Integrated canopy, building energy and radiosity model for 3D urban design

We present an integrated, three dimensional, model of urban canopy, building energy and radiosity, for early stage urban designs and test it on four urban morphologies. All sub-models share a common descriptions of the urban morphology, similar to 3D urban design master plans and have simple parameters. The canopy model is a multilayer model, with a new discrete layer approach that does not rely on simplified geometry such as canyon or regular arrays. The building energy model is a simplified RC equivalent model, with no hypotheses on internal zoning or wall composition. We use the CitySim software for the radiosity model. We study the effects of convexity, the number of buildings and building height, at constant density and thermal characteristics. Our results suggest that careful three dimensional morphology design can reduce heat demand by a factor of 2, especially by improving insolation of lower levels. The most energy efficient morphology in our simulations has both the highest surface/volume ratio and the biggest impact on the urban climate

Robust estimation of fetal heart rate from US Doppler signals

International audienceIn utero, Monitoring of fetal wellbeing or suffering is today an open challenge, due to the high number of clinicalparameters to be considered. An automatic monitoring of fetal activity, dedicated for quantifying fetal wellbeing, becomes necessary. For this purpose and in a view to supply an alternative for the Manning test, we used an ultrasound multitransducer muligate Doppler system. One important issue (and first step in our investigation) is the accurate estimation of fetal heart rate (FHR). An estimation of the FHR is obtained by evaluating the autocorrelation function of the Doppler signals for ills and healthiness foetus. However, this estimator is not enough robust since about 20% of FHR are not detected in comparison to a reference system. These non detections are principally due to the fact that the Doppler signal generated by the fetal moving is strongly disturbed by the presence of others several Doppler sources (mother' s moving, pseudo breathing, etc.). By modifying the existing method (autocorrelation method) and by proposing new time and frequency estimators used in the audio' s domain, we reduce to 5% the probability of non-detection of the fetal heart rate. These results are really encouraging and they enable us to plan the use of automatic classification techniques in order to discriminate between healthy and in suffering foetus

SAPOLL : A cross-border action plan for wild pollinators

Wild pollinators in the France-Wallonia-Vlaanderen cross-border zone represent a valuable but highly endangered resource. In order to protect these pollinators, it is essential to set up a cross-border organization that enables coordinated actions and synergies between regions. Indeed, isolated actions on both sides of the border are unlikely to lead to the sustainable management of this indispensable resource. The challenge is huge because wild pollinators, wild bees, syrphs and butterflies, are essential to maintaining agriculture and ecosystems in our regions. In order to meet this challenge, the SAPOLL project initiates the implementation of a cross-border action plan for wild pollinators with the actors from Wallonia, Flanders and northern France. This plan is the initiator of actions in favor of pollinators, bringing the necessary scientific, didactic and applied context to citizens, decision-makers, entrepreneurs or enrionmental managers. It is also adapted to the regional context of each area. The action plan, which is co-built with the partners in the cross-border territory. The SAPOLL project also organizes activities that aim to homogenize and share scientific knowledge, awareness-raising experience and naturalistic competences

A defective Krab-domain zinc-finger transcription factor contributes to altered myogenesis in myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is an RNA-mediated disorder caused by a non-coding CTG repeat expansion that, in particular, provokes functional alteration of CUG-binding proteins. As a consequence, several genes with misregulated alternative splicing have been linked to clinical symptoms. In our search for additional molecular mechanisms that would trigger functional defects in DM1, we took advantage of mutant gene-carrying human embryonic stem cell lines to identify differentially expressed genes. Among the different genes found to be misregulated by DM1 mutation, one strongly downregulated gene encodes a transcription factor, ZNF37A. In this paper, we show that this defect in expression, which derives from a loss of RNA stability, is controlled by the RNA-binding protein, CUGBP1, and is associated with impaired myogenesis—a functional defect reminiscent of that observed in DM1. Loss of the ZNF37A protein results in changes in the expression of the subunit α1 of the receptor for the interleukin 13. This suggests that the pathological molecular mechanisms linking ZNF37A and myogenesis may involve the signaling pathway that is known to promote myoblast recruitment during development and regeneratio

The Antitumor Activity of Combinations of Cytotoxic Chemotherapy and Immune Checkpoint Inhibitors Is Model-Dependent

In spite of impressive response rates in multiple cancer types, immune checkpoint inhibitors (ICIs) are active in only a minority of patients. Alternative strategies currently aim to combine immunotherapies with conventional agents such as cytotoxic chemotherapies. Here, we performed a study of PD-1 or PDL-1 blockade in combination with reference chemotherapies in four fully immunocompetent mouse models of cancer. We analyzed both the in vivo antitumor response, and the tumor immune infiltrate 4 days after the first treatment. in vivo tumor growth experiments revealed variable responsiveness to ICIs between models. We observed enhanced antitumor effects of the combination of immunotherapy with chemotherapy in the MC38 colon and MB49 bladder models, a lack of response in the 4T1 breast model, and an inhibition of ICIs activity in the MBT-2 bladder model. Flow cytometry analysis of tumor samples showed significant differences in all models between untreated and treated mice. At baseline, all the tumor models studied were predominantly infiltrated with cells harboring an immunosuppressive phenotype. Early alterations of the tumor immune infiltrate after treatment were found to be highly variable. We found that the balance between effector cells and immunosuppressive cells in the tumor microenvironment could be altered with some treatment combinations, but this effect was not always correlated with an impact on in vivo tumor growth. These results show that the combination of cytotoxic chemotherapy with ICIs may result in enhanced, similar or reduced antitumor activity, in a model- and regimen-dependent fashion. The present investigations should help to select appropriate combination regimens for ICIs

SAPOLL - A cross-border action plan for wild pollinators

Pollinators such as wild bees, hoverflies or butterflies represent a valuable resource in Europe but are greatly threatened. To protect these pollinators, that are not limited by the borders of the countries, it is necessary to develop adapted tools at large scales. The SAPOLL project rises to this challenge by initiating the creation of a cross-border action plan for pollinators in Belgium and in the north of France. This plan will encourage the development of concerted actions for pollinators conservation by spreading scientific, didactic and applied contexts to all the citizens and stakeholders. The SAPOLL project also organises additional actions that are essential for the creation and the success of the cross-border action plan. These actions will facilitate the sharing of skills and the homogenisation of knowledge between regions and will focus on three aspects: (i) Communication and awareness raising for the general public in order to inform the general public of the pollinator decline. (ii) Organisation and homogenisation of naturalist networks in the cross-border area through the animation of working groups and training courses. (iii) Global scientific monitoring of wild pollinators on the whole cross-border territory. The area of high importance for pollination service will be demarcated

SAPOLL - A cross border action plan for wild pollinators

Pollinators such as wild bees, hoverflies or butterflies represent a valuable resource in Europe but are greatly threatened. To protect these pollinators, that are not limited by the borders of the countries, it is necessary to develop adapted tools at large scales. The Interreg SAPOLL project rises to this challenge by initiating the creation of a cross-border action plan for pollinators in Belgium and in the north of France. This plan will encourage the development of concerted actions for pollinators conservation by spreading scientific, didactic and applied contexts to all the citizens and stakeholders

Superplasticity in Fine Grain Ti-6Al-4V Alloy: Mechanical Behavior and Microstructural Evolution

Titanium Ti-6Al-4V alloys are known to exhibit interesting superplastic properties for different conditions of temperature and strain rate, depending on the initial grain size. Even if superplasticity is generally explained in terms of grain boundary sliding (GBS) accompanied by several accommodation mechanisms, it appears that the micromechanisms of superplasticity are still controversial especially at the grain scale and even more at lower scale. These micromechanisms, involving microstructural evolution, depend also on the SPF conditions (temperature, strain rate and initial microstructure). In this study, the flow stress in the Ti-6Al-4V alloy is investigated for different strain rate and for temperature in the range of the α/β transformation. The preferred orientation evolution of alpha phase grains for different percentage of deformation is studied for a non-optimal SPF regime (920°C-10-4 s-1) in order to highlight the microstructural evolution and so the deformation mechanisms involved. For that, mechanical interrupted test combined with Scanning Electron Microscopy (SEM) and Electron Back Scatter Diffraction (EBSD) are used

Evidence of coat color variation sheds new light on ancient canids.

International audienceWe have used a paleogenetics approach to investigate the genetic landscape of coat color variation in ancient Eurasian dog and wolf populations. We amplified DNA fragments of two genes controlling coat color, Mc1r (Melanocortin 1 Receptor) and CBD103 (canine-β-defensin), in respectively 15 and 19 ancient canids (dogs and wolf morphotypes) from 14 different archeological sites, throughout Asia and Europe spanning from ca. 12 000 B.P. (end of Upper Palaeolithic) to ca. 4000 B.P. (Bronze Age). We provide evidence of a new variant (R301C) of the Melanocortin 1 receptor (Mc1r) and highlight the presence of the beta-defensin melanistic mutation (CDB103-K locus) on ancient DNA from dog-and wolf-morphotype specimens. We show that the dominant K(B) allele (CBD103), which causes melanism, and R301C (Mc1r), the variant that may cause light hair color, are present as early as the beginning of the Holocene, over 10 000 years ago. These results underline the genetic diversity of prehistoric dogs. This diversity may have partly stemmed not only from the wolf gene pool captured by domestication but also from mutations very likely linked to the relaxation of natural selection pressure occurring in-line with this process

Targeted hematopoietic stem cell depletion through SCF-blockade

Background: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for many diverse blood and immune diseases. However, HSCT regimens currently commonly utilize genotoxic chemotherapy and/or total body irradiation (TBI) conditioning which causes significant morbidity and mortality through inducing broad tissue damage triggering infections, graft vs. host disease, infertility, and secondary cancers. We previously demonstrated that targeted monoclonal antibody (mAb)-based HSC depletion with anti(α)-CD117 mAbs could be an effective alternative conditioning approach for HSCT without toxicity in severe combined immunodeficiency (SCID) mouse models, which has prompted parallel clinical αCD117 mAbs to be developed and tested as conditioning agents in clinical trials starting with treatment of patients with SCID. Subsequent efforts have built upon this work to develop various combination approaches, though none are optimal and how any of these mAbs fully function is unknown. Methods: To improve efficacy of mAb-based conditioning as a stand-alone conditioning approach for all HSCT settings, it is critical to understand the mechanistic action of αCD117 mAbs on HSCs. Here, we compare the antagonistic properties of αCD117 mAb clones including ACK2, 2B8, and 3C11 as well as ACK2 fragments in vitro and in vivo in both SCID and wildtype (WT) mouse models. Further, to augment efficacy, combination regimens were also explored. Results: We confirm that only ACK2 inhibits SCF binding fully and prevents HSC proliferation in vitro. Further, we verify that this corresponds to HSC depletion in vivo and donor engraftment post HSCT in SCID mice. We also show that SCF-blocking αCD117 mAb fragment derivatives retain similar HSC depletion capacity with enhanced engraftment post HSCT in SCID settings, but only full αCD117 mAb ACK2 in combination with αCD47 mAb enables enhanced donor HSC engraftment in WT settings, highlighting that the Fc region is not required for single-agent efficacy in SCID settings but is required in immunocompetent settings. This combination was the only non-genotoxic conditioning approach that enabled robust donor engraftment post HSCT in WT mice. Conclusion: These findings shed new insights into the mechanism of αCD117 mAb-mediated HSC depletion. Further, they highlight multiple approaches for efficacy in SCID settings and optimal combinations for WT settings. This work is likely to aid in the development of clinical non-genotoxic HSCT conditioning approaches that could benefit millions of people world-wide