Construire l’espace public : du diagnostic au projet. La mission d'étude de diagnostic de la loi MOP adaptée aux projets de paysage

Ce document, réalisé à partir de contributions provenant de l\u27INHP, du STAP 37 et de l\u27ADAC1, a pour principale fonction d’expliciter les étapes préalables aux projets d’aménagement d’espaces publics dans le cadre de la loi MOP2. Il est principalement destiné aux maîtres d\u27ouvrage et aux maîtres d’oeuvre. La loi MOP fixe les différentes étapes d’élaboration d\u27un projet de maîtrise d\u27oeuvre. Dans le cadre des projets d\u27aménagement d\u27espaces publics, il semble de plus en plus évident que la mission de base définie par la loi n\u27est pas toujours suffisante pour intégrer en amont de la phase de conception l\u27ensemble des enjeux et des contraintes qui soustendent l\u27émergence d\u27un projet d\u27aménagement. Il existe un complément à la mission de base intitulé "études de diagnostic", qui permet d\u27intégrer une étude en amont mais qui est principalement destinée aux projets de réhabilitation. Concernant les projets d’aménagement d’espaces publics, nous sommes convaincus qu\u27une mission similaire pourrait être intégrée à la procédure d\u27élaboration du projet et qu\u27elle doit conduire à l\u27élaboration de schémas d\u27articulation posant les enjeux et les bases des futurs projets. A ce titre, il nous semble important, puisqu\u27elle ne fait pas partie intégrante de la mission de base, qu\u27elle soit réalisée dans le cadre du marché, sous la forme d\u27une mission complémentaire préalable demandée par le maître d\u27ouvrage. Dans ce contexte, elle diffère quelque peu de la version utilisée pour la réhabilitation, même si les étapes imposées peuvent être transposées dans un environnement urbain. L\u27objet de ce document est d\u27expliciter ce que recouvre la notion d\u27analyse préalable, sur le base du contenu de la mission complémentaire d\u27étude de diagnostic, et de proposer une méthodologie permettant de la mener à bien

Mechanisms involved in the promoting activity of fibroblasts in HTLV-1-mediated lymphomagenesis: Insights into the plasticity of lymphomatous cells

Among the mechanisms leading to progression to Adult T-cell Leukaemia/Lymphoma in Human T-cell Leukaemia Virus type 1 (HTLV-1)-infected subjects, the contribution of stromal components remains poorly understood. To dissect the role of fibroblasts in HTLV-1-mediated lymphomagenesis, transcriptome studies, cytofluorimetric and qRT-PCR analyses of surface and intracellular markers linked to plasticity and stemness in coculture, and in vivo experiments were performed. A transcriptomic comparison between a more lymphomagenic (C91/III) and the parental (C91/PL) cell line evidenced hyperactivation of the PI3K/Akt pathway, confirmed by phospho-ELISA and 2-DE and WB analyses. C91/III cells also showed higher expression of mesenchymal and stemness genes. Short-term coculture with human foreskin fibroblasts (HFF) induced these features in C91/PL cells, and significantly increased not only the cancer stem cells (CSCs)-supporting CD10+GPR77+ HFF subpopulation, but also the percentage of ALDH1bright C91/PL cells. A non-cytotoxic acetylsalicylic acid treatment decreased HFF-induced ALDH1bright C91/PL cells, downregulated mesenchymal and stemness genes in cocultured cells, and delayed lymphoma growth in immunosuppressed mice, thus hindering the supportive activity of HFF on CSCs. These data suggest that crosstalk with HFF significantly intensifies the aggressiveness and plasticity of C91/PL cells, leading to the enrichment in lymphoma-initiating cells. Additional research is needed to better characterize these preliminary findings

The generalized cusp in ABJ(M) N = 6 Super Chern-Simons theories

We construct a generalized cusped Wilson loop operator in N = 6 super Chern-Simons-matter theories which is locally invariant under half of the supercharges. It depends on two parameters and interpolates smoothly between the 1/2 BPS line or circle and a pair of antiparallel lines, representing a natural generalization of the quark-antiquark potential in ABJ(M) theories. For particular choices of the parameters we obtain 1/6 BPS configurations that, mapped on S^2 by a conformal transformation, realize a three-dimensional analogue of the wedge DGRT Wilson loop of N = 4. The cusp couples, in addition to the gauge and scalar fields of the theory, also to the fermions in the bifundamental representation of the U(N)xU(M) gauge group and its expectation value is expressed as the holonomy of a suitable superconnection. We discuss the definition of these observables in terms of traces and the role of the boundary conditions of fermions along the loop. We perform a complete two-loop analysis, obtaining an explicit result for the generalized cusp at the second non-trivial order, from which we read off the interaction potential between heavy 1/2 BPS particles in the ABJ(M) model. Our results open the possibility to explore in the three-dimensional case the connection between localization properties and integrability, recently advocated in D = 4.Comment: 53 pages, 10 figures, added references, this is the version appeared on JHE

Generalized cusp in AdS_4 x CP^3 and more one-loop results from semiclassical strings

We evaluate the exact one-loop partition function for fundamental strings whose world-surface ends on a cusp at the boundary of AdS_4 and has a "jump" in CP^3. This allows us to extract the stringy prediction for the ABJM generalized cusp anomalous dimension Gamma_{cusp}^{ABJM} (phi,theta) up to NLO in sigma-model perturbation theory. With a similar analysis, we present the exact partition functions for folded closed string solutions moving in the AdS_3 parts of AdS_4 x CP^3 and AdS_3 x S^3 x S^3 x S^1 backgrounds. Results are obtained applying to the string solutions relevant for the AdS_4/CFT_3 and AdS_3/CFT_2 correspondence the tools previously developed for their AdS_5 x S^5 counterparts.Comment: 48 pages, 2 figures, version 3, corrected misprints in formulas 2.12, B.86, C.33, added comment on verification of the light-like limi

Distinct Mechanisms for Induction and Tolerance Regulate the Immediate Early Genes Encoding Interleukin 1β and Tumor Necrosis Factor α

Interleukin-1β and Tumor Necrosis Factor α play related, but distinct, roles in immunity and disease. Our study revealed major mechanistic distinctions in the Toll-like receptor (TLR) signaling-dependent induction for the rapidly expressed genes (IL1B and TNF) coding for these two cytokines. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), hallmarks of poised immediate-early (IE) genes. In contrast, unstimulated IL1B displayed very low levels of both TBP and paused Pol II, requiring the lineage-specific Spi-1/PU.1 (Spi1) transcription factor as an anchor for induction-dependent interaction with two TLR-activated transcription factors, C/EBPβ and NF-κB. Activation and DNA binding of these two pre-expressed factors resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of elongation factor P-TEFb. This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Furthermore, the dependence on phosphoinositide 3-kinase for P-TEFb recruitment to IL1B paralleled a greater sensitivity to the metabolic state of the cell and a lower sensitivity to the phenomenon of endotoxin tolerance than was evident for TNF. Such differences in induction mechanisms argue against the prevailing paradigm that all IE genes possess paused Pol II and may further delineate the specific roles played by each of these rapidly expressed immune modulators. © 2013 Adamik et al

Predictive clinico-pathological factors to identify BCG, unresponsive patients, after re-resection for T1 high grade non-muscle invasive bladder cancer

Introduction: Seventy-five percent of bladder cancers are non-muscle invasive. The treatment strategy includes the transurethral resection of bladder tumor (TURB) followed by intravesical immunotherapy with the bacillus of Calmette-Guerin (BCG) or chemotherapy, depending on the grade of bladder tumor. Despite a proper BCG intravesical instillations schedule, up to 40% of patients present a failure within 2 years. The aim of this retrospective study was to investigate the predictive factors in the response to BCG in patients with a high-grade non-muscle invasive bladder cancer diagnosis. Materials and methods: Patients with non-muscle invasive bladder cancer from 13 hospitals and academic institutions were identified and treated, from January 1, 2002, until December 31, 2012, with TURB and a subsequent re-TURB for restaging before receiving BCG. Follow-up was performed with urine cytology and cystoscopy every 3 months for 1 year and, successively every 6 months. Univariate and multivariate Cox regression models addressed the response to BCG therapy. Kaplan-Meier overall survival (OS) and cancer-specific survival (CSS) estimates were determined for BCG responsive vs. BCG unresponsive patients. Results: A total of 1,228 patients with non-muscle invasive bladder cancer were enrolled. Of 257 (20.9%) patients were BCG unresponsive. Independent predictive factors for response to BCG were: multifocality (HR: 1.4; 95% CI 1.05-1.86; P = 0.019), lymphovascular invasion (HR: 1.75; 95% CI 1.22-2.49; P = 0.002) and high-grade on re-TURB (HR: 1.39; 95% CI 1.02-1.91; P = 0.037). Overall survival was significantly reduced in BCG-unresponsive patients compared to BCG-responsive patients at 5 years (82.9% vs. 92.4%, P < 0.0001) and at 10 years (44.2% vs. 74.4%, P < 0.0001). Similarly, cancer-specific survival was reduced in BCG-unresponsive patients at 5 years (90.6% vs. 97.3%, P < 0.0001) and at 10 years (72.3% vs. 87.2%, P < 0.0001). Conclusion: Multifocality, lymphovascular invasion, and high-grade on re-TURB were independent predictors for response to BCG treatment. BCG-unresponsive patients reported worse oncological outcomes

Islet transplantation and insulin administration relieve long-term complications and rescue the residual endogenous pancreatic cells

Islet transplantation is a poorly investigated Long-term strategy for insulin replacement and for treatment of complications in patients with diabetes. We investigated whether islet transplantation and insulin treatment can relieve diabetic neuropathy and rescue the residual endogenous pancreatic beta cells. We used a multimodal approach, with five groups of Sprague-Dawley rats studied for 8 months: control rats, diabetic rats, insulin-treated diabetic rats with moderate or mild hyperglycemia, and diabetic rats transplanted with microencapsulated islets. Islet transplantation normalized glycemia and increased body and muscle weight; it was also effective in reducing proteinuria and altered liver function. Transplantation significantly improved tail nerve conduction velocity, Na+-K+-ATPase activity, and morphological alterations in the sciatic nerve as evidenced by decrease in g-ratio; it also restored thermal and ameliorated mechanical nociceptive thresholds. Morphometric analysis of pancreas indicated a significant beta-cell volume increase in transplanted rats, compared with mildly and moderately hyperglycemic rats. Thus, allogeneic islet transplantation had a positive systemic effect in diabetic rats and induced regression of the established neuropathy and restitution of the typical characteristics of the islets. These findings strongly reinforce the need for improving glycemic control, not only to reverse established diabetic complications but also to improve beta-cell status in diabetic pancreas

Fabrication of 3D Oriented MOF Micropatterns with Anisotropic Fluorescent Properties

Published online: May 2, 2023Micropatterning crystalline materials with oriented pores is necessary for the fabrication of devices with anisotropic properties. Crystalline and porous metal–organic frameworks (MOFs) are ideal materials as their chemical and structural mutability enables precise tuning of functional properties for applications ranging from microelectronics to photonics. Herein, a patternable oriented MOF film is designed: by using a photomask under X-ray exposure, the MOF film decomposes in the irradiated areas, remaining intact in the unexposed regions. The MOF film acts simultaneously as a resist and as functional porous material. While the heteroepitaxial growth from aligned Cu(OH)₂ nanobelts is used to deposit oriented MOF films, the sensitivity to radiation is achieved by integrating a brominated dicarboxylate ligand (Br₂BDC) into a copper-based MOF Cu₂L₂DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane; L = BDC/Br₂BDC). The lithographed samples act as diffraction gratings upon irradiation with a laser, thus confirming the quality of the extended MOF micropattern. Furthermore, the oriented MOF patterns are functionalized with fluorescent dyes. As a result, by rotating the polarization angle of the laser excitation, the alignment of the dye in the MOF is demonstrated. By controlling the functional response to light, this MOF patterning protocol can be used for the microfabrication of optical components for photonic devices.Miriam de J. Velásquez-Hernández, Mercedes Linares-Moreau, Lea A. Brandner, Benedetta Marmiroli, Mariano Barella, Guillermo P. Acuna, Simone Dal Zilio, Margot F. K. Verstreken, Dmitry E. Kravchenko, Oliver M. Linder-Patton, Jack D. Evans, Helmar Wiltsche, Francesco Carraro, Heimo Wolinski, Rob Ameloot, Christian Doonan, and Paolo Falcar

GMO detection using a bioluminescent real time reporter (BART) of loop mediated isothermal amplification (LAMP) suitable for field use

<p>Abstract</p> <p>Background</p> <p>There is an increasing need for quantitative technologies suitable for molecular detection in a variety of settings for applications including food traceability and monitoring of genetically modified (GM) crops and their products through the food processing chain. Conventional molecular diagnostics utilising real-time polymerase chain reaction (RT-PCR) and fluorescence-based determination of amplification require temperature cycling and relatively complex optics. In contrast, isothermal amplification coupled to a bioluminescent output produced in real-time (BART) occurs at a constant temperature and only requires a simple light detection and integration device.</p> <p>Results</p> <p>Loop mediated isothermal amplification (LAMP) shows robustness to sample-derived inhibitors. Here we show the applicability of coupled LAMP and BART reactions (LAMP-BART) for determination of genetically modified (GM) maize target DNA at low levels of contamination (0.1-5.0% GM) using certified reference material, and compare this to RT-PCR. Results show that conventional DNA extraction methods developed for PCR may not be optimal for LAMP-BART quantification. Additionally, we demonstrate that LAMP is more tolerant to plant sample-derived inhibitors, and show this can be exploited to develop rapid extraction techniques suitable for simple field-based qualitative tests for GM status determination. We also assess the effect of total DNA assay load on LAMP-BART quantitation.</p> <p>Conclusions</p> <p>LAMP-BART is an effective and sensitive technique for GM detection with significant potential for quantification even at low levels of contamination and in samples derived from crops such as maize with a large genome size. The resilience of LAMP-BART to acidic polysaccharides makes it well suited to rapid sample preparation techniques and hence to both high throughput laboratory settings and to portable GM detection applications. The impact of the plant sample matrix and genome loading within a reaction must be controlled to ensure quantification at low target concentrations.</p

Uncoordinated Transcription and Compromised Muscle Function in the Lmna-Null Mouse Model of Emery-Dreifuss Muscular Dystrophy

LMNA encodes both lamin A and C: major components of the nuclear lamina. Mutations in LMNA underlie a range of tissue-specific degenerative diseases, including those that affect skeletal muscle, such as autosomal-Emery-Dreifuss muscular dystrophy (A-EDMD) and limb girdle muscular dystrophy 1B. Here, we examine the morphology and transcriptional activity of myonuclei, the structure of the myotendinous junction and the muscle contraction dynamics in the lmna-null mouse model of A-EDMD. We found that there were fewer myonuclei in lmna-null mice, of which ∼50% had morphological abnormalities. Assaying transcriptional activity by examining acetylated histone H3 and PABPN1 levels indicated that there was a lack of coordinated transcription between myonuclei lacking lamin A/C. Myonuclei with abnormal morphology and transcriptional activity were distributed along the length of the myofibre, but accumulated at the myotendinous junction. Indeed, in addition to the presence of abnormal myonuclei, the structure of the myotendinous junction was perturbed, with disorganised sarcomeres and reduced interdigitation with the tendon, together with lipid and collagen deposition. Functionally, muscle contraction became severely affected within weeks of birth, with specific force generation dropping as low as ∼65% and ∼27% of control values in the extensor digitorum longus and soleus muscles respectively. These observations illustrate the importance of lamin A/C for correct myonuclear function, which likely acts synergistically with myotendinous junction disorganisation in the development of A-EDMD, and the consequential reduction in force generation and muscle wasting