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Reinforcement learning for temporal logic control synthesis with probabilistic satisfaction guarantees
No full textWe present a model-free reinforcement learning algorithm to synthesize control policies that maximize the probability of satisfying high-level control objectives given as Linear Temporal Logic (LTL) formulas. Uncertainty is considered in the workspace properties, the structure of the workspace, and the agent actions, giving rise to a Probabilistically-Labeled Markov Decision Process (PL-MDP) with unknown graph structure and stochastic behaviour, which is even more general than a fully unknown MDP. We first translate the LTL specification into a Limit Deterministic Büchi Automaton (LDBA), which is then used in an on-the-fly product with the PL-MDP. Thereafter, we define a synchronous reward function based on the acceptance condition of the LDBA. Finally, we show that the RL algorithm delivers a policy that maximizes the satisfaction probability asymptotically. We provide experimental results that showcase the efficiency of the proposed method
Medieval Islamic Views of the Cosmos. The Books of Curiosities: Teaching materials
No full textIn June 2002, the Bodleian Library acquired an illustrated manuscript of a hitherto unknown Arabic cosmographical treatise, the Kitāb Gharāʾib al-funūn wa-mulaḥ al-ʿuyūn, known as the Book of Curiosities. The manuscript is a copy, probably made in Egypt in the late 12th or early 13th century, of an anonymous work compiled in the first half of the 11th century in Egypt. The treatise is extraordinarily important for the history of science, especially for astronomy and cartography, and contains an unparalleled series of diagrams of the heavens and maps of the earth.
The acquisition of the Book of Curiosities was made possible by a grant from the Heritage Lottery Fund and generous donations from the National Arts Collections Fund, the Friends of the Bodleian, Saudi Aramco, several Oxford colleges, and private individuals.
These grants and donations, along with the Arts & Humanities Research Council, have also funded the project to prepare a full study of the treatise, including an edition of the Arabic text and English translation, and to disseminate the results as widely as possible through the internet, exhibitions, and an outreach programme.
This dataset contains a teachers’ pack that explores the themes of the Book of Curiosities which are to do with the Earth and the Heavens from the perspective of an 11th-century writer. It can be used at Key Stage 3 of the UK National Curriculum (aimed at 11-14 year olds) in the study of History, Geography, English, Science
Quantum mechanics and salvation: A new meeting point for science and theology
No full textQuantum mechanics has recently indicated that temporal order is not always fixed, a finding that has far-reaching philosophical and theological implications. The phenomena, termed “indefinite causal order,” shows that events can be in a superposition with regard to their order. In the experimental setting with which this article is concerned, two events, A and B, were shown to be in the ordering relations “A before B” and “B before A” at the same time. This article introduces an ongoing project that seeks to make sense of this result, with a particular focus on the methodology by which this research will be undertaken. Specific research questions, particularly regarding what indefinite causal order might mean for the metaphysics of time and the doctrine of salvation, are introduced. The collaborative approach detailed brings together the disciplinary skills of a working scientist and a working theologian. What is offered is a collaborative methodology for interaction between science and religion that is more than the sum of its parts. Alister McGrath’s idea of multiple rationalities is employed as an epistemological framework within which this research takes place. Within an epistemologically pluralistic model, collaborative efforts are not only encouraged but necessary. Complex reality requires an equally complex, usually interdisciplinary, explanation. I argue that such dialogue is both theologically justified and culturally valuable and indicates the direction in which this research will be taken
Tetrahydrobiopterin and nitric oxide synthase recouplers
No full textGeneration of nitric oxide (NO) by the nitric oxide synthase (NOS) enzymes plays multiple signalling roles in every organ system, with crucial roles in the cardiovascular system, mediated by endothelial nitric oxide synthase (eNOS, encoded by NOS3) and neuronal nitric oxide synthase (nNOS, encoded by NOS1) in regulation of blood pressure, flow, oxygen delivery and cardiac function. Loss of normal NO-mediated functions in cardiovascular disease state is associated with changes in nitroso-redox signalling that are not dependent solely upon altered NO generation, but increased generation of reactive oxygen species (ROS). The NOS enzymes can also generate ROS, in a catalytic mode whereby the generation of NO from L-arginine is 'uncoupled' from the reduction of molecular oxygen. NOS uncoupling is determined by several factors, including the availability and oxidation state of the required NOS cofactor, tetrahydrobiopterin (BH4). The duality of NOS functions as enzymes that generate both NO and ROS under different regulatory states has emerged as an important pathophysiologic mechanism, and is a potential therapeutic target, via agents that can maintain or restore NOS coupling, for example via effects on BH4 availability
ReN VM spheroids in matrix: A neural progenitor three-dimensional in vitro model reveals DYRK1A inhibitors as potential regulators of radio-sensitivity
No full textIntroduction
Pre-clinical testing of small molecules for therapeutic development across many pathologies relies on the use of in-vitro and in-vivo models. When designed and implemented well, these models serve to predict the clinical outcome as well as the toxicity of the evaluated therapies. The two-dimensional (2D) reductionist approach where cells are incubated in a mono-layer on hard plastic microtiter plates is relatively inexpensive but not physiologically relevant. In contrast, well developed and applied three dimensional (3D) in vitro models could be employed to bridge the gap between 2D in vitro primary screening and expensive in vivo rodent models by incorporating key features of the tissue microenvironment to explore differentiation, cortical development, cancers and various neuronal dysfunctions. These features include an extracellular matrix, co-culture, tension and perfusion and could replace several hundred rodents in the drug screening validation cascade.
Methods
Human neural progenitor cells from middle brain (ReN VM, Merck Millipore, UK) were expanded as instructed by the supplier (Merck Millipore, UK), and then seeded in 96-well low-attachment plates (Corning, UK) to form multicellular spheroids followed by adding a Matrigel layer to mimic extracellular matrix around neural stem cell niche. ReN VM cells were then differentiated via EGF and bFGF deprivation for 7 days and were imaged at day 7. Radiotherapy was mimicked via gamma-radiation at 2Gy in the absence and presence of selected DYRK1A inhibitors Harmine, INDY and Leucettine 41 (L41). Cell viability was measured by AlamarBlue assay. Immunofluorescence staining was used to assess cell pluripotency marker SOX2 and differentiation marker GFAP.
Results
After 7 days of differentiation, neuron early differentiation marker (GFAP, red) started to be expressed among the cells expressing neural stem cell marker SOX2 (green). Radiation treatment caused significant morphology change including the reduced viability of the spheroids. These spheroids also revealed sensitizing potential of DYRK1A inhibitors tested in this study, including Harmine, INDY and L41.
Discussion & conclusions
Combined with the benefit of greatly reducing the issues associated with in vivo rodent models, including reducing numbers of animals used in a drug screening cascade, cost, ethics, and potential animal welfare burden, we feel the well-developed and applied 3D neural spheroid model presented in this study will provide a crucial tool to evaluate combinatorial therapies, optimal drug concentrations and treatment dosages
The ends of 30 big depressions
No full textHow did countries recover from the Great Depression? In this paper we explore the argument that leaving the gold standard helped by boosting inflationary expectations and lowering real interest rates. We do so for a sample of 30 countries, using modern nowcasting methods and a new dataset containing more than 230,000 monthly and quarterly observations for over 1,500 variables. In those cases where the departure from gold happened on clearly defined dates, it seems clear that inflationary expectations rose in the wake of departure. Synthetic matching techniques suggest that the relationship is causal
E-commerce promotes trade in invasive turtles in China
No full textHabitats in China are suited to many invasive alien turtle species. Consequently, raising turtles in aquaculture facilities, and the trade in turtles this supplies, poses risks to wetland habitats and ecological cascades when exotic turtles escape or are released deliberately. Online trade (e-commerce) is making an increasing contribution to turtle sales in China, seemingly driving greater demand and so potentially exacerbating these risks. Here we document the scale and spatial pattern of online sales of non-native turtles over 90 days via China’s Taobao.com e-commerce site. Recorded sales were biased toward the ecologically sensitive middle and lower Yangtze-river-basin for both North American slider (Trachemys scripta elegans; >840,000 individuals - 82.35% in middle and lower Yangtze-river-basin) and snapping turtles (Chelydridae spp.; >100,000 individuals - 68.26% in middle and lower Yangtze-river-basin). Concurrently, over 2008-2018, we found 104 mentions of feral turtle issues listed on Baidu News, where, among the 53 prefectures mentioned, issues with invasive populations were also focused predominantly in the middle and lower Yangtze-river-basin. Although circumstantial, this association implies that the substantial online sale of alien turtles is having detrimental effects in China’s Yangtze-river-basin. It is thus important to safeguard these wetland habitats of global biodiversity importance through developing better policies detecting and regulating invasive alien turtle issues in the future and through warning consumers about the ecological hazard their purchases risk
A multi-centre prospective randomised equivalence trial of a soft bandage and immediate discharge versus current treatment with rigid immobilisation for torus fractures of the distal radius in children: Protocol for the Forearm Fracture Recovery in Children Evaluation Trial (FORCE)
No full textIntroduction: Torus fractures are the most common childhood fracture, accounting for 500,000 UK emergency attendances per year. UK treatment varies widely due to lack of scientific evidence. This is the protocol for a randomised controlled equivalence trial of ‘the offer of a soft bandage and immediate discharge’ versus ‘rigid immobilisation and follow-up as per the protocol of the treating centre’ in the treatment of torus fractures of the distal radius.
Methods and analysis: Children aged 4 to 15 years old inclusive who have sustained a torus/buckle fracture of the distal radius with/without an injury to the ulna are eligible to take part. Baseline pain as measured by the Wong Baker FACES Pain Scale, function using the PROMIS upper extremity, and quality of life (QoL) assessed with the EuroQol EQ-5D-Y will be collected.
Each patient will be randomly allocated (1:1, stratified by centre and age group (4-7 years and ≥8 years)) to either a regimen of the offer of a soft bandage and immediate discharge or rigid immobilisation and follow-up as per the protocol of the treating centre.
At day 1, 3 and 7, data on pain, function, QoL, immobilisation and analgesia will be collected. Three and six weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the Wong-Baker FACEs pain scale at 3 days post-randomisation. All data will be obtained through electronic questionnaires completed by the participants and/or parents
Type-I contributions to the one and two level densities of quadratic Dirichlet L–functions over function fields
No full textUsing the Ratios Conjecture, we write down precise formulas with lower order terms for the one and the two level densities of zeros of quadratic Dirichlet L–functions over function fields. We denote the various terms arising as Type-0, Type-I and Type-II contributions. When the support of the Fourier transform of the test function is sufficiently restricted, we rigorously compute the Type-0 and Type-I terms and confirm that they match the conjectured answer. When the restrictions on the support are relaxed, our results suggest that Type-II contributions become important in the two level density
Baseline quality of life in people with hip fracture: results from the multicentre WHiTE cohort study
No full textAims
To assess the variation in pre-fracture quality of life (QoL) within the UK hip fracture population, and quantify the nature and strength of associations between QoL and other routinely collected patient characteristics and treatment choices.
Methods
The World Hip Trauma Evaluation (WHiTE) study, an observational cohort study of UK hip fracture patients, collects a range of routine data and a health-related QoL score (EuroQol five-dimension questionnaire (EQ-5D)). Pre-fracture QoL data are summarized and statistical models fitted to understand associations between QoL, patient characteristics, fracture types, and operations.
Results
Fitting a multiple linear regression model indicated that 36.5% of the variance in pre-fracture EQ-5D scores was explained by routinely collected patient characteristics: sex (0.14%), age (0.17%), American Society of Anesthesiologists (ASA) score (0.73%), Abbreviated Mental Test Score (AMTS; 1.3%), pre-fracture mobility (11.2%), and EQ-5D respondent (participant, relative, or carer; 23.0%). There was considerable variation in pre-fracture EQ-5D scores between operations within fracture types. Participants with trochanteric fractures reported statistically significant but not clinically relevant lower pre-fracture QoL than those with intracapsular fractures. Participants with intracapsular fractures treated with internal fixation or total hip arthroplasty (THA) reported better QoL than those treated with hemiarthroplasty with the overall fittest group receiving THA.
Conclusion
Pre-fracture QoL varies considerably between hip fracture patients; it is generally higher in younger than older patients, patients with better mobility, and those patients who live more independently. Pre-fracture QoL is significantly associated with a range of patient characteristics (e.g. age, mobility, residency). These data explain ~35% of the variation in QoL