Mechanically-driven Stem Cell Separation in Tissues caused by Proliferating Daughter Cells

The homeostasis of epithelial tissue relies on a balance between the self-renewal of stem cell populations, cellular differentiation, and loss. Although this balance needs to be tightly regulated to avoid pathologies, such as tumor growth, the regulatory mechanisms, both cell-intrinsic and collective, which ensure tissue steady-state are still poorly understood. Here, we develop a computational model that incorporates basic assumptions of stem cell renewal into distinct populations and mechanical interactions between cells. We find that the model generates unexpected dynamic features: stem cells repel each other in the bulk tissue and are thus found rather isolated, as in a number of in vivo contexts. By mapping the system onto a gas of passive Brownian particles with effective repulsive interactions, that arise from the generated flows of differentiated cells, we show that we can quantitatively describe such stem cell distribution in tissues. The interaction potential between a pair of stem cells decays exponentially with a characteristic length that spans several cell sizes, corresponding to the volume of cells generated per stem cell division. Our findings may help understanding the dynamics of normal and cancerous epithelial tissues

Preschool children's health and its association with parental education and individual living conditions in East and West Germany

BACKGROUND: Social inequalities in health exist globally and are a major public health concern. This study focus on a systematic investigation into the associations between health indicators, living conditions and parental educational level as indicator of the social status of 6-year-old children living in West and East Germany in the decade after re-unification. Explanations of observed associations between parental education and health indicators were examined. METHODS: All boys and girls entering elementary school and living in predefined areas of East and West Germany were invited to participate in a series of cross-sectional surveys conducted between 1991 and 2000. Data of 28,888 German children with information on parental education were included in the analysis. Information about educational level of the parents, individual living conditions, symptoms and diagnoses of infectious diseases and allergies were taken from questionnaire. At the day of investigation, atopic eczema was diagnosed by dermatologists, blood was taken for the determination of allergen-specific immuno-globulin E, height and weight was measured and lung function tests were done in subgroups. Regression analysis was applied to investigate the associations between the health indicators and parental educational level as well as the child's living conditions. Gender, urban/rural residency and year of survey were used to control for confounding. RESULTS: Average response was 83% in East Germany and 71% in West Germany. Strong associations between health indicators and parental education were observed. Higher educated parents reported more diagnoses and symptoms than less educated. Children of higher educated parents were also more often sensitized against grass pollen or house dust mites, but had higher birth weights, lower airway resistance and were less overweight at the age of six. Furthermore, most of the health indicators were significantly associated with one or more living conditions such as living as a single child, unfavourable indoor air, damp housing condition, maternal smoking during pregnancy or living near a busy road. The total lung capacity and the prevalence of an atopic eczema at the day of investigation were the only health indicators those did not show associations with any of the predictor variables. CONCLUSION: Despite large differences in living conditions and evidence that some poor health outcomes were directly associated with poor living conditions, only few indicators demonstrated poorer health in social disadvantaged children. These were in both parts of Germany increased levels of overweight, higher airway resistance and, in East Germany only, reduced height in children with lower educated parents compared to those of higher education. In both East and West Germany, higher prevalence of airway symptoms was associated with a damp housing condition, and lower birth weight, reduced height and increased airway resistance at the age of six were associated with maternal smoking during pregnancy. The latter explained to a large extent the difference in birth weight and airway resistance between the educational groups

Dynamic and thermodynamic properties of the generalised diamond chain model for azurite

The natural mineral azurite Cu3(CO3)2(OH)2 is an interesting spin-1/2 quantum antiferromagnet. Recently, a generalised diamond chain model has been established as a good description of the magnetic properties of azurite with parameters placing it in a highly frustrated parameter regime. Here we explore further properties of this model for azurite. First, we determine the inelastic neutron scattering spectrum in the absence of a magnetic field and find good agreement with experiments, thus lending further support to the model. Furthermore, we present numerical data for the magnetocaloric effect and predict that strong cooling should be observed during adiabatic (de)magnetisation of azurite in magnetic fields slightly above 30T. Finally, the presence of a dominant dimer interaction in azurite suggests the use of effective Hamiltonians for an effective low-energy description and we propose that such an approach may be useful to fully account for the three-dimensional coupling geometry.Comment: 19 pages, 6 figures; to appear in: J. Phys.: Condens. Matter (special issue on geometrically frustrated magnetism

Booting the booters: Evaluating the effects of police interventions in the market for Denial-of-Service attacks

Illegal booter services offer denial of service (DoS) attacks for a fee of a few tens of dollars a month. Internationally, police have implemented a range of different types of intervention aimed at those using and offering booter services, including arrests and website takedown. In order to measure the impact of these interventions we look at the usage reports that booters themselves provide and at measurements of reflected UDP DoS attacks, leveraging a five year measurement dataset that has been statistically demonstrated to have very high coverage. We analysed time series data (using a negative binomial regression model) to show that several interventions have had a statistically significant impact on the number of attacks. We show that, while there is no consistent effect of highly-publicised court cases, takedowns of individual booters precede significant, but short-lived, reductions in recorded attack numbers. However, more wide-ranging disruptions have much longer effects. The closure of HackForums' booter market reduced attacks for 13 weeks globally (and for longer in particular countries) and the FBI's coordinated operation in December 2018, which involved both takedowns and arrests, reduced attacks by a third for at least 10 weeks and resulted in lasting change to the structure of the booter market.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/M020320/1]

Predictors of overweight and obesity in five to seven-year-old children in Germany: Results from cross-sectional studies

BACKGROUND: Childhood obesity is a serious public health problem and epidemiological studies are important to identify predictive factors. It is the aim of this study to analyse factors associated with overweight/obesity in samples of German children. METHODS: 35,434 five to seven year-old children (50.9% boys) participated in cross-sectional studies between 1991 and 2000 in several rural and urban areas in East and West Germany. Weight and height were measured and body mass index was calculated. International cut-off points, recommended by the International Obesity Task Force, were used to classify childhood overweight and obesity. Predictive modelling was employed to analyse independently associated factors, using logistic regression to adjust for confounding. RESULTS: 15.5% were overweight, and 4.3% were obese. Female sex, other than German nationality, smoking in the living place and increasing birth weight were found to increase the odds of overweight and obesity, while increasing educational level, living space > 75 m2 and breastfeeding for more than three months were inversely associated. CONCLUSION: The findings add to the evidence informing public health action, both through health promotion strategies (promoting breastfeeding, tackling smoking) and wider societal change management (addressing children from migrant families and families with low educational level)

Spectroscopic evidence of large aspherical β-NAT particles involved in denitrification in the December 2011 Arctic stratosphere

We analyze polar stratospheric cloud (PSC) signatures in airborne MIPAS-STR (Michelson Interferometer for Passive Atmospheric Sounding – STRatospheric aircraft) observations in the spectral regions from 725 to 990 and 1150 to 1350 cm−1 under conditions suitable for the existence of nitric acid trihydrate (NAT) above northern Scandinavia on 11 December 2011. The high-resolution infrared limb emission spectra of MIPAS-STR show a characteristic “shoulder-like” signature in the spectral region around 820 cm−1, which is attributed to the ν2 symmetric deformation mode of NO3− in β-NAT. Using radiative transfer calculations involving Mie and T-Matrix methods, the spectral signatures of spherical and aspherical particles are simulated. The simulations are constrained using collocated in situ particle measurements. Simulations assuming highly aspherical spheroids with aspect ratios (AR) of 0.1 or 10.0 and a lognormal particle mode with a mode radius of 4.8 µm reproduce the observed spectra to a high degree. A smaller lognormal mode with a mode radius of 2.0 µm, which is also taken into account, plays only a minor role. Within the scenarios analyzed, the best overall agreement is found for elongated spheroids with AR  =  0.1. Simulations of spherical particles and spheroids with AR  =  0.5 and 2.0 return results very similar to each other and do not allow us to reproduce the signature around 820 cm−1. The observed “shoulder-like” signature is explained by the combination of the absorption/emission and scattering characteristics of large highly aspherical β-NAT particles. The size distribution supported by our results corresponds to ∼ 9 ppbv of gas-phase equivalent HNO3 at the flight altitude of ∼ 18.5 km. The results are compared with the size distributions derived from the in situ observations, a corresponding Chemical Lagrangian Model of the Stratosphere (CLaMS) simulation, and excess gas-phase HNO3 observed in a nitrification layer directly below the observed PSC. The presented results suggest that large highly aspherical β-NAT particles involved in denitrification of the polar stratosphere can be identified by means of passive infrared limb emission measurements

Heavy Ion Carcinogenesis and Human Space Exploration

Prior to the human exploration of Mars or long duration stays on the Earth s moon, the risk of cancer and other diseases from space radiation must be accurately estimated and mitigated. Space radiation, comprised of energetic protons and heavy nuclei, has been show to produce distinct biological damage compared to radiation on Earth, leading to large uncertainties in the projection of cancer and other health risks, while obscuring evaluation of the effectiveness of possible countermeasures. Here, we describe how research in cancer radiobiology can support human missions to Mars and other planets

Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85×10−20 and 7.08×10−19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78×10−4 and P = 1.95×10−3). The “top” SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28×10−7−4.46×10−8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels

Bringing New Opportunities to Develop Statistical Software and Data Analysis Tools in Romania

In the last decade, open source programming technology is widely used among statisticians for developing a new statistical software and data analysis. This is R software environment and the main objective of this paper is to underline the importance of R for statistical computations, data analysis, visualization and applications in various fields. Regarding to this, the paper is primarily intended for people already familiar with common statistical concepts. Thus the statistical methods used to illustrate the R performance are not explained in detail. The main intention is to offer an overview to get started, to motivate beginners by illustrating the flexibility of R, and to show how simply it enables the user to carry out statistical computations