Transport studies of LPA electron beam towards the FEL amplification at COXINEL

Laser Plasma Acceleration (LPA) [1] is an emerging concept enabling to generate electron beams with high energy, high peak current and small transverse emittance within a very short distance. The use of LPA can be applied to the Free Electron Laser (FEL) [2] case in order to investigate whether it is suitable for the light amplification in the undulator. However, capturing and guiding of such beams to the undulator is very challenging, because of the large divergence and high energy spread of the electron beams at the plasma exit, leading to large chromatic emittances. A specific beam manipulation scheme was recently proposed for the COXINEL (Coherent X-ray source inferred from electrons accelerated by laser) setup, which makes an advantage from the intrinsically large chromatic emittance of such beams [3]. The electron beam transport is studied using two simulation codes: a SOLEIL in-house one and ASTRA [4]. The influence of the collective effects on the electron beam performance is also examined

The ARC-EN-CIEL radiation sources

MOPC005International audienceThe ARC-EN-CIEL (Accelerator-Radiation for Enhanced Coherent Intense Extended Light) project proposes a panoply of light sources for the scientific community on a 1 GeV superconducting LINAC (phase 2) on which two ERL loops (1 and 2 GeV) are added in phase 3. LEL1 (200-1.5 nm), LEL2 (10-0.5 nm) and LEL4 (2-0.2 nm) are three kHz High Gain Harmonic Generation Free Electron Laser sources seeded with the High order Harmonics generated in Gas, with 100-30 FWHM pulses. A collaboration, which has been set-up with the SCSS Prototype Accelerator in Japan to test this key concept of ARC-EN-CIEL, has led to the experimental demonstration of the seeding with HHG and the observation up the 7th non linear harmonic with a seed at 160 nm. LEL3 (40-8 nm) installed on the 1 GeV loop is a MHz FEL oscillator providing higher average power and brilliance. In addition, in vacuum undulator spontaneous emission source extend the spectral range above 10 keV and intense THz radiation is generated by edge radiation of bending magnets. Optimisations and light sources characteristics are described

Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities.

The mammary epithelium depends on specific lineages and their stem and progenitor function to accommodate hormone-triggered physiological demands in the adult female. Perturbations of these lineages underpin breast cancer risk, yet our understanding of normal mammary cell composition is incomplete. Here, we build a multimodal resource for the adult gland through comprehensive profiling of primary cell epigenomes, transcriptomes, and proteomes. We define systems-level relationships between chromatin-DNA-RNA-protein states, identify lineage-specific DNA methylation of transcription factor binding sites, and pinpoint proteins underlying progesterone responsiveness. Comparative proteomics of estrogen and progesterone receptor-positive and -negative cell populations, extensive target validation, and drug testing lead to discovery of stem and progenitor cell vulnerabilities. Top epigenetic drugs exert cytostatic effects; prevent adult mammary cell expansion, clonogenicity, and mammopoiesis; and deplete stem cell frequency. Select drugs also abrogate human breast progenitor cell activity in normal and high-risk patient samples. This integrative computational and functional study provides fundamental insight into mammary lineage and stem cell biology

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Phase space analysis of velocity bunched beams

Peak current represents a key demand for new generation electron beam photoinjectors. Many beam applications, such as free electron laser, inverse Compton scattering, terahertz radiation generation, have efficiencies strongly dependent on the bunch length and current. A method of beam longitudinal compression (called velocity bunching) has been proposed some years ago, based on beam longitudinal phase space rotation in a rf field potential. The control of such rotation can lead to a compression factor in excess of 10, depending on the initial longitudinal emittance. Code simulations have shown the possibility to fully compensate the transverse emittance growth during rf compression, and this regime has been experimentally proven recently at SPARC. The key point is the control of transverse beam plasma oscillations, in order to freeze the emittance at its lowest value at the end of compression. Longitudinal and transverse phase space distortions have been observed during the experiments, leading to asymmetric current profiles and higher final projected emittances. In this paper we discuss in detail the results obtained at SPARC in the regime of velocity bunching, analyzing such nonlinearities and identifying the causes. The beam degradation is discussed, both for slice and projected parameters. Analytical tools are derived to experimentally quantify the effect of such distortions on the projected emittanc

Resonant Lifetime of Core-Excited Organic Adsorbates from First Principles

We investigate by first-principles simulations the resonant electron-transfer lifetime from the excited state of an organic adsorbate to a semiconductor surface, namely isonicotinic acid on rutile TiO$_2$(110). The molecule-substrate interaction is described using density functional theory, while the effect of a truly semi-infinite substrate is taken into account by Green's function techniques. Excitonic effects due to the presence of core-excited atoms in the molecule are shown to be instrumental to understand the electron-transfer times measured using the so-called core-hole-clock technique. In particular, for the isonicotinic acid on TiO$_2$(110), we find that the charge injection from the LUMO is quenched since this state lies within the substrate band gap. We compute the resonant charge-transfer times from LUMO+1 and LUMO+2, and systematically investigate the dependence of the elastic lifetimes of these states on the alignment among adsorbate and substrate states.Comment: 24 pages, 6 figures, to appear in Journal of Physical Chemistry

Status of the SOLEIL femtosecond X-ray source

http://accelconf.web.cern.ch/AccelConf/FEL2012/papers/wepd04.pdfInternational audienceAn electron bunch slicing setup is presently under construction on the SOLEIL storage ring for delivering 100 fs (rms) long photon pulses to two undulator-based beamlines providing soft (TEMPO) and hard X-rays (CRISTAL). Thanks to the non-zero dispersion function present in all straight sections of the storage ring, the sliced bunches can be easily separated from the core bunches. The modulator is a wiggler composed of 20 periods of 164.4 mm. It produces a magnetic field of 1.8 T at a minimum gap of 14.5 mm. To modulate the kinetic energy of the electrons in the wiggler, a Ti:Sa laser will be used, which produces 50 fs pulses at 800 nm with a repetition rate of 2.5 kHz. The laser beam is splitted into two branches in order to provide 2 mJ to the modulator and 0.5 mJ as pump pulse for the CRISTAL and TEMPO end stations. Focusing optics and beam path, from the laser hutch to the inside of the storage ring tunnel are presently under finalization. In this paper, we will report on the specificities of the SOLEIL setup, the status of its installation and the expected performances

LUNEX5 : A FEL PROJECT TOWARDS THE FIFTH GENERATION IN FRANCE

ISBN978-3-95450-117-5 - http://accelconf.web.cern.ch/AccelConf/FEL2011/papers/tupa09.pdfInternational audienc

Resident macrophages influence stem cell activity in the mammary gland

Introduction Macrophages in the mammary gland are essential for morphogenesis of the ductal epithelial tree and have been implicated in promoting breast tumor metastasis. Although it is well established that macrophages influence normal mammopoiesis, the mammary cell types that these accessory cells influence have not been determined. Here we have explored a role for macrophages in regulating mammary stem cell (MaSC) activity, by assessing the ability of MaSCs to reconstitute a mammary gland in a macrophage-depleted fat pad. Methods Two different in vivo models were used to deplete macrophages from the mouse mammary fat pad, allowing us to examine the effect of macrophage deficiency on the mammary repopulating activity of MaSCs. Both the Csf1(op/op) mice and clodronate liposome-mediated ablation models entailed transplantation studies using the MaSC-enriched population. Results We show that mammary repopulating ability is severely compromised when the wild-type MaSC-enriched subpopulation is transplanted into Csf1(op/op) fat pads. In reciprocal experiments, the MaSC-enriched subpopulation from Csf1(op/op) glands had reduced regenerative capacity in a wildtype environment. Utilizing an alternative strategy for selective depletion of macrophages from the mammary gland, we demonstrate that co-implantation of the MaSC-enriched subpopulation with clodronate-liposomes leads to a marked decrease in repopulating frequency and outgrowth potential. Conclusions Our data reveal a key role for mammary gland macrophages in supporting stem/progenitor cell function and suggest that MaSCs require macrophage-derived factors to be fully functional. Macrophages may therefore constitute part of the mammary stem cell nich