It\u27s Pronounced Zine

https://digitalcommons.chapman.edu/feminist_zines/1036/thumbnail.jp

Transgenic analysis of the Leishmania MAP kinase MPK10 reveals an auto-inhibitory mechanism crucial for stage-regulated activity and parasite viability

Protozoan pathogens of the genus Leishmania have evolved unique signaling mechanisms that can sense changes in the host environment and trigger adaptive stage differentiation essential for host cell infection. The signaling mechanisms underlying parasite development remain largely elusive even though Leishmania mitogen-activated protein kinases (MAPKs) have been linked previously to environmentally induced differentiation and virulence. Here, we unravel highly unusual regulatory mechanisms for Leishmania MAP kinase 10 (MPK10). Using a transgenic approach, we demonstrate that MPK10 is stage-specifically regulated, as its kinase activity increases during the promastigote to amastigote conversion. However, unlike canonical MAPKs that are activated by dual phosphorylation of the regulatory TxY motif in the activation loop, MPK10 activation is independent from the phosphorylation of the tyrosine residue, which is largely constitutive. Removal of the last 46 amino acids resulted in significantly enhanced MPK10 activity both for the recombinant and transgenic protein, revealing that MPK10 is regulated by an auto-inhibitory mechanism. Over-expression of this hyperactive mutant in transgenic parasites led to a dominant negative effect causing massive cell death during amastigote differentiation, demonstrating the essential nature of MPK10 auto-inhibition for parasite viability. Moreover, phosphoproteomics analyses identified a novel regulatory phospho-serine residue in the C-terminal auto-inhibitory domain at position 395 that could be implicated in kinase regulation. Finally, we uncovered a feedback loop that limits MPK10 activity through dephosphorylation of the tyrosine residue of the TxY motif. Together our data reveal novel aspects of protein kinase regulation in Leishmania, and propose MPK10 as a potential signal sensor of the mammalian host environment, whose intrinsic pre-activated conformation is regulated by auto-inhibition

Status of Diamond Detector Development for Beam Halo Investigation at ATF2

Work supported by Chinese Scholarship Council - THPME092, ISBN 978-3-95450-132-8International audienceWe are developing a diamond detector for beam halo and Compton spectrum diagnostics after the interaction point (IP) of ATF2, a low energy (1.3 GeV) prototype of the final focus system for ILC and CLIC linear collider projects. Tests of a 500 μm thick sCVD diamond detector with a dimension of 4.5 mm×4.5 mm have been carried out with radioactive sources and with electron beam from PHIL low energy (<10 MeV) photo-injector at LAL. The tests at PHIL were done with different beam intensities in air, just after the exit window at the end of the beam line, to test the response of the diamond detector and the readout electronics. We have successfully detected signals from single electrons, using a 40 dB amplifier, and from an electron beam of 108 electrons, using a 24 dB attenuator. A diamond sensor with 4 strips has been designed and fabricated for installation in the vacuum chambers of ATF2 and PHIL, with the aim to scan both the beam halo (with 2 strips of 1.5 mm×4 mm) and the beam core (with 2 strips of 0.1 mm×4 mm) transverse distributions

PHIL photoinjector test line

LAL is now equiped with its own platform for photoinjectors tests and Research and Developement, named PHIL (PHotoInjectors at LAL). This facility has two main purposes: push the limits of the photoinjectors performances working on both the design and the associated technology and provide a low energy (MeV) short pulses (ps) electron beam for the interested users. Another very important goal of this machine will be to provide an opportunity to form accelerator physics students, working in a high technology environment. To achieve this goal a test line was realised equipped with an RF source, magnets and beam diagnostics. In this article we will desrcibe the PHIL beamline and its characteristics together with the description of the first two photoinjector realised in LAL and tested: the ALPHAX and the PHIN RF Guns

Erratum to: Providing Patients with Implantable Cardiac Device Data through a Personal Health Record: A Qualitative Study

Erratum to: Providing Patients with Implantable Cardiac Device Data through a Personal Health Record: A Qualitative Study. [Appl Clin Inform. 2017

Low Energy Beam Measurements Using PHIL Accelerator at LAL, Comparison with PARMELA Simulations

http://accelconf.web.cern.ch/AccelConf/PAC2011/papers/wep210.pdfInternational audiencePHIL ("PHo­to-In­jec­tor at LAL") is a new elec­tron beam ac­cel­er­a­tor at LAL. This ac­cel­er­a­tor is ded­i­cat­ed to test and char­ac­ter­ize elec­tron RF-guns and to de­liv­er elec­tron beam to users. This ma­chine has been de­signed to pro­duce and char­ac­terise low en­er­gy (E<10 MeV), small emit­tance (e<10 p.​mm.​mrad), high bril­liance elec­trons bunch at low rep­e­ti­tion fre­quen­cy (n<10Hz). The first beam has been ob­tained on the 4th of Novem­ber 2009. The cur­rent RF-gun test­ed on PHIL is the Al­phaX gun, a 2.5 cell S-band cav­i­ty de­signed by LAL for the plas­ma ac­cel­er­a­tor stud­ies per­formed at the Strath­clyde uni­ver­si­ty. This paper will pre­sent the first Al­phaX RF-gun char­ac­ter­i­za­tions per­formed at LAL on PHIL ac­cel­er­a­tor, and will show com­par­isons be­tween mea­sure­ments and PARMELA sim­u­la­tions

InterGEO: a digital platform for university education on geomorphological heritage

The project InterGEO was carried out with the objective to disseminate knowledge on geomorphological heritage by developing a digital learning platform. It aims at improving students' autonomy by the reduction of face-to-face teaching and increasing autonomous learning as well as promoting international interactions between students interested in geomorphological heritage. A completely free-access virtual course on geomorphosites was developed with the Learning Management System Moodle. The course is divided into 24 thematic chapters, each of them containing a short description, a list of references and selected publications, as well as other educational material (videos, virtual fieldtrips, etc.). In particular, several videos allow presenting in a dynamic way concepts and examples. The paper presents the tool and its use in academic programmes in six European universities, where it was tested, in various contexts (Bachelors' and Masters' programmes; students in geography or geology; general courses in geomorphology and specific courses on geoheritage and geoconservation), before discussing the advantages and challenges the tool is facing. The InterGEO platform is an easy-to-use and friendly educational tool, which allows developing blended learning activities; it is flexible and adaptable in various learning contexts.The coordination tasks (appointment of an assistant) and two workshops in Lausanne were financed by the University of Lausanne (Teaching Innovation Fund and Investment Fund of the Faculty of Geosciences and Environment, FGSE). The videos were designed and created with support of the universities of Lausanne (TIF) and Savoie Mont Blanc (IDEFI Promising and ReflexPro; LabEx ITEM)

Commissioning of the ALTO 50 MeV electron linac

online : http://accelconf.web.cern.ch/AccelConf/e06/PAPERS/MOPLS113.pdfThe ALTO 50 MeV electron linac is dedicated to the production of neutron-rich radioactive nuclei using the photo-fission process and the optimisation of the targetion source system for SPIRAL 2 and EURISOL projects. The accelerator consists of a 3 MeV injector (old test station of LAL, Laboratoire de l'Accélérateur Linéaire d'Orsay), LIL (Linac Injector of LEP) accelerating structure, RF power plant, beam line, control system and diagnostics. Specified and measured beam parameters will be compared to show the performances of the photofission process and eventually other applications

Risk factors for tuberculosis treatment failure, default, or relapse and outcomes of retreatment in Morocco

<p>Abstract</p> <p>Background</p> <p>Patients with tuberculosis require retreatment if they fail or default from initial treatment or if they relapse following initial treatment success. Outcomes among patients receiving a standard World Health Organization Category II retreatment regimen are suboptimal, resulting in increased risk of morbidity, drug resistance, and transmission.. In this study, we evaluated the risk factors for initial treatment failure, default, or early relapse leading to the need for tuberculosis retreatment in Morocco. We also assessed retreatment outcomes and drug susceptibility testing use for retreatment patients in urban centers in Morocco, where tuberculosis incidence is stubbornly high.</p> <p>Methods</p> <p>Patients with smear- or culture-positive pulmonary tuberculosis presenting for retreatment were identified using clinic registries in nine urban public clinics in Morocco. Demographic and outcomes data were collected from clinical charts and reference laboratories. To identify factors that had put these individuals at risk for failure, default, or early relapse in the first place, initial treatment records were also abstracted (if retreatment began within two years of initial treatment), and patient characteristics were compared with controls who successfully completed initial treatment without early relapse.</p> <p>Results</p> <p>291 patients presenting for retreatment were included; 93% received a standard Category II regimen. Retreatment was successful in 74% of relapse patients, 48% of failure patients, and 41% of default patients. 25% of retreatment patients defaulted, higher than previous estimates. Retreatment failure was most common among patients who had failed initial treatment (24%), and default from retreatment was most frequent among patients with initial treatment default (57%). Drug susceptibility testing was performed in only 10% of retreatment patients. Independent risk factors for failure, default, or early relapse after initial treatment included male gender (aOR = 2.29, 95% CI 1.10-4.77), positive sputum smear after 3 months of treatment (OR 7.14, 95% CI 4.04-13.2), and hospitalization (OR 2.09, 95% CI 1.01-4.34). Higher weight at treatment initiation was protective. Male sex, substance use, missed doses, and hospitalization appeared to be risk factors for default, but subgroup analyses were limited by small numbers.</p> <p>Conclusions</p> <p>Outcomes of retreatment with a Category II regimen are suboptimal and vary by subgroup. Default among patients receiving tuberculosis retreatment is unacceptably high in urban areas in Morocco, and patients who fail initial tuberculosis treatment are at especially high risk of retreatment failure. Strategies to address risk factors for initial treatment default and to identify patients at risk for failure (including expanded use of drug susceptibility testing) are important given suboptimal retreatment outcomes in these groups.</p