New cutaneous vaccine adjuvant that STINGs a little less

Cutaneous vaccination can be a challenge because the development of local skin inflammation is often unavoidable. Thus, it is important to identify and validate new vaccine adjuvants that enhance immunization without the burden of inflammation. Wang et al. now report on a cyclic GMP-AMP adjuvant, the natural stimulator of interferon genes agonist, providing evidence for potent immune responses without inflammation

Cytokine regulation of lung Th17 response to airway immunization using LPS adjuvant

Infections caused by bacteria in the airway preferentially induce a Th17 response. However, the mechanisms involved in the regulation of CD4 T-cell responses in the lungs are incompletely understood. Here, we have investigated the mechanisms involved in the regulation of Th17 differentiation in the lungs in response to immunization with lipopolysaccharide (LPS) as an adjuvant. Our data show that both Myd88 and TRIF are necessary for Th17 induction. This distinctive fate determination can be accounted for by the pattern of inflammatory cytokines induced by airway administration of LPS. We identified the production of interleukin (IL)-1β and IL-6 by small macrophages and IL-23 by alveolar dendritic cells (DCs), favoring Th17 responses, and IL-10 repressing interferon (IFN)-γ production. Furthermore, we show that exogenous IL-1β can drastically alter Th1 responses driven by influenza and lymphocytic choriomeningitis virus infection models and induce IL-17 production. Thus, the precision of the lung immune responses to potential threats is orchestrated by the cytokine microenvironment, can be repolarized and targeted therapeutically by altering the cytokine milieu. These results indicate that how the development of Th17 responses in the lung is regulated by the cytokines produced by lung DCs and macrophages in response to intranasal immunization with LPS adjuvant

Climate change mitigation policies for developing countries

Following the Paris Agreement, many low- and middle-income countries (LMICs) have adopted climate change targets. They will need climate policies that are suited to their socioeconomic and institutional contexts. Conventional policy prescriptions are geared toward high-income countries with entrenched high-carbon structures, universal energy access, deep financial markets, formal economies, privatized power markets, a capable public sector, and relative macroeconomic stability. Not all of these assumptions generalize to LMICs. Here, we synthesize what is known about emissions reduction policies in LMICs. We find a strong emphasis on finance interventions and regulatory measures, including the need for power sector reform. Current scholarship focuses heavily on removing existing price distortions, with less emphasis on carbon pricing. Carbon pricing is discussed mostly for middle-income countries, where some pilot schemes exist and institutional capacity constraints are less severe. Prescriptions for skills-related policies focus on capacity building and preparing a young population for a changing labor market rather than reskilling the existing workforce

Concilier architectonique du béton et performance passive

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Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4

The chemokine receptor, CXC chemokine receptor 4 (CXCR4), is selective for CXC chemokine ligand 12 (CXCL12), is broadly expressed in blood and tissue cells, and is essential during embryogenesis and hematopoiesis. CXCL14 is a homeostatic chemokine with unknown receptor selectivity and preferential expression in peripheral tissues. Here, we demonstrate that CXCL14 synergized with CXCL12 in the induction of chemokine responses in primary human lymphoid cells and cell lines that express CXCR4. Combining subactive concentrations of CXCL12 with 100–300 nM CXCL14 resulted in chemotaxis responses that exceeded maximal responses that were obtained with CXCL12 alone. CXCL14 did not activate CXCR4-expressing cells (i.e., failed to trigger chemotaxis and Ca2+ mobilization, as well as signaling via ERK1/2 and the small GTPase Rac1); however, CXCL14 bound to CXCR4 with high affinity, induced redistribution of cell-surface CXCR4, and enhanced HIV-1 infection by >3-fold. We postulate that CXCL14 is a positive allosteric modulator of CXCR4 that enhances the potency of CXCR4 ligands. Our findings provide new insights that will inform the development of novel therapeutics that target CXCR4 in a range of diseases, including cancer, autoimmunity, and HIV.—Collins, P. J., McCully, M. L., Mart´ınez-Muñoz, L., Santiago, C.,Wheeldon, J., Caucheteux, S., Thelen, S., Cecchinato, V., Laufer, J.M., Purvanov, V.,Monneau, Y. R., Lortat-Jacob, H., Legler, D. F., Uguccioni, M., Thelen, M., Piguet, V., Mellado, M., Moser, B. Epithelial chemokine CXCL14 synergizes with CXCL12 via allosteric modulation of CXCR4. FASEB J. 31, 000–000 (2017). www.fasebj.or

Detection of Faults and Drifts in the Energy Performance of a Building Using Bayesian Networks

Despite improved commissioning practices, malfunctions or degradation of building systems still contribute to increase up to 20% the energy consumption. During operation and maintenance stage, project and building technical managers need appropriate methods for the detection and diagnosis of faults and drifts of energy performances in order to establish effective preventive maintenance strategies. This paper proposes a hybrid and multilevel fault detections and diagnosis (FDD) tool dedicated to the identification and prioritization of corrective maintenance actions helping to ensure the energy performance of buildings. For this purpose, we use dynamic Bayesian networks (DBN) to monitor the energy consumption and detect malfunctions of building equipment and systems by considering both measured occupancy and the weather conditions (number of persons on site, temperature, relative humidity (RH), etc.). The hybrid FDD approach developed makes possible the use of both measured and simulated data. The training of the Bayesian network for functional operating mode relies on on-site measurements. As far as dysfunctional operating modes are concerned, they rely mainly on knowledge extracted from dynamic thermal analysis simulating various operational faults and drifts. The methodology is applied to a real building and demonstrates the way in which the prioritization of most probable causes can be set for a fault affecting energy performance. The results have been obtained for a variety of simulated situations with faults deliberately injected, such as increase in heating preset temperature and deterioration of the transmission coefficient of the building\u27s glazing. The limitations of the methodology are discussed and are translated in terms of the ability to optimize the experiment design, control period, or threshold adjustment on the control charts used

Tolerance of the fetus by the maternal immune system: role of inflammatory mediators at the feto-maternal interface

The adaptive immune system of placental mammals has evolved to tolerate the fetus. Rejection of the fetus by adaptive immune responses is therefore a rare event, with abortion being caused more frequently by inflammation in the placenta. This review will cover recent aspects of immune privilege and the innate immune system at the feto-maternal interface, citing examples of the role played by microbial infections in fetal demise

Measurement Uncertainties and Building Energy Performance Evaluation

International audienc

Construction Of Temporal Data Files For Building Energy Simulation

International audienc