The multi-vehicle dial-a-ride problem with interchange and perceived passenger travel times

The Dial-a-Ride Problem (DARP) introduced in the early 1980s is the NP-Hard optimization problem of developing the most cost-efficient vehicle schedules for a number of available vehicles that have to start from a depot, pick up and deliver a set of passengers, and return back to the same depot. DARP has been used in many modern applications, including the scheduling of demand-responsive transit and car pooling. This study departs from the original definition of DARP and it extends it by considering an interchange point where vehicles can exchange their picked-up passengers with other vehicles in order to shorten their delivery routes and reduce their running times. In addition to that, this study introduces the concept of generalized passenger travel times in the DARP formulation which translates the increased in-vehicle crowdedness to increased perceived passenger travel times. This addresses a key issue because the perceived in-vehicle travel times of passengers might increase when the vehicle becomes more crowded (i.e., passengers might feel that their travel time is higher when they are not able to find a seat or they are too close to each other increasing the risk of virus transmission or accidents). Given these considerations, this study introduces the Dial-a-Ride Problem with interchange and perceived travel times (DARPi) and models it as a nonlinear programming problem. DARPi is then reformulated to a MILP with the use of linearizations and its search space is tightened with the addition of valid inequalities that are employed when solving the problem to global optimality with Branch-and-Cut. For large problem instances, this study introduces a tabu search-based metaheuristic and performs experiments in benchmark instances used in past literature demonstrating the computation times and solution stability of our approach. The effect of the perceived passenger travel times to the vehicle running costs is also explored in extensive numerical experiments.</p

Neural tube closure: cellular, molecular and biomechanical mechanisms.

Neural tube closure has been studied for many decades, across a range of vertebrates, as a paradigm of embryonic morphogenesis. Neurulation is of particular interest in view of the severe congenital malformations - 'neural tube defects' - that result when closure fails. The process of neural tube closure is complex and involves cellular events such as convergent extension, apical constriction and interkinetic nuclear migration, as well as precise molecular control via the non-canonical Wnt/planar cell polarity pathway, Shh/BMP signalling, and the transcription factors Grhl2/3, Pax3, Cdx2 and Zic2. More recently, biomechanical inputs into neural tube morphogenesis have also been identified. Here, we review these cellular, molecular and biomechanical mechanisms involved in neural tube closure, based on studies of various vertebrate species, focusing on the most recent advances in the field

Deliverable 9.1 - Report on mixtures and implementation strategy in Europe – Assessment of chemical mixtures under consideration of current and future regulatory requirements and scientific approaches

This report gives an overview on the regulatory processes and requirements for risk assessment of chemical mixtures, identifies gaps in the European legislation and summarises potential approaches for the health risk assessment of chemical mixtures

Impact of urban albedo on microclimate: Computational investigation in London

The urban albedo (UA), defined as the ratio of the reflected to the incoming shortwave radiation at the upper edge of urban canyons, quantifies their ability to reflect solar radiation towards the sky. This research investigates the impact of real-world urban geometries and optical properties of facades and roads materials on the UA and street level microclimate in London. The Indexed Sphere (IVS) algorithm of ENVI-met 4.4.4 is used to compute the UA of several canyon configurations. The accuracy of the IVS algorithm is evaluated against measurements on a 1:10 physical model reproducing the geometry and materials of the case study area. The simulation results show that reflective materials applied to the canyon surfaces are more effective in increasing the UA of canyons with low aspect ratios. The use of reflective materials in urban canyons always increases the amount of reflections at the street level, increasing the mean radiant temperature in most cases. Air temperature is not affected by the canyon’s façades reflectivity while it shows a significant daytime reduction for increased roads’ reflectivity. The results provide preliminary guidelines for the control of UA and the improvement of microclimate in London.EPSRC UK under the project ‘Urban albedo computation in high latitude locations: An experimental approach’ (EP/P02517X/1).https://www.conftool.org/plea2020/index.php/SC-5-4-Impact_Of_Urban_Albedo_On_Microclimate_Salvati_1751_b.pdf?page=downloadPaper&filename=SC-5-4-Impact_Of_Urban_Albedo_On_Microclimate_Salvati_1751_b.pdf&form_id=1751&form_index=2&form_version=fina

Impact of reflective materials on urban canyon albedo, outdoor and indoor microclimates

The urban canyon albedo (UCA) quantifies the ability of street canyons to reflect solar radiation back to the sky. The UCA is controlled by the solar reflectance of road and façades and the street geometry. This study investigates the variability of UCA in a typical residential area of London and its impact on outdoor and indoor microclimates. The results are based on radiation measurements in real urban canyons and on a 1:10 physical model and simulations using ENVImet v 4.4.6 and EnergyPlus. Different scenarios with increased solar reflectance of roads and façades were simulated to investigate the impact on UCA and street level microclimate. The results showed that increasing the road reflectance has high absolute and relative impact on UCA in wide canyons. In deeper canyons, the absolute impact of the road reflectance is reduced while the relative impact of the walls' reflectance is increased. Results also showed that increasing surface reflectance in urban canyons has a detrimental impact on outdoor thermal comfort, due to increased interreflections between surfaces leading to higher mean radiant temperatures. Increasing the road reflectance also increases the incident diffuse radiation on adjacent buildings, producing a small increase in indoor operative temperatures. The findings were used to discuss the best design strategies to improve the urban thermal environment by using reflective materials in urban canyons without compromising outdoor thermal comfort or indoor thermal environments.This work was funded by EPSRC UK under the project ‘Urban albedo computation in high latitude locations: An experimental approach’ (EP/ P02517X/1)

Prostaglandin D2/J2 signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: potential novel therapeutic targets

Background: Prostaglandins are products of the cyclooxygenase pathway, which is implicated in Parkinson’s disease (PD). Limited knowledge is available on mechanisms by which prostaglandins contribute to PD neurodegeneration. To address this gap, we focused on the prostaglandin PGD2/J2 signaling pathway, because PGD2 is the most abundant prostaglandin in the brain, and the one that increases the most under pathological conditions. Moreover, PGJ2 is spontaneously derived from PGD2. Methods: In this study, we determined in rats the impact of unilateral nigral PGJ2-microinfusions on COX-2, lipocalin-type PGD2 synthase (L-PGDS), PGD2/J2 receptor 2 (DP2), and 15 hydroxyprostaglandin dehydrogenase (15-PGDH). Nigral dopaminergic (DA) and microglial distribution and expression levels of these key factors of the prostaglandin D2/J2 pathway were evaluated by immunohistochemistry. PGJ2-induced motor deficits were assessed with the cylinder test. We also determined whether oral treatment with ibuprofen improved the PD-like pathology induced by PGJ2. Results: PGJ2 treatment induced progressive PD-like pathology in the rats. Concomitant with DA neuronal loss in the substantia nigra pars compacta (SNpc), PGJ2-treated rats exhibited microglia and astrocyte activation and motor deficits. In DA neurons, COX-2, L-PGDS, and 15-PGDH levelsincreased significantly in PGJ2-treated rats compared to controls, while DP2 receptor levels were unchanged. In microglia, DP2 receptors were basically non-detectable, while COX-2 and L-PGDS levels increased upon PGJ2-treatment, and 15-PGDH remained unchanged. 15-PGDH was also detected in oligodendrocytes. Notably, ibuprofen prevented most PGJ2-induced PD-like pathology. Conclusions: The PGJ2-induced rat model develops progressive PD pathology, which is a hard-to-mimic aspect of this disorder. Moreover, prevention of most PGJ2-induced PD-like pathology with ibuprofen suggests a positive feedback mechanism between PGJ2 and COX-2 that could lead to chronic neuroinflammation. Notably, this is the first study that analyzes the nigral dopaminergic and microglial distribution and levels of factors of the PGD2/J2 signaling pathway in rodents. Our findings support the notions that upregulation of COX-2 and L-PGDS may be important in the PGJ2 evoked PD-like pathology, and that neuronal DP2 receptor antagonists and L-PGDS inhibitors may be novel pharmacotherapeutics to relieve neuroinflammation-mediated neurodegeneration in PD, circumventing the adverse side effects of cyclooxygenase inhibitors

Vangl2 disruption alters the biomechanics of late spinal neurulation leading to spina bifida in mouse embryos

peer-reviewedHuman mutations in the planar cell polarity component VANGL2 are associated with the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents initiation of neural tube closure, precluding analysis of its subsequent roles in neurulation. Spinal neurulation involves rostral-to-caudal ‘zippering’ until completion of closure is imminent, when a caudal-to-rostral closure point, ‘Closure 5’, arises at the caudal-most extremity of the posterior neuropore (PNP). Here, we used Grhl3Cre to delete Vangl2 in the surface ectoderm (SE) throughout neurulation and in an increasing proportion of PNP neuroepithelial cells at late neurulation stages. This deletion impaired PNP closure after the ∼25-somite stage and resulted in caudal spina bifida in 67% of Grhl3Cre/+Vangl2Fl/Fl embryos. In the dorsal SE, Vangl2 deletion diminished rostrocaudal cell body orientation, but not directional polarisation of cell divisions. In the PNP, Vangl2 disruption diminished mediolateral polarisation of apical neuroepithelial F-actin profiles and resulted in eversion of the caudal PNP. This eversion prevented elevation of the caudal PNP neural folds, which in control embryos is associated with formation of Closure 5 around the 25-somite stage. Closure 5 formation in control embryos is associated with a reduction in mechanical stress withstood at the main zippering point, as inferred from the magnitude of neural fold separation following zippering point laser ablation. This stress accommodation did not happen in Vangl2-disrupted embryos. Thus, disruption of Vangl2-dependent planar-polarised processes in the PNP neuroepithelium and SE preclude zippering point biomechanical accommodation associated with Closure 5 formation at the completion of PNP closure

Engrained experience—a comparison of microclimate perception schemata and microclimate measurements in Dutch urban squares

Acceptance of public spaces is often guided by perceptual schemata. Such schemata also seem to play a role in thermal comfort and microclimate experience. For climate-responsive design with a focus on thermal comfort it is important to acquire knowledge about these schemata. For this purpose, perceived and “real” microclimate situations were compared for three Dutch urban squares. People were asked about their long-term microclimate perceptions, which resulted in “cognitive microclimate maps”. These were compared with mapped microclimate data from measurements representing the common microclimate when people stay outdoors. The comparison revealed some unexpected low matches; people clearly overestimated the influence of the wind. Therefore, a second assumption was developed: that it is the more salient wind situations that become engrained in people’s memory. A comparison using measurement data from windy days shows better matches. This suggests that these more salient situations play a role in the microclimate schemata that people develop about urban places. The consequences from this study for urban design are twofold. Firstly, urban design should address not only the “real” problems, but, more prominently, the “perceived” problems. Secondly, microclimate simulations addressing thermal comfort issues in urban spaces should focus on these perceived, salient situations

Conforto térmico em espaços públicos de passagem: estudos em ruas de pedestres no estado de São Paulo

Este artigo apresenta resultados de um estudo sobre conforto térmico em espaços públicos de passagem, em ruas de pedestres nas cidades de Campinas, Bauru e Presidente Prudente, no Estado de São Paulo. O estudo foi desenvolvido dentro de uma pesquisa mais ampla sobre o conforto térmico em diferentes tipos de espaços urbanos abertos, nas mesmas cidades. A metodologia empregada envolveu o monitoramento microclimático (temperatura, temperatura de globo, umidade relativa do ar, velocidade do ar e radiação solar global), em diferentes condições de tempo, e entrevistas estruturadas, para identificar a sensação térmica e as variáveis pessoais dos usuários. A análise dos resultados permitiu identificar diferenças entre a sensação térmica real (ASV) e o conforto calculado pela temperatura fisiológica equivalente (PET). Os limites de conforto térmico variaram entre as cidades: 20-29 ºC para Campinas, 21-30 ºC para Bauru, e 14-24 ºC para Presidente Prudente. Entretanto, a sensação de neutralidade térmica para 59,5% do total da amostra (308 de 519 indivíduos) foi de 18 a 26 ºC. Esses resultados são compatíveis com os limites propostos por Monteiro e Alucci (2007) para a cidade de São Paulo e podem contribuir como parâmetro de avaliação da qualidade térmica de outros espaços públicos de passagem nas mesmas cidades