Calibration and Validation of A Shared space Model: A Case Study

Shared space is an innovative streetscape design that seeks minimum separation between vehicle traffic and pedestrians. Urban design is moving toward space sharing as a means of increasing the community texture of street surroundings. Its unique features aim to balance priorities and allow cars and pedestrians to coexist harmoniously without the need to dictate behavior. There is, however, a need for a simulation tool to model future shared space schemes and to help judge whether they might represent suitable alternatives to traditional street layouts. This paper builds on the authors’ previously published work in which a shared space microscopic mixed traffic model based on the social force model (SFM) was presented, calibrated, and evaluated with data from the shared space link typology of New Road in Brighton, United Kingdom. Here, the goal is to explore the transferability of the authors’ model to a similar shared space typology and investigate the effect of flow and ratio of traffic modes. Data recorded from the shared space scheme of Exhibition Road, London, were collected and analyzed. The flow and speed of cars and segregation between pedestrians and cars are greater on Exhibition Road than on New Road. The rule-based SFM for shared space modeling is calibrated and validated with the real data. On the basis of the results, it can be concluded that shared space schemes are context dependent and that factors such as the infrastructural design of the environment and the flow and speed of pedestrians and vehicles affect the willingness to share space

Effects of plasma membrane cholesterol level and cytoskeleton F-actin on cell protrusion mechanics.

Protrusions are deformations that form at the surface of living cells during biological activities such as cell migration. Using combined optical tweezers and fluorescent microscopy, we quantified the mechanical properties of protrusions in adherent human embryonic kidney cells in response to application of an external force at the cell surface. The mechanical properties of protrusions were analyzed by obtaining the associated force-length plots during protrusion formation, and force relaxation at constant length. Protrusion mechanics were interpretable by a standard linear solid (Kelvin) model, consisting of two stiffness parameters, k0 and k1 (with k0>k1), and a viscous coefficient. While both stiffness parameters contribute to the time-dependant mechanical behavior of the protrusions, k0 and k1 in particular dominated the early and late stages of the protrusion formation and elongation process, respectively. Lowering the membrane cholesterol content by 25% increased the k0 stiffness by 74%, and shortened the protrusion length by almost half. Enhancement of membrane cholesterol content by nearly two-fold increased the protrusion length by 30%, and decreased the k0 stiffness by nearly two-and-half-fold as compared with control cells. Cytoskeleton integrity was found to make a major contribution to protrusion mechanics as evidenced by the effects of F-actin disruption on the resulting mechanical parameters. Viscoelastic behavior of protrusions was further characterized by hysteresis and force relaxation after formation. The results of this study elucidate the coordination of plasma membrane composition and cytoskeleton during protrusion formation

Methotrexate hepatotoxicity in patients with rheumatoid arthritis.

BACKGROUND Increases in aminotransferases (transaminitis) are potential major adverse reactions seen with long-term use of methotrexate (MTX). The aim of this study, therefore was to evaluate the incidence of MTX induced hepatotoxicity and its risk factors among rheumatoid arthritis (RA) patients. METHODS This retrospective study described 286 patients with RA who received ≥ 7.5 mg MTX weekly in an academic rheumatology clinic over a 15 year period. The results of serial liver function tests, concurrent MTX dose, cumulative dose and use of hepatotoxic drugs were collected and statistically analyzed according to a consecutive elevation in aminotransferases which occurred over at least a two week interval. RESULTS During the study period, 286 patients (84.4% female) with mean age of 46.6±12.7 years (18-84 years) were enrolled. Transaminitis occurred among 23.7% of patients (incidence: 6.9 per 100 person-years) during 40.5±34.6 month's exposure to MTX (989.6 person-years). The time difference between onset of therapy and occurrence of transaminitis was 22.1±22.0 months. The only significant factor related to the occurrence of transaminitis was the duration of MTX therapy. The average duration of treatment among patients with transaminitis (59.6±42.3 months) was greater than those with no transaminitis (p<0.001). The cumulative dose of MTX was significantly related to the occurrence of transaminitis (p<0.001). CONCLUSION MTX hepatotoxicity is a common complication of long-term treatment with MTX. It is associated with mild liver enzyme elevation and related to the duration of therapy