Meiotic sex chromosome cohesion and autosomal synapsis are supported by Esco2.

In mitotic cells, establishment of sister chromatid cohesion requires acetylation of the cohesin subunit SMC3 (acSMC3) by ESCO1 and/or ESCO2. Meiotic cohesin plays additional but poorly understood roles in the formation of chromosome axial elements (AEs) and synaptonemal complexes. Here, we show that levels of ESCO2, acSMC3, and the pro-cohesion factor sororin increase on meiotic chromosomes as homologs synapse. These proteins are less abundant on the largely unsynapsed sex chromosomes, whose sister chromatid cohesion appears weaker throughout the meiotic prophase. Using three distinct conditional Esco2 knockout mouse strains, we demonstrate that ESCO2 is essential for male gametogenesis. Partial depletion of ESCO2 in prophase I spermatocytes delays chromosome synapsis and further weakens cohesion along sex chromosomes, which show extensive separation of AEs into single chromatids. Unsynapsed regions of autosomes are associated with the sex chromatin and also display split AEs. This study provides the first evidence for a specific role of ESCO2 in mammalian meiosis, identifies a particular ESCO2 dependence of sex chromosome cohesion and suggests support of autosomal synapsis by acSMC3-stabilized cohesion

Addition of cetuximab to first-line chemotherapy in patients with advanced non-small-cell lung cancer: a cost-utility analysis

Background: Adding cetuximab to standard chemotherapy results in a moderate increase of overall survival in patients with advanced non-small-cell lung cancer (NSCLC), but the cost-effectiveness is unknown. Materials and methods: A Markov model was constructed based on the results of the First-Line ErbituX in lung cancer randomized trial, adding cetuximab to cisplatin-vinorelbine first-line chemotherapy in patients with advanced NSCLC. The primary outcome was the incremental cost-effectiveness ratio (ICER) of adding cetuximab, expressed as cost per quality-adjusted life year (QALY) gained, and relative to a willingness-to-pay threshold of €60 000/QALY. The impact of cetuximab intermittent dosing schedules on the ICER was also evaluated. Results: Adding cetuximab to standard chemotherapy leads to a gain of 0.07 QALYs per patient at an additional cost of €26 088. The ICER for adding cetuximab to chemotherapy was €376 205 per QALY gained. Intermittent cetuximab dosing schedules resulted in ICERs per QALY gained between €31 300 and €83 100, under the assumption of equal efficacy. Conclusions: From a health economic perspective, the addition of cetuximab to standard first-line chemotherapy in patients with epidermal growth factor receptor-expressing advanced NSCLC cannot be recommended to date, due to a high ICER compared with other health care interventions. Treatment schedules resulting in more favorable cost-utility ratios should be evaluate

Test of the REX-RFQ and status of the front part of the REX-ISOLDE linac

For REX-ISOLDE (Radioactive beam EXperiments at ISOLDE/CERN), a test beamline is built up at the Garching Accelerator Lab. to perform He$^{1+}$-experiments with the RFQ, the matching (rebunching) section between RFQ and IH-DT-linac, the IH-structure and several electrostatic lenses of the REX-ISOLDE-mass separator. In a first step, the beamline is conceived for tests with the RFQ. This paper presents the parameters and the status of the REX-RFQ, the experimental setup and the particle dynamics simulations with the COSY infinity code for beam injection and beam analysis. Furthermore it shows the design and status of the mass separator, the IH- structure and the buncher section. (5 refs)

A Closed Contour of Integration in Regge Calculus

The analytic structure of the Regge action on a cone in $d$ dimensions over a boundary of arbitrary topology is determined in simplicial minisuperspace. The minisuperspace is defined by the assignment of a single internal edge length to all 1-simplices emanating from the cone vertex, and a single boundary edge length to all 1-simplices lying on the boundary. The Regge action is analyzed in the space of complex edge lengths, and it is shown that there are three finite branch points in this complex plane. A closed contour of integration encircling the branch points is shown to yield a convergent real wave function. This closed contour can be deformed to a steepest descent contour for all sizes of the bounding universe. In general, the contour yields an oscillating wave function for universes of size greater than a critical value which depends on the topology of the bounding universe. For values less than the critical value the wave function exhibits exponential behaviour. It is shown that the critical value is positive for spherical topology in arbitrary dimensions. In three dimensions we compute the critical value for a boundary universe of arbitrary genus, while in four and five dimensions we study examples of product manifolds and connected sums.Comment: 16 pages, Latex, To appear in Gen. Rel. Gra

Sequential and direct two-photon double ionization of D2 at FLASH

ABSTRACT: Sequential and direct two-photon double ionization (DI) of D2 molecule is studied experimentally and theoretically at a photon energy of 38.8 eV. Experimental and theoretical kinetic energy releases of D++D+ fragments, consisting of the contributions of sequential DI via the D2+(1ssg) state and direct DI via a virtual state, agree well with each other

Sequential versus nonsequential two-photon double ionization of the D2 molecule at 38 eV

ABSTRACT: A simple theoretical model is used to interpret recent experimental results for two-photon double ionization (DI) of D2 at 38 eV. We show that the measured kinetic energy distribution associated with emission of two protons can be interpreted as a sum of two processes: a sequential and an instantaneous absorption of the two incident photons. These processes lead to peaks in di erent regions of the spaectrum

Discrete populations of isotype-switched memory B lymphocytes are maintained in murine spleen and bone marrow

At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility

REX-ISOLDE: post-accelerated radioactive BEAMS at CERN-ISOLDE

The ISOLDE RIB-facility at CERN has today been producing a vast range of radioactive beams since more than 30 years. The low-energy beams of ISOLDE will be complemented by a post-accelerator, REX-ISOLDE, currently being assembled. In order to convert the pseudo-DC, singly-charged beam from the ISOLDE mass separators into a cooled and bunched beam at higher charge states a novel scheme of trapping, cooling and charge-state breeding has been devised, using a linear Penning trap and an Electron Beam Ion Source (EBIS). This allows for subsequent acceleration by a short, cost-effective LINAC consisting of an RFQ, an IH-structure and three seven-gap resonators, reaching 0.8 - 2.2 MeV/u. The installation of REX-ISOLDE is well underway and the first post-accelerated radioactive beams are expected to be obtained during late 2000