Socially Compliant Navigation in Dense Crowds

International audienceNavigating in complex and highly dynamic environments such as crowds is still a major challenge for autonomous vehicle such as autonomous wheelchairs or even autonomous cars. This article presents a new way of navigating in crowds by using behavioral clustering for the surrounding agents and representing the crowd as a set of moving polygons. Once the environment has been modelled in this way and the robot has all the information it needs, we then propose a navigation algorithm that is able to guide the vehicle through the scene. The key-points of this algorithm are that (1) it can avoid densely-populated areas in order to minimize the risk of being on a collision course with any of the surrounding dynamic obstacles, (2) it generates socially compliant trajectories

Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth.

peer reviewedRationale: 17β-estradiol (E2) can directly promote the growth of ERα-negative cancer cells through activation of endothelial ERα in the tumor microenvironment, thereby increasing a normalized tumor angiogenesis. ERα acts as a transcription factor through its nuclear transcriptional AF-1 and AF-2 transactivation functions, but membrane ERα plays also an important role in endothelium. The present study aims to decipher the respective roles of these two pathways in ERα-negative tumor growth. Moreover, we delineate the actions of tamoxifen, a Selective Estrogen Receptor Modulator (SERM) in ERα-negative tumors growth and angiogenesis, since we recently demonstrated that tamoxifen impacts vasculature functions through complex modulation of ERα activity. Methods: ERα-negative B16K1 cancer cells were grafted into immunocompetent mice mutated for ERα-subfunctions and tumor growths were analyzed in these different models in response to E2 and/or tamoxifen treatment. Furthermore, RNA sequencings were analyzed in endothelial cells in response to these different treatments and validated by RT-qPCR and western blot. Results: We demonstrate that both nuclear and membrane ERα actions are required for the pro-tumoral effects of E2, while tamoxifen totally abrogates the E2-induced in vivo tumor growth, through inhibition of angiogenesis but promotion of vessel normalization. RNA sequencing indicates that tamoxifen inhibits the E2-induced genes, but also initiates a specific transcriptional program that especially regulates angiogenic genes and differentially regulates glycolysis, oxidative phosphorylation and inflammatory responses in endothelial cells. Conclusion: These findings provide evidence that tamoxifen specifically inhibits angiogenesis through a reprogramming of endothelial gene expression via regulation of some transcription factors, that could open new promising strategies to manage cancer therapies affecting the tumor microenvironment of ERα-negative tumors

A 'small-world-like' model for comparing interventions aimed at preventing and controlling influenza pandemics

BACKGROUND: With an influenza pandemic seemingly imminent, we constructed a model simulating the spread of influenza within the community, in order to test the impact of various interventions. METHODS: The model includes an individual level, in which the risk of influenza virus infection and the dynamics of viral shedding are simulated according to age, treatment, and vaccination status; and a community level, in which meetings between individuals are simulated on randomly generated graphs. We used data on real pandemics to calibrate some parameters of the model. The reference scenario assumes no vaccination, no use of antiviral drugs, and no preexisting herd immunity. We explored the impact of interventions such as vaccination, treatment/prophylaxis with neuraminidase inhibitors, quarantine, and closure of schools or workplaces. RESULTS: In the reference scenario, 57% of realizations lead to an explosive outbreak, lasting a mean of 82 days (standard deviation (SD) 12 days) and affecting 46.8% of the population on average. Interventions aimed at reducing the number of meetings, combined with measures reducing individual transmissibility, would be partly effective: coverage of 70% of affected households, with treatment of the index patient, prophylaxis of household contacts, and confinement to home of all household members, would reduce the probability of an outbreak by 52%, and the remaining outbreaks would be limited to 17% of the population (range 0.8%–25%). Reactive vaccination of 70% of the susceptible population would significantly reduce the frequency, size, and mean duration of outbreaks, but the benefit would depend markedly on the interval between identification of the first case and the beginning of mass vaccination. The epidemic would affect 4% of the population if vaccination started immediately, 17% if there was a 14-day delay, and 36% if there was a 28-day delay. Closing schools when the number of infections in the community exceeded 50 would be very effective, limiting the size of outbreaks to 10% of the population (range 0.9%–22%). CONCLUSION: This flexible tool can help to determine the interventions most likely to contain an influenza pandemic. These results support the stockpiling of antiviral drugs and accelerated vaccine development

Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

Les microparticules circulantes de malades atteints de cirrhose diminuent la réponse aux agents vasoconstructeurs selon un mécanisme dépendant de la cyclo-oxygénase de type 1

Les Microparticules (MPs) sont des vésicules membranaires de 0,1 à 1 m libérées après activation ou apoptose cellulaire capables de moduler le tonus vasculaire. Dans la cirrhose, la vasodilatation systémique contribue à majorer l hypertension portale. Le but de cette étude était de caractériser les MPs circulantes des malades cirrhotiques et d évaluer l impact de ces MPs sur le tonus vasculaire. Les MPs provenant du plasma de 33 malades cirrhotiques et de 25 témoins sains ont été isolées et caractérisées par cytométrie en flux. L effet des MPs circulantes sur le tonus vasculaire a été évalué sur des anneaux aortiques de rats après 24 heures d incubation avec des MPs à leur concentration circulante, du plasma dépourvu de MPs ou du milieu de culture. Les réponses à l acétylcholine, à la phényléphrine et au KCl ont été étudiée seules, avec ou sans endothélium, puis en présence d inhibiteurs de NO-synthase (L-NA), de cyclo-oxygénases, de transcription et de traduction et de fusion cellulaire des MPs. Les taux de MPs érythrocytaires et leucocytaires sont supérieurs chez les malades atteints de cirrhose. Les MPs circulantes altèrent la contraction à la phényléphrine et au KCl via l activation de la cyclo-oxygénase 1, selon un mécanisme dépendant d une modification post-transcriptionnelle et de la captation des MPs par la cellule endothéliale. Conclusion: Les MPs circulantes des malades cirrhotiques diminuent la réponse aux agents vasoconstricteurs par un mécanisme dépendant des cyclo-oxygénases 1. Elles pourraient contribuer à la vasodilatation systémique existant au cours de la cirrhosePARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Connaître, documenter et conserver la photographie de studio indienne : l’exploration d’un fonds photographique d’Inde du Sud

International audienceDeux pans importants de la photographie en Inde sont encore peu ou mal connus : l’histoire de la photographie commerciale de studio et les conditions de conservation des matériaux photographiques, dans un contexte climatique propice à leur dégradation. Un fonds récemment constitué à partir d’archives de studios photographiques du Tamil Nadu (Inde du Sud) éclaire ces deux thématiques. Il permet d’étudier la production et la consommation courantes de photographie en Inde aux périodes coloniale et postcoloniale. Il soulève également des problématiques particulières de conservation, soulignant l’importance et l’intérêt de croiser les regards et les expertises sur cet objet d’étude

Connaître, documenter et conserver la photographie de studio indienne : l’exploration d’un fonds photographique d’Inde du Sud

Deux pans importants de la photographie en Inde sont encore peu ou mal connus : l’histoire de la photographie commerciale de studio et les conditions de conservation des matériaux photographiques, dans un contexte climatique propice à leur dégradation. Un fonds récemment constitué à partir d’archives de studios photographiques du Tamil Nadu (Inde du Sud) éclaire ces deux thématiques. Il permet d’étudier la production et la consommation courantes de photographie en Inde aux périodes coloniale et postcoloniale. Il soulève également des problématiques particulières de conservation, soulignant l’importance et l’intérêt de croiser les regards et les expertises sur cet objet d’étude.Two important aspects of photography in India are still little or poorly known: the history of commercial photography studios and the conditions for conserving photographic materials in a climate tending to cause their deterioration. A collection recently assembled from the archives of photography studios in Tamil Nadu (South India) sheds light on these two themes. It has enabled us to study the everyday production and consumer use of photography in India during the colonial and post-colonial periods. It also raises questions of relevance to conservation, underlining the importance and usefulness of exchanging views and expertise on this object of research

Fis family members synergistically control the virulence of Legionella pneumophila

ABSTRACT Legionella pneumophila virulence is controlled in a growth phase-dependent manner by a complex regulatory network involving several two-component systems, small regulatory RNAs and the translational CsrA regulator. Here, we address the additional role of Nucleoid-associated proteins (NAP) regulators in this network, by investigating the regulatory functions of the three Fis paralogs (Fis1, Fis2, Fis3), a unique feature among bacteria, in the infection cycle of L. pneumophila . Specifically, we show that deletion of fis1 has a major impact on L. pneumophila virulence, and that deletion of fis2 enhances the intensity of this phenotype. Consistently, RNA-seq analysis and reporter gene fusions demonstrate the predominant role of Fis1 in the regulation of many virulence-related genes, including those involved in the flagellum, pili biosynthesis, and Dot/Icm type 4 secretion machinery, as well as several genes encoding Dot/Icm effectors. Both Fis1 and Fis2 bind to AT-rich motifs upstream their target genes, but Fis1 with higher affinity than Fis2. Importantly, Fis1 and Fis2 would be capable of forming heterodimers that could bind with variable affinity to this AT-rich motif. It is also important to note that the three Fis proteins are not produced at the same time and in the same amounts. We therefore hypothesize that the duplication of fis genes in L. pneumophila is not simply a back-up system to compensate for potentially deleterious mutations in a fis gene, but rather a means to fine-tune the expression of targeted genes, particularly virulence genes. IMPORTANCE Appropriate control of virulence gene expression is crucial to the success of bacterial infection. Nucleoid-associated protein regulators, including Fis proteins, have been shown to participate in the virulence of several human pathogens. The importance of our discovery lies in the fact that L. pneumophila possesses three non-homologous Fis proteins instead of just one. We demonstrate that Fis1 and Fis2 are not functional duplicates of each other. On the contrary, Fis1 and Fis2 are synthesized neither simultaneously nor in equal amounts during the bacterial growth phase, and they cooperate to regulate virulence gene expression by targeting similar AT-rich motifs, albeit with distinct affinity, and by being capable of forming heterodimers. Taken together, our data suggest that the high conservation of fis gene duplication results from the need for fine-tuned control of Legionella virulence in response to its different environmental and human hosts, rather than from functional redundancy to circumvent deleterious fis mutations

Alimentation des premiers mois de vie et prévention de l'allergie

National audienceAllergy consists in the different manifestations resulting from immune reactions triggered by food or respiratory allergens. Both its frequency and severity are increasing. The easiest intervention process for allergy prevention is the reduction of the allergenic load which, for a major allergen such as peanuts, has to begin in utero. The primary prevention strategy relies first on the detection of at risk newborns, i.e. with allergic first degree relatives. In this targeted population, as well as for the general population, exclusive breastfeeding is recommended until the age of 6 months. The elimination from the mother's diet of major food allergens potentially transmitted via breast milk may be indicated on an individual basis, except for peanut, which is systematically retrieved. In the absence of breastfeeding, prevention consists in feeding at-risk newborns until the age of 6 months with a hypoallergenic formula, provided that its efficiency has been demonstrated by well-designed clinical trials. Soy based formulae are not recommended for allergy prevention. Complementary feeding should not be started before the age of 6 months. Introduction of egg and fish into the diet can be made after 6 months but the introduction of potent food allergens (kiwi, celery, crustaceans, seafood, nuts, especially tree nuts and peanuts) should be delayed after 1 year. This preventive policy seems partially efficacious on early manifestations of allergy but does not restrain the allergic march, especially in its respiratory manifestations. Probiotics, prebiotics as well as n-3 fatty polyunsaturated acids have not yet demonstrated any definitive protective effect.L’allergie correspond à l’ensemble des tableaux cliniques résultant d’un mécanisme physiopathologique d’ordre immunologique, développé vis-à-vis d’allergènes alimentaires ou respiratoires. Sa fréquence et sa sévérité augmentent. La modalité de prévention de l’allergie la plus réalisable est la réduction de la charge allergénique qui, pour l’arachide, doit débuter dès la vie intra-utérine. La prévention primaire de l’allergie alimentaire repose d’abord sur la détection des enfants à risque ayant des antécédents familiaux au 1er degré d’allergie. Pour cette population ciblée comme pour la population générale, l’allaitement maternel exclusif est recommandé jusqu’à l’âge de 6 mois. L’éviction du régime de la mère des trophallergènes majeurs potentiellement transmis par le lait de mère est discutée au cas par cas, sauf pour l’arachide, systématiquement exclue.A défaut d’allaitement maternel ou en cas de biberons de complément, la prévention consiste, chez les enfants à risque, à donner une formule hypoallergénique jusqu’à 6 mois, en choisissant une de celles dont l’efficacité a été démontrée par des études contrôlées. Les formules à base de soja n’ont pas leur place en prévention. La diversification alimentairene doit pas débuter avant l’âge de 6mois. L’introduction de l’oeuf et du poisson peut débuter après 6 mois, mais celle des aliments à fort pouvoir allergénique (kiwi, céleri, arachide, fruits à coque, crustacés) doit être retardée après 1 an. Ces précautions ne modifient pas sensiblement la marche allergique ultérieure, en particulier dans ses expressions respiratoires. L’intérêt des probiotiques, prébiotiques et des acides gras polyinsaturés de la série n-3 reste à confirmer