Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages.

Genome-wide investigations of host-pathogen interactions are often limited by analyses of mixed populations of infected and uninfected cells, which lower sensitivity and accuracy. To overcome these obstacles and identify key mechanisms by which Zika virus (ZIKV) manipulates host responses, we developed a system that enables simultaneous characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring uninfected primary human macrophages. We demonstrate that transcriptional responses in ZIKV-infected macrophages differed radically from those in uninfected neighbors and that studying the cell population as a whole produces misleading results. Notably, the uninfected population of macrophages exhibits the most rapid and extensive changes in gene expression, related to type I IFN signaling. In contrast, infected macrophages exhibit a delayed and attenuated transcriptional response distinguished by preferential expression of IFNB1 at late time points. Biochemical and genomic studies of infected macrophages indicate that ZIKV infection causes both a targeted defect in the type I IFN response due to degradation of STAT2 and reduces RNA polymerase II protein levels and DNA occupancy, particularly at genes required for macrophage identity. Simultaneous evaluation of transcriptomic and epigenetic features of infected and uninfected macrophages thereby reveals the coincident evolution of dominant proviral or antiviral mechanisms, respectively, that determine the outcome of ZIKV exposure

Mindfulness meditation targets transdiagnostic symptoms implicated in stress-related disorders: Understanding relationships between changes in mindfulness, sleep quality, and physical symptoms

Mindfulness-Based Stress Reduction (MBSR) is an 8-week meditation program known to improve anxiety, depression, and psychological well-being. Other health-related effects, such as sleep quality, are less well established, as are the psychological processes associated with therapeutic change. This prospective, observational study (n=213) aimed to determine whether perseverative cognition, indicated by rumination and intrusive thoughts, and emotion regulation, measured by avoidance, thought suppression, emotion suppression, and cognitive reappraisal, partly accounted for the hypothesized relationship between changes in mindfulness and two health-related outcomes: sleep quality and stress-related physical symptoms. As expected, increased mindfulness following the MBSR program was directly correlated with decreased sleep disturbance (r=-0.21, p=0.004) and decreased stress-related physical symptoms (r=-0.38, p<0.001). Partial correlations revealed that pre-post changes in rumination, unwanted intrusive thoughts, thought suppression, experiential avoidance, emotion suppression, and cognitive reappraisal each uniquely accounted for up to 32% of the correlation between the change in mindfulness and change in sleep disturbance and up to 30% of the correlation between the change in mindfulness and change in stress-related physical symptoms. Results suggest that the stress-reducing effects of MBSR are due, in part, to improvements in perseverative cognition and emotion regulation, two “transdiagnostic” mental processes that cut across stress-related disorders

SRG110 Stirling Generator Dynamic Simulator Vibration Test Results and Analysis Correlation

The U.S. Department of Energy (DOE), Lockheed Martin (LM), and NASA Glenn Research Center (GRC) have been developing the Stirling Radioisotope Generator (SRG110) for use as a power system for space science missions. The launch environment enveloping potential missions results in a random input spectrum that is significantly higher than historical radioisotope power system (RPS) launch levels and is a challenge for designers. Analysis presented in prior work predicted that tailoring the compliance at the generator-spacecraft interface reduced the dynamic response of the system thereby allowing higher launch load input levels and expanding the range of potential generator missions. To confirm analytical predictions, a dynamic simulator representing the generator structure, Stirling convertors and heat sources were designed and built for testing with and without a compliant interface. Finite element analysis was performed to guide the generator simulator and compliant interface design so that test modes and frequencies were representative of the SRG110 generator. This paper presents the dynamic simulator design, the test setup and methodology, test article modes and frequencies and dynamic responses, and post-test analysis results. With the compliant interface, component responses to an input environment exceeding the SRG110 qualification level spectrum were all within design allowables. Post-test analysis included finite element model tuning to match test frequencies and random response analysis using the test input spectrum. Analytical results were in good overall agreement with the test results and confirmed previous predictions that the SRG110 power system may be considered for a broad range of potential missions, including those with demanding launch environments

Stress-induced changes in the expression of monocytic β2-integrins: The impact of arousal of negative affect and adrenergic responses to the Anger Recall Interview

Adhesion of circulating monocytes to the vascular endothelium is one of the earliest steps in the development of atherosclerosis. This leukocyte-to-endothelium interaction is mediated in part by β2-integrins, a group of cell adhesion molecules that bind to endothelial ligands. Given the significance of this interaction to atherogenesis, we examined the effects of stress, operationalized as the arousal of negative affect (NA) and cardiovascular and catecholamine responses to the Anger Recall Interview (ARI), on the expression of LFA-1 (CD11a), Mac-1 (CD11b) and p150/95 (CD11c) on circulating monocytes (CD14+). Subjects were 173 healthy, nonsmoking men and women (60% men, 40% minorities, aged 18–49 year). Arousal of NA, cardiovascular responses (heart rate [HR], systolic blood pressure [SBP], diastolic blood pressure [DBP]), circulating catecholamines (epinephrine [Epi], norepinephrine [Ne]) and β2-integrin (CD11/CD18) expression were determined prior to and following the ARI. The principal findings were that the ARI, on average, induced a decrease in monocyte expression of β2-integrins. However, after adjusting for age, sex, body mass index, exercise status, and baseline level of β2-integrin expression, those individuals who showed the largest increases in NA, Ne and DBP during the ARI showed an increase in monocyte β2-integrin expression. Thus, heightened psychological and physiological stress responses induced phenotypic changes in monocytic expression of β2-integrins that are consistent with the role of monocytes/macrophages in vascular inflammation and increased risk of atherosclerotic cardiovascular disease

E-commerce y su influencia en la rentabilidad de la empresa Grupo Balboa Morales S.A.C., Lima, SJL, 2022

La presente investigación tuvo como objetivo general determinar la influencia del E-commerce en la rentabilidad de la empresa Grupo Balboa Morales S.A.C., Lima, SJL, 2022. El tipo de investigación fue explicativa con diseño correlacional (no experimental-transversal). Se obtuvo como población y muestra 20 trabajadores de dicha empresa. La técnica utilizada fue la encuesta, teniendo como instrumento el cuestionario y se validó mediante la correlación lineal entre las variables de estudio donde se contrastó las 4 hipótesis específicas y 1 general. La investigación llegó a la conclusión que el E-commerce sí influye significativamente en la variable independiente (rentabilidad) de la empresa Grupo Balboa Morales S.A.C., debido a que se obtuvo que el p valor de 0.006, menor a 0.05, por lo cual se acepta la hipótesis alterna y se rechaza la hipótesis nula, es decir que el E-commerce tiene un efecto sobre la rentabilidad de la empres

SRG110 Stirling Generator Dynamic Simulator Vibration Test Results and Analysis Correlation

The U.S. Department of Energy (DOE), Lockheed Martin (LM), and NASA Glenn Research Center (GRC) have been developing the Stirling Radioisotope Generator (SRG110) for use as a power system for space science missions. The launch environment enveloping potential missions results in a random input spectrum that is significantly higher than historical RPS launch levels and is a challenge for designers. Analysis presented in prior work predicted that tailoring the compliance at the generator-spacecraft interface reduced the dynamic response of the system thereby allowing higher launch load input levels and expanding the range of potential generator missions. To confirm analytical predictions, a dynamic simulator representing the generator structure, Stirling convertors and heat sources was designed and built for testing with and without a compliant interface. Finite element analysis was performed to guide the generator simulator and compliant interface design so that test modes and frequencies were representative of the SRG110 generator. This paper presents the dynamic simulator design, the test setup and methodology, test article modes and frequencies and dynamic responses, and post-test analysis results. With the compliant interface, component responses to an input environment exceeding the SRG110 qualification level spectrum were all within design allowables. Post-test analysis included finite element model tuning to match test frequencies and random response analysis using the test input spectrum. Analytical results were in good overall agreement with the test results and confirmed previous predictions that the SRG110 power system may be considered for a broad range of potential missions, including those with demanding launch environments

Influenza research database: an integrated bioinformatics resource for influenza research and surveillance.

BackgroundThe recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics.DesignThe Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly-accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user-friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in-protected 'workbench' spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature.ResultsTo demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross-protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks.ConclusionsThe IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics

What goes around comes around. Exploring how skilled migrant founder–managers of SMEs recruit and retain international talent

Abstract Purpose – This micro-level study unpacks the recruitment and retention of international professionals to small and medium-sized enterprises (SMEs). The study highlights the influence of the founders’ international experience when applying organisational-level (meso) policies and practices. With their insider experience as skilled migrants, we share how the founders in each of the SMEs mobilised career capital into human resource management (HRM) strategies. Design/methodology/approach – Combining literature on SMEs and skilled migrants’ careers, we draw upon intelligent career theory to illuminate the recruitment and retention of self-initiated expatriates and skilled migrants in SMEs. With three SME case studies as samples–one micro, one small and one medium-sized organisation in Ireland–we consider the influence of the founders’ international experience in the design and application of formal and informal HRM strategies (at the organisational level) that are operationalised to recruit and retain international talent to/in these organisations. Findings – The HRM practices in the three SME cases in this paper, each run by migrant founders, vary from formalised (for our medium-sized organisation), semi-formalised (for our small-sized organisation) to ad hoc and tailor-made (for our micro-sized organisation). These particular SMEs were often more receptive to hiring other migrants. The important role of the three SME case studies’ skilled migrant founders and their own international career experiences was apparent in the particular HRM approaches they adopted. The relevance of intelligent career theory when applying micro-level findings at the meso-organisational level is shown. Originality/value – The paper presents how the international experience of founder–managers, in turn, impacts on the HRM practices and policies that are implemented to recruit and retain international employees. The study highlights how both organisation size and founder-manager international experience influence the degree of customisation of HRM practices and policies in SMEs, specifically pertaining to the recruitment and retention of self-initiated expatriates and skilled migrant employees. The heterogeneity within the sub-categories encompassed under the umbrella label of SME is emphasised; validating our case study approach, where nuance and detail of the specific organisation can be shared

Decreased symptoms of depression after mindfulness-based stress reduction: potential moderating effects of religiosity, spirituality, trait mindfulness, sex, and age

Objective: mindfulness-based stress reduction (MBSR) is a secular meditation training program that reduces depressive symptoms. Little is known, however, about the degree to which a participant's spiritual and religious background, or other demographic characteristics associated with risk for depression, may affect the effectiveness of MBSR. Therefore, this study tested whether individual differences in religiosity, spirituality, motivation for spiritual growth, trait mindfulness, sex, and age affect MBSR effectiveness.Methods: as part of an open trial, multiple regression was used to analyze variation in depressive symptom outcomes among 322 adults who enrolled in an 8-week, community-based MBSR program.Results: as hypothesized, depressive symptom severity decreased significantly in the full study sample (d=0.57; p&lt;0.01). After adjustment for baseline symptom severity, moderation analyses revealed no significant differences in the change in depressive symptoms following MBSR as a function of spirituality, religiosity, trait mindfulness, or demographic variables. Paired t tests found consistent, statistically significant (p&lt;0.01) reductions in depressive symptoms across all subgroups by religious affiliation, intention for spiritual growth, sex, and baseline symptom severity. After adjustment for baseline symptom scores, age, sex, and religious affiliation, a significant proportion of variance in post-MBSR depressive symptoms was uniquely explained by changes in both spirituality (?=?0.15; p=0.006) and mindfulness (?=?0.17; p&lt;0.001).Conclusions: these findings suggest that MBSR, a secular meditation training program, is associated with improved depressive symptoms regardless of affiliation with a religion, sense of spirituality, trait level of mindfulness before MBSR training, sex, or age. Increases in both mindfulness and daily spiritual experiences uniquely explained improvement in depressive symptom