These include multifunctional cell surface receptors (syndecans and CD44) and discoidin domain receptors, which together coordinate ligand binding with direct or indirect cytoskeletal coupling and intracellular signalling. We review the way that the different adhesion systems for ECM components impact cell migration in two- and three-dimensional migration models. We further discuss the hierarchy of these concurrent adhesion systems, their specific tasks in cell migration and their contribution to migration in three-dimensional multi-ligand tissue environments

An early history of T cell-mediated cytotoxicity.

After 60 years of intense fundamental research into T cell-mediated cytotoxicity, we have gained a detailed knowledge of the cells involved, specific recognition mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular mechanisms. What could not be anticipated at the outset was how discovery of the mechanisms regulating the activation and function of cytotoxic T cells would lead to new developments in cancer immunotherapy. Given the profound recent interest in therapeutic manipulation of cytotoxic T cell responses, it is an opportune time to look back on the early history of the field. This Timeline describes how the early findings occurred and eventually led to current therapeutic applications

Capturing geographically-varying uncertainty in earthquake ground motion models or what we think we know may change

Our knowledge of earthquake ground motions of engineering significance varies geographically. The prediction of earthquake shaking in parts of the globe with high seismicity and a long history of observations from dense strong-motion networks, such as coastal California, much of Japan and central Italy, should be associated with lower uncertainty than ground-motion models for use in much of the rest of the world, where moderate and large earthquakes occur infrequently and monitoring networks are sparse or only recently installed. This variation in uncertainty, however, is not often captured in the models currently used for seismic hazard assessments, particularly for national or continental-scale studies. In this theme lecture, firstly I review recent proposals for developing ground-motion logic trees and then I develop and test a new approach for application in Europe. The proposed procedure is based on the backbone approach with scale factors that are derived to account for potential differences between regions. Weights are proposed for each of the logic-tree branches to model large epistemic uncertainty in the absence of local data. When local data are available these weights are updated so that the epistemic uncertainty captured by the logic tree reduces. I argue that this approach is more defensible than a logic tree populated by previously published ground-motion models. It should lead to more stable and robust seismic hazard assessments that capture our doubt over future earthquake shaking

Non-emphysematous chronic obstructive pulmonary disease is associated with diabetes mellitus

Background: Chronic obstructive pulmonary disease (COPD) has been classically divided into blue bloaters and pink puffers. The utility of these clinical subtypes is unclear. However, the broader distinction between airway-predominant and emphysema-predominant COPD may be clinically relevant. The objective was to define clinical features of emphysema-predominant and non-emphysematous COPD patients. Methods: Current and former smokers from the Genetic Epidemiology of COPD Study (COPDGene) had chest computed tomography (CT) scans with quantitative image analysis. Emphysema-predominant COPD was defined by low attenuation area at -950 Hounsfield Units (LAA-950) ≥10%. Non-emphysematous COPD was defined by airflow obstruction with minimal to no emphysema (LAA-950 < 5%). Results: Out of 4197 COPD subjects, 1687 were classified as emphysema-predominant and 1817 as non-emphysematous; 693 had LAA-950 between 5-10% and were not categorized. Subjects with emphysema-predominant COPD were older (65.6 vs 60.6 years, p < 0.0001) with more severe COPD based on airflow obstruction (FEV1 44.5 vs 68.4%, p < 0.0001), greater exercise limitation (6-minute walk distance 1138 vs 1331 ft, p < 0.0001) and reduced quality of life (St. George's Respiratory Questionnaire score 43 vs 31, p < 0.0001). Self-reported diabetes was more frequent in non-emphysematous COPD (OR 2.13, p < 0.001), which was also confirmed using a strict definition of diabetes based on medication use. The association between diabetes and non-emphysematous COPD was replicated in the ECLIPSE study. Conclusions: Non-emphysematous COPD, defined by airflow obstruction with a paucity of emphysema on chest CT scan, is associated with an increased risk of diabetes. COPD patients without emphysema may warrant closer monitoring for diabetes, hypertension, and hyperlipidemia and vice versa