Neuronal plasticity: cell-based strategy for target identification and validation

While growing neurites are relatively plastic during development, their plasticity levels drop rapidly as neurons mature and become integrated into neuronal networks. As a consequence, the central nervous system ability to reorganize itself in response to injury or disease is insufficient. One of the main limitations for the design of therapeutic strategies to enhance neurite sprouting following neurological diseases is our poor understanding of the mechanisms underlying neurite structural plasticity. 

To overcome this limitation, we have implemented a strategy to identify, characterize and validate the most therapeutically relevant drug targets to modulate neuronal plasticity. This strategy is based on the hypothesis that the molecular regulation of the neurite shaft (controlling its ability to sprout) shares similarities with other cell systems. In an initial selection step (1), candidate targets are identified from the literature based on predetermined criteria (e.g. involvement in cell migration and growth cone collapse). (2) Compounds acting on those targets are tested in a neuronal cell-based assay for their effects on neurite sprouting as well as for early detection of undesired effects. (3) The selected targets are further analyzed during a verification step where their subcellular expression and activity is assessed. The regulation of the activity of the potential targets by branching factors is also determined at this point. (4) Once the biological relevance has been established, the signalling pathway in which the potential targets operates within neurons is mapped using activity reporters to uncover additional potential targets. 

This candidate approach, combined with the use of primary neurons, is designed to increase the probability of identifying suitable targets at the same time that it minimizes costs and time to validation. By using this strategy, we have been able to identify a set of proteins controlling neuronal sprouting together with an unsuspected mechanism of regulation of structural plasticity in neurons

Use of Solr and Xapian in the Invenio document repository software

Invenio is a free comprehensive web-based document repository and digital library software suite originally developed at CERN. It can serve a variety of use cases from an institutional repository or digital library to a web journal. In order to fully use full-text documents for efficient search and ranking, Solr was integrated into Invenio through a generic bridge. Solr indexes extracted full-texts and most relevant metadata. Consequently, Invenio takes advantage of Solr's efficient search and word similarity ranking capabilities. In this paper, we first give an overview of Invenio, its capabilities and features. We then present our open source Solr integration as well as scalability challenges that arose for an Invenio-based multi-million record repository: the CERN Document Server. We also compare our Solr adapter to an alternative Xapian adapter using the same generic bridge. Both integrations are distributed with the Invenio package and ready to be used by the institutions using or adopting Invenio

Galois coverings of weakly shod algebras

We investigate the Galois coverings of weakly shod algebras. For a weakly shod algebra not quasi-tilted of canonical type, we establish a correspondence between its Galois coverings and the Galois coverings of its connecting component. As a consequence, we show that a weakly shod algebra is simply connected if and only if its first Hochschild cohomology group vanishes.Comment: Some references were added. The proof of Lemma 6.5 was modifie

A double continuum hydrological model for glacier applications

Peer reviewedPublisher PD

About the connection between the CℓC_{\ell} power spectrum of the Cosmic Microwave Background and the Γm\Gamma_{m} Fourier spectrum of rings on the sky

In this article we present and study a scaling law of the $m\Gamma_m$ CMB Fourier spectrum on rings which allows us (i) to combine spectra corresponding to different colatitude angles (e.g. several detectors at the focal plane of a telescope), and (ii) to recover the $C_l$ power spectrum once the $\Gamma_m$ coefficients have been measured. This recovery is performed numerically below the 1% level for colatitudes $\Theta> 80^\circ$ degrees. In addition, taking advantage of the smoothness of the $C_l$ and of the $\Gamma_m$, we provide analytical expressions which allow to recover one of the spectrum at the 1% level, the other one being known.Comment: 8 pages, 8 figure

HFI L2 DPC destripping and mapmaking modules

PoS(CMB2006)049International audienceThe data processing of the data from the High Frequency Instrument (HFI) of the Planck mission will use several modules. Destriping is expected to play a central role in the mapmaking stage. This paper outlines two existing HFI l2 DPC destriping modules together with estimations of their performances. MOKAPIX is a temperature data destriping tool based on scanning redundancies on the sky. We have developped another modules, BOGOPIX , based on the same philosophy, to perform simultaneously destriping and relative intercalibration

The Development of Functional Overreaching Is Associated with a Faster Heart Rate Recovery in Endurance Athletes

Purpose The aim of the study was to investigate whether heart rate recovery (HRR) may represent an effective marker of functional overreaching (f-OR) in endurance athletes. Methods and Results Thirty-one experienced male triathletes were tested (10 control and 21 overload subjects) before (Pre), and immediately after an overload training period (Mid) and after a 2-week taper (Post). Physiological responses were assessed during an incremental cycling protocol to exhaustion, including heart rate, catecholamine release and blood lactate concentration. Ten participants from the overload group developed signs of f-OR at Mid (i.e. -2.1 ± 0.8% change in performance associated with concomitant high perceived fatigue). Additionally, only the f-OR group demonstrated a 99% chance of increase in HRR during the overload period (+8 ± 5 bpm, large effect size). Concomitantly, this group also revealed a >80% chance of decreasing blood lactate (-11 ± 14%, large), plasma norepinephrine (-12 ± 37%, small) and plasma epinephrine peak concentrations (-51 ± 22%, moderate). These blood measures returned to baseline levels at Post. HRR change was negatively correlated to changes in performance, peak HR and peak blood metabolites concentrations. Conclusion These findings suggest that i) a faster HRR is not systematically associated with improved physical performance, ii) changes in HRR should be interpreted in the context of the specific training phase, the athletes perceived level of fatigue and the performance response; and, iii) the faster HRR associated with f-OR may be induced by a decreased central commandand by a lower chemoreflex activity

GUINEA-PIG++ : an upgraded version of the linear collider beam-beam interaction simulation code GUINEA-PIG

http://cern.ch/AccelConf/p07/PAPERS/THPMN010.PDFInternational audienceGUINEA-PIG++ is a newly developed object-oriented version of the Linear Collider beam-beam simulation program GUINEA-PIG. The main goals of this project are to provide an reliable, modular, documented and versatile framework enabling convenient implementation of new features and functionalities

Contextual cropping and scaling of TV productions

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11042-011-0804-3. Copyright @ Springer Science+Business Media, LLC 2011.In this paper, an application is presented which automatically adapts SDTV (Standard Definition Television) sports productions to smaller displays through intelligent cropping and scaling. It crops regions of interest of sports productions based on a smart combination of production metadata and systematic video analysis methods. This approach allows a context-based composition of cropped images. It provides a differentiation between the original SD version of the production and the processed one adapted to the requirements for mobile TV. The system has been comprehensively evaluated by comparing the outcome of the proposed method with manually and statically cropped versions, as well as with non-cropped versions. Envisaged is the integration of the tool in post-production and live workflows

Photolytic modification of seasonal nitrate isotope cycles in East Antarctica

Nitrate in Antarctic snow has seasonal cycles in nitrogen and oxygen isotopic ratios that reflect its sources and atmospheric formation processes, and as a result, nitrate archived in Antarctic ice should have great potential to record atmospheric chemistry changes over thousands of years. However, sunlight that strikes the snow surface results in photolytic nitrate loss and isotopic fractionation that can completely obscure the nitrate's original isotopic values. To gain insight into how photolysis overwrites the seasonal atmospheric cycles, we collected 244 snow samples along an 850 km transect of East Antarctica during the 2013–2014 CHICTABA traverse. The CHICTABA route's limited elevation change, consistent distance between the coast and the high interior plateau, and intermediate accumulation rates offered a gentle environmental gradient ideal for studying the competing pre- and post-depositional influences on archived nitrate isotopes. We find that nitrate isotopes in snow along the transect are indeed notably modified by photolysis after deposition, and drier sites have more intense photolytic impacts. Still, an imprint of the original seasonal cycles of atmospheric nitrate isotopes is present in the top 1–2 m of the snowpack and likely preserved through archiving in glacial ice at these sites. Despite this preservation, reconstructing past atmospheric values from archived nitrate in similar transitional regions will remain a difficult challenge without having an independent proxy for photolytic loss to correct for post-depositional isotopic changes. Nevertheless, nitrate isotopes should function as a proxy for snow accumulation rate in such regions if multiple years of deposition are aggregated to remove the seasonal cycles, and this application can prove highly valuable in its own right.</p