On the potential of significance-driven execution for energy-aware HPC

Dynamic Voltage and Frequency Scaling (DVFS) exhibits fundamental limitations as a method to reduce energy consumption in computing systems. In the HPC domain, where performance is of highest priority and codes are heavily optimized to minimize idle time, DVFS has limited opportunity to achieve substantial energy savings. This paper explores if operating processors Near the transistor Threshold Volt- age (NTV) is a better alternative to DVFS for break- ing the power wall in HPC. NTV presents challenges, since it compromises both performance and reliability to reduce power consumption. We present a first of its kind study of a significance-driven execution paradigm that selectively uses NTV and algorithmic error tolerance to reduce energy consumption in performance- constrained HPC environments. Using an iterative algorithm as a use case, we present an adaptive execution scheme that switches between near-threshold execution on many cores and above-threshold execution on one core, as the computational significance of iterations in the algorithm evolves over time. Using this scheme on state-of-the-art hardware, we demonstrate energy savings ranging between 35% to 67%, while compromising neither correctness nor performance.

Monocyte-derived dendritic cells: a potential target for therapy in multiple sclerosis (MS)

Monocytes can differentiate into dendritic cells (DC), cells with a pivotal role in both protective immunity and tolerance. Defects in the maturation or function of DC may be important in the development of autoimmune disease. We sought to establish if there were differences in the cytokine (granulocyte-macrophage colony-stimulating factor and IL-4)-driven maturation of monocytes to DC in patients with MS and whether drugs used to treat MS affected this process in vitro. We have demonstrated that there is no defect in the ability of magnetic activated cell sorting (MACS)-purified monocytes from patients with MS to differentiate to DC, but equally they show no tendency to acquire a DC phenotype without exogenous cytokines. Interferon-beta1a prevents the acquisition of a full DC phenotype as determined by light and electron microscopy and by flow cytometry. Methylprednisolone not only prevents the development of monocyte-derived DC but totally redirects monocyte differentiation towards a macrophage phenotype. Evidence is evolving for a role for DC in central nervous system immunity, either within the brain or in cervical lymph nodes. The demonstrated effect of both drugs on monocyte differentiation may represent an important site for immune therapy in MS.

Laser-driven proton scaling laws and new paths towards energy increase

The past few years have seen remarkable progress in the development of laser-based particle accelerators. The ability to produce ultrabright beams of multi-megaelectronvolt protons routinely has many potential uses from engineering to medicine, but for this potential to be realized substantial improvements in the performances of these devices must be made. Here we show that in the laser-driven accelerator that has been demonstrated experimentally to produce the highest energy protons, scaling laws derived from fluid models and supported by numerical simulations can be used to accurately describe the acceleration of proton beams for a large range of laser and target parameters. This enables us to evaluate the laser parameters needed to produce high-energy and high-quality proton beams of interest for radiography of dense objects or proton therapy of deep-seated tumours.

One-dimensional particle simulation of the filamentation instability: Electrostatic field driven by the magnetic pressure gradient force

Two counterpropagating cool and equally dense electron beams are modeled with particle-in-cell simulations. The electron beam filamentation instability is examined in one spatial dimension, which is an approximation for a quasiplanar filament boundary. It is confirmed that the force on the electrons imposed by the electrostatic field, which develops during the nonlinear stage of the instability, oscillates around a mean value that equals the magnetic pressure gradient force. The forces acting on the electrons due to the electrostatic and the magnetic field have a similar strength. The electrostatic field reduces the confining force close to the stable equilibrium of each filament and increases it farther away, limiting the peak density. The confining time-averaged total potential permits an overlap of current filaments with an opposite flow direction.

Protein kinase B/Akt activity is involved in renal TGF-beta 1-driven epithelial-mesenchymal transition in vitro and in vivo

The molecular pathogenesis of diabetic nephropathy (DN), the leading cause of end-stage renal disease worldwide, is complex and not fully understood. Transforming growth factor-beta (TGF-beta1) plays a critical role in many fibrotic disorders, including DN. In this study, we report protein kinase B (PKB/Akt) activation as a downstream event contributing to the pathophysiology of DN. We investigated the potential of PKB/Akt to mediate the profibrotic bioactions of TGF-beta1 in kidney. Treatment of normal rat kidney epithelial cells (NRK52E) with TGF-beta1 resulted in activation of phosphatidylinositol 3-kinase (PI3K) and PKB/Akt as evidenced by increased Ser473 phosphorylation and GSK-3beta phosphorylation. TGF-beta1 also stimulated increased Smad3 phosphorylation in these cells, a response that was insensitive to inhibition of PI3K or PKB/Akt. NRK52E cells displayed a loss of zona occludins 1 and E-cadherin and a gain in vimentin and alpha-smooth muscle actin expression, consistent with the fibrotic actions of TGF-beta1. These effects were blocked with inhibitors of PI3K and PKB/Akt. Furthermore, overexpression of PTEN, the lipid phosphatase regulator of PKB/Akt activation, inhibited TGF-beta1-induced PKB/Akt activation. Interestingly, in the Goto-Kakizaki rat model of type 2 diabetes, we also detected increased phosphorylation of PKB/Akt and its downstream target, GSK-3beta, in the tubules, relative to that in control Wistar rats. Elevated Smad3 phosphorylation was also detected in kidney extracts from Goto-Kakizaki rats with chronic diabetes. Together, these data suggest that TGF-beta1-mediated PKB/Akt activation may be important in renal fibrosis during diabetic nephropathy.

Observation and characterization of laser-driven Phase Space Electron Holes

The direct observation and full characterization of a phase space electron hole (EH) generated during laser-matter interaction is presented. This structure, propagating in a tenuous, nonmagnetized plasma, has been detected via proton radiography during the irradiation with a ns laser pulse (I?2 ˜ 1014 W/cm2) of a gold hohlraum. This technique has allowed the simultaneous detection of propagation velocity, potential, and electron density spatial profile across the EH with fine spatial and temporal resolution allowing a detailed comparison with theoretical and numerical models.

Freestanding polymer-metal oxide nanocomposite films for light-driven oxygen scavenging

Freestanding films containing nanocrystalline TiO2 and a suitable electron donor embedded in a cellulose matrix deoxygenate a closed environment (see Figure) upon UV illumination as a result of the photocatalytic properties of TiO2. This opens up the potential use of semiconductor photocatalysis in active packaging to achieve light-driven deoxygenation of closed environments.

Laser-Driven Fast Electron Collimation in Targets with Resistivity Boundary

We demonstrate experimentally that the relativistic electron flow in a dense plasma can be efficiently confined and guided in targets exhibiting a high-resistivity-core-low-resistivity-cladding structure analogous to optical waveguides. The relativistic electron beam is shown to be confined to an area of the order of the core diameter (50 mu m), which has the potential to substantially enhance the coupling efficiency of electrons to the compressed fusion fuel in the Fast Ignitor fusion in full-scale fusion experiments.

Scaling of proton acceleration driven by petawatt-laser-plasma interactions

The possibility of using high-power lasers to generate high-quality beams of energetic ions is attracting large global interest. The prospect of using laser-accelerated protons in medicine attracts particular interest, as these schemes may lead to compact and relatively low-cost sources. Among the challenges remaining before these sources can be used in medicine is to increase the numbers and energies of the ions accelerated. Here, we extend the energy and intensity range over which proton scaling is experimentally investigated, up to 400 J and 6 x 10(20) W cm(-2) respectively, and find a slower proton scaling than previously predicted. With the aid of plasma-expansion simulation tools, our results suggest the importance of time-dependent and multidimensional effects in predicting the maximum proton energy in this ultrahigh-intensity regime. The implications of our new understanding of proton scaling for potential medical applications are discussed.

Sheath dynamics observed in a 13.56 MHz-driven plasma

We have established, through time correlated plasma emission and electrode and plasma potential measurements, that the near electrode emission observed in asymmetric capacitively coupled 13.56 MHz-driven hydrogen plasmas is caused by field reversal that leads to sheath collapse. Near-electrode emission has now been observed in Ar and He. The field reversal appears to be due to collision-induced electron drag. (C) 1997 American Institute of Physics.

Assessing the extent to which temporal changes in waterbird community composition are driven by either local, regional or global factors.

1. Lough Neagh and Lough Beg Special Protection Area (SPA, hereafter Lough Neagh) is an important non-estuarine site in Britain and Ireland for overwintering wildfowl. Multivariate analysis of the winter counts showed a state-shift in the waterbird community following winter 2000/2001, mostly due to rapid declines in abundance (46–57% declines in the mean mid-winter January counts between 1993–2000 and 2002–2009) of members of the diving duck guild (pochard Aythya ferina, tufted duck Aythya fuligula and goldeneye Bucephala clangula) and coot (Fulica atra), a submerged macrophyte feeder.
2. Only pochard showed correlations between declines at Lough Neagh and those of overall species flyway population indices to suggest that global changes could contribute to declines at the site. However, indices from the Republic of Ireland showed no overall decline in the rest of Ireland. Tufted duck indices at the site were inversely related to indices in Great Britain. Lough Neagh goldeneye indices were positively correlated with indices in the Republic of Ireland and Great Britain, suggesting that short-stopping could contribute to declines at the site. Coot declines at Lough Neagh did not correlate with trends elsewhere, suggesting local factors involved in the decline.
3. These analyses indicate that although there are potentially different explanations for the dramatic declines in these four waterbird species at this site, the simultaneous nature of the declines across two feeding guilds strongly
suggest that local factors (such as loss of submerged macrophytes and benthic invertebrates) were involved. An assessment of the food supply, local disturbance and other factors at Lough Neagh is required to find an explanation for the observed adverse trends in wintering numbers of the affected species.
4. This study highlights the potential of waterbird community structure to reflect the status of aquatic systems, but confirms the need to establish site-specific factors responsible for the observed changes in abundance of key waterbird species at a site.

Radiobiology at ultra-high dose rates employing laser-driven ions

The potential that laser based particle accelerators offer to solve sizing and cost issues arising with conventional proton therapy has generated great interest in the understanding and development of laser ion acceleration, and in investigating the radiobiological effects induced by laser accelerated ions. Laser-driven ions are produced in bursts of ultra-short duration resulting in ultra-high dose rates, and an investigation at Queen's University Belfast was carried out to investigate this virtually unexplored regime of cell rdaiobiology. This employed the TARANIS terawatt laser producing protons in the MeV range for proton irradiation, with dose rates exceeding 10 Gys on a single exposure. A clonogenic assay was implemented to analyse the biological effect of proton irradiation on V79 cells, which, when compared to data obtained with the same cell line irradiated with conventionally accelerated protons, was found to show no significant difference. A Relative Biological effectiveness of 1.4±0.2 at 10 % Survival Fraction was estimated from a comparison with a 225 kVp X-ray source. © 2013 SPIE.

ELIMED:A new hadron therapy concept based on laser driven ion beams

Laser accelerated proton beams have been proposed to be used in different research fields. A great interest has risen for the potential replacement of conventional accelerating machines with laser-based accelerators, and in particular for the development of new concepts of more compact and cheaper hadrontherapy centers. In this context the ELIMED (ELI MEDical applications) research project has been launched by INFN-LNS and ASCR-FZU researchers within the pan-European ELI-Beamlines facility framework. The ELIMED project aims to demonstrate the potential clinical applicability of optically accelerated proton beams and to realize a laser-accelerated ion transport beamline for multi-disciplinary user applications. In this framework the eye melanoma, as for instance the uveal melanoma normally treated with 62 MeV proton beams produced by standard accelerators, will be considered as a model system to demonstrate the potential clinical use of laser-driven protons in hadrontherapy, especially because of the limited constraints in terms of proton energy and irradiation geometry for this particular tumour treatment. Several challenges, starting from laser-target interaction and beam transport development up to dosimetry and radiobiology, need to be overcome in order to reach the ELIMED final goals. A crucial role will be played by the final design and realization of a transport beamline capable to provide ion beams with proper characteristics in terms of energy spectrum and angular distribution which will allow performing dosimetric tests and biological cell irradiation. A first prototype of the transport beamline has been already designed and other transport elements are under construction in order to perform a first experimental test with the TARANIS laser system by the end of 2013. A wide international collaboration among specialists of different disciplines like Physics, Biology, Chemistry, Medicine and medical doctors coming from Europe, Japan, and the US is growing up around the ELIMED project with the aim to work on the conceptual design, technical and experimental realization of this core beamline of the ELI Beamlines facility. © 2013 SPIE.