Reducing computational time via order reduction of a class of reaction–diffusion systems

In this paper, we consider a class of reaction– diffusion PDEs. For this class, a suitable state transformation allows conversion to a heat equation together with a lower order PDE set. By giving an explicit solution to the heat equation we are able to obtain a complete solution to the original PDE. By focusing on the computational load, we give a comparison of the pure numerical, analytical/numerical, analytical/approximated, and approximated methods of solving the PDE. In some examples, we note an almost order of magnitude improvement in computational load

Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives.

The emergence of human intratumoural immunotherapy (HIT-IT) is a major step forward in the management of unresectable melanoma. The direct injection of treatments into melanoma lesions can cause cell lysis and induce a local immune response, and might be associated with a systemic immune response. Directly injecting immunotherapies into tumours achieves a high local concentration of immunostimulatory agent while minimising systemic exposure and, as such, HIT-IT agents are associated with lower toxicity than systemic immune checkpoint inhibitors (CPIs), enabling their potential use in combination with other therapies. Consequently, multiple HIT-IT agents, including oncolytic viruses, pattern-recognition receptor agonists, injected CPIs, cytokines and immune glycolipids, are under investigation. This review considers the current clinical development status of HIT-IT agents as monotherapy and in combination with systemic CPIs, and the practical aspects of administering and assessing the response to these agents. The future of HIT-IT probably lies in its use in combination with systemic CPIs; data from Phase 2 trials indicate a synergy between HIT-IT and CPIs. Data also suggest that the addition of HIT-IT to a CPI might generate responses in CPI-refractory tumours, thereby overcoming resistance and addressing a current unmet need in unresectable and metastatic melanoma for treatment options following progression after CPI treatment

The three-dimensional random field Ising magnet: interfaces, scaling, and the nature of states

The nature of the zero temperature ordering transition in the 3D Gaussian random field Ising magnet is studied numerically, aided by scaling analyses. In the ferromagnetic phase the scaling of the roughness of the domain walls, $w\sim L^\zeta$, is consistent with the theoretical prediction $\zeta = 2/3$. As the randomness is increased through the transition, the probability distribution of the interfacial tension of domain walls scales as for a single second order transition. At the critical point, the fractal dimensions of domain walls and the fractal dimension of the outer surface of spin clusters are investigated: there are at least two distinct physically important fractal dimensions. These dimensions are argued to be related to combinations of the energy scaling exponent, $\theta$, which determines the violation of hyperscaling, the correlation length exponent $\nu$, and the magnetization exponent $\beta$. The value $\beta = 0.017\pm 0.005$ is derived from the magnetization: this estimate is supported by the study of the spin cluster size distribution at criticality. The variation of configurations in the interior of a sample with boundary conditions is consistent with the hypothesis that there is a single transition separating the disordered phase with one ground state from the ordered phase with two ground states. The array of results are shown to be consistent with a scaling picture and a geometric description of the influence of boundary conditions on the spins. The details of the algorithm used and its implementation are also described.Comment: 32 pp., 2 columns, 32 figure

A first-in-human phase I study to determine the maximum tolerated dose of the oral Src/ABL inhibitor AZD0424

BACKGROUND: Src is involved in cancer invasion and metastasis. AZD0424, an oral inhibitor of Src and ABL1, has shown evidence of anti-tumour activity in pre-clinical studies. METHODS: A phase Ia, dose escalation study was performed to assess the safety of continuous oral dosing with AZD0424 in advanced solid tumours. Secondary objectives included investigation of AZD0424 pharmacokinetics, effect on Src activity using markers of bone turnover, and anti-tumour activity. RESULTS: 41 patients were treated; 34 received AZD0424 once-daily at doses ranging from 5 mg to 150 mg, and 7 received 40 mg bi-daily 41.5% of patients experienced at least one AZD0424-related adverse event that was Grade 3-5 in severity, with patients treated at doses above 60 mg per day experiencing multiple treatment-related toxicities. The most commonly observed AZD0424-related adverse events were nausea, fatigue, anorexia and alopecia. Cmaxand AUC increased linearly with dose and the mean±standard deviation t1/2was 8.4±2.8 h. Clear evidence of Src target inhibition was seen at doses ⩾20 mg per day. No responses were observed and 7 patients (17.1%) achieved stable disease lasting 6 weeks or more. CONCLUSIONS: AZD0424 displayed no evidence of efficacy as monotherapy despite a clear pharmacodynamic effect. Further evaluation of AZD0424 monotherapy in patients with solid tumours is not recommended

Metastable States in Spin Glasses and Disordered Ferromagnets

We study analytically M-spin-flip stable states in disordered short-ranged Ising models (spin glasses and ferromagnets) in all dimensions and for all M. Our approach is primarily dynamical and is based on the convergence of a zero-temperature dynamical process with flips of lattice animals up to size M and starting from a deep quench, to a metastable limit. The results (rigorous and nonrigorous, in infinite and finite volumes) concern many aspects of metastable states: their numbers, basins of attraction, energy densities, overlaps, remanent magnetizations and relations to thermodynamic states. For example, we show that their overlap distribution is a delta-function at zero. We also define a dynamics for M=infinity, which provides a potential tool for investigating ground state structure.Comment: 34 pages (LaTeX); to appear in Physical Review

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective leg blood flow (LBF), muscle microvascular blood volume (MBV) and MPS were measured under postabsorptive and postprandial (I.V glamin, dextrose to sustain glucose ~7.5 mmol·l-1) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time as nutrition began. Leg [femoral artery] blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound (CEUS) using DefinityTM perflutren contrast agent and MPS using [1, 2-13C2] leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters