The GANIL beam lines

http://accelconf.web.cern.ch/AccelConf/c81/papers/ep-36.pdfInternational audienceThe general optical functions of the beam lines are described. The principle of beam lines composed of sections with separated functions was adopted. The main technological characteristics of the equipments (guiding system, buncher, stripper, beam diagnostics and pumping system) are given

FLOQUET SOLUTION FOR A SPINNING SYMMETRIC RIGID BODY WITH CONSTANT TRANSVERSE TORQUES

In this paper we analyze the problem of large angular excursions of the spin axis of a rigid body using Floquet theory. This approach involves transforming the nonlinear equations into a linear periodic system and then computing solutions using Fourier series expansions. Numerical simulations confirm that the solutions are highly accurate when applied to typical spacecraft maneuvers

Cervical visual inspection with acetic acid (VIA) and oncogenic human papillomavirus screening in rural indigenous guatemalan women: Time to rethink VIA

Single-visit “screen-and-treat” strategies using visual inspection with acetic acid (VIA) and cryotherapy (liquid nitrous oxide ablation) in low-resource settings are commonly used to de-tect and treat precancerous lesions for cervical cancer prevention. This study compared VIA sensi-tivity and specificity in rural indigenous Guatemalan communities, to that of oncogenic human papillomavirus (HPV) testing for detection of precancerous changes, using cytology as the reference standard. Between 3–8 September 2017, trained nurses examined 222 women aged 23–58 years with VIA. Specimens for liquid-based cytology and HPV testing were obtained prior to VIA with a cyto-brush and transported in PreservCyt to a US clinical laboratory. VIA and HPV test sensitivities were assessed as proportions of women with abnormal cytology that had abnormal VIA or HPV results, respectively, and specificities, as proportions with normal cytology with normal VIA or negative HPV tests. Of 222 women, 18 (8.1%) had abnormal cytology (1 carcinoma in a participant who received VIA-based cryotherapy in 2015, 4 high-and 5 low-grade squamous intraepithelial lesions, and 8 atypical squamous cells of undetermined significance (ASCUS)). Excluding ASCUS, sensitivities of VIA and HPV were 20.0% and 100%, respectively. VIA-based screening may not be accepta-ble for detecting precancerous lesions, and field cryotherapy for preventing malignancy. The World Health Organization recommended in 2021 “…using HPV DNA detection as the primary screening test rather than VIA or cytology.”

Circumbinary Gas Accretion onto a Central Binary: Infrared Molecular Hydrogen Emission from GG Tau A

We present high spatial resolution maps of ro-vibrational molecular hydrogen emission from the environment of the GG Tau A binary component in the GG Tau quadruple system. The H2 v= 1-0 S(1) emission is spatially resolved and encompasses the inner binary, with emission detected at locations that should be dynamically cleared on several hundred-year timescales. Extensions of H2 gas emission are seen to ~100 AU distances from the central stars. The v = 2-1 S(1) emission at 2.24 microns is also detected at ~30 AU from the central stars, with a line ratio of 0.05 +/- 0.01 with respect to the v = 1-0 S(1) emission. Assuming gas in LTE, this ratio corresponds to an emission environment at ~1700 K. We estimate that this temperature is too high for quiescent gas heated by X-ray or UV emission from the central stars. Surprisingly, we find that the brightest region of H2 emission arises from a spatial location that is exactly coincident with a recently revealed dust "streamer" which seems to be transferring material from the outer circumbinary ring around GG Tau A into the inner region. As a result, we identify a new excitation mechanism for ro-vibrational H2 stimulation in the environment of young stars. The H2 in the GG Tau A system appears to be stimulated by mass accretion infall as material in the circumbinary ring accretes onto the system to replenish the inner circumstellar disks. We postulate that H2 stimulated by accretion infall could be present in other systems, particularly binaries and "transition disk" systems which have dust cleared gaps in their circumstellar environments.Comment: 18 pages, including 4 figures. Accepted for publication in Ap

Obesity Accelerates Acute Promyelocytic Leukemia in Mice and Reduces Sex Differences in Latency and Penetrance

Objective: Obesity has emerged as a prominent risk factor for multiple serious disease states, including a variety of cancers, and is increasingly recognized as a primary contributor to preventable cancer risk. However, few studies of leukemia have been conducted in animal models of obesity. This study sought to characterize the impact of obesity, diet, and sex in a murine model of acute promyelocytic leukemia (APL). Methods: Male and female C57BL/6J.mCG+/PR mice, genetically predisposed to sporadic APL development, and C57BL/6J (wild type) mice were placed on either a high-fat diet (HFD) or a low-fat diet (LFD) for up to 500 days. Results: Relative to LFD-fed mice, HFD-fed animals displayed increased disease penetrance and shortened disease latency as indicated by accelerated disease onset. In addition, a diet-responsive sex difference in APL penetrance and incidence was identified, with LFD-fed male animals displaying increased penetrance and shortened latency relative to female counterparts. In contrast, both HFD-fed male and female mice displayed 100% disease penetrance and insignificant differences in disease latency, indicating that the sexual dimorphism was reduced through HFD feeding. Conclusions: Obesity and obesogenic diet promote the development of APL in vivo, reducing sexual dimorphisms in disease latency and penetrance

Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.

Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10(-4)) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10(-6)) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout.We thank Kerra Pearce (UCL Genomics) for array processing, and Tim Fell and Jonathan Best (CellCentric), Jason Wray (UCL) and Rosemary Drake (TAP Biosystems) for discussions. We also thank Minal Patel, Chris Kirton, Anja Kolb-Kokocinski, Willem H. Ouwehand, Richard Durbin and Fiona M. Watt on behalf of the Human Induced Pluripotent Stem Cell Initiative (HipSci) funded by grant WT098503 from the Wellcome Trust and the Medical Research Council, for sharing data and materials. This work was supported in part by a TSB/EPSRC grant (TS/H000933/1). The Vallier lab is supported by the Cambridge Hospitals National Institute for Health Research Biomedical Research Center and an ERC Starting Grant (Relieve IMDS). F.A.C.S. is funded by a PhD studentship from Fundação para a Ciência e a Tecnologia (SFRH/BD/69033/2010). The Ferguson-Smith lab is supported by grants from the MRC and Wellcome Trust, and EU-FP7 projects EPIGENESYS (257082) and BLUEPRINT (282510). The Beck lab is supported by the Wellcome Trust (084071), a Royal Society Wolfson Research Merit Award (WM100023), and EU-FP7 projects EPIGENESYS (257082) and BLUEPRINT (282510).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1045

Clinical validation of the in silico prediction of immunogenicity of a human recombinant therapeutic protein

Antibodies elicited by protein therapeutics can cause serious side effects in humans. We studied immunogenicity of a recombinant fusion protein (FPX) consisting of two identical, biologically active, peptides attached to human Fc fragment. EpiMatrix, an in silico epitope-mapping tool, predicted promiscuous T-cell epitope(s) within the 14-amino-acid carboxy-terminal region of the peptide portion of FPX. On administration of FPX in 76 healthy human subjects, 37% developed antibodies after a single injection. A memory T-cell response against the above carboxy-terminus of the peptide was observed in antibody-positive but not in antibody-negative subjects. Promiscuity of the predicted T-cell epitope(s) was confirmed by representation of all common HLA alleles in antibody-positive subjects. As predicted by EpiMatrix, HLA haplotype DRB1*0701/1501 was associated with the highest T-cell and antibody response. In conclusion, in silico prediction can be successfully used to identify Class II restricted T-cell epitopes within therapeutic proteins and predict immunogenicity thereof in humans

Limited Sampling Strategy to Predict AUC of the CYP3A Phenotyping Probe Midazolam in Adults: Application to Various Assay Techniques

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97211/1/00912700222011418.pd