CD8
T cell tissue resident memory (T
) cells are especially suited to control pathogen spread at mucosal sites. However, their maintenance in lung is short-lived. TCR-dependent NFkB signaling is ...crucial for T cell memory but how and when NFkB signaling modulates tissue resident and circulating T cell memory during the immune response is unknown. Here, we find that enhancing NFkB signaling in T cells once memory to influenza is established, increases pro-survival Bcl-2 and CD122 levels thus boosting lung CD8
T
maintenance. By contrast, enhancing NFkB signals during the contraction phase of the response leads to a defect in CD8
T
differentiation without impairing recirculating memory subsets. Specifically, inducible activation of NFkB via constitutive active IKK2 or TNF interferes with TGFβ signaling, resulting in defects of lung CD8
T
imprinting molecules CD69, CD103, Runx3 and Eomes. Conversely, inhibiting NFkB signals not only recovers but improves the transcriptional signature and generation of lung CD8
T
. Thus, NFkB signaling is a critical regulator of tissue resident memory, whose levels can be tuned at specific times during infection to boost lung CD8
T
.
This complete and fully assembled genome sequence of Mycoplasma bovis type strain PG45 is the first available for this species and offers a framework for comparison with additional pathogenic ...isolates. The single circular chromosome of 1,003,404 bp reveals multiple gene sets and mechanisms involved in variable expression of surface antigens and the incursion of numerous and assorted mobile elements, despite its reduced size.
Over the last decade, there has been enormous effort to measure neutrino interaction cross sections important to oscillation experiments. However, a number of results from modern experiments appear ...to be in tension with each other, despite purporting to measure the same processes. The TENSIONS2016 workshop was held at University of Pittsburgh July 24–31, 2016 and was sponsored by the Pittsburgh Particle Physics, Astronomy, and Cosmology Center (PITT PACC). The focus was on bringing experts from three experimental collaborations together to compare results in detail and try to find the source of tension by clarifying and comparing signal definitions and the analysis strategies used for each measurement. A set of comparisons between the measurements using a consistent set of models was also made. This paper summarizes the main conclusions of that work.
The NEUT intranuclear cascade model is described and fit to a large body of π± -nucleus scattering data. Methods are developed to deal with deficiencies in the available historical data, and robust ...uncertainty estimates are produced. The results are compared to a variety of simulation packages and the data. This work provides a method for tuning final state interaction models, which are of particular interest to neutrino experiments that operate in the few-GeV energy region, and provides results which can be used directly by the T2K and Super-Kamiokande Collaborations, for whom NEUT is the primary simulation package.
The skin concentration of a substance after a topical application or exposure determines both local treatment outcomes and the dermal toxicity assessment of various products. However, quantifying the ...time course of those concentrations at skin effect sites, such as the viable epidermal, superficial dermis and appendages in humans is especially problematic in vivo, making physiologically based mathematical modelling an essential tool to meet this need. This work further develops our published physiologically based pharmacokinetic and COMSOL based dermal transport modelling by considering the impact of the superficial subpapillary dermal plexus, which we represent as two well stirred compartments. The work also studied the impact on dermal concentrations of subpapillary plexus size, depth, blood velocity and density of subpapillary plexus vessels. Sensitivity analyses are used to define the most important transport determinants of skin concentrations after topical application of a substance, with previously published results used to validate the resulting analyses. This resulting model describes the available experimental data better than previous models, especially at deeper dermal depths.
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The stratum corneum is the main barrier to transdermal drug delivery which has previously resulted in mathematical modelling of solute transport in the skin being primarily directed ...at this skin layer. However, for topical treatment and skin toxicity studies, the concentration in the epidermis and dermis is important and needs to be modelled mathematically. Hitherto, mathematical models for viable skin layers typically simplified the clearance of solute by blood, either assuming sink condition at the top of the skin capillary loops or assuming a distributed clearance in the dermis. This paper is an attempt to develop a physiologically based mathematical model of drug transport in the viable skin. It incorporates explicit modelling of the capillary loops within the dermis and employs COMSOL Multiphysics® software to model the transport in three dimensions. Previously derived simplified models were compared to the results from this new numerical model. The results of this comparison showed that the simplified model reasonably described the average concentration in the viable skin layers when parameters of the models were chosen appropriately. When the recruitment of the capillary loops in the dermis was full and the top of capillary loops was at a depth of 100μm, the effective depth to place a sink condition in the simpler models was found to be at 150μm. However, when there was only partial recruitment of the capillaries, the effective depth increased to 180μm. The presented modelling is also essential for determining a transdermal flux when the stratum corneum barrier is compromised by such methods as microporation, application of chemical enhancers or microneedles.
Mycoplasma putrefaciens is a causative agent of contagious agalactia in goats. Reported herein is the complete genome sequence of the M. putrefaciens type strain KS1.
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