Finite element modeling of the impact of heavy vehicles on highway and pedestrian bridge decks

Collisions of over-height vehicles, such as tipper trucks or exceptional convoys, with highway and pedestrian bridge decks can compromise the safety of road users and cause major economic losses due to road closures required by structural inspections and urgent repairs. Several studies proposed to reduce the probability of occurrence of such events by using steel pedestals, static road signs or impact detection systems. In spite of these preventive solutions, bridge decks are still frequently impacted by heavy vehicles as a result of the densification of transportation networks. In this study, a practical finite element approach is proposed to investigate the key parameters influencing the dynamic response of a bridge deck subjected to an impact from an excavator or other heavy construction equipment trailed on a flatbed truck. The developed finite element models are used to carry out a parametric study on vehicle-bridge systems with varying properties such as the lateral stiffness and mass of the bridge deck, and the mass and the velocity of the colliding vehicle. It is first shown that contact compliance is a critical factor that should be selected carefully after several numerical tests supported by engineering judgment. The obtained results confirm that dynamic effects are key factors to be taken into account when studying vehicle-bridge collisions. The trends characterizing the collisions between a heavy vehicle and the bridge deck are studied in terms of contact forces and their duration, the structural response of the bridge deck, as well as kinetic energy of the impacting vehicle. Some of the results obtained are compared to analytical predictions proposed in Eurocode

TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria

Phagocytosis, which is essential for the immune response to pathogens, is initiated by specific interactions between pathogens and cell surface receptors expressed by phagocytes. This study identifies triggering receptor expressed on myeloid cells 2 (TREM-2) and its signaling counterpart DAP12 as a molecular complex that promotes phagocytosis of bacteria. Expression of TREM-2–DAP12 enables nonphagocytic Chinese hamster ovary cells to internalize bacteria. This function depends on actin cytoskeleton dynamics and the activity of the small guanosine triphosphatases Rac and Cdc42. Internalization also requires src kinase activity and tyrosine phosphorylation. In bone marrow–derived macrophages, phagocytosis is decreased in the absence of DAP12 and can be restored by expression of TREM-2–DAP12. Depletion of TREM-2 inhibits both binding and uptake of bacteria. Finally, TREM-2–dependent phagocytosis is impaired in Syk-deficient macrophages. This study highlights a novel role for TREM-2–DAP12 in the immune response to bacterial pathogens

Targeted delivery of lopinavir to HIV reservoirs in the mesenteric lymphatic system by lipophilic ester prodrug approach

© 2020 Elsevier B.V. The combined antiretroviral therapy (cART) can efficiently suppress HIV replication, but the cessation of cART usually results in viral rebound, mostly due to the presence of viral reservoirs. The mesenteric lymphatic system, including mesenteric lymph nodes (MLNs), is an important viral reservoir into which antiretroviral drugs poorly penetrate. In this work, we proposed a novel lipophilic ester prodrug approach, combined with oral lipid-based formulation, to efficiently deliver lopinavir (LPV) to the mesenteric lymph and MLNs. A series of prodrugs was designed using an in-silico model for prediction of affinity to chylomicrons (CMs), and then synthesized. The potential for mesenteric lymphatic targeting and bioconversion to LPV in physiologically relevant media was assessed in vitro and ex vivo. Subsequently, LPV and selected prodrug candidates were evaluated for their in vivo pharmacokinetics and biodistribution in rats. Oral co-administration of lipids alone could not facilitate the delivery of unmodified LPV to the mesenteric lymphatic system and resulted in undetectable levels of LPV in these tissues. However, a combination of the lipophilic prodrug approach with lipid-based formulation resulted in efficient targeting of LPV to HIV reservoirs in mesenteric lymph and MLNs. The maximum levels of LPV in mesenteric lymph were 1.6- and 16.9-fold higher than protein binding-adjusted IC90 (PA-IC90) of LPV for HIV-1 (140 ng/mL) following oral administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Moreover, the concentrations of LPV in MLNs were 1.1- and 7.2-fold higher than PA-IC90 following administration of simple alkyl ester prodrug and activated ester prodrug, respectively. Furthermore, the bioavailability of LPV was also substantially increased following oral administration of activated ester prodrug compared to unmodified LPV. This approach, especially if can be translated to other antiretroviral drugs, has potential for reducing the size of HIV reservoirs within the mesenteric lymphatic system

Stratification of asthma phenotypes by airway proteomic signatures

© 2019 Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies

Discurso e identidade: breve caracterização linguístico-discursiva do populismo

Este artigo tem como objetivo discutir a relaçãoentre discurso e identidade no âmbito linguístico-discursivo, de modo a caracterizar o discurso político presidencial populista no contexto histórico brasileiro da década de 1950. Identificamos no populismo um objeto de estudo a ser explorado em função da escassa literatura referente à análise linguística desse fenômeno político, o qual marcou os governos latino-americanos entre as décadas de 1950 e 1960. Interessa-nos, assim, estabelecer uma aproximação teórica entre a análise retórica do discurso e o contexto histórico em que os pronunciamentos de Vargas foram realizados, de modo a contribuir para a caracterização discursivo-identitária, ainda que breve, do populismo. Para procedermos às análises, foram selecionados discursos proferidos por Getúlio Vargas no período de seu segundo mandato como presidente da República (1951-54), extraídos do livro O governo trabalhista do Brasil – volumes III e IV, reunidos e editados pela Livraria José Olympio, em 1969. Como aporte teórico sobre discurso político, recorremos aos trabalhos de Aquino (2005, 2003 e 1997) e Charaudeau (2006); sobre populismo, aos de Capelato (2001), Ferreira (2001) e Weffort (1982); e, finalmente, acerca de gêneros textuais, aos de Bakhtin (2003 [1927]) e Grillo (2006). Buscamos explicitar, ao longo do trabalho, as estratégias de seleção lexical que contribuem para a constituição identitária do populismo como fenômeno discursivo

La cupule Durom TM LDH TM (résultats précoces du couple de frottement métal - métal en grand diamètre à propos de 101 cas)

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Changing climate increases discharge and attenuates its seasonal distribution in the northeastern United States

Study region: The Hubbard Brook Experimental Forest is well-established as a Long-Term Ecological Research (LTER) site for climate change and anthropogenic impacts studies on hydrological processes. It is located at the headwater regions of the Merrimack Watershed, the fourth largest basin in New England, USA. The watershed is mostly forested (67%) with some developed regions (16%). Study focus: We assessed the scale-dependency of streamflow response to climate variation, river regulation, and development for dry, average, and wet years using long-term precipitation and discharge records. New hydrological insights for the region: The effects of basin scale were limited to discharges with exceedance probability less than 15% and greater than 60% and were expressed as lagged discharge in large sub-basins and earlier discharge in small catchments. Annual discharge responded to increases in annual precipitation but not to river regulation or land development. In general, the temporal trends showed less discharge in dry and greater discharge in wet hydrologic flow classes. Keywords: Climate change, Land development, Hydrologic indicator, Scale dependency, Merrimack river, Northeastern United State

Zaza : pièce en cinq actes /

Cover: 3. mille ; t.p.: 2. mille.Mode of access: Internet.Forms part of the Louis Verneuil French Play Collection