Radiation Induces Metabolic Dysregulation in Pulmonary Fibroblasts

Rationale: Exposure of the lung to ionizing radiation, such as during radiotherapy, can result in pulmonary fibrosis (PF), which has few treatment options. PF is characterized by an accumulation of extracellular matrix proteins that form scar tissue, resulting in dyspnea, disruption of gas exchange, and even death. We and others have shown that metabolic reprogramming is a hallmark of idiopathic pulmonary fibrosis (IPF). IPF lung tissue, and lung fibroblasts treated with TGF-β, exhibit increased aerobic glycolysis with increased expression of lactate dehydrogenase A (LDHA) and excess production of lactate, leading to reduced extracellular pH that activates latent TGF-β. Here, we hypothesized that ionizing radiation would cause aerobic glycolytic metabolic dysregulation in primary human lung fibroblasts. Results: Primary non-fibrotic HLFs exposed to irradiation exhibited significant upregulation of Pyruvate Dehydrogenase Kinase (PDK1 (0.5 – 3-fold, p\u3c0.05) and LDHA (1.4-fold, p\u3c0.05). Cell viability was unaffected by increased radiation dose. Conclusions: Radiation increased fibroblast expression of genes involved in fibrotic phenotypes (αSMA) and aerobic glycolysis (PDK1 and LDHA), in a similar pattern to that seen in IPF fibroblasts. The metabolic changes are closely associated with creating a profibrotic extracellular environment in IPF by promoting an acidic environment. Our evidence suggests this phenomenon can be driven by radiation in lung fibroblasts and affirm that glycolytic reprogramming may also be a hallmark of radiation-induced fibrosis. Further understanding of the common mechanisms that create this metabolic shift could provide novel therapeutics for fibrosis treatment.https://scholarscompass.vcu.edu/gradposters/1158/thumbnail.jp

Logics for Unranked Trees: An Overview

Labeled unranked trees are used as a model of XML documents, and logical languages for them have been studied actively over the past several years. Such logics have different purposes: some are better suited for extracting data, some for expressing navigational properties, and some make it easy to relate complex properties of trees to the existence of tree automata for those properties. Furthermore, logics differ significantly in their model-checking properties, their automata models, and their behavior on ordered and unordered trees. In this paper we present a survey of logics for unranked trees

Exotic spacetimes, superconducting strings with linear momentum, and (not quite) all that

We derive the general exact vacuum metrics associated with a stationary (non static), non rotating, cylindrically symmetric source. An analysis of the geometry described by these vacuum metrics shows that they contain a subfamily of metrics that, although admitting a consistent time orientation, display "exotic" properties, such as "trapping" of geodesics and closed causal curves through every point. The possibility that such spacetimes could be generated by a superconducting string, endowed with a neutral current and momentum, has recently been considered by Thatcher and Morgan. Our results, however, differ from those found by Thatcher and Morgan, and the discrepancy is explained. We also analyze the general possibility of constructing physical sources for the exotic metrics, and find that, under certain restrictions, they must always violate the dominant energy condition (DEC). We illustrate our results by explicitly analyzing the case of concentric shells, where we find that in all cases the external vacuum metric is non exotic if the matter in the shells satisfies the DEC.Comment: 13 pages with no figures. Accepted in PR

Minimizing Tree Automata for Unranked Trees

International audienceAutomata for unranked trees form a foundation for XML schemas, querying and pattern languages. We study the problem of efficiently minimizing such automata. We start with the unranked tree automata (UTAs) that are standard in database theory, assuming bottom-up determinism and that horizontal recursion is represented by deterministic finite automata. We show that minimal UTAs in that class are not unique and that minimization is NP-hard. We then study more recent automata classes that do allow for polynomial time minimization. Among those, we show that bottom-up deterministic stepwise tree automata yield the most succinct representations

The transformative potential of reflective diaries for elite English cricketers

The sport of cricket has a history of its players suffering from mental health issues. The psychological study of cricket and, in particular, the attendant demands of participating at an elite level has not previously received rigorous academic attention. This study explored ten elite male cricketers’ experiences of keeping a daily reflective diary for one month during the competitive season. The aim was to assess how valuable qualitative diaries are in this field. Participants were interviewed regarding their appraisal of the methodology as a self‐help tool that could assist coping with performance pressures and wider life challenges. Three outcomes were revealed: first, that diary keeping was an effective opportunity to reflect upon the past and enhance one’s self (both as an individual and a performer); second, that diary keeping acted as a form of release that allowed participants to progress; and third, that diary keeping allowed participants to discover personal patterns of success that increased the likeliness of optimum performance

Association between exposure to environmental tobacco smoke and biomarkers of oxidative stress among patients hospitalised with acute myocardial infarction

Objective To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.<p></p> Design An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.<p></p> Setting Nine acute hospitals in Scotland.<p></p> Participants Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).<p></p> Intervention None.<p></p> Main outcome measures Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.<p></p> Results After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).<p></p> Conclusions Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.<p></p&gt

Adaptive walks on time-dependent fitness landscapes

The idea of adaptive walks on fitness landscapes as a means of studying evolutionary processes on large time scales is extended to fitness landscapes that are slowly changing over time. The influence of ruggedness and of the amount of static fitness contributions are investigated for model landscapes derived from Kauffman's $NK$ landscapes. Depending on the amount of static fitness contributions in the landscape, the evolutionary dynamics can be divided into a percolating and a non-percolating phase. In the percolating phase, the walker performs a random walk over the regions of the landscape with high fitness.Comment: 7 pages, 6 eps-figures, RevTeX, submitted to Phys. Rev.

The mortality rates and the space-time patterns of John Snow’s cholera epidemic map

Background Snow’s work on the Broad Street map is widely known as a pioneering example of spatial epidemiology. It lacks, however, two significant attributes required in contemporary analyses of disease incidence: population at risk and the progression of the epidemic over time. Despite this has been repeatedly suggested in the literature, no systematic investigation of these two aspects was previously carried out. Using a series of historical documents, this study constructs own data to revisit Snow’s study to examine the mortality rate at each street location and the space-time pattern of the cholera outbreak. Methods This study brings together records from a series of historical documents, and prepares own data on the estimated number of residents at each house location as well as the space-time data of the victims, and these are processed in GIS to facilitate the spatial-temporal analysis. Mortality rates and the space-time pattern in the victims’ records are explored using Kernel Density Estimation and network-based Scan Statistic, a recently developed method that detects significant concentrations of records such as the date and place of victims with respect to their distance from others along the street network. The results are visualised in a map form using a GIS platform. Results Data on mortality rates and space-time distribution of the victims were collected from various sources and were successfully merged and digitised, thus allowing the production of new map outputs and new interpretation of the 1854 cholera outbreak in London, covering more cases than Snow’s original report and also adding new insights into their space-time distribution. They confirmed that areas in the immediate vicinity of the Broad Street pump indeed suffered from excessively high mortality rates, which has been suspected for the past 160 years but remained unconfirmed. No distinctive pattern was found in the space-time distribution of victims’ locations. Conclusions The high mortality rates identified around the Broad Street pump are consistent with Snow’s theory about cholera being transmitted through contaminated water. The absence of a clear space-time pattern also indicates the water-bourne, rather than the then popular belief of air bourne, nature of cholera. The GIS data constructed in this study has an academic value and would cater for further research on Snow’s map