Rebalancing shared mobility systems by user incentive scheme via reinforcement learning

Shared mobility systems regularly suffer from an imbalance of vehicle supply within the system, leading to users being unable to receive service. If such imbalance problems are not mitigated some users will not be serviced. There is an increasing interest in the use of reinforcement learning (RL) techniques for improving the resource supply balance and service level of systems. The goal of these techniques is to produce an effective user incentivization policy scheme to encourage users of a shared mobility system to slightly alter their travel behavior in exchange for a small monetary incentive. These slight changes in user behavior are intended to over time increase the service level of the shared mobility system and improve user experience. In this thesis, two important questions are explored: (1) What state-action representation should be used to produce an effective user incentive scheme for a shared mobility system? (2) How effective are reinforcement learning-based solutions on the rebalancing problem under varying levels of resource supply, user demand, and budget? Our extensive empirical results based on data-driven simulation show that: 1. A state space with predicted user behavior coupled with a simple action mechanism produces an effective incentive scheme under varying environment scenarios. 2. The reinforcement learning-based incentive mechanisms perform at varying degrees of effectiveness under different environmental scenarios in terms of service level

New insights on the origin of Barra Volcanic Ridge System, offshore Ireland : a long distance influence of the Iceland mantle plume

Acknowledgements This project was funded by the Irish Centre for Research in Applied Geosciences (iCRAG), Science Foundation Ireland (SFI), Irish Shelf and Petroleum Studies Group (ISPSG) of the Petroleum Infrastructure Programme (PiP) and Dublin Institute for Advanced Studies (DIAS). This publication uses data and survey results acquired during a project undertaken on behalf of the Irish Shelf Petroleum Studies Group (ISPSG) of the Irish Petroleum Infrastructure programme Group 4. The ISPSG comprises: AzEire Petroleum Ltd, Cairn Energy Plc, BP Exploration Operating Company Ltd, CNOOC Petroleum Europe Limited, ENI Ireland BV, Equinor Energy Ireland Limited, Europa Oil & Gas Plc, ExxonMobil E&P Ireland (Offshore) Ltd, Husky Energy, Petroleum Affairs Division of the Department of Communications, Climate Action and Environment, Providence Resources plc, Repsol Exploración SA, Sosina Exploration Ltd, Total EP, Tullow Oil Plc and Woodside Energy (Ireland) Pty Ltd. processing is done by using ECHOS software from Paradigm. We are very thankful to Dr. J. Kim Welford for providing us with the 3D Moho map of Irelands offshore. We acknowledge the Geological Survey Ireland and the Marine Institute (INFOMAR), for providing the data for this work. We also acknowledge Schlumberger for providing an academic license of Petrel software for this study. SR further acknowledges research funding from Science Foundation Ireland (SFI) and PIP. This publication derives from research supported in part by a research grant from SFI under Grant Number 13/RC/2092 and co-funded under the European Regional Development Fund and by iCRAG industry partners. Sincere thanks to Tim Minshul, Laurent Gernigon and a third reviewer for providing helpful reviews and insightful comments on the paper, which greatly improved the quality of the manuscript.Peer reviewe

Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma

Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Arginine metabolism in Trichomonas vaginalis infected with Mycoplasma hominis

Both Mycoplasma hominis and Trichomonas vaginalis utilize arginine as an energy source via the arginine dihydrolase (ADH) pathway. It has been previously demonstrated that M. hominis forms a stable intracellular relationship with T. vaginalis; hence, in this study we examined the interaction of two localized ADH pathways by comparing T. vaginalis strain SS22 with the laboratory-generated T. vaginalis strain SS22-MOZ2 infected with M. hominis MOZ2. The presence of M. hominis resulted in an approximately 16-fold increase in intracellular ornithine and a threefold increase in putrescine, compared with control T. vaginalis cultures. No change in the activity of enzymes of the ADH pathway could be demonstrated in SS22-MOZ2 compared with the parent SS22, and the increased production of ornithine could be attributed to the presence of M. hominis. Using metabolic flow analysis it was determined that the elasticity of enzymes of the ADH pathway in SS22-MOZ2 was unchanged compared with the parent SS22; however, the elasticity of ornithine decarboxylase (ODC) in SS22 was small, and it was doubled in SS22-MOZ2 cells. The potential benefit of this relationship to both T. vaginalis and M. hominis is discussed

Advancing science and policy through a coordinated international study of physical activity and built environments: IPEN Adult methods

Background: National and international strategies to increase physical activity emphasize environmental and policy changes that can have widespread and long-lasting impact. Evidence from multiple countries using comparable methods is required to strengthen the evidence base for such initiatives. Because some environment and policy changes could have generalizable effects and others may depend on each country’s context, only international studies using comparable methods can identify the relevant differences. Methods: Currently 12 countries are participating in the International Physical Activity and the Environment Network (IPEN) study. The IPEN Adult study design involves recruiting adult participants from neighborhoods with wide variations in environmental walkability attributes and socioeconomic status (SES). Results: Eleven of twelve countries are providing accelerometer data and 11 are providing GIS data. Current projections indicate that 14,119 participants will provide survey data on built environments and physical activity and 7145 are likely to provide objective data on both the independent and dependent variables. Though studies are highly comparable, some adaptations are required based on the local context. Conclusions: This study was designed to inform evidence-based international and country-specific physical activity policies and interventions to help prevent obesity and other chronic diseases that are high in developed countries and growing rapidly in developing countries

A Randomised, Double-Blind, Controlled Vaccine Efficacy Trial of DNA/MVA ME-TRAP Against Malaria Infection in Gambian Adults

BACKGROUND: Many malaria vaccines are currently in development, although very few have been evaluated for efficacy in the field. Plasmodium falciparum multiple epitope (ME)– thrombospondin-related adhesion protein (TRAP) candidate vaccines are designed to potently induce effector T cells and so are a departure from earlier malaria vaccines evaluated in the field in terms of their mechanism of action. ME-TRAP vaccines encode a polyepitope string and the TRAP sporozoite antigen. Two vaccine vectors encoding ME-TRAP, plasmid DNA and modified vaccinia virus Ankara (MVA), when used sequentially in a prime-boost immunisation regime, induce high frequencies of effector T cells and partial protection, manifest as delay in time to parasitaemia, in a clinical challenge model. METHODS AND FINDINGS: A total of 372 Gambian men aged 15–45 y were randomised to receive either DNA ME-TRAP followed by MVA ME-TRAP or rabies vaccine (control). Of these men, 296 received three doses of vaccine timed to coincide with the beginning of the transmission season (141 in the DNA/MVA group and 155 in the rabies group) and were followed up. Volunteers were given sulphadoxine/pyrimethamine 2 wk before the final vaccination. Blood smears were collected weekly for 11 wk and whenever a volunteer developed symptoms compatible with malaria during the transmission season. The primary endpoint was time to first infection with asexual P. falciparum. Analysis was per protocol. DNA ME-TRAP and MVA ME-TRAP were safe and well-tolerated. Effector T cell responses to a non-vaccine strain of TRAP were 50-fold higher postvaccination in the malaria vaccine group than in the rabies vaccine group. Vaccine efficacy, adjusted for confounding factors, was 10.3% (95% confidence interval, −22% to +34%; p = 0.49). Incidence of malaria infection decreased with increasing age and was associated with ethnicity. CONCLUSIONS: DNA/MVA heterologous prime-boost vaccination is safe and highly immunogenic for effector T cell induction in a malaria-endemic area. But despite having produced a substantial reduction in liver-stage parasites in challenge studies of non-immune volunteers, this first generation T cell–inducing vaccine was ineffective at reducing the natural infection rate in semi-immune African adults