"Re-educating" tumor-associated macrophages by targeting NF-kappaB

The nuclear factor kappaB (NF-kappaB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-kappaB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive "alternative" phenotype that requires IkappaB kinase beta-mediated NF-kappaB activation. When NF-kappaB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a "classically" activated phenotype; IL-12(high), major histocompatibility complex II(high), but IL-10(low) and arginase-1(low). Targeting NF-kappaB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12-dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to "re-educate" the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies

Enabling a High Throughput Real Time Data Pipeline for a Large Radio Telescope Array with GPUs

The Murchison Widefield Array (MWA) is a next-generation radio telescope currently under construction in the remote Western Australia Outback. Raw data will be generated continuously at 5GiB/s, grouped into 8s cadences. This high throughput motivates the development of on-site, real time processing and reduction in preference to archiving, transport and off-line processing. Each batch of 8s data must be completely reduced before the next batch arrives. Maintaining real time operation will require a sustained performance of around 2.5TFLOP/s (including convolutions, FFTs, interpolations and matrix multiplications). We describe a scalable heterogeneous computing pipeline implementation, exploiting both the high computing density and FLOP-per-Watt ratio of modern GPUs. The architecture is highly parallel within and across nodes, with all major processing elements performed by GPUs. Necessary scatter-gather operations along the pipeline are loosely synchronized between the nodes hosting the GPUs. The MWA will be a frontier scientific instrument and a pathfinder for planned peta- and exascale facilities.Comment: Version accepted by Comp. Phys. Com

Adsorption-desorption kinetics in nanoscopically confined oligomer films under shear

The method of molecular dynamics computer simulations is employed to study oligomer melts confined in ultra-thin films and subjected to shear. The focus is on the self-diffusion of oligomers near attractive surfaces and on their desorption, together with the effects of increasing energy of adsorption and shear. It is found that the mobility of the oligomers near an attractive surface is strongly decreased. Moreover, although shearing the system forces the chains to stretch parallel to the surfaces and thus increase the energy of adsorption per chain, flow also promotes desorption. The study of chain desorption kinetics reveals the molecular processes responsible for the enhancement of desorption under shear. They involve sequences of conformations starting with a desorbed tail and proceeding in a very fast, correlated, segment-by-segment manner to the desorption of the oligomers from the surfaces.

Stem cankers on sunflower (Helianthus annuus) in Australia reveal a complex of pathogenic Diaporthe (Phomopsis) species

The identification of Diaporthe (anamorph Phomopsis) species associated with stem canker of sunflower (Helianthus annuus) in Australia was studied using morphology, DNA sequence analysis and pathology. Phylogenetic analysis revealed three clades that did not correspond with known taxa, and these are believed to represent novel species. Diaporthe gulyae sp. nov. is described for isolates that caused a severe stem canker, specifically pale brown to dark brown, irregularly shaped lesions centred at the stem nodes with pith deterioration and mid-stem lodging. This pathogenicity of D. gulyae was confirmed by satisfying Koch’s Postulates. These symptoms are almost identical to those of sunflower stem canker caused by D. helianthi that can cause yield reductions of up to 40 % in Europe and the USA, although it has not been found in Australia. We show that there has been broad misapplication of the name D. helianthi to many isolates of Diaporthe (Phomopsis) found causing, or associated with, stem cankers on sunflower. In GenBank, a number of isolates had been identified as D. helianthi, which were accommodated in several clades by molecular phylogenetic analysis. Two less damaging species, D. kochmanii sp. nov. and D. kongii sp. nov., are also described from cankers on sunflower in Australia

Molecular scale contact line hydrodynamics of immiscible flows

From extensive molecular dynamics simulations on immiscible two-phase flows, we find the relative slipping between the fluids and the solid wall everywhere to follow the generalized Navier boundary condition, in which the amount of slipping is proportional to the sum of tangential viscous stress and the uncompensated Young stress. The latter arises from the deviation of the fluid-fluid interface from its static configuration. We give a continuum formulation of the immiscible flow hydrodynamics, comprising the generalized Navier boundary condition, the Navier-Stokes equation, and the Cahn-Hilliard interfacial free energy. Our hydrodynamic model yields interfacial and velocity profiles matching those from the molecular dynamics simulations at the molecular-scale vicinity of the contact line. In particular, the behavior at high capillary numbers, leading to the breakup of the fluid-fluid interface, is accurately predicted.Comment: 33 pages for text in preprint format, 10 pages for 10 figures with captions, content changed in this resubmissio

Microscopic multicluster description of neutron-halo nuclei with a stochastic variational method

To test a multicluster approach for halo nuclei, we give a unified description for the ground states of $^6$He and $^8$He in a model comprising an $\alpha$ cluster and single-neutron clusters. The intercluster wave function is taken a superposition of terms belonging to different arrangements, each defined by a set of Jacobi coordinates. Each term is then a superposition of products of gaussian functions of the individual Jacobi coordinates with different widths, projected to angular momenta $l=0$ or 1. To avoid excessively large dimensions and ``overcompleteness", stochastic methods were tested for selecting the gaussians spanning the basis. For $^6$He, we were able to calculate ground-state energies that are virtully exact within the subspace defined by the arrangements and $l$ values, and we found that preselected random sets of bases (with or without simulated annealing) yield excellent numerical convergence to this ``exact" value with thoroughly truncated bases. For $^8$He good energy convergence was achieved in a state space comprising three arrangements with all $l=0$, and there are indications showing that the contributions of other subspaces are likely to be small. The $^6$He and $^8$He energies are reproduced by the same effective force very well, and the matter radii obtained are similar to those of other sophisticated calculations.Comment: Latex , 8 figures available on request, ATOMKI-4-1993-

Results from the adaptive optics coronagraph at the William Herschel Telescope

Described here is the design and commissioning of a coronagraph facility for the 4.2-m William Herschel Telescope (WHT) and its Nasmyth Adaptive Optics for Multi-purpose Instrumentation (NAOMI). The use of the NAOMI system gives an improved image resolution of 0.15 arcsec at a wavelength of 2.2 μm. This enables the Optimised Stellar Coronagraph for Adaptive optics (OSCA) to suppress stellar light using smaller occulting masks and thus allows regions closer to bright astronomical objects to be imaged. OSCA provides a selection of 10 different occulting masks with sizes of 0.25–2.0 arcsec in diameter, including two with full grey-scale Gaussian profiles. There is also a choice of different sized and shaped Lyot stops (pupil plane masks). Computer simulations of the different coronagraphic options with the NAOMI segmented mirror have relevance for the next generation of highly segmented extremely large telescopes

Modeling and Evaluation of a Plug In Hybrid Fuel Cell Shuttle Bus

The Center for Electromechanics at The University of Texas at Austin acquired a plug-in hybrid fuel cell bus for demonstration and model development under a program funded through the USDOT-FTA. The purpose of this program was to evaluate the performance and use of the bus while developing a model that could predict overall performance and energy consumption on daily driving routes. A model of the fuel cell bus was developed using PSAT (Powertrain Analysis Toolkit). The model development involved verifying component characteristics and a parametric study of drivetrain efficiencies to relate predicted to measured vehicle energy consumption data from on-road testing. The PSAT model was able to predict net energy consumption to within 5% over varying route profiles and vehicle conditions. Further investigations with advanced energy storage were performed to evaluate the benefits of ultracapacitor assisted batteries by using the correlated PSAT model. Ultracapacitors act as an additional load leveling device in the hybrid vehicle for peak propulsion and braking vehicle loads, thereby reducing stress on the batteries. The model simulation results show that ultracapacitors can increase overall vehicle economy by 2 to 4% and deliver a net increase in battery efficiency of 3 to 4%.Center for Electromechanic

Topology and chiral symmetry breaking in SU(N) gauge theories

We study the low-lying eigenmodes of the lattice overlap Dirac operator for SU(N) gauge theories with N=2,3,4 and 5 colours. We define a fermionic topological charge from the zero-modes of this operator and show that, as N grows, any disagreement with the topological charge obtained by cooling the fields, becomes rapidly less likely. By examining the fields where there is a disagreement, we are able to show that the Dirac operator does not resolve instantons below a critical size of about rho = 2.5 a, but resolves the larger, more physical instantons. We investigate the local chirality of the near-zero modes and how it changes as we go to larger N. We observe that the local chirality of these modes, which is prominent for SU(2) and SU(3), becomes rapidly weaker for larger N and is consistent with disappearing entirely in the limit of N -> infinity. We find that this is not due to the observed disappearance of small instantons at larger N.Comment: 41 pages, 12 figures, RevTe