Restrictions on the lifetime of sterile neutrinos from primordial nucleosynthesis

We analyze the influence of decaying sterile neutrinos with the masses in the range 1-140 MeV on the primordial Helium-4 abundance, explicitly solving the Boltzmann equations for all particle species, taking into account neutrino flavour oscillations, and paying special attention to systematic uncertainties. We show that the Helium abundance depends only on the sterile neutrino lifetime and not on the way the active-sterile mixing is distributed between flavours, and derive an upper bound on the lifetime. We also demonstrate that the recent results of Izotov & Thuan [arXiv:1001.4440], who find 2sigma higher than predicted by the standard primordial nucleosynthesis value of Helium-4 abundance, are consistent with the presence in the plasma of sterile neutrinos with the lifetime 0.01-2 seconds. The decay of these particles perturbs the spectra of (decoupled) neutrinos and heats photons, changing the ratio of neutrino to photon energy density, that can be interpreted as extra neutrino species at the recombination epoch.Comment: 17 pp. + Appendices. Analysis of deuterium bounds and more accurate account of CMB bounds on Helium-4 is added. Final version to appear in JCA

Computational Approach to the Geometry of Compact Riemann Surfaces

The goal of this document is to provide a generalmethod for the computational approach to the topology and geometry of compact Riemann surfaces. The approach is inspired by the paradigms of object oriented programming. Our methods allow us in particular to model, for numerical and computational purposes, a compact Riemann surface given by Fenchel-Nielsen parameters with respect to an arbitrary underlying graph, this in a uniformand robust manner. With this programming model established we proceed by proposing an algorithmthat produces explicit compact fundamental domains of compact Riemann surfaces as well as generators of the corresponding Fuchsian groups. In particular, we shall explain how onemay obtain convex geodesic canonical fundamental polygons. In a second part we explain in what manner simple closed geodesics are represented in our model. This will lead us to an algorithm that enumerates all these geodesics up to a given prescribed length. Finally, we shall briefly overview a number of possible applications of our method, such as finding the systoles of a Riemann surface, or drawing its Birman-Series set in a fundamental domain

ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence.

Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2). Notably, patients with a T cell-to-MDSC ratio of less than 1 showed dramatically lower recurrence-free survival than did patients with a ratio of greater than 1. Analysis of early and later time points indicated that this patient dichotomy existed prior to BCG treatment. ILC2 frequency was associated with detectable IL-13 in the urine and correlated with the level of recruited M-MDSCs, which highly expressed IL-13 receptor α1. In vitro, ILC2 were increased and potently expressed IL-13 in the presence of BCG or tumor cells. IL-13 induced the preferential recruitment and suppressive function of monocytes. Thus, the T cell-to-MDSC balance, associated with a skewing toward type 2 immunity, may predict bladder tumor recurrence and influence the mortality of patients with muscle-invasive cancer. Moreover, these results underline the ILC2/IL-13 axis as a targetable pathway to curtail the M-MDSC compartment and improve bladder cancer treatment

Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data.

Immune cells infiltrating tumors can have important impact on tumor progression and response to therapy. We present an efficient algorithm to simultaneously estimate the fraction of cancer and immune cell types from bulk tumor gene expression data. Our method integrates novel gene expression profiles from each major non-malignant cell type found in tumors, renormalization based on cell-type-specific mRNA content, and the ability to consider uncharacterized and possibly highly variable cell types. Feasibility is demonstrated by validation with flow cytometry, immunohistochemistry and single-cell RNA-Seq analyses of human melanoma and colorectal tumor specimens. Altogether, our work not only improves accuracy but also broadens the scope of absolute cell fraction predictions from tumor gene expression data, and provides a unique novel experimental benchmark for immunogenomics analyses in cancer research (http://epic.gfellerlab.org)

Mirebel – Château Reculet-les-Mirebel

Lors des premiers relevés de masse du château de Mirebel (Jura), au regard de la topographie très escarpée des lieux (éperon rocheux de 400 m sur 20 m), s'est posée la question de l'emplacement de l'entrée principale de la forteresse, compte tenu de l'existence d'un chemin ancien partant de l'église. En juillet 2008, grâce au dégagement du pavage du chemin et d'une large ornière, la fouille a permis de confirmer qu'il s'agissait bien du chemin d'accès principal au château. La campagne de sond..

Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis.

Group 2 innate lymphoid cells (ILC2s) are involved in human diseases, such as allergy, atopic dermatitis and nasal polyposis, but their function in human cancer remains unclear. Here we show that, in acute promyelocytic leukaemia (APL), ILC2s are increased and hyper-activated through the interaction of CRTH2 and NKp30 with elevated tumour-derived PGD2 and B7H6, respectively. ILC2s, in turn, activate monocytic myeloid-derived suppressor cells (M-MDSCs) via IL-13 secretion. Upon treating APL with all-trans retinoic acid and achieving complete remission, the levels of PGD2, NKp30, ILC2s, IL-13 and M-MDSCs are restored. Similarly, disruption of this tumour immunosuppressive axis by specifically blocking PGD2, IL-13 and NKp30 partially restores ILC2 and M-MDSC levels and results in increased survival. Thus, using APL as a model, we uncover a tolerogenic pathway that may represent a relevant immunosuppressive, therapeutic targetable, mechanism operating in various human tumour types, as supported by our observations in prostate cancer.Group 2 innate lymphoid cells (ILC2s) modulate inflammatory and allergic responses, but their function in cancer immunity is still unclear. Here the authors show that, in acute promyelocytic leukaemia, tumour-activated ILC2s secrete IL-13 to induce myeloid-derived suppressor cells and support tumour growth

Título: Guía clinica para el estudio de los signos característicos de las enfermedades

Copia digital. España : Ministerio de Cultura. Subdirección General de Coordinación Bibliotecaria, d2024Rústica.Registro de la Propiedad Intelectual: Ley de 1847: 8535; n. de solicitud de ingreso: "3451"; fecha y datos de ingreso: "Nov.e 2/64"; firma del depositante: "Bailly-Bailliere

Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients.

The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets