Warping and F-term uplifting

We analyse the effective supergravity model of a warped compactification with matter on D3 and D7-branes. We find that the main effect of the warp factor is to modify the F-terms while leaving the D-terms invariant. Hence warped models with moduli stabilisation and a small positive cosmological constant resulting from a large warping can only be achieved with an almost vanishing D-term and a F-term uplifting. By studying string-motivated examples with gaugino condensation on magnetised D7-branes, we find that even with a vanishing D-term, it is difficult to achieve a Minkowski minimum for reasonable parameter choices. When coupled to an ISS sector the AdS vacua is uplifted, resulting in a small gravitino mass for a warp factor of order 10^-5.Comment: 24 pages, v3: typos, minor clarifications adde

Nursing home nurses’ and community-dwelling older adults’ reported knowledge, attitudes, and behavior toward antibiotic use

Abstract Background Antibiotic overuse causes antibiotic resistance, one of the most important threats to human health. Older adults, particularly those in nursing homes, often receive antibiotics when they are not indicated. Methods To understand knowledge, attitudes, and behaviors of nursing home (NH) nurses and community-dwelling older adults towards antibiotic use, especially in clinical situations consistent with antibiotic overuse, we conducted a mixed-method survey in two NHs and one Family Medicine clinic in North Carolina, among English-speaking nurses and community-dwelling, cognitively intact adults aged 65 years or older. Based on the Knowledge-Attitude-Practice model, the survey assessed knowledge, attitudes, and behavior towards antibiotic use, including three vignettes designed to elicit possible antibiotic overuse: asymptomatic bacteriuria (ASB), a viral upper respiratory illness (URI), and a wound from a fall. Results Of 31 NH nurses and 66 community-dwelling older adults, 70% reported knowledge of the dangers of taking antibiotics. Nurses more often reported evidence-based attitudes towards antibiotics than older adults, except 39% agreed with the statement “by the time I am sick enough to go to the doctor with a cold, I expect an antibiotic”, while only 28% of older adults agreed with it. A majority of nurses did not see the need for antibiotics in any of the three vignettes: 77% for the ASB vignette, 87% for the URI vignette, and 97% for the wound vignette. Among older adults, 50% did not perceive a need for antibiotics in the ASB vignette, 58% in the URI vignette, and 74% in the wound vignette. Conclusions While a substantial minority had no knowledge of the dangers of antibiotic use, non-evidence-based attitudes towards antibiotics, and behaviors indicating inappropriate management of suspected infections, most NH nurses and community-dwelling older adults know the harms of antibiotic use and demonstrate evidence-based attitudes and behaviors. However, more work is needed to improve the knowledge, attitudes and behaviors that may contribute to antibiotic overuse

Activation of caspase-1 by the NLRP3 inflammasome regulates the NADPH oxidase NOX2 to control phagosome function

Phagocytosis is a fundamental cellular process that is pivotal for immunity as it coordinates microbial killing, innate immune activation and antigen presentation. An essential step in this process is phagosome acidification, which regulates a number of functions of these organelles that allow them to participate in processes essential to both innate and adaptive immunity. Here we report that acidification of phagosomes containing Gram-positive bacteria is regulated by the NLRP3-inflammasome and caspase-1. Active caspase-1 accumulates on phagosomes and acts locally to control the pH by modulating buffering by the NADPH oxidase NOX2. These data provide insight into a mechanism by which innate immune signals can modify cellular defenses and establish a new function for the NLRP3-inflammasome and caspase-1 in host defense

Multifunctional proteins revealed by overlapping clustering in protein interaction network

Motivation: Multifunctional proteins perform several functions. They are expected to interact specifically with distinct sets of partners, simultaneously or not, depending on the function performed. Current graph clustering methods usually allow a protein to belong to only one cluster, therefore impeding a realistic assignment of multifunctional proteins to clusters

In vitro neutrophil migration is associated with inhaled corticosteroid treatment and serum cytokines in pediatric asthma.

Background: Different asthma phenotypes are driven by molecular endotypes. A Th1-high phenotype is linked to severe, therapy-refractory asthma, subclinical infections and neutrophil inflammation. Previously, we found neutrophil granulocytes (NGs) from asthmatics exhibit decreased chemotaxis towards leukotriene B4 (LTB4), a chemoattractant involved in inflammation response. We hypothesized that this pattern is driven by asthma in general and aggravated in a Th1-high phenotype. Methods: NGs from asthmatic nd healthy children were stimulated with 10 nM LTB4/100 nM N-formylmethionine-leucyl-phenylalanine and neutrophil migration was documented following our prior SiMA (simplified migration assay) workflow, capturing morphologic and dynamic parameters from single-cell tracking in the images. Demographic, clinical and serum cytokine data were determined in the ALLIANCE cohort. Results: A reduced chemotactic response towards LTB4 was confirmed in asthmatic donors regardless of inhaled corticosteroid (ICS) treatment. By contrast, only NGs from ICS-treated asthmatic children migrate similarly to controls with the exception of Th1-high donors, whose NGs presented a reduced and less directed migration towards the chemokines. ICS-treated and Th1-high asthmatic donors present an altered surface receptor profile, which partly correlates with migration. Conclusions: Neutrophil migration in vitro may be affected by ICS-therapy or a Th1-high phenotype. This may be explained by alteration of receptor expression and could be used as a tool to monitor asthma treatment