Relativistic Collisionless Shocks in Inhomogeneous Magnetized Plasmas

Relativistic collisionless shocks are associated with efficient particle acceleration when propagating into weakly magnetized homogeneous media; as the magnetization increases, particle acceleration becomes suppressed. We demonstrate that this changes when the upstream carries kinetic-scale inhomogeneities, as is often the case in astrophysical environments. We use fully-kinetic simulations to study relativistic perpendicular shocks in magnetized pair plasmas interacting with upstream density perturbations. The upstream fluctuations are found to corrugate the shock front and generate large-scale turbulent shear motions in the downstream, which in turn are capable of accelerating particles. This can revive relativistic magnetized shocks as viable energization sites in astrophysical systems, such as jets and accretion disks. The generation of large-scale magnetic structures also has important implications for polarization signals from blazars.Comment: 8 pages, 5 figure

Shock corrugation to the rescue of the internal shock model in microquasars: The single-scale MHD view

Questions regarding energy dissipation in astrophysical jets are open to date, despite of numerous attempts to limit the diversity of models. Some of the most popular models assume that energy is transferred to particles via internal shocks, which develop as a consequence of non-uniform velocity of the jet matter. In this context, we study the structure and energy deposition of colliding plasma shells, focusing our attention on the case of initially inhomogeneous shells. This leads to formation of distorted (corrugated) shock fronts -- a setup that has recently been shown to revive particle acceleration in relativistic magnetized perpendicular shocks. Our studies show that the radiative power of the far downstream of non-relativistic magnetized perpendicular shocks is moderately enhanced with respect to the flat shock cases. Based on the decay rate of downstream magnetic field, we make predictions for multiwavelength polarization properties.Comment: 17 pages, 8 figures; Accepted for publication in Ap

Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives

BACKGROUND: Median survival of metastatic malignant melanoma is 6.0 to 7.5 months, with a 5-year survival of ~6.0%. Although long-term complete remissions are rare, few reports describe cases after chemotherapy. Fifty-three patients with metastatic melanoma were treated with Cystemustine, a chloroethyl nitrosourea (CENU) (60 or 90 mg/m(2)). CASE PRESENTATION: We describe 5 cases, presenting with complete response with long-term disease-free survival of long-term remission of 14, 12, 9, 7 and 6 years after Cystemustine therapy alone. CONCLUSION: Long-term survival has already been described in literature, but in all cases they have been obtained after chemotherapy associated with or followed by surgery. But despite these noteworthy and encouraging but also rare results, it appears essential to increase cystemustine efficiency

Impact of relative dose intensity (RDI) in CHOP combined with rituximab (R-CHOP) on survival in diffuse large B-cell lymphoma

<p>Abstract</p> <p>Background</p> <p>Recently, maintaining higher relative dose intensity (RDI) of chemotherapeutic drugs has become a widespread practice in an attempt to achieve better outcomes in the treatment of aggressive lymphoma. The addition of rituximab to chemotherapy regimens has significantly improved outcome in diffuse large B-cell lymphoma (DLBL). However, it is unknown if higher RDI in chemotherapy when combined with rituximab leads to a better outcome in aggressive B-cell lymphoma.</p> <p>Methods</p> <p>We retrospectively evaluated the impact of the RDI of initial chemotherapy (consisting of cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) on outcome in 100 newly diagnosed DLBL patients.</p> <p>Results</p> <p>A multivariate Cox regression model showed that RDI trended towards a significant association with mortality [hazard ratio per 0.1 of RDI = 0.8; 95% confidence interval 0.6–1.0; <it>P </it>= 0.08]. Additionally, on multivariate logistic analysis, advanced age was a significant factor for reduced RDI.</p> <p>Conclusion</p> <p>Our data suggest that in DLBL patients, mortality was affected by RDI of R-CHOP as the initial treatment, and the retention of a high RDI could therefore be crucial.</p

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64–91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation

Anti-Cripto Mab inhibit tumour growth and overcome MDR in a human leukaemia MDR cell line by inhibition of Akt and activation of JNK/SAPK and bad death pathways

Doxorubicin (DOX) selection of CCRF-CEM leukaemia cell line resulted in multidrug resistance (MDR) CEM/A7R cell line, which overexpresses MDR, 1 coded P-glycoprotein (Pgp). Here, we report for the first time that oncoprotein Cripto, a founding member of epidermal growth factor-Cripto-FRL, 1-Criptic family is overexpressed in the CEM/A7R cells, and anti-Cripto monoclonal antibodies (Mab) inhibited CEM/A7R cell growth both in vitro and in an established xenograft tumour in severe combined immunodeficiency mice. Cripto Mab synergistically enhanced sensitivity of the MDR cells to Pgp substrates epirubicin (EPI), daunorubicin (DAU) and non-Pgp substrates nucleoside analogue cytosine arabinoside (AraC). In particular, the combination of anti-Cripto Mab at less than 50% of inhibition concentrations with noncytotoxic concentrations of EPI or DAU inhibited more than 90% of CEM/A7R cell growth. Cripto Mab slightly inhibited Pgp expression, and had little effect on Pgp function, indicating that a mechanism independent of Pgp was involved in overcoming MDR. We demonstrated that anti-Cripto Mab-induced CEM/A7R cell apoptosis, which was associated with an enhanced activity of the c-Jun N-terminal kinase/stress-activated protein kinase and inhibition of Akt phosphorylation, resulting in an activation of mitochondrial apoptosis pathway as evidenced by dephosphorylation of Bad at Ser136, Bcl-2 at Ser70 and a cleaved caspase-9

Chocs, turbulence et accélération de particules dans le contexte de la magnétohydrodynamique relativiste : études numériques et théoriques

Quels sont les processus physiques à l’origine des propriétés non-thermiques observées dans les sources astrophysiques de haute énergie ? D’où viennent les rayons cosmiques de haute énergie ? Les réponses à ces questions semblent être intimement liées à la physique des chocs, de la turbulence et de l’accélération de particules. Notamment, comprendre les chocs non-collisionnels, qui sont parmi les sites d’accélération les plus activement explorés par l’astrophysique moderne, implique de rendre compte de dépendances complexes entre ces trois composantes.Nous plaçant ici dans le cadre de travail de la magnétohydrodynamique (MHD) relativiste, nous examinons tour à tour différents aspects impliqués dans la physique non-linéaire et multi-échelle qui régit ces systèmes. Dans un premier temps, nous traitons d’un problème en lien avec la problématique des interactions choc-turbulence, à savoir la réponse d’un choc rapide perpendiculaire à des ondes magnétohydrodynamiques en provenance de l’amont du choc. Nous démontrons numériquement que cette réponse est dans certaines conditions résonantes, comme cela avait été prédit par une étude linéaire dans la limite relativiste. Par le biais de simulations bidimensionnelles à haute résolution effectuées avec un code à maillage adaptatif, MPI-AMRVAC, nous sondons ce phénomène dans les régimes sub-relativiste et relativiste ainsi que son évolution non-linéaire. On se concentre ensuite sur le problème de particules test interagissant avec une turbulence MHD relativiste pour étudier de manière analytique et numérique la physique de l’accélération stochastique, en insistant sur les spécificités du régime relativiste, qui demeure peu exploré. Au niveau analytique, nous dérivons des expressions pour les coefficients de diffusion de l’angle d’attaque et de la quantité de mouvement pour différents modèles phénoménologiques de turbulence largement acceptés dans la littérature. Nous nous affranchissons de certaines limites de la théorie quasi-linéaire standard en incorporant des effets d’élargissement de résonance dus à la décorrélation des ondes qui composent la turbulence et à des perturbations non-linéaires de la trajectoire des particules sujettes aux réflexions de miroirs magnétiques. Nous montrons que ces estimations analytiques sont en bon accord avec nos simulations de particules test évoluant dans une turbulence prescrite. Enfin, on présente les premiers résultats de nos simulations de MHD relativiste tridimensionnelles de turbulence forcée avec évolution temporelle, utilisées pour explorer l’accélération stochastique dans un plasma relativiste chaud de magnétisation de l’ordre de l’unité. On trouve en particulier que le coefficient de diffusion en quantité de mouvement a une dépendance Dpp ~p2, ce qui est cohérent avec nos prédictions analytiques pour une turbulence faite de perturbations de type ondes d’Alfvén et avec de récentes simulations « Particule en cellule » ayant sondé un régime similaire.What are the physical processes underlying the non-thermal features observed in high-energy astrophysical sources? What are the origins of high-energy cosmic rays? The answers to these questions seem to be intimately related to the physics of shocks, turbulence and particle acceleration. Notably, understanding collisionless shocks, which are among the most prominent potential acceleration sites considered in modern astrophysics, implies to account for a complex interplay between these three components. Relying on the framework of special relativistic magnetohydrodynamics (SRMHD), we investigate in turn different aspects involved in the non-linear and multi-scale physics governing such systems. First, we examine a problem related to the issue of shock-turbulence interactions; namely the response of a perpendicular fast shock to upstream magnetohydrodynamic waves and demonstrate numerically that this response can be resonant, as predicted by a recent linear study in the relativistic limit. By means of high resolution two-dimensional SRMHD simulations carried out with the adaptive mesh code MPI-AMRVAC, we probe this phenomenon in the relativistic and sub-relativistic regimes, as well as its non-linear evolution. We then shift the focus towards the problem of test particles interacting with SRMHD turbulence to investigate analytically and numerically the physics of stochastic acceleration, emphasizing the specifities of the relativistic regime, which remains largely unexplored. On the analytic level, we provide expressions for the quasi-linear pitch angle and momentum diffusion coefficients for widely accepted phenomenological models of MHD turbulence, going beyond standard quasi-linear theory by incorporating resonance broadening effects due to the decorrelation of the waves composing the turbulence and non-linear perturbations to the trajectories of particles subjected to magnetic mirroring. These analytical estimations are shown to be in good agreement the results of our simulations of test particles involving in synthetic turbulence. Finally, we introduce the first results from three-dimensional time evolving SRMHD simulations of driven turbulence, used to probe stochastic acceleration in relativistically hot plasmas with magnetization of order unity. We derive in particular momentum diffusion coefficients scaling as Dpp ~p2 consistent with our analytic predictions for turbulence made of Alfven like perturbations and recent Particle-In-Cell simulations, which explored a similar regime

H-NMR Spectroscopy-Based Metabolomic Analysis of Human Liver Tissues Reveals Metabolic Biomarkers of Hepato-Cellular Carcinoma Developed in Cirrhotic or Non- Cirrhotic Disease

National audienc