Graphics mini manual

The computer graphics capabilities available at the Center are introduced and their use is explained. More specifically, the manual identifies and describes the various graphics software and hardware components, details the interfaces between these components, and provides information concerning the use of these components at LaRC

Oxygen-Mediated Suppression of CD8+ T Cell Proliferation by Macrophages: Role of Pharmacological Inhibitors of HIF Degradation.

Myeloid cell interactions with cells of the adaptive immune system are an essential aspect of immunity. A key aspect of that interrelationship is its modulation by the microenvironment. Oxygen is known to influence myelosuppression of T cell activation in part via the Hypoxia inducible (HIF) transcription factors. A number of drugs that act on the HIF pathway are currently in clinical use and it is important to evaluate how they act on immune cell function as part of a better understanding of how they will influence patient outcomes. We show here that increased activation of the HIF pathway, either through deletion of the negative regulator of HIF, the von Hippel-Lindau (VHL) gene, in myeloid cells, or through pharmacological inhibitors of VHL-mediated degradation of HIF, potently suppresses T cell proliferation in myeloid cell/T cell culture. These data demonstrate that both pharmacological and genetic activation of HIF in myeloid cells can suppress adaptive cell immune response

Oxygen regulation of TET enzymes.

Hypoxia has a significant impact on many physiological and pathological processes. Over the recent years, its role in modulation of epigenetic remodelling has also become clearer. In cancer, low oxygen environments and aberrant epigenomes often go hand in hand, and changes in DNA methylation are now commonly recognised as potential outcome indicators. TET (ten-eleven translocation) family enzymes are alpha-ketoglutarate-, iron- and oxygen-dependent DNA demethylases and are key players in these processes. Although TETs have historically been considered tumour suppressors, recent studies suggest that their functions in cancer might not be straightforward. Recently, inhibition of TETs has been reported to have positive impact in cancer immunotherapy and vaccination studies. This underlines the current interest in developing targeted pharmaceutical inhibitors of these enzymes. Here, we will survey the complexity of TET roles in cancer, and its hypoxic modulation, as well as highlight the potential of these enzymes as therapeutic targets

Shock formation and the ideal shape of ramp compression waves

We derive expressions for shock formation based on the local curvature of the flow characteristics during dynamic compression. Given a specific ramp adiabat, calculated for instance from the equation of state for a substance, the ideal nonlinear shape for an applied ramp loading history can be determined. We discuss the region affected by lateral release, which can be presented in compact form for the ideal loading history. Example calculations are given for representative metals and plastic ablators. Continuum dynamics (hydrocode) simulations were in good agreement with the algebraic forms. Example applications are presented for several classes of laser-loading experiment, identifying conditions where shocks are desired but not formed, and where long duration ramps are desired

String Theoretic Bounds on Lorentz-Violating Warped Compactification

We consider warped compactifications that solve the 10 dimensional supergravity equations of motion at a point, stabilize the position of a D3-brane world, and admit a warp factor that violates Lorentz invariance along the brane. This gives a string embedding of ``asymmetrically warped'' models which we use to calculate stringy (\alpha') corrections to standard model dispersion relations, paying attention to the maximum speeds for different particles. We find, from the dispersion relations, limits on gravitational Lorentz violation in these models, improving on current limits on the speed of graviton propagation, including those derived from field theoretic loops. We comment on the viability of models that use asymmetric warping for self-tuning of the brane cosmological constant.Comment: 20pg, JHEP3; v2 additional references, slight change to intro; v3. added referenc

Measurement of the Casimir force between dissimilar metals

The first precise measurement of the Casimir force between dissimilar metals is reported. The attractive force, between a Cu layer evaporated on a microelectromechanical torsional oscillator, and an Au layer deposited on an Al$_2$O$_3$ sphere, was measured dynamically with a noise level of 6 fN/$\sqrt{\rm{Hz}}$. Measurements were performed for separations in the 0.2-2 $\mu$m range. The results agree to better than 1% in the 0.2-0.5 $\mu$m range with a theoretical model that takes into account the finite conductivity and roughness of the two metals. The observed discrepancies, which are much larger than the experimental precision, can be attributed to a lack of a complete characterization of the optical properties of the specific samples used in the experiment.Comment: 6 pages, 4 figure

A criterion for admissible singularities in brane world

When gravity couples to scalar fields in Anti-de Sitter space, the geometry becomes non-AdS and develops singularities generally. We propose a criterion that the singularity is physically admissible if the integral of the on-shell Lagrangian density over the finite range is finite everywhere. For all classes of the singularities studied here, the criterion suggested in this paper coincides with an independent proposal made by Gubser that the potential should be bounded from above in the solution. This gives a reason why Gubser's conjecture works.Comment: 14 pages, revtex, 1 table, references added, two other criteria include

Quantum-Chromodynamic Potential Model for Light-Heavy Quarkonia and the Heavy Quark Effective Theory

We have investigated the spectra of light-heavy quarkonia with the use of a quantum-chromodynamic potential model which is similar to that used earlier for the heavy quarkonia. An essential feature of our treatment is the inclusion of the one-loop radiative corrections to the quark-antiquark potential, which contribute significantly to the spin-splittings among the quarkonium energy levels. Unlike $c\bar{c}$ and $b\bar{b}$, the potential for a light-heavy system has a complicated dependence on the light and heavy quark masses $m$ and $M$, and it contains a spin-orbit mixing term. We have obtained excellent results for the observed energy levels of $D^0$, $D_s$, $B^0$, and $B_s$, and we are able to provide predicted results for many unobserved energy levels. Our potential parameters for different quarkonia satisfy the constraints of quantum chromodynamics. We have also used our investigation to test the accuracy of the heavy quark effective theory. We find that the heavy quark expansion yields generally good results for the $B^0$ and $B_s$ energy levels provided that $M^{-1}$ and $M^{-1}\ln M$ corrections are taken into account in the quark-antiquark interactions. It does not, however, provide equally good results for the energy levels of $D^0$ and $D_s$, which indicates that the effective theory can be applied more accurately to the $b$ quark than the $c$ quark.Comment: 17 pages of LaTeX. To appear in Physical Review D. Complete PostScript file is available via WWW at http://gluon.physics.wayne.edu/wsuhep/jim/heavy.p

Lactate exposure shapes the metabolic and transcriptomic profile of CD8+ T cells

IntroductionCD8+ T cells infiltrate virtually every tissue to find and destroy infected or mutated cells. They often traverse varying oxygen levels and nutrient-deprived microenvironments. High glycolytic activity in local tissues can result in significant exposure of cytotoxic T cells to the lactate metabolite. Lactate has been known to act as an immunosuppressor, at least in part due to its association with tissue acidosis.MethodsTo dissect the role of the lactate anion, independently of pH, we performed phenotypical and metabolic assays, high-throughput RNA sequencing, and mass spectrometry, on primary cultures of murine or human CD8+ T cells exposed to high doses of pH-neutral sodium lactate.ResultsThe lactate anion is well tolerated by CD8+ T cells in pH neutral conditions. We describe how lactate is taken up by activated CD8+ T cells and can displace glucose as a carbon source. Activation in the presence of sodium lactate significantly alters the CD8+ T cell transcriptome, including the expression key effector differentiation markers such as granzyme B and interferon-gamma.DiscussionOur studies reveal novel metabolic features of lactate utilization by activated CD8+ T cells, and highlight the importance of lactate in shaping the differentiation and activity of cytotoxic T cells