Affinity and dose of TCR engagement yield proportional enhancer and gene activity in CD4+ T cells.

Affinity and dose of T cell receptor (TCR) interaction with antigens govern the magnitude of CD4+ T cell responses, but questions remain regarding the quantitative translation of TCR engagement into downstream signals. We find that while the response of mouse CD4+ T cells to antigenic stimulation is bimodal, activated cells exhibit analog responses proportional to signal strength. Gene expression output reflects TCR signal strength, providing a signature of T cell activation. Expression changes rely on a pre-established enhancer landscape and quantitative acetylation at AP-1 binding sites. Finally, we show that graded expression of activation genes depends on ERK pathway activation, suggesting that an ERK-AP-1 axis plays an important role in translating TCR signal strength into proportional activation of enhancers and genes essential for T cell function

Polyploidy breaks speciation barriers in Australian burrowing frogs Neobatrachus

Polyploidy has played an important role in evolution across the tree of life but it is still unclear how polyploid lineages may persist after their initial formation. While both common and well-studied in plants, polyploidy is rare in animals and generally less understood. The Australian burrowing frog genus Neobatrachus is comprised of six diploid and three polyploid species and offers a powerful animal polyploid model system. We generated exome-capture sequence data from 87 individuals representing all nine species of Neobatrachus to investigate species-level relationships, the origin and inheritance mode of polyploid species, and the population genomic effects of polyploidy on genus-wide demography. We describe rapid speciation of diploid Neobatrachus species and show that the three independently originated polyploid species have tetrasomic or mixed inheritance. We document higher genetic diversity in tetraploids, resulting from widespread gene flow between the tetraploids, asymmetric inter-ploidy gene flow directed from sympatric diploids to tetraploids, and isolation of diploid species from each other. We also constructed models of ecologically suitable areas for each species to investigate the impact of climate on differing ploidy levels. These models suggest substantial change in suitable areas compared to past climate, which correspond to population genomic estimates of demographic histories. We propose that Neobatrachus diploids may be suffering the early genomic impacts of climate-induced habitat loss, while tetraploids appear to be avoiding this fate, possibly due to widespread gene flow. Finally, we demonstrate that Neobatrachus is an attractive model to study the effects of ploidy on the evolution of adaptation in animals

Mycobacterium bovis Strains Causing Smear-Positive Human Tuberculosis, Southwest Ireland

Mycobacterium bovis caused 3% of human tuberculosis cases in southwest Ireland during 1998–2006. Of 11 M. bovis strains genotyped, 9 belonged to common animal spoligotypes. Seven strains were from sputum and potential sources of human-centered disease transmission. Ten-locus variable-number tandem repeat typing gave unique strain profiles and would detect disease outbreaks

Actively Controlling Buffet-Induced Excitations

High performance aircraft, especially those with twin vertical tails, encounter unsteady buffet loads when flying at high angles of attack. These loads result in significant random stresses, which may cause fatigue damage leading to restricted capabilities and availability of the aircraft. An international collaborative research activity among Australia, Canada and the United States, conducted under the auspices of The Technical Cooperation Program (TTCP) contributed resources toward a program that coalesced a broad range of technical knowledge and expertise into a single investigation to demonstrate the enhanced performance and capability of the advanced active BLA control system in preparation for a flight test demonstration. The research team investigated the use of active structural control to alleviate the damaging structural response to these loads by applying advanced directional piezoelectric actuators, the aircraft rudder, switch mode amplifiers, and advanced control strategies on an F/A-18 aircraft empennage. Some results of the full-scale investigation are presented herein

Control of proton energy in ultra-high intensity laser-matter interaction

Recent breakthroughs in short pulse laser technology resulted in (i) generation of ultra-high intensity (2×1022 W/cm2) and (ii) ultra-high contrast (10−11) short pulses at the Hercules facility of the University of Michigan, which has created the possibility of exploring a new regime of ion acceleration – the regime of Directed Coulomb Explosion (DCE). In this regime of sufficiently high laser intensities and target thicknesses approaching the relativistic plasma skin depth it is possible to expel electrons from the target focal volume by the laser's ponderomotive force allowing for direct laser ion acceleration combined with a Coulomb explosion. That results in greater than 100 MeV protons with a quasi-monoenergetic energy spectrum. The utilization of beam shaping, namely, the use of flat-top beams, leads to more efficient proton acceleration due to the increase of the longitudinal field. According to the results of 2D PIC simulations a 500 TW laser pulse with a super-Gaussian beam profile interacting with 0.1 micron aluminium-hydrogen foil is able to produce monoenergetic protons with the energy up to 240 MeV.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85403/1/jpconf10_244_042025.pd

Controlling Buffeting Loads by Rudder and Piezo-Actuation

High performance aircraft, especially those with twin vertical tails, encounter unsteady buffet loads when flying at high angles of attack. These stochastic loads result in significant stresses, which may cause fatigue damage leading to restricted capabilities and availability of the aircraft. An international collaborative research activity among Australia, Canada and the United States, conducted under the auspices of The Technical Cooperation Program (TTCP) contributed resources toward a program that coalesced a broad range of technical knowledge and expertise into a single investigation to demonstrate the enhanced performance and capability of the advanced active Buffet Load Alleviation ( ) control system in preparation for a flight test demonstration. The research team investigated the use of active structural control to alleviate the damaging structural response to these loads by applying advanced directional piezoelectric actuators, the aircraft rudder, switch mode amplifiers, and advanced control strategies on an F/A-18 aircraft empennage. Some results of the full-scale investigation are presented herein

A survey of recent results for the generalizations of ordinary differential equations

This is a review paper on recent results for different types of generalized ordinary differential equations. Its scope ranges from discontinuous equations to equations on time scales. We also discuss their relation with inclusion and highlight the use of generalized integration to unify many of them under one single formulation

Composites research at NASA Lewis Research Center

Composites research at NASA Lewis is focused on their applications in aircraft propulsion, space propulsion, and space power, with the first being predominant. Research on polymer-, metal-, and ceramic-matrix composites is being carried out from an integrated materials and structures viewpoint. This paper outlines some of the topics being pursued from the standpoint of key technical issues, current status, and future directions