Equilibrium Beam Distribution and Halo in the LHC

The equilibrium LHC beam distribution at large amplitudes is a crucial input to the collimation and machine protection design, as well as to background studies. Its estimation requires a knowledge of the diffusion rates at which beam particles are transported to large transverse or longitudinal amplitudes. Important known mechanisms of particle diffusion include Touschek scattering, synchrotron radiation, intrabeam scattering (IBS) the nonlinear motion due to the long-range (LR) beam-beam (BB) collisions at top energy, persistent-current field errors during injection and at the start of acceleration, and Coulomb scattering off the residual gas. We summarize the expected contributions from different sources, introduce a diffusion model, and illustrate the evolution of the beam distribution at 7 TeV

Effects of HDM2 antagonism on sunitinib resistance, p53 activation, SDF-1 induction, and tumor infiltration by CD11b+/Gr-1+ myeloid derived suppressor cells

Background: The studies reported herein were undertaken to determine if the angiostatic function of p53 could be exploited as an adjunct to VEGF-targeted therapy in the treatment of renal cell carcinoma (RCC). Methods: Nude/beige mice bearing human RCC xenografts were treated with various combinations of sunitinib and the HDM2 antagonist MI-319. Tumors were excised at various time points before and during treatment and analyzed by western blot and IHC for evidence of p53 activation and function. Results: Sunitinib treatment increased p53 levels in RCC xenografts and transiently induced the expression of p21waf1, Noxa, and HDM2, the levels of which subsequently declined to baseline (or undetectable) with the emergence of sunitinib resistance. The development of resistance and the suppression of p53-dependent gene expression temporally correlated with the induction of the p53 antagonist HDMX. The concurrent administration of MI-319 markedly increased the antitumor and anti-angiogenic activities of sunitinib and led to sustained p53-dependent gene expression. It also suppressed the expression of the chemokine SDF-1 (CXCL12) and the influx of CD11b+/Gr-1+ myeloid-derived suppressor cells (MDSC) otherwise induced by sunitinib. Although p53 knockdown markedly reduced the production of the angiostatic peptide endostatin, the production of endostatin was not augmented by MI-319 treatment. Conclusions: The evasion of p53 function (possibly through the expression of HDMX) is an essential element in the development of resistance to VEGF-targeted therapy in RCC. The maintenance of p53 function through the concurrent administration of an HDM2 antagonist is an effective means of delaying or preventing the development of resistance

Atomic Multiplet and Charge Transfer Effects in the Resonant Inelastic X-Ray Scattering (RIXS) Spectra at the Nickel L2,3 Edge of NiF2

Resonant inelastic x-ray scattering (RIXS) is used to study the electronic structure of NiF2, which is the most ionic of the nickel compounds. RIXS can be viewed as a coherent two-steps process involving the absorption and the emission of x-rays. The soft x-ray absorption spectrum (XAS) at the metal L2,3 edge indicate the importance of atomic multiplet effects. RIXS spectra at L2,3 contain clearly defined emission peaks corresponding to d-excited states of Ni2+ at energies few eV below the elastic emission, which is strongly suppressed. These results are confirmed by atomic multiplet calculations using the Kramers-Heisenberg formula for RIXS processes. For larger energy losses, the emission spectra have a broad charge-transfer peak that results from the decay of hybridized Ni(3d)-F(2p) valence states. This is confirmed by comparison of the absorption and emission spectra recorded at the nickel L and fluorine K edges with F p and Ni d partial density of states using LDA + U calculations

Size effects in statistical fracture

We review statistical theories and numerical methods employed to consider the sample size dependence of the failure strength distribution of disordered materials. We first overview the analytical predictions of extreme value statistics and fiber bundle models and discuss their limitations. Next, we review energetic and geometric approaches to fracture size effects for specimens with a flaw. Finally, we overview the numerical simulations of lattice models and compare with theoretical models.Comment: review article 19 pages, 5 figure

Generalized Central Limit Theorem and Renormalization Group

We introduce a simple instance of the renormalization group transformation in the Banach space of probability densities. By changing the scaling of the renormalized variables we obtain, as fixed points of the transformation, the L\'evy strictly stable laws. We also investigate the behavior of the transformation around these fixed points and the domain of attraction for different values of the scaling parameter. The physical interest of a renormalization group approach to the generalized central limit theorem is discussed.Comment: 16 pages, to appear in J. Stat. Phy

High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma (RCC) responds to agents that inhibit vascular endothelial growth factor (VEGF) pathway. Sorafenib, a multikinase inhibitor of VEGF receptor, is effective at producing tumor responses and delaying median progression free survival in patients with cytokine refractory RCC. However, resistance to therapy develops at a median of 5 months. In an effort to increase efficacy, we studied the effects of increased sorafenib dose and intermittent scheduling in a murine RCC xenograft model.</p> <p>Methods</p> <p>Mice bearing xenografts derived from the 786-O RCC cell line were treated with sorafenib according to multiple doses and schedules: 1) Conventional dose (CD) continuous therapy; 2) high dose (HD) intermittent therapy, 3) CD intermittent therapy and 4) HD continuous therapy. Tumor diameter was measured daily. Microvessel density was assessed after 3 days to determine the early effects of therapy, and tumor perfusion was assessed serially by arterial spin labeled (ASL) MRI at day 0, 3, 7 and 10.</p> <p>Results</p> <p>Tumors that were treated with HD sorafenib exhibited slowed tumor growth as compared to CD using either schedule. HD intermittent therapy was superior to CD continous therapy, even though the total dose of sorafenib was essentially equivalent, and not significantly different than HD continuous therapy. The tumors exposed to HD sorafenib had lower microvessel density than the untreated or the CD groups. ASL MRI showed that tumor perfusion was reduced to a greater extent with the HD sorafenib at day 3 and at all time points thereafter relative to CD therapy. Further the intermittent schedule appeared to maintain RCC sensitivity to sorafenib as determined by changes in tumor perfusion.</p> <p>Conclusions</p> <p>A modification of the sorafenib dosing schedule involving higher dose intermittent treatment appeared to improve its efficacy in this xenograft model relative to conventional dosing. MRI perfusion imaging and histologic analysis suggest that this benefit is related to enhanced and protracted antiangiogenic activity. Thus, better understanding of dosing and schedule issues may lead to improved therapeutic effectiveness of VEGF directed therapy in RCC and possibly other tumors.</p

On the nature of transport in near-critical dissipative-trapped-electron-mode turbulence: Effect of a subdominant diffusive channel

9 pages, 4 figures.-- PACS nrs.: 52.35.Ra, 52.55.-s.The change in nature of radial transport in numerical simulations of near-critical dissipative-trapped-electron-mode turbulence is characterized as the relative strength of an additional diffusive transport channel (subdominant to turbulence) is increased from zero. In its absence, radial transport exhibits the lack of spatial and temporal scales characteristic of self-organized-critical systems. This dynamical regime survives up to diffusivity values which, for the system investigated here, greatly exceeds the expected neoclassical value. These results, obtained using a novel Lagrangian method, complete and extend previous works based instead on the use of techniques imported from the study of cellular automata [ J. A. Mier et al., Phys. Plasmas 13, 102308 (2006) ]. They also shed further light on why some features of self-organized criticality seem to be observed in magnetically confined plasmas in spite of the presence of mechanisms which apparently violate the conditions needed for its establishment.This research was sponsored by DGICYT (Dirección General de Investigaciones Científicas y Tecnológicas) of Spain under Project No. ENE2006-15244-C03-01/FTN. Research sponsored in part by the Laboratory Research and Development Program of Oak Ridge National Laboratory, managed by UT-Battelle, LLC, for the U.S. Department of Energy under Contract No. DE-AC05-00OR22725. Research supported in part by DOE Office of Science Grant No. DEFG02-04ER5741 at the University of Alaska.Publicad

Assessing Gale Crater as an Exploration Zone for the First Human Mission to Mars

Mars is the "horizon goal" for human space flight [1]. Towards that endeavor, one must consider several factors in regards to choosing a landing site suitable for a human-rated mission including: entry, descent, and landing (EDL) characteristics, scientific diversity, and possible insitu resources [2]. Selecting any one place is a careful balance of reducing risks and increasing scientific return for the mission