The Role of the Fondation Le Corbusier in the Conservation of the Le Corbusier's Architectural Work

Le Corbusier died on 27 August 1965 at Roquebrune-CapMartin, near his Cabanon. Without direct heirs and driven by the fear that his carefully conserved archives and works be scattered after his death, Le Corbusier spent the last fifteen years of his life conceiving and implementing, down to its smallest details, the project of a Foundation that would bear his name. Today the activity of the Fondation Le Corbusier comprises two main undertakings: circulating his work and spreading his ideas; preserving the architect’s work and collections. Indeed as the legatee and direct offshoot of its creator Le Corbusier, the Foundation holds the moral rights to this work and therefore has a duty to constantly watch over his architectural work (and indeed the artist’s entire legacy). For the Foundation each of his buildings constitute a piece of art in and of itself. Each issue concerned in the restoration of Le Corbusier’s buildings is effectively governed by this specificity

Transcriptomic and metabolic responses of Staphylococcus aureus exposed to supra-physiological temperatures

<p>Abstract</p> <p>Background</p> <p>Previous evaluation by different molecular and physiological assays of <it>Staphylococcus aureus </it>(<it>S. aureus</it>) responses to heat shock exposure yielded a still fragmentary view of the mechanisms determining bacterial survival or death at supra-physiological temperatures. This study analyzed diverse facets of <it>S. aureus </it>heat-shock adjustment by recording global transcriptomic and metabolic responses of bacterial cultures shifted for 10 min from 37°C to a sub-lethal (43°C) or eventually lethal (48°C) temperature. A relevant metabolic model of the combined action of specific stress response mechanisms with more general, energy-regulating metabolic pathways in heat-shocked <it>S. aureus </it>is presented.</p> <p>Results</p> <p>While <it>S. aureus </it>cultures shifted to 43°C or left at 37°C showed marginal differences in growth and survival rates, bacterial cultures exposed to 48°C showed a rapid growth arrest followed by a subsequent decline in viable counts. The most substantial heat shock-induced changes at both 43°C and 48°C occurred in transcript levels of HrcA- and CtsR-regulated genes, encoding classical chaperones DnaK and GroESL, and some Hsp100/Clp ATPases components, respectively. Other metabolic pathways up-regulated by <it>S. aureus </it>exposure at 48°C included genes encoding several enzymes coping with oxidative stress, and DNA damage, or/and impaired osmotic balance. Some major components of the pentose phosphate cycle and gluconeogenesis were also up-regulated, which reflected depletion of free glucose by bacterial cultures grown in Mueller-Hinton broth prior to heat shock. In contrast, most purine- and pyrimidine-synthesis pathway components and amino acyl-tRNA synthetases were down-regulated at 48°C, as well as arginine deiminase and major fermentative pathway components, such as alcohol, lactate and formate dehydrogenases. Despite the heat-induced, increased requirements for ATP-dependent macromolecular repair mechanisms combined with declining energy sources, intracellular ATP levels remained remarkably constant during heat shock.</p> <p>Conclusion</p> <p>The sequential loss of replication and viability at 48°C cannot be explained by significant reductions in intracellular ATP levels, but may reflect ATP rerouting for macromolecular repair mechanisms and cell survival. Our metabolic model also suggests that heat-stressed <it>S. aureus </it>should down-regulate the production of potential, DNA-damaging reactive oxygen species that might result from electron transport-generated ATP, involving excessive levels of free heavy metals, in particular iron.</p

0401: Which parameters can predict the response to exercise training in cardiac patients?

AimsBenefit effects of exercise training are well known and validated after a cardiac event, but some patients fail to ameliorate their functional capacity. This retrospective study determined which parameters in the initial cardio pulmonary exercise test could predict an improvement of functional capacity after training in cardiac patients.Methods and results292 cardiac patients with a complete training intervention were divided in two groups at the end of their rehabilitation : one group with a gain equal or more than 1 MET (148 patients) and one group with a gain less than 1 MET (144 patients) when the initial and final cardio pulmonary exercise tests were compared. The cardiac event (coronary revascularization 38%, aortic valvular surgery 23%, coronary stenting 18%) was similar in both group. The initial peak VO2 was not different (100 watts vs 110 watts, 15.6ml/kg/min vs 16.1ml/kg/min) neither the ventilator threshold nor the training intervention (19.3 sessions vs 17.9). At the end of the exercise training intervention, the gain of peak VO2 was 4.1ml/kg/min (+28%) in the global population and 6.8ml/kg/min (+46%) in the group ≥1 METS vs 1.29ml/kg/min (9.3%) in the group < 1 MET. Clinical predictor factors for a gain ≥1 MET were: age (58.3 years vs 62**p < 0,05), sex male (92% vs 83%*), ejection fraction (LVEF 52,5% vs 49,9%****p < 0,001). The initial discriminated exercise parameters were the energetic cost per watt (VO2/watt) 11,4 vs 12,2** the ventilatory cost (VE/watt) 0.62 vs 0.67*, the intensity per body kilogram (watts/kg) 1.43 vs 1.31* and the cardiac frequency per 1 liter of VO2 was lower 102 vs 110*.ConclusionThe benefit on functional capacity after exercise training intervention depended more of the initial physical condition than of the cardiac pathology in patients discharged in our cardiac rehabilitation centers. The exercise training should be more directed by the initial excise test

Reduced cancer incidence in Huntington's disease: analysis in the Registry study

We dedicate this paper to the memory of Raviram Ramesh. BACKGROUND People with Huntington’s disease have been observed to have lower rates of cancers. OBJECTIVE To investigate the relationship between age of onset of HD, CAG repeat length and cancer diagnosis. METHODS Data were obtained from the European Huntington’s disease network REGISTRY study for 6540 subjects. Population cancer incidence was ascertained from the GLOBOCAN database to obtain standardised incidence ratios of cancers in the REGISTRY subjects. RESULTS 173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22-0.30). Individual cancers showed a lower age-standardised incidence rate compared with the control population with prostate and colorectal cancers showing the lowest rates. There was no effect of CAG length on the likelihood of cancer, but a cancer diagnosis within the last year was associated with a greatly increased rate of HD onset (Hazard Ratio 18.94, p<0.001). CONCLUSIONS Cancer is less common than expected in the HD population, confirming previous reports. However, this does not appear to be related to CAG length in HTT. A recent diagnosis of cancer increases the risk of HD onset at any age, likely due to increased investigation following a cancer diagnosis

Prognostic Significance of New Immunohistochemical Markers in Refractory Classical Hodgkin Lymphoma: A Study of 59 Cases

Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score) used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders) for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment

Patient-reported outcome measures for pain in autosomal dominant polycystic kidney disease: A systematic review.

Pain is a common symptom in people with autosomal dominant polycystic kidney disease (ADPKD), but it is assessed and reported inconsistently in research, and the validity of the measures remain uncertain. The aim of this study was to identify the characteristics, content, and psychometric properties of measures for pain used in ADPKD. We conducted a systematic review including all trials and observational studies that reported pain in people with ADPKD. Items from all measures were categorized into content and measurement dimensions of pain. We assessed the general characteristics and psychometric properties of all measures. 118 studies, we identified 26 measures: 12 (46%) measures were developed for a non-ADPKD population, 1 (4%) for chronic kidney disease, 2 (8%) for polycystic liver disease and 11 (42%) specifically for ADPKD. Ten anatomical sites were included, with the lower back the most common (10 measures [39%]), four measurement dimensions (intensity (23 [88%]), frequency (3 [12%]), temporality (2 [8%]), and sensory (21 [81%]), two pain types, nociceptive including visceral (15 [58%]) and somatic (5 [20%]), and neuropathic (2 [8%]), and twelve impact dimensions, where the most frequent was work (5 [31%]). The validation data for the measures were variable and only the ADPKD Impact Scale reported all psychometric domains. The measures for pain in ADPKD varied in terms of content and length, and most had not been validated in ADPKD. A standardized psychometrically robust measure that captures patient-important dimensions of pain is needed to evaluate and manage this debilitating complication of ADPKD

Invaginating endoderm pulls on the extending ectoderm

How genetic programs generate cell-intrinsic forces to shape embryos is actively studied, but less so how tissue-scale physical forces impact morphogenesis. Here we address the role of the latter during axis extension, using Drosophila germband extension (GBE) as a model. We found previously that cells elongate in the anteroposterior (AP) axis in the extending germband, suggesting that an extrinsic tensile force contributed to body axis extension. Here we further characterized the AP cell elongation patterns during GBE, by tracking cells and quantifying their apical cell deformation over time. AP cell elongation forms a gradient culminating at the posterior of the embryo, consistent with an AP-oriented tensile force propagating from there. To identify the morphogenetic movements that could be the source of this extrinsic force, we mapped gastrulation movements temporally using light sheet microscopy to image whole Drosophila embryos. We found that both mesoderm and endoderm invaginations are synchronous with the onset of GBE. The AP cell elongation gradient remains when mesoderm invagination is blocked but is abolished in the absence of endoderm invagination. This suggested that endoderm invagination is the source of the tensile force. We next looked for evidence of this force in a simplified system without polarized cell intercalation, in acellular embryos. Using Particle Image Velocimetry, we identify posteriorwards Myosin II flows towards the presumptive posterior endoderm, which still undergoes apical constriction in acellular embryos as in wildtype. We probed this posterior region using laser ablation and showed that tension is increased in the AP orientation, compared to dorsoventral orientation or to either orientations more anteriorly in the embryo. We propose that apical constriction leading to endoderm invagination is the source of the extrinsic force contributing to germband extension. This highlights the importance of physical interactions between tissues during morphogenesis.This work was funded by a Biotechnology and Biological Sciences Research Council grant BB/ J010278/1 to GBB, RJA and BS, a Wellcome Trust Investigator Award 099234/Z/12/Z to BS and a Herchel Smith Postdoctoral Fellowship from the University of Cambridge to C

The international post-graduate Master programme for space exploration, SEEDS: education and training from a System Engineering perspective

The SEEDS (SpacE Exploration Development Systems) initiative was initially conceived and promoted by Politecnico di Torino and Thales Alenia Space-Italy in 2005. It aimed at establishing a post-graduate International Master Program in space exploration to offer an opportunity to young engineers to get prepared for the future of Europe in space and specifically in human space exploration. ISAE-Supaero in France and University of Leicester in UK participate to SEEDS together with Politecnico di Torino (Italy). Turin, Toulouse and Leicester have a long common tradition of space activities at both the industrial and academic level and within the SEEDS initiative they represent three poles of European cooperation in space programs. The Master course comprises two different steps in sequence: an initial learning phase and a Project Work phase. Both phases pursue a multidisciplinary approach, where all specialized disciplines are integrated to make the students able to acquire the system view and then to accomplish the conceptual design of a selected case-study. The distinguishing feature of SEEDS is the Project Work activity, performed by all students together under the supervision of academic and industrial tutors. Main objective of the Project Work is to train the students on the basic principles of the system engineering design, through their application to a well-defined project related to a specific human space exploration mission. The Project Work includes the Preparatory Work, during which the students identify the complete architecture and overall scenario of the mission, and the conceptual design activities, performed in the three European sites to develop a limited number of building blocks. Seven academic years of activities have passed and seven project works have been successfully completed, dealing with various space exploration themes. The eighth edition is currently under way with the aim of designing a “Transit and return habitable Mars orbital port”. The paper focuses on the description of the Master Program, both from the point of view of its contents, structure and multidisciplinary design methodologies, and on the main results achieved in terms of Project Work activities. The positive experience of seven years of SEEDS is brought to evidence and the lessons learned are discussed