Alien Registration- Levesque, George A. (Limestone, Aroostook County)

https://digitalmaine.com/alien_docs/34916/thumbnail.jp

The Effective Temperatures and Physical Properties of Magellanic Cloud Red Supergiants: The Effects of Metallicity

We use the MARCS stellar atmosphere to derive the physical properties of 36 red supergiants (RSGs) in the LMC, and 39 RSGs in the SMC using moderate-resolution optical spectrophotometry (4000-9000A) and broad-band colors (V-R, V-K). The results from the dereddened V-R colors are in good agreement with those derived from the spectrophotometry, but the dereddened V-K colors give temperatures that are 3-4% warmer for the SMC data, with the LMC and Milky Way showing a smaller but similar effect. We conclude that this discrepancy is due to the limitations of 1D models. Our newly derived effective temperatures and bolometric luminosities bring the Magellanic Cloud RSGs into good agreement with stellar evolutionary models that include the effects of rotation. A typical M2~I in the SMC is about 150 K cooler than its Galactic counterpart; one in the LMC is about 50 K cooler. This is in the sense expected due to the lower chemical abundances in the SMC and LMC, although it is not sufficient to explain the shift in average RSG spectral type seen between the SMC, LMC, and Milky Way. Instead, that is due primarily to the change in Hayashi limit with metallicity, as first proposed by Elias et al. (1985). Finally, our study confirms that many RSGs in the Magellanic Clouds are significantly more reddened than OB stars, consistent with our recent findings for Galactic stars that circumstellar dust may contribute several magnitudes of extra visual extinction.Comment: Accepted by the Astrophysical Journa

Liquid-Liquid Phase Transition for an Attractive Isotropic Potential with Wide Repulsive Range

Recent experimental and theoretical results have shown the existence of a liquid-liquid phase transition in isotropic systems, such as biological solutions and colloids, whose interaction can be represented via an effective potential with a repulsive soft-core and an attractive part. We investigate how the phase diagram of a schematic general isotropic system, interacting via a soft-core squared attractive potential, changes by varying the parameters of the potential. It has been shown that this potential has a phase diagram with a liquid-liquid phase transition in addition to the standard gas-liquid phase transition and that, for a short-range soft-core, the phase diagram resulting from molecular dynamics simulations can be interpreted through a modified van der Waals equation. Here we consider the case of soft-core ranges comparable with or larger than the hard-core diameter. Because an analysis using molecular dynamics simulations of such systems or potentials is too time-demanding, we adopt an integral equation approach in the hypernetted-chain approximation. Thus we can estimate how the temperature and density of both critical points depend on the potential's parameters for large soft-core ranges. The present results confirm and extend our previous analysis, showing that this potential has two fluid-fluid critical points that are well separated in temperature and in density only if there is a balance between the attractive and repulsive part of the potential. We find that for large soft-core ranges our results satisfy a simple relation between the potential's parameters

Le FORUM, Vol. 37 No. 4

https://digitalcommons.library.umaine.edu/francoamericain_forum/1039/thumbnail.jp

Selective APRIL Blockade Delays Systemic Lupus Erythematosus in Mouse

SLE pathogenesis is complex, but it is now widely accepted that autoantibodies play a key role in the process by forming excessive immune complexes; their deposits within tissues leading to inflammation and functional damages. A proliferation inducing ligand (APRIL) is a member of the tumor necrosis factor (TNF) superfamily mediating antibody-producing plasma cell (PC)-survival that may be involved in the duration of pathogenic autoantibodies in lupus. We found significant increases of APRIL at the mRNA and protein levels in bone marrow but not spleen cells from NZB/W lupus mice, as compared to control mice. Selective antibody-mediated APRIL blockade delays disease development in this model by preventing proteinuria, kidney lesions, and mortality. Notably, this was achieved by decreasing anti-DNA and anti-chromatin autoantibody levels, without any perturbation of B- and T- cell homeostasis. Thus, anti-APRIL treatment may constitute an alternative therapy in SLE highly specific to PCs compared to other B-cell targeting therapies tested in this disease, and likely to be associated with less adverse effects than any anti-inflammatory and immunosuppressant agents previously used

Destruction of Lymphoid Organ Architecture and Hepatitis Caused by CD4+ T Cells

Immune responses have the important function of host defense and protection against pathogens. However, the immune response also causes inflammation and host tissue injury, termed immunopathology. For example, hepatitis B and C virus infection in humans cause immunopathological sequel with destruction of liver cells by the host's own immune response. Similarly, after infection with lymphocytic choriomeningitis virus (LCMV) in mice, the adaptive immune response causes liver cell damage, choriomeningitis and destruction of lymphoid organ architecture. The immunopathological sequel during LCMV infection has been attributed to cytotoxic CD8+ T cells. However, we now show that during LCMV infection CD4+ T cells selectively induced the destruction of splenic marginal zone and caused liver cell damage with elevated serum alanin-transferase (ALT) levels. The destruction of the splenic marginal zone by CD4+ T cells included the reduction of marginal zone B cells, marginal zone macrophages and marginal zone metallophilic macrophages. Functionally, this resulted in an impaired production of neutralizing antibodies against LCMV. Furthermore, CD4+ T cells reduced B cells with an IgMhighIgDlow phenotype (transitional stage 1 and 2, marginal zone B cells), whereas other B cell subtypes such as follicular type 1 and 2 and germinal center/memory B cells were not affected. Adoptive transfer of CD4+ T cells lacking different important effector cytokines and cytolytic pathways such as IFNγ, TNFα, perforin and Fas-FasL interaction did reveal that these cytolytic pathways are redundant in the induction of immunopathological sequel in spleen. In conclusion, our results define an important role of CD4+ T cells in the induction of immunopathology in liver and spleen. This includes the CD4+ T cell mediated destruction of the splenic marginal zone with consecutively impaired protective neutralizing antibody responses

Corrigendum to “A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm” [Toxicology and Applied Pharmacology volume 394C (2020) 114961]

© 2020 The Author(s) The authors regret that one affiliation address is mistaken in the published paper. Matthew Bridgland-Taylor's affiliation was incorrectly listed as Clinical Pharmacology & Safety Sciences, R&D, AstraZeneca, Cambridge, United Kingdom. The correct affiliation is Clinical Pharmacology & Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom. The authors would like to apologise for any inconvenience caused

Status and prospects for renewable energy using wood pellets from the southeastern United States

The ongoing debate about costs and benefits of wood-pellet based bioenergy production in the southeastern United States (SE USA) requires an understanding of the science and context influencing market decisions associated with its sustainability. Production of pellets has garnered much attention as US exports have grown from negligible amounts in the early 2000s to 4.6 million metric tonnes in 2015. Currently, 98% of these pellet exports are shipped to Europe to displace coal in power plants. We ask, ‘How is the production of wood pellets in the SE USA affecting forest systems and the ecosystem services they provide?’ To address this question, we review current forest conditions and the status of the wood products industry, how pellet production affects ecosystem services and biodiversity, and what methods are in place to monitor changes and protect vulnerable systems. Scientific studies provide evidence that wood pellets in the SE USA are a fraction of total forestry operations and can be produced while maintaining or improving forest ecosystem services. Ecosystem services are protected by the requirement to utilize loggers trained to apply scientifically based best management practices in planning and implementing harvest for the export market. Bioenergy markets supplement incomes to private rural landholders and provide an incentive for forest management practices that simultaneously benefit water quality and wildlife and reduce risk of fire and insect outbreaks. Bioenergy also increases the value of forest land to landowners, thereby decreasing likelihood of conversion to nonforest uses. Monitoring and evaluation are essential to verify that regulations and good practices are achieving goals and to enable timely responses if problems arise. Conducting rigorous research to understand how conditions change in response to management choices requires baseline data, monitoring, and appropriate reference scenarios. Long-term monitoring data on forest conditions should be publicly accessible and utilized to inform adaptive management

The Flagellum of Pseudomonas aeruginosa Is Required for Resistance to Clearance by Surfactant Protein A

Surfactant protein A (SP-A) is an important lung innate immune protein that kills microbial pathogens by opsonization and membrane permeabilization. We investigated the basis of SP-A-mediated pulmonary clearance of Pseudomonas aeruginosa using genetically-engineered SP-A mice and a library of signature-tagged P. aeruginosa mutants. A mutant with an insertion into flgE, the gene that encodes flagellar hook protein, was preferentially cleared by the SP-A(+/+) mice, but survived in the SP-A(-/-) mice. Opsonization by SP-A did not play a role in flgE clearance. However, exposure to SP-A directly permeabilized and killed the flgE mutant, but not the wild-type parental strain. P. aeruginosa strains with mutation in other flagellar genes, as well as mucoid, nonmotile isolates from cystic fibrosis patients, were also permeabilized by SP-A. Provision of the wild-type fliC gene restored the resistance to SP-A-mediated membrane permeabilization in the fliC-deficient bacteria. In addition, non-mucoid, motile revertants of CF isolates reacquired resistance to SP-A-mediated membrane permeability. Resistance to SP-A was dependent on the presence of an intact flagellar structure, and independent of flagellar-dependent motility. We provide evidence that flagellar-deficient mutants harbor inadequate amounts of LPS required to resist membrane permeabilization by SP-A and cellular lysis by detergent targeting bacterial outer membranes. Thus, the flagellum of P. aeruginosa plays an indirect but important role resisting SP-A-mediated clearance and membrane permeabilization

A systematic strategy for estimating hERG block potency and its implications in a new cardiac safety paradigm

© 2020 Introduction: hERG block potency is widely used to calculate a drug's safety margin against its torsadogenic potential. Previous studies are confounded by use of different patch clamp electrophysiology protocols and a lack of statistical quantification of experimental variability. Since the new cardiac safety paradigm being discussed by the International Council for Harmonisation promotes a tighter integration of nonclinical and clinical data for torsadogenic risk assessment, a more systematic approach to estimate the hERG block potency and safety margin is needed. Methods: A cross-industry study was performed to collect hERG data on 28 drugs with known torsadogenic risk using a standardized experimental protocol. A Bayesian hierarchical modeling (BHM) approach was used to assess the hERG block potency of these drugs by quantifying both the inter-site and intra-site variability. A modeling and simulation study was also done to evaluate protocol-dependent changes in hERG potency estimates. Results: A systematic approach to estimate hERG block potency is established. The impact of choosing a safety margin threshold on torsadogenic risk evaluation is explored based on the posterior distributions of hERG potency estimated by this method. The modeling and simulation results suggest any potency estimate is specific to the protocol used. Discussion: This methodology can estimate hERG block potency specific to a given voltage protocol. The relationship between safety margin thresholds and torsadogenic risk predictivity suggests the threshold should be tailored to each specific context of use, and safety margin evaluation may need to be integrated with other information to form a more comprehensive risk assessment