Preface: BITS2014, the annual meeting of the Italian Society of Bioinformatics

This Preface introduces the content of the BioMed Central journal Supplements related to BITS2014 meeting, held in Rome, Italy, from the 26th to the 28th of February, 2014

Eomesodermin controls a unique differentiation program in human IL-10 and IFN-γ coproducing regulatory T cells

Whether human IL-10-producing regulatory T cells (“Tr1”) represent a distinct differentiation lineage or an unstable activation stage remains a key unsolved issue. Here, we report that Eomesodermin (Eomes) acted as a lineage-defining transcription factor in human IFN-γ/IL-10 coproducing Tr1-like cells. In vivo occurring Tr1-like cells expressed Eomes, and were clearly distinct from all other CD4 + T-cell subsets, including conventional cytotoxic CD4 + T cells. They expressed Granzyme (Gzm) K, but had lost CD40L and IL-7R expression. Eomes antagonized the Th17 fate, and directly controlled IFN-γ and GzmK expression. However, Eomes binding to the IL-10 promoter was not detectable in human CD4 + T cells, presumably because critical Tbox binding sites of the mouse were not conserved. A precommitment to a Tr1-like fate, i.e. concominant induction of Eomes, GzmK, and IFN-γ, was promoted by IL-4 and IL-12-secreting myeloid dendritic cells. Consistently, Th1 effector memory cells contained precommitted Eomes + GzmK + T cells. Stimulation with T-cell receptor (TCR) agonists and IL-27 promoted the generation of Tr1-like effector cells by inducing switching from CD40L to IL-10. Importantly, CD4 + Eomes + T-cell subsets were present in lymphoid and nonlymphoid tissues, and their frequencies varied systemically in patients with inflammatory bowel disease and graft-versus-host disease. We propose that Eomes + Tr1-like cells are effector cells of a unique GzmK-expressing CD4 + T-cell subset

Two-pass two-way acceleration in a superconducting continuous wave linac to drive low jitter x-ray free electron lasers

We present a design study of an innovative scheme to generate high rep rate (MHz-class) GeV electron beams by adopting a two-pass two-way acceleration in a Superconducting (SC) linac operated in Continuous Wave (CW) mode. The electron beam is accelerated twice by being re-injected in opposite direction of propagation into the linac after the first passage. Acceleration in opposite directions is accomplished thanks to standing waves supported in RF cavities. The task of recirculating the electron beam when it leaves the linac after first pass is performed by a Bubble-shaped Arc Compressor composed by a sequence of Double Bend Achromat. In this paper we address the main issues inherent to the two-pass acceleration process and the preservation of the electron beam quality parameters (emittance, energy spread, peak current) required to operate X-ray Free Electron Lasers with low jitters in the amplitude, spectral and temporal domain, as achieved by operating in seeding and/or oscillator mode a CW FEL up to 1 MHz rep rate. Detailed start-to-end simulations are shown to assess the capability of this new scheme to double the electron beam energy as well as to compress the electron bunch length from picoseconds down to tens of femtoseconds. The advantage of such a scheme is to halve the requested linac length for the same final electron beam energy, which is typically in the few GeV range, as needed to drive an X-ray FEL. The AC power to supply the cryogenic plant is also significantly reduced with respect to a conventional single-pass SC linac for the same final energy. We are reporting also X-ray FEL simulations for typical values of wavelengths of interest (in the 200 eV \u2013 8 keV photon energy range) to better illustrate the potentiality of this new scheme

Monitoring the FLASH Cryomodule Transportation from DESY Hamburg to CEA Saclay: Coupler Contact, Vacuum, Acceleration and Vibration Analysis

With a view to the series production of one hundred, 12 m long XFEL 1.3 GHz cryomodules and their transportation from the assembly site at CEA Saclay (F) to the installation site at DESY Hamburg (D) a test transportation of a FLASH cryomodule has been performed, in the condition foreseen for the mass transportation. The present study examines the stresses induced on the module and verifies the damping capabilities of the transport frame in order to minimize risk of damage to the most critical components. During the transportation, acceleration and vibration have been monitored as well as coupler antenna contacts and vacuum performances. This paper describes the analysis performed and compares those results to the data of a similar transportation study at Fermilab for the CM1 cryomodule

First Observation of Self-Amplified Spontaneous Emission in a Free-Electron Laser at 109 nm Wavelength

We present the first observation of Self-Amplified Spontaneous Emission (SASE) in a free-electron laser (FEL) in the Vacuum Ultraviolet regime at 109 nm wavelength (11 eV). The observed free-electron laser gain (approx. 3000) and the radiation characteristics, such as dependency on bunch charge, angular distribution, spectral width and intensity fluctuations all corroborate the existing models for SASE FELs.Comment: 6 pages including 6 figures; e-mail: [email protected]

Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes

<p>Abstract</p> <p>Background</p> <p>Congenital nephrogenic diabetes insipidus (NDI) is characterised by an inability to concentrate urine despite normal or elevated plasma levels of the antidiuretic hormone arginine vasopressin. We report a Japanese extended family with NDI caused by an 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>Rho GTPase-activating protein 4 </it>(<it>ARHGAP4</it>) locus. ARHGAP4 belongs to the RhoGAP family, Rho GTPases are critical regulators of many cellular activities, such as motility and proliferation which enhances intrinsic GTPase activity.</p> <p>ARHGAP4 is expressed at high levels in hematopoietic cells, and it has been reported that an NDI patient lacking <it>AVPR2 </it>and all of <it>ARHGAP4 </it>showed immunodeficiency characterised by a marked reduction in the number of circulating CD3+ cells and almost complete absence of CD8+ cells.</p> <p>Methods</p> <p>PCR and sequencing were performed to identify the deleted region in the Japanese NDI patients. Immunological profiles of the NDI patients were analysed by flow cytometry. We also investigated the gene expression profiles of peripheral blood mononuclear cells (PBMC) from NDI patients and healthy controls in microarray technique.</p> <p>Results</p> <p>We evaluated subjects (one child and two adults) with 11.2-kb deletion that includes the entire <it>AVPR2 </it>locus and approximately half of the <it>ARHGAP4</it>. Hematologic tests showed a reduction of CD4+ cells in one adult patient, a reduction in CD8+ cells in the paediatric patient, and a slight reduction in the serum IgG levels in the adult patients, but none of them showed susceptibility to infection. Gene expression profiling of PBMC lacking <it>ARHGAP4 </it>revealed that expression of RhoGAP family genes was not influenced greatly by the lack of <it>ARHGAP4</it>.</p> <p>Conclusion</p> <p>These results suggest that loss of <it>ARHGAP4 </it>expression is not compensated for by other family members. ARHGAP4 may play some role in lymphocyte differentiation but partial loss of <it>ARHGAP4 </it>does not result in clinical immunodeficiency.</p