Bucolic Complexes

We introduce and investigate bucolic complexes, a common generalization of systolic complexes and of CAT(0) cubical complexes. They are defined as simply connected prism complexes satisfying some local combinatorial conditions. We study various approaches to bucolic complexes: from graph-theoretic and topological perspective, as well as from the point of view of geometric group theory. In particular, we characterize bucolic complexes by some properties of their 2-skeleta and 1-skeleta (that we call bucolic graphs), by which several known results are generalized. We also show that locally-finite bucolic complexes are contractible, and satisfy some nonpositive-curvature-like properties.Comment: 45 pages, 4 figure

Two-loop cusp anomaly in ABJM at strong coupling

We compute the null cusp anomalous dimension of ABJM theory at strong coupling up to two-loop order. This is done by evaluating corrections to the corresponding superstring partition function, weighted by the AdS 4 × ℂℙ3 action in AdS light-cone gauge. We compare our result, where we use an anomalous shift in the AdS 4 radius, with the cusp anomaly of N = 4 SYM, and extract the two-loop contribution to the non-trivial integrable coupling h(λ) of ABJM theory. It coincides with the strong coupling expansion of the exact expression for h(λ) recently conjectured by Gromov and Sizov. Our work provides thus a non-trivial perturbative check for the latter, as well as evidence for two-loop UV-finiteness and quantum integrability of the Type IIA AdS 4 × ℂℙ3 superstring in this gauge

Document segmentation by interest areas detection

This paper presents a new approach of document structuring by the description of a foveated vision system implied in extracting visual and eye-catching information of a document . The simulation system is based on psycho-perceptive rules for visual data capturing. It allows us to obtain a representation of segmented document by using simple low-level processing . The low-level process is based on a visual integrative memory which displays the unequal importance of information in the visual field . The resulting segmentation enhances the fact that the access of information is directly linked to the search of attractive areas . The technical approach of the segmentation (using a space-variant geometry and a multiresolution process) lays a sound basis for elaborating the kinetic of the ocular displacement on a document. It provides not only a document representation in blocks, but shows a unified view corresponding to the integration of time-variant representations of the same visual field . The resulting blocks (text, graphs, image) are determined and localized all the better, such that the number of fixation points increases and yields a more complete and detailed description of components .Cette étude présente une nouvelle approche de la structuration de documents imprimés basée sur l'exploitation de la dynamique du regard dans le repérage de l'information. Le système qui a été mis en place nous permet d'obtenir une représentation du document segmenté en faisant appel à des procédures d'extraction de primitives géométriques simples (traitements de bas niveau) relevant de la prise en compte de certains comportements caractéristiques chez l'homme dans l'extraction d'information. Il utilise une série de représentations de type multirésolution du document où la nature du sous-échantillonnage est une fonction de la position du regard. Cette approche est basée sur la recherche des zones de focalisation de l'attention permettant de conserver une description précise des éléments dans les zones de fixation, tout en résumant les régions présentant un « intérêt » moindre. La simulation du parcours de l'oeil sur le document que nous avons retenue traduit la segmentation que ferait un lecteur qui aborde le document sans a priori sur ce qu'il veut trouver. Pour cela, nous nous sommes inspirés d'une stratégie exploratoire particulière : le survol. Celle-ci s'appuie essentiellement sur l'aspect visuel du document, c'est-à-dire sur les caractéristiques visuelles de bas niveau de l'image. Elle permet en outre une perception équilibrée des données en privilégiant l'organisation globale du document. La technique mise en oeuvre s'appuie sur un partitionnement évolutif de l'espace, en zones centrées aux points de fixation successifs. C'est sur la base de ce partitionnement, que la description des différentes régions ciblées du document évolue et converge vers une représentation segmentée

Muon-induced background in the EDELWEISS dark matter search

A dedicated analysis of the muon-induced background in the EDELWEISS dark matter search has been performed on a data set acquired in 2009 and 2010. The total muon flux underground in the Laboratoire Souterrain de Modane (LSM) was measured to be $\Phi_{\mu}=(5.4\pm 0.2 ^{+0.5}_{-0.9})$\,muons/m$^2$/d. The modular design of the muon-veto system allows the reconstruction of the muon trajectory and hence the determination of the angular dependent muon flux in LSM. The results are in good agreement with both MC simulations and earlier measurements. Synchronization of the muon-veto system with the phonon and ionization signals of the Ge detector array allowed identification of muon-induced events. Rates for all muon-induced events $\Gamma^{\mu}=(0.172 \pm 0.012)\, \rm{evts}/(\rm{kg \cdot d})$ and of WIMP-like events $\Gamma^{\mu-n} = 0.008^{+0.005}_{-0.004}\, \rm{evts}/(\rm{kg \cdot d})$ were extracted. After vetoing, the remaining rate of accepted muon-induced neutrons in the EDELWEISS-II dark matter search was determined to be $\Gamma^{\mu-n}_{\rm irred} < 6\cdot 10^{-4} \, \rm{evts}/(\rm{kg \cdot d})$ at 90%\,C.L. Based on these results, the muon-induced background expectation for an anticipated exposure of 3000\,\kgd\ for EDELWEISS-3 is $N^{\mu-n}_{3000 kg\cdot d} < 0.6$ events.Comment: 21 pages, 16 figures, Accepted for publication in Astropart. Phy

A siRNA-Based Screen for Genes Involved in Chromosome End Protection

Telomeres are nucleoprotein complexes which protect the ends of linear chromosomes from detection as DNA damage and provide a sequence buffer against replication-associated shortening. In mammals, telomeres consist of repetitive DNA sequence (TTAGGG) and associated proteins. The telomeric core complex is called shelterin and is comprised of the proteins TRF1, TRF2, POT1, TIN2, TPP1 and RAP1. Excessive telomere shortening or de-protection of telomeres through the loss of shelterin subunits allows the detection of telomeres as DNA damage, which can be visualized as DNA damage protein foci at chromosome ends called TIF (Telomere Dysfunction-Induced Foci). We sought to exploit the TIF phenotype as marker for telomere dysfunction to identify novel genes involved in telomere protection by siRNA-mediated knock-down of a set of 386 candidates. Here we report the establishment, specificity and feasibility of such a screen and the results of the genes tested. Only one of the candidate genes showed a unique TIF phenotype comparable to the suppression of the main shelterin components TRF2 or TRF1 and that gene was identified as a TRF1-like pseudogene. We also identified a weak TIF phenotype for SKIIP (SNW1), a splicing factor and transcriptional co-activator. However, the knock-down of SKIIP also induced a general, not telomere-specific DNA damage response, which complicates conclusions about a telomeric role. In summary, this report is a technical demonstration of the feasibility of a cell-based screen for telomere deprotection with the potential of scaling it to a high-throughput approach

The NIKA2 instrument, a dual-band kilopixel KID array for millimetric astronomy

NIKA2 (New IRAM KID Array 2) is a camera dedicated to millimeter wave astronomy based upon kilopixel arrays of Kinetic Inductance Detectors (KID). The pathfinder instrument, NIKA, has already shown state-of-the-art detector performance. NIKA2 builds upon this experience but goes one step further, increasing the total pixel count by a factor $\sim$10 while maintaining the same per pixel performance. For the next decade, this camera will be the resident photometric instrument of the Institut de Radio Astronomie Millimetrique (IRAM) 30m telescope in Sierra Nevada (Spain). In this paper we give an overview of the main components of NIKA2, and describe the achieved detector performance. The camera has been permanently installed at the IRAM 30m telescope in October 2015. It will be made accessible to the scientific community at the end of 2016, after a one-year commissioning period. When this happens, NIKA2 will become a fundamental tool for astronomers worldwide.Comment: Proceedings of the 16th Low Temperature Detectors workshop. To be published in the Journal of Low Temperature Physics. 8 pages, 4 figures, 1 tabl

The Crystal Structure of PPIL1 Bound to Cyclosporine A Suggests a Binding Mode for a Linear Epitope of the SKIP Protein

BACKGROUND: The removal of introns from pre-mRNA is carried out by a large macromolecular machine called the spliceosome. The peptidyl-prolyl cis/trans isomerase PPIL1 is a component of the human spliceosome and binds to the spliceosomal SKIP protein via a binding site distinct from its active site. PRINCIPAL FINDINGS: Here, we have studied the PPIL1 protein and its interaction with SKIP biochemically and by X-ray crystallography. A minimal linear binding epitope derived from the SKIP protein could be determined using a peptide array. A 36-residue region of SKIP centred on an eight-residue epitope suffices to bind PPIL1 in pull-down experiments. The crystal structure of PPIL1 in complex with the inhibitor cyclosporine A (CsA) was obtained at a resolution of 1.15 A and exhibited two bound Cd(2+) ions that enabled SAD phasing. PPIL1 residues that have previously been implicated in binding of SKIP are involved in the coordination of Cd(2+) ions in the present crystal structure. Employing the present crystal structure, the determined minimal binding epitope and previously published NMR data, a molecular docking study was performed. In the docked model of the PPIL1.SKIP interaction, a proline residue of SKIP is buried in a hydrophobic pocket of PPIL1. This hydrophobic contact is encircled by several hydrogen bonds between the SKIP peptide and PPIL1. CONCLUSION: We characterized a short, linear epitope of SKIP that is sufficient to bind the PPIL1 protein. Our data indicate that this SKIP peptide could function in recruiting PPIL1 into the core of the spliceosome. We present a molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area

Protein Kinase A Regulates Molecular Chaperone Transcription and Protein Aggregation

Heat shock factor 1 (HSF1) regulates one of the major pathways of protein quality control and is essential for deterrence of protein-folding disorders, particularly in neuronal cells. However, HSF1 activity declines with age, a change that may open the door to progression of neurodegenerative disorders such as Huntington's disease. We have investigated mechanisms of HSF1 regulation that may become compromised with age. HSF1 binds stably to the catalytic domain of protein kinase A (PKAcα) and becomes phosphorylated on at least one regulatory serine residue (S320). We show here that PKA is essential for effective transcription of HSP genes by HSF1. PKA triggers a cascade involving HSF1 binding to the histone acetylase p300 and positive translation elongation factor 1 (p-TEFb) and phosphorylation of the c-terminal domain of RNA polymerase II, a key mechanism in the downstream steps of HSF1-mediated transcription. This cascade appears to play a key role in protein quality control in neuronal cells expressing aggregation-prone proteins with long poly-glutamine (poly-Q) tracts. Such proteins formed inclusion bodies that could be resolved by HSF1 activation during heat shock. Resolution of the inclusions was inhibited by knockdown of HSF1, PKAcα, or the pTEFb component CDK9, indicating a key role for the HSF1-PKA cascade in protein quality control

The Menin Tumor Suppressor Protein Is Phosphorylated in Response to DNA Damage

Multiple endocrine neoplasia type 1 (MEN1) is a heritable cancer syndrome characterized by tumors of the pituitary, pancreas and parathyroid. Menin, the product of the MEN1 gene, is a tumor suppressor protein that functions in part through the regulation of transcription mediated by interactions with chromatin modifying enzymes.Here we show menin association with the 5' regions of DNA damage response genes increases after DNA damage and is correlated with RNA polymerase II association but not with changes in histone methylation. Furthermore, we were able to detect significant levels of menin at the 3' regions of CDKN1A and GADD45A under conditions of enhanced transcription following DNA damage. We also demonstrate that menin is specifically phosphorylated at Ser394 in response to several forms of DNA damage, Ser487 is dynamically phosphorylated and Ser543 is constitutively phosphorylated. Phosphorylation at these sites however does not influence the ability to interact with histone methyltransferase activity. In contrast, the interaction between menin and RNA polymerase II is influenced by phosphorylation, whereby a phospho-deficient mutant had a higher affinity for the elongating form of RNA polymerase compared to wild type. Additionally, a subset of MEN1-associated missense point mutants, fail to undergo DNA damage dependent phosphorylation.Together, our findings suggest that the menin tumor suppressor protein undergoes DNA damage induced phosphorylation and participates in the DNA damage transcriptional response