Representing Spatial Hybridities: A Pragmatic Approach to the Representation of Emergent Figures of Public Space

As the paper's title suggests, we will associate a number of terms among which the relations may not immediately be obvious. One of these is the "figure” – understood in the sense of figureground relations, derived from gestaltist psychology of form, as they appear in the field of architectural and urbanistic theory. A second term, no less important here, is that of hybridity; it refers to emergent spatial environmental conditions that can be defined in terms existing elements (or fragments of them) which recombine to produce new territorial figures that seem to resist classification within pre-existing categories. The objective of this presentation is to examine each of these terms separately in light of certain difficulties related to the understanding of the contemporary territory, and then to associate the two in a way that carries some implications for the study of and design within it

Germline TP53 mutational spectrum in French Canadians with breast cancer

Abstract Background Specific germline mutations in the hereditary breast-ovarian cancer susceptibility (HBC/HBOC) genes, BRCA1, BRCA2 and PALB2, have been shown to recur in French Canadians of Quebec, Canada, and this has been attributed to common ancestors. Germline TP53 mutation carriers are known to segregate in Li-Fraumeni syndrome families, which feature young age of onset breast cancer. We have reported rare TP53 mutation carriers in French Canadian HBC families, though none recurred possibly due to the limited number of cancer families investigated. Here we describe TP53 germline mutations found in French Canadian cancer families provided from hereditary cancer clinics; investigate 37 new BRCA1 and BRCA2 mutation-negative HBC/HBOC families for the TP53 mutations; and assess the frequency of TP53 mutations in a 1235 French Canadian breast cancer cases not selected for family history of cancer. Methods TP53 mutation-positive pedigrees from French Canadian cancer families were provided from local hereditary cancer clinics. Bidirectional Sanger sequencing of all protein encoding exons of TP53 was performed using peripheral blood lymphocyte DNA from breast/ovarian cancer probands from 37 HBC/HBOC families of French Canadian descent. Targeted bidirectional Sanger sequencing assay of regions containing the identified TP53 mutations was performed on 1235 French Canadian breast cancer cases not selected for family history cancer. Results Five new TP53 mutations were identified in six pedigrees from hereditary cancer clinics. No deleterious mutations were identified in cancer probands from 37 HBC/HBOC families. A targeted mutation screen of the 1235 breast cancer cases identified a c.844C>T [p.Arg282Trp] mutation carrier. This mutation was also found among the six mutation-positive cancer families provided by the local hereditary cancer clinics. The targeted screen also uncovered a new TP53 mutation, c.685T>C [p.Cys229Arg] that was found in two breast cancer cases. All TP53 mutation carriers were among the 656 women with breast cancer diagnosed less than 50 years of age. Conclusions In all six new TP53 mutations were identified in French Canadians, where two each occurred in independently ascertained cases/families. Although all newly identified breast cancer mutation carriers reported a family history of cancer, none were consistent with features of Li-Fraumeni syndrome families

Reproduction of Twentieth Century Intradecadal to Multidecadal Surface Temperature Variability in Radiatively Forced Coupled Climate Models

[1] Coupled Model Intercomparison Project 3 simulations that included time-varying radiative forcings were ranked according to their ability to consistently reproduce twentieth century intradecadal to multidecadal (IMD) surface temperature variability at the 5° by 5° spatial scale. IMD variability was identified using the running Mann-Whitney Z method. Model rankings were given context by comparing the IMD variability in preindustrial control runs to observations and by contrasting the IMD variability among the ensemble members within each model. These experiments confirmed that the inclusion of time-varying external forcings brought simulations into closer agreement with observations. Additionally, they illustrated that the magnitude of unforced variability differed between models. This led to a supplementary metric that assessed model ability to reproduce observations while accounting for each model\u27s own degree of unforced variability. These two metrics revealed that discernable differences in skill exist between models and that none of the models reproduced observations at their theoretical optimum level. Overall, these results demonstrate a methodology for assessing coupled models relative to each other within a multimodel framework

Can a combination of poly(ethylene glycol) and dense phase carbon dioxide improve processing of polylactide? A high pressure rheology investigation

High temperature melts or use of organic solvents are not practicable approaches for encapsulating protein based or thermally labile drugs into degradable polymers. Here, we demonstrate that poly(ethylene glycol) (PEG) in combination with supercritical carbon dioxide (scCO2) can dramatically reduce the viscosity of polymer melts allowing enhanced uptake of CO2 into poly(D,L-lactide) (PLA). Both PEG and CO2 are approved excipients in drug delivery and it is well documented that individually both are effective plasticisers. Using high pressure rheology techniques (scCO₂ at 14 MPa) we demonstrate a synergistic impact leading to significantly lower processing temperatures with PEG employed as both a blended additive and as a component of a block copolymer

Confined granular packings: structure, stress, and forces

The structure and stresses of static granular packs in cylindrical containers are studied using large-scale discrete element molecular dynamics simulations in three dimensions. We generate packings by both pouring and sedimentation and examine how the final state depends on the method of construction. The vertical stress becomes depth-independent for deep piles and we compare these stress depth-profiles to the classical Janssen theory. The majority of the tangential forces for particle-wall contacts are found to be close to the Coulomb failure criterion, in agreement with the theory of Janssen, while particle-particle contacts in the bulk are far from the Coulomb criterion. In addition, we show that a linear hydrostatic-like region at the top of the packings unexplained by the Janssen theory arises because most of the particle-wall tangential forces in this region are far from the Coulomb yield criterion. The distributions of particle-particle and particle-wall contact forces $P(f)$ exhibit exponential-like decay at large forces in agreement with previous studies.Comment: 11 pages, 11 figures, submitted to PRE (v2) added new references, fixed typo

SARS-CoV-2 Infections Among Patients With Liver Disease and Liver Transplantation Who Received COVID-19 Vaccination.

Many safe and effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations dramatically reduce risks of coronavirus disease 2019 (COVID-19) complications and deaths. We aimed to describe cases of SARS-CoV-2 infection among patients with chronic liver disease (CLD) and liver transplant (LT) recipients with at least one prior COVID-19 vaccine dose. The SECURE-Liver and COVID-Hep international reporting registries were used to identify laboratory-confirmed COVID-19 in CLD and LT patients who received a COVID-19 vaccination. Of the 342 cases of lab-confirmed SARS-CoV-2 infections in the era after vaccine licensing, 40 patients (21 with CLD and 19 with LT) had at least one prior COVID-19 vaccination, including 12 who were fully vaccinated (≥2 weeks after second dose). Of the 21 patients with CLD (90% with cirrhosis), 7 (33%) were hospitalized, 1 (5%) was admitted to the intensive care unit (ICU), and 0 died. In the LT cohort (n = 19), there were 6 hospitalizations (32%), including 3 (16%) resulting in mechanical ventilation and 2 (11%) resulting in death. All three cases of severe COVID-19 occurred in patients who had a single vaccine dose within the last 1-2 weeks. In contemporary patients with CLD, rates of symptomatic infection, hospitalization, ICU admission, invasive ventilation, and death were numerically higher in unvaccinated individuals. Conclusion: This case series demonstrates the potential for COVID-19 infections among patients with CLD and LT recipients who had received the COVID-19 vaccination. Vaccination against SARS-CoV-2 appears to result in favorable outcomes as attested by the absence of mechanical ventilation, ICU, or death among fully vaccinated patients

Transcriptional repressor ZEB2 promotes terminal differentiation of CD8⁺ effector and memory T cell populations during infection

ZEB2 is a multi-zinc-finger transcription factor known to play a significant role in early neurogenesis and in epithelial-mesenchymal transition-dependent tumor metastasis. Although the function of ZEB2 in T lymphocytes is unknown, activity of the closely related family member ZEB1 has been implicated in lymphocyte development. Here, we find that ZEB2 expression is up-regulated by activated T cells, specifically in the KLRG1(hi) effector CD8(+) T cell subset. Loss of ZEB2 expression results in a significant loss of antigen-specific CD8(+) T cells after primary and secondary infection with a severe impairment in the generation of the KLRG1(hi) effector memory cell population. We show that ZEB2, which can bind DNA at tandem, consensus E-box sites, regulates gene expression of several E-protein targets and may directly repress Il7r and Il2 in CD8(+) T cells responding to infection. Furthermore, we find that T-bet binds to highly conserved T-box sites in the Zeb2 gene and that T-bet and ZEB2 regulate similar gene expression programs in effector T cells, suggesting that T-bet acts upstream and through regulation of ZEB2. Collectively, we place ZEB2 in a larger transcriptional network that is responsible for the balance between terminal differentiation and formation of memory CD8(+) T cells

L'ambiance est dans l'air : la dimension atmosphérique des ambiances architecturales et urbaines dans les approches environnementalistes

EQUIPEDirection scientifiqueNicolas Tixier, Laboratoire Cresson – UMR CNRS 1563 – ENSA de GrenoblePilotage des travaux de terrain et assistance à la coordination scientifiqueDamien Masson, Laboratoire Cresson – UMR CNRS n°1563 – ENSA de GrenobleResponsable séminaire São-PauloCintia Okamura (CETESB Agence de protection environnementale de São Paulo)Chercheurs impliqués et équipes partenairesPascal Amphoux, Laure Brayer, Sandra Fiori, Guillaume Meigneux, Steven Melemis (Laboratoire Cresson)Gilles Debizet, Jean-Michel Roux (UMR CNRS PACTE)Frédéric Pousin (UMR CNRS Géographie-cités)Carlos Celso do Amaral e Silva (Université de São Paulo)Patricia Mendes, Carolina Rodriguez (Univ. Campinas)Vincent Puig (IRI), Elena Cogato Lanza (EPFL)Partenaires mobilisésPatrice Coindet, Benoît Adeline, Max Montmayeur (Ville de Grenoble)Ana Claudia (CETESB Agence de protection environnementale de São Paulo)Murielle Pezet-Kuhn, Cédric Lomakine (AURG : Agence d’Urbanisme de l’Agglomération Grenobloise)Hélène Poimboeuf (La Métro : Communauté d’agglomération de Grenoble)Naïm Aït Sidhoum, Pierre Bouchon Cesaro, Thibaut Candela (Zoom Architecture)Can an urban cross-section be used to bring together global environmental issues and situated local ambiental ones that take account of the sensorial dimensions of space and city dwellers’ practices? Starting from this assumption of an urban cross-section as a basis for representing and expressing what are usually separate, i.e., built objects, the sensorial world and social practices, we have conducted exploratory research tailored to environmental concerns based on two themes for which we can readily mobilize both researchers and a decent body of research, namely urban heat (City of Grenoble) and solid waste (City of São Paulo).We have dealt with two categories of questions based on existing research and a series of experiments:• Those relating to the different registers of knowledge inherent in ambiance and the environment as understood by technicians, elected representatives, scientists and users. When and how are actors able to articulate (or more effectively articulate) their knowledge of territory, i.e., more implicit user knowledge or the more explicit-type knowledge of scientists?• Those relating to representation / communication / bargaining tools. How and with what representational basis is it possible to “cross-check data” and move from a phase of reflection to a project-based mindset? For both of these questions and realms, we need to ascertain the operational capability of an urban cross-section both for handing environmental issues in local development as well as for its ability to factor the narratives and practices of inhabitants into the whole urban project process. In light of this dual objective, these experiments propose expanding the standard applications of an urban cross-section to a tool that could be used as a practical field instrument, a representation technique, or possibly even as a project basis, namely an urban transect.The transect could then be a process somewhere between a “clinical” profile and a sensorial perspective, drawing upon both techniques in order to “hybridize” them; as a field-based technique, the transect would be produced from drawings, photos, text and video. By rehabilitating the atmospheric dimension in architectural and urban representations and facilitating the incorporation of narratives, the transect could be harnessed to explore and express sensorial space and practical experiences of the fit between analysis and design.The “long-table” analytic approach has been used to debate these issues and to depict and pool representations. It has proved very effective in generating speech, collating ratings and revealing actual experiences – three very useful properties for establishing a shared prospective diagnosis.La coupe urbaine peut-elle être un lieu de rencontre entre les enjeux environnementaux globaux et les enjeux locaux d'ambiances situées prenant en compte les dimensions sensibles de l'espace et les pratiques habitantes ? Sur cette hypothèse de départ de la coupe urbaine comme mode de représentation permettant d'articuler ce qui habituellement est séparé, à savoir les objets construits, le monde sensible et les pratiques sociales, nous avons mené un travail exploratoire appliqué aux préoccupations environnementales, ceci à travers deux thématiques pour lesquelles nous pouvions aisément mobiliser corpus et acteurs, celles des chaleurs urbaines (Ville de Grenoble) et celle des déchets solides (Ville de São Paulo). Deux catégories de questions sont traitées à partir de corpus existants et d'une série d'expérimentations que nous avons menées : * Celles qui concernent les différents registres de connaissance impliqués lorsqu'on parle d'ambiance et d'environnement, ceci entre techniciens, élus, scientifiques et usagers. Quand et comment les acteurs arrivent-ils (ou pourraient-ils mieux arriver) à articuler leurs connaissances du territoire, qu'elles soient principalement implicites (comme dans le cas des usagers) ou plutôt explicite (notamment chez les scientifiques) ? * Celles qui concernent les outils de représentation / communication / négociation. Comment, et grâce à quels moyens de représentation, arrive-t-on à " croiser des données " et à faire le passage du domaine de la réflexion à celui du projet ? Pour ces deux questions et pour ces deux terrains, il s'agissait donc d'éprouver l'opérationnalité de la coupe urbaine tant pour la gestion des enjeux environnementaux dans le développement local que pour sa capacité de prise en compte du récit et des pratiques habitantes dans le processus de projet urbain. A cette double fin, ces expérimentations proposent d'élargir les champs d'applications ordinaires de la coupe urbaine à un outil qui se veut à la fois pratique de terrain, technique de représentation et peut-être même posture de projet, à savoir le transect urbain. Le transect se présente alors comme un dispositif se situant entre la coupe " clinique " et le parcours sensible empruntant à ces deux techniques pour les hybrider ; le transect se construit par le dessin, la photo, le texte, la vidéo autant qu'il se pratique in situ. Réhabilitant de fait la dimension atmosphérique dans les représentations architecturales et urbaines, rendant possible l'inscription des récits, le transect peut devenir alors un mode d'interrogation et d'expression de l'espace sensible et des pratiques vécues à l'articulation entre analyse et conception. Un principe de " table longue " a été mis en place pour débattre de ces enjeux et permettre une mise en situation et un partage des représentations. Ce dispositif s'avère être générateur de paroles, collecteur de notations et révélateur de réalités vécues, trois propriétés utiles à l'établissement d'un diagnostique prospectif partagé