Behavioural analysis of vehicle-pedestrian interactions: The case of street designs with elements of shared space

This paper describes the development and implementation of qualitative behavioural criteria in order to analyse the conduct of pedestrians and vehicles when they are required to interact with each other, with particular interest to street designs with elements of shared space. The new behavioural analysis technique is developed by identifying the fundamental principles that underpin existing traffic analyses, such as traffic conflicts techniques, and adapting those to a qualitative framework that describes the mindset and rationale of road users. The technique is then applied to a case study in London, using video data from periods before and after the redevelopment of the Exhibition Road site from a conventional dual carriageway to a modern design with some elements of shared space. With the main goals being to assess the pedestrians’ confidence and the vehicles’ tolerance/patience when forced to interact with each other, behavioural trends are related to instantaneous characteristics of the vehicle flow (vehicle approach speed and traffic density). The data produced are used to develop and validate qualitative behavioural relationships for pedestrian-vehicle interactions, as well as location-specific conclusions for the Exhibition Road site

Behavioural analysis of interactions between pedestrians and vehicles in street designs with elements of shared space

This paper describes the development and implementation of qualitative behavioural criteria in order to analyse the conduct of pedestrians and vehicles when they are required to interact with each other, with particular interest to street designs with elements of shared space. The new behavioural analysis technique is developed by identifying the fundamental principles that underpin existing traffic analyses, such as traffic conflicts techniques, and adapting those to a qualitative framework that describes the mindset and rationale of road users. The technique is then applied to a case study in London, using video data from periods before and after the redevelopment of the Exhibition Road site from a conventional dual carriageway to a modern design with some elements of shared space. With the main goals being to assess the pedestrians’ confidence and the vehicles’ tolerance/patience when forced to interact with each other, behavioural trends are related to instantaneous characteristics of the vehicle flow (vehicle approach speed and traffic density). The data produced are used to develop and validate qualitative behavioural relationships for pedestrian-vehicle interactions, as well as location-specific conclusions for the Exhibition Road site

Hijacking SARS-CoV-2/ACE2 Receptor Interaction by Natural and Semi-synthetic Steroidal Agents Acting on Functional Pockets on the Receptor Binding Domain

The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In light of the urgent need to identify novel approaches to be used in the emergency phase, we have embarked on an exploratory campaign aimed at repurposing natural substances and clinically available drugs as potential anti-SARS-CoV2-2 agents by targeting viral proteins. Here we report on a strategy based on the virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike's protein receptor binding domain (RBD). By combining an in silico approach and molecular in vitro testing we have been able to identify several triterpenoid/steroidal agents that inhibit interaction of the Spike RBD with the carboxypeptidase domain of the Angiotensin Converting Enzyme (ACE2). In detail, we provide evidence that potential binding sites exist in the RBD of the SARS CoV-2 Spike protein and that occupancy of these pockets reduces the ability of the RBD to bind to the ACE2 consensus in vitro. Naturally occurring and clinically available triterpenoids such as glycyrrhetinic and oleanolic acids, as well as primary and secondary bile acids and their amidated derivatives such as glyco-ursodeoxycholic acid and semi-synthetic derivatives such as obeticholic acid reduces the RBD/ACE2 binding. In aggregate, these results might help to define novel approaches to COVID-19 based on SARS-CoV-2 entry inhibitors

Inhibition of Immune Synapse by Altered Dendritic Cell Actin Distribution: A New Pathway of Mesenchymal Stem Cell Immune Regulation

n/

GLP-1 Mediates Regulation of Colonic ACE2 Expression by the Bile Acid Receptor GPBAR1 in Inflammation

Background & Aims: ACE2, a carboxypeptidase that generates Ang-(1-7) from Ang II, is highly expressed in the lung, small intestine and colon. GPBAR1, is a G protein bile acid receptor that promotes the release of the insulinotropic factor glucagon-like peptide (GLP)-1 and attenuates intestinal inflammation. Methods: We investigated the expression of ACE2, GLP-1 and GPBAR1 in two cohorts of Crohn’s disease (CD) patients and three mouse models of colitis and Gpbar1−/− mice. Activation of GPBAR1 in these models and in vitro was achieved by BAR501, a selective GPBAR1 agonist. Results: In IBD patients, ACE2 mRNA expression was regulated in a site-specific manner in response to inflammation. While expression of ileal ACE2 mRNA was reduced, the colon expression was induced. Colon expression of ACE2 mRNA in IBD correlated with expression of TNF-α and GPBAR1. A positive correlation occurred between GCG and GPBAR1 in human samples and animal models of colitis. In these models, ACE2 mRNA expression was further upregulated by GPABR1 agonism and reversed by exendin-3, a GLP-1 receptor antagonist. In in vitro studies, liraglutide, a GLP-1 analogue, increased the expression of ACE2 in colon epithelial cells/macrophages co-cultures. Conclusions: ACE2 mRNA expression in the colon of IBD patients and rodent models of colitis is regulated in a TNF-α-and GLP-1-dependent manner. We have identified a GPBAR1/GLP-1 mechanism as a positive modulator of ACE2

Discovery of a AHR pelargonidin agonist that counter-regulates Ace2 expression and attenuates ACE2-SARS-CoV-2 interaction

The severe acute respiratory syndrome (SARS)-CoV-2 is the pathogenetic agent of Corona Virus Induced Disease (COVID)19. The virus enters the human cells after binding to the angiotensin converting enzyme (ACE)2 receptor in target tissues. ACE2 expression is induced in response to inflammation. The colon expression of ACE2 is upregulated in patients with inflammatory bowel disease (IBD), highlighting a potential risk of intestinal inflammation in promoting viral entry in the human body. Because mechanisms that regulate ACE2 expression in the intestine are poorly understood and there is a need of anti-SARS-CoV-2 therapies, we have settled to investigate whether natural flavonoids might regulate the expression of Ace2 in intestinal models of inflammation. The results of these studies demonstrated that pelargonidin activates the Aryl hydrocarbon Receptor (AHR) in vitro and reverses intestinal inflammation caused by chronic exposure to high fat diet or to the intestinal braking-barrier agent TNBS in a AhR-dependent manner. In these two models, development of colon inflammation associated with upregulation of Ace2 mRNA expression. Colon levels of Ace2 mRNA were directly correlated with Tnf-α mRNA levels. Molecular docking studies suggested that pelargonidin binds a fatty acid binding pocket on the receptor binding domain of SARS-CoV-2 Spike protein. In vitro studies demonstrated that pelargonidin significantly reduces the binding of SARS-CoV-2 Spike protein to ACE2 and reduces the SARS-CoV-2 replication in a concentration-dependent manner. In summary, we have provided evidence that a natural flavonoid might hold potential in reducing intestinal inflammation and ACE2 induction in the inflamed colon in a AhR-dependent manner

Changes in maternal body composition and metabolism of dairy goats during pregnancy.

Abstract: The objective of this study was to evaluate the mobilization of nutrients in goats of different gestation types and pregnancy stages. Forty-four Saanen and Oberhasli goats were studied. The goats of each breed and gestation type (single or twin) were slaughtered at different gestational ages (80, 110, and 140 days of pregnancy), forming a completely randomized design in a 2 × 3 × 2 factorial arrangement (two breeds, three gestational ages, and two types of pregnancy). The slaughter procedure involved separating the empty body, mammary glands, uterus with membranes and fetal fluid, and fetus(es). For the females slaughtered at 140 days of pregnancy, blood was collected to analyze metabolites and hormones every 15 days during gestation. The dry matter (DM) intake was lower in goats with twin pregnancies. The relative daily retention rate of the nutrients in the body was positive at 100 days of pregnancy but became negative at 140 days (-0.18±0.25 g DM kg-1 of maternal body d-1) and did not differ with breed or number of fetuses. Fetal growth in twin pregnancies was 66% higher than in single pregnancies. The highest levels of ß-hydroxybutyrate and non-esterified fatty acids were observed beginning at 100 days of gestation. Serum total protein and albumin levels decreased after 125 days of gestation. Serum urea levels were reduced after 80 days of gestation. Plasma 17ß-estradiol levels increased with the advance of pregnancy, and IGF-1 was highest between 60 and 80 days of gestation. The maternal metabolism throughout pregnancy does not vary with the type of pregnancy, and pregnant goats need greater nutritional intake during the final third of the gestational period regardless of the breed or type of pregnancy