On the master equation approach to diffusive grain-surface chemistry: the H, O, CO system

We have used the master equation approach to study a moderately complex network of diffusive reactions occurring on the surfaces of interstellar dust particles. This network is meant to apply to dense clouds in which a large portion of the gas-phase carbon has already been converted to carbon monoxide. Hydrogen atoms, oxygen atoms, and CO molecules are allowed to accrete onto dust particles and their chemistry is followed. The stable molecules produced are oxygen, hydrogen, water, carbon dioxide (CO2), formaldehyde (H2CO), and methanol (CH3OH). The surface abundances calculated via the master equation approach are in good agreement with those obtained via a Monte Carlo method but can differ considerably from those obtained with standard rate equations.Comment: 13 pages, 5 figure

Hot Cores : Probes of High-Redshift Galaxies

The very high rates of second generation star formation detected and inferred in high redshift objects should be accompanied by intense millimetre-wave emission from hot core molecules. We calculate the molecular abundances likely to arise in hot cores associated with massive star formation at high redshift, using several independent models of metallicity in the early Universe. If the number of hot cores exceeds that in the Milky Way Galaxy by a factor of at least one thousand, then a wide range of molecules in high redshift hot cores should have detectable emission. It should be possible to distinguish between independent models for the production of metals and hence hot core molecules should be useful probes of star formation at high redshift.Comment: Updated to correspond to version accepted by MNRA

On the Influence of Uncertainties in Chemical Reaction Rates on Results of the Astrochemical Modelling

With the chemical reaction rate database UMIST95 (Millar et al. 1997) we analyze how uncertainties in rate constants of gas-phase chemical reactions influence the modelling of molecular abundances in the interstellar medium. Random variations are introduced into the rate constants to estimate the scatter in theoretical abundances. Calculations are performed for dark and translucent molecular clouds where gas phase chemistry is adequate. Similar approach was used by Pineau des Forets & Roueff (2000) for the study of chemical bistability. All the species are divided into 6 sensitivity groups according to the value of the scatter in their model abundances computed with varied rate constants. It is shown that the distribution of species within these groups depends on the number of atoms in a molecule and on the adopted physical conditions. The simple method is suggested which allows to single out reactions that are most important for the evolution of a given species.Comment: 4 pages. To appear in the proceedings of the 4th Cologne-Bonn Zermatt Symposiu

Carbon monoxide in the solar atmosphere I. Numerical method and two-dimensional models

The radiation hydrodynamic code CO5BOLD has been supplemented with the time-dependent treatment of chemical reaction networks. Advection of particle densities due to the hydrodynamic flow field is also included. The radiative transfer is treated frequency-independently, i.e. grey, so far. The upgraded code has been applied to two-dimensional simulations of carbon monoxide (CO) in the non-magnetic solar photosphere and low chromosphere. For this purpose a reaction network has been constructed, taking into account the reactions which are most important for the formation and dissociation of CO under the physical conditions of the solar atmosphere. The network has been strongly reduced to 27 reactions, involving the chemical species H, H2, C, O, CO, CH, OH, and a representative metal. The resulting CO number density is highest in the cool regions of the reversed granulation pattern at mid-photospheric heights and decreases strongly above. There, the CO abundance stays close to a value of 8.3 on the usual logarithmic abundance scale with [H]=12 but is reduced in hot shock waves which are a ubiquitous phenomenon of the model atmosphere. For comparison, the corresponding equilibrium densities have been calculated, based on the reaction network but also under assumption of instantaneous chemical equilibrium by applying the Rybicki & Hummer (RH) code by Uitenbroek (2001). Owing to the short chemical timescales, the assumption holds for a large fraction of the atmosphere, in particular the photosphere. In contrast, the CO number density deviates strongly from the corresponding equilibrium value in the vicinity of chromospheric shock waves. Simulations with altered reaction network clearly show that the formation channel via hydroxide (OH) is the most important one under the conditions of the solar atmosphere.Comment: 15 pages, 6 figures, final version will contain online materia

Mesenchymal Transition and PDGFRA Amplification/Mutation Are Key Distinct Oncogenic Events in Pediatric Diffuse Intrinsic Pontine Gliomas

Diffuse intrinsic pontine glioma (DIPG) is one of the most frequent malignant pediatric brain tumor and its prognosis is universaly fatal. No significant improvement has been made in last thirty years over the standard treatment with radiotherapy. To address the paucity of understanding of DIPGs, we have carried out integrated molecular profiling of a large series of samples obtained with stereotactic biopsy at diagnosis. While chromosomal imbalances did not distinguish DIPG and supratentorial tumors on CGHarrays, gene expression profiling revealed clear differences between them, with brainstem gliomas resembling midline/thalamic tumours, indicating a closely-related origin. Two distinct subgroups of DIPG were identified. The first subgroup displayed mesenchymal and pro-angiogenic characteristics, with stem cell markers enrichment consistent with the possibility to grow tumor stem cells from these biopsies. The other subgroup displayed oligodendroglial features, and appeared largely driven by PDGFRA, in particular through amplification and/or novel missense mutations in the extracellular domain. Patients in this later group had a significantly worse outcome with an hazard ratio for early deaths, ie before 10 months, 8 fold greater that the ones in the other subgroup (p = 0.041, Cox regression model). The worse outcome of patients with the oligodendroglial type of tumors was confirmed on a series of 55 paraffin-embedded biopsy samples at diagnosis (median OS of 7.73 versus 12.37 months, p = 0.045, log-rank test). Two distinct transcriptional subclasses of DIPG with specific genomic alterations can be defined at diagnosis by oligodendroglial differentiation or mesenchymal transition, respectively. Classifying these tumors by signal transduction pathway activation and by mutation in pathway member genes may be particularily valuable for the development of targeted therapies

Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study)

A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer. A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models. The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20). Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcome