Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development

An Evolutionary Method for the Minimum Toll Booth Problem: the Methodology

This paper considers the minimum toll booth problem (MINTB) for determining a tolling strategy in a transportation network that requires the least number of toll locations, and simultaneously causes the most efficient use of the network. The paper develops a methodology for using the genetic algorithm to solve MINTB and presents the algorithm GAMINTB. The proposed method is tested and validated through a computational study with six example networks. Additional numerical test discovers some interesting properties for the proposed method, and provides guidelines for further application of the GAMINTB

Identifying barriers to vaccination intention at walk-in vaccination facilities in deprived neighbourhoods:A cross-sectional survey

Objectives: Low COVID-19 vaccination adherence in deprived neighbourhoods is problematic since the prevalence of chronic diseases associated with mortality rates due to COVID-19 is higher in these populations. The aim of this study is to provide an insight about beliefs and considerations relating to vaccination intention among inhabitants of deprived neighbourhoods in the Netherlands. Design: Cross-sectional survey. Setting: Easily accessible vaccination facilities at markets in deprived neighbourhoods in the Netherlands. Participants: Participants were recruited at three vaccination facilities that were set up at markets in deprived neighbourhoods in Rotterdam. A total of 124 surveys were retained for analysis. Main outcome measure: Intention to get vaccinated against COVID-19. Results: The survey was filled out by 124 respondents; 62 % had - prior to visiting the easily accessible locations - intended to get a COVID-19 vaccine and 38 % were hesitant (22.3 % had doubts and 15.7 % did not plan to get vaccinated). Many people mentioned the convenience of an easily accessible location nearby. At the bivariate level, the influence of information from the family was associated with vaccination intention (p &lt; 0.01). In a logistic regression model, both fear of vaccination and fear of side-effects were significantly associated with vaccination intention (ORs 0.56 (CI 0.35–0.89) and 0.47 (CI 0.30–0.73)). Conclusion: The accessibility of a vaccination facility, family influence and fear are relevant factors for the intention to get vaccinated against COVID-19 in people living in deprived neighbourhoods. Interventions should address these factors in order to increase vaccination uptake.</p

Радиационный контроль в современных процессах нефтедобычи

Рассмотрены вопросы радиоэкологического контроля на нефтедобывающих предприятиях. Показана возможность использования программных продуктов для обеспечения комплексной оценки радиационной обстановки на объектах и территориях нефтедобывающих предприятий. Освещены основные аспекты взаимодействия научно-исследовательских лабораторий с Центрами экологической безопасности предприятий и их значение для эффективного ресурсосбережения в современных процессах нефтедобычи

Why does entrepreneurial orientation affect company performance?

© 2019 Strategic Management Society Research summary: To better understand why entrepreneurial orientation (EO) is positively associated with company performance, we propose and test a reconceptualization of how the components of EO (risk-taking, innovativeness, proactiveness) combine in driving performance. Drawing on financial economics theory, our conceptualization highlights that all three components positively contribute to performance, but in different ways. Risk-taking has a direct positive relationship with performance, which can be understood through the risk–return tradeoff that is central in financial economics theory. The relationship between risk-taking and performance is conditional on the level of innovativeness and thus innovativeness contributes to performance through its effect on the type of risk-taking. Proactiveness contributes to performance through its positive effect on the level of risk-taking. Managerial summary: This study analyzes three key drivers of company performance: risk-taking, innovativeness, and proactiveness. We show that constructive risk-taking is the central driver of company performance, mirroring the principle of risk and return in financial investment settings. Risk- taking that is associated with innovation has a particularly strong positive relationship with performance, consistent with innovation being a driver of growth and profitability. More proactive firms tend to take on more risk and thus also perform better than less proactive firms

A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.

Most MPN patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells we developed a novel strategy (KISMET) which utilises the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional siRNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the MAPK pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by MPL-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34-cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34+ progenitors. These data link aberrant MAPK activation to the MPN phenotype and identify it as a potential therapeutic target in CALR-mutant positive MPNs.Leukemia accepted article preview online, 14 October 2016. doi:10.1038/leu.2016.280.Work in the Green lab is supported by Leukemia and Lymphoma Research, Cancer Research UK, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre and the Leukemia & Lymphoma Society of America. WW is supported by the Austrian Science Foundation (J 3578-B21). CGA is supported by Kay Kendall Leukaemia Fund clinical research fellowship. UM is supported by a Cancer Research UK Clinician Scientist Fellowship. Work in the Huntly lab is supported by the European Research Council, the MRC (UK), Bloodwise, the Cambridge NIHR funded BRC, KKLF and a WT/MRC Stem Cell centre grant. Work in the Green and Huntly Labs is supported by core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research (100140/z/12/z) and Wellcome Trust-MRC Cambridge Stem Cell Institute (097922/Z/11/Z)

The Crystal Ball Data Acquisition System

The data acquisition system for the Crystal Ball project at SLAC is described. A PDP-11/t55 using RSX-11M connected to the SLAC Triplex is the basis of the system. A "physics pipeline" allows physicists to write their own equipment-monitoring or physics tasks which require event sampling. As well, an interactive analysis package (MULTI) is in the pipeline. Histogram collection and display on the PDP are implemented using the Triplex histogramming package. Various interactive event displays are also implemented

Callisto's Atmosphere and Its Space Environment: Prospects for the Particle Environment Package on Board JUICE

The JUpiter ICy moons Explorer (JUICE) of the European Space Agency will investigate Jupiter and its icy moons Europa, Ganymede, and Callisto, with the aim to better understand the origin and evolution of our Solar System and the emergence of habitable worlds around gas giants. The Particle Environment Package (PEP) on board JUICE is designed to measure neutrals and ions and electrons at thermal, suprathermal, and radiation belt energies (eV to MeV). In the vicinity of Callisto, PEP will characterize the plasma environment, the outer parts of Callisto's atmosphere and ionosphere and their interaction with Jupiter's dynamic magnetosphere. Roughly 20 Callisto flybys with closest approaches between 200 and 5,000 km altitude are planned over the course of the JUICE mission. In this article, we review the state of the art regarding Callisto's ambient environment and magnetospheric interaction with recent modeling efforts for Callisto's atmosphere and ionosphere. Based on this review, we identify science opportunities for the PEP observations to optimize scientific insight gained from the foreseen JUICE flybys. These considerations will inform both science operation planning of PEP and JUICE and they will guide future model development for Callisto's atmosphere, ionosphere, and their interaction with the plasma environment