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Dynamic asset (and liability) management under market and credit risk
We introduce a modelling paradigm which integrates credit risk and market
risk in describing the random dynamical behaviour of the underlying fixed income assets.
We then consider an asset and liability management (ALM) problem and develop a mul-
tistage stochastic programming model which focuses on optimum risk decisions. These
models exploit the dynamical multiperiod structure of credit risk and provide insight
into the corrective recourse decisions whereby issues such as the timing risk of default is
appropriately taken into consideration. We also present a index tracking model in which
risk is measured (and optimised) by the CVaR of the tracking portfolio in relation to the
index. Both in- and out-of-sample (backtesting) experiments are undertaken to validate
our approach. In this way we are able to demonstrate the feasibility and flexibility of
the chosen framework
A prospective study of MRI biomarkers in the brain and lower limb muscles for prediction of lower limb motor recovery following stroke
Prediction of anti-Alzheimer’s activity of flavonoids targeting acetylcholinesterase in silico
Introduction – Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AchE) inhibitory, anticholinergic, antiinflammatory, antimicrobial, antioxidant, antiproliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer’s disease. Objective – The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AchE inhibition linking to the potential treatment of Alzheimer’s disease. Methodology – Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and QSAR were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman’s method. Results – In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AchE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50 was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative number 20 was the best scorer i.e., -31.6392 and IC50 was predicted as 6.025 nM. Conclusion – Results indicated that flavonoids could be efficient inhibitors of AchE and thus, could be useful in the management of Alzheimer’s disease
Modelling the Effects of Traits and Abiotic Factors on Viral Lysis in Phytoplankton
A mechanistic system dynamics description is developed of the interactions between a single lytic-virus – phytoplankton-host couple. The model has state variables for virus, uninfected and infected host biomass, and describes virus and host allometry and physiology. The model, analogous to experimental laboratory virus-host systems but more amenable to hypothesis testing, enables us to explore the relative importance of some of the poorly understood factors suspected to impact plankton virus-host dynamics. Model behaviour is explored with respect to abiotic factors (light, mixed layer
depth, nutrient and suspended particle loading), host traits (size, growth rate, motility) and virus traits (size, latent period and burst size including linkage to compromised host physiology, and decay rates). Simulations show that the optimal performance of
a virus (i.e., optimal trait characterisation) is a function of many factors relating to the virus, its host, and the environment. In general, smaller viruses and smaller motile hosts give rise to more productive infection outcomes that result in rapid demise of the host and high post-infection virus abundance. However, the timing of the development of the interaction (relative abundance of virus to host at the start of rapid host population growth), overlain on the growth rate and physiological status of the host, was seen to
be critical. Thus, for any one configuration of the model, the inoculum level of the virus (multiplicity of infection- MOI) displayed an optimum time-point between the infection developing too quickly, limiting biomass accumulation, or too late so that nutrient or
light limitation compromised host physiology and hence the burst size. Importantly, the success of an infection depended also upon the suspended particle load which, if high enough, adsorbs so many viruses that the infection does not develop. We conclude that adding viruses to plankton ecosystem models in a realistic fashion is a complicated process due to the way that the individual and coupled virus-host processes interact with the environment
A mutate-and-map protocol for inferring base pairs in structured RNA
Chemical mapping is a widespread technique for structural analysis of nucleic
acids in which a molecule's reactivity to different probes is quantified at
single-nucleotide resolution and used to constrain structural modeling. This
experimental framework has been extensively revisited in the past decade with
new strategies for high-throughput read-outs, chemical modification, and rapid
data analysis. Recently, we have coupled the technique to high-throughput
mutagenesis. Point mutations of a base-paired nucleotide can lead to exposure
of not only that nucleotide but also its interaction partner. Carrying out the
mutation and mapping for the entire system gives an experimental approximation
of the molecules contact map. Here, we give our in-house protocol for this
mutate-and-map strategy, based on 96-well capillary electrophoresis, and we
provide practical tips on interpreting the data to infer nucleic acid
structure.Comment: 22 pages, 5 figure
“Boom‐and‐busted‐dynamics” of phytoplankton‐virus interactions explain the paradox of the plankton
Rapid virus proliferation can exert a powerful control on phytoplankton host populations, playing a significant role in marine biogeochemistry and ecology. We explore how marine lytic viruses impact phytoplankton succession, affecting host and nonhost populations.
Using an in silico food web we conducted simulation experiments under a range of different abiotic and biotic conditions, exploring virus–host–grazer interactions and manipulating competition, allometry, motility and cyst cycles.
Virus-host and predator–prey interactions, and interactions with competitors, generate bloom dynamics with a pronounced ‘boom-and-busted’ dynamic (BBeD) which leads to the suppression of otherwise potentially successful phytoplankton species. The BBeD is less pronounced at low nutrient loading through distancing of phytoplankton hosts, while high sediment loading and high nonhost biomass decrease the abundance of viruses through adsorption. Larger hosts are inherently more distanced, but motility increases virus attack, while cyst cycles promote spatial and temporal distancing.
Virus control of phytoplankton bloom development appears more important than virus-induced termination of those blooms. This affects plankton succession – not only the growth of species infected by the virus, but also those that compete for the same resources and are collectively subjected to common grazer control. The role of viruses in structuring plankton communities via BBeDs can thus provide an explanation for the paradox of the plankton
Development process of a clinical guideline to manage type 2 diabetes in adults by Ayurvedic practitioners
Background: Type 2 diabetes mellitus (T2DM), a common chronic health condition, has major health and socioeconomic consequences. In the Indian subcontinent, it is a health condition for which individuals commonly consult Ayurvedic (traditional medical system) practitioners and use their medicines. However, to date, a good quality T2DM clinical guideline for Ayurvedic practitioners, grounded on the best available scientific evidence, is not available. Therefore, the study aimed to systematically develop a clinical guideline for Ayurvedic practitioners to manage T2DM in adults. Methods: The development work was guided by the UK’s National Institute for Health and Care Excellence (NICE) manual for developing guidelines, the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, and the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. First, a comprehensive systematic review was conducted which evaluated Ayurvedic medicines’ effectiveness and safety in managing T2DM. In addition, the GRADE approach was used for assessing the certainty of the findings. Next, using the GRADE approach, the Evidence-to-Decision framework was developed, and we focused on glycemic control and adverse events. Subsequently, based on the Evidence-to-Decision framework, a Guideline Development Group of 17 international members made recommendations on Ayurvedic medicines’ effectiveness and safety in T2DM. These recommendations formed the basis of the clinical guideline, and additional generic content and recommendations were adapted from the T2DM Clinical Knowledge Summaries of the Clarity Informatics (UK). The feedback given by the Guideline Development Group on the draft version was used to amend and finalize the clinical guideline. Results: A clinical guideline for managing T2DM in adults by Ayurvedic practitioners was developed, which focuses on how practitioners can provide appropriate care, education, and support for people with T2DM (and their carers and family). The clinical guideline provides information on T2DM, such as its definition, risk factors, prevalence, prognosis, and complications; how it should be diagnosed and managed through lifestyle changes like diet and physical activity and Ayurvedic medicines; how the acute and chronic complications of T2DM should be detected and managed (including referral to specialists); and advice on topics like driving, work, and fasting including during religious/socio-cultural festivals. Conclusion: We systematically developed a clinical guideline for Ayurvedic practitioners to manage T2DM in adults
Hairy black holes and solitons in global AdS 5
We use a mix of analytic and numerical methods to exhaustively study a class
of asymptotically global AdS solitons and hairy black hole solutions in
negative cosmological constant Einstein Maxwell gravity coupled to a charged
massless scalar field. Our results depend sensitively on the charge 'e' of the
scalar field. The solitonic branch of solutions we study hit the Chandrashekhar
limit at finite mass at small 'e', but extends to arbitrarily large mass at
larger 'e'. At low values of 'e' no hairy black holes exist. At intermediate
values of 'e' hairy black holes exist above a critical charge. At large 'e'
hairy black holes exist at all values of the charge. The lowest mass hairy
black holes is a smooth zero entropy soliton at small charge, but a (probably)
singular nonzero entropy hairy black hole at larger charge. In a phase diagram
of solutions, the hairy black holes merge with the familiar
Reissner-Nordstrom-AdS black holes along a curve that is determined by the
onset of the superradiant instability in the latter family.Comment: 80 pages. 25 Figures. RevTex4 format. v2: added discussions on second
soliton branch and on planar limit; matches published versio
A priority paper for the societal and ethical aspects of synthetic biology
As synthetic biology develops into a promising science and engineering field, we need to have clear ideas and priorities regarding its safety, security, ethical and public dialogue implications. Based on an extensive literature search, interviews with scientists, social scientists, a 4 week long public e-forum, and consultation with several stakeholders from science, industry and civil society organisations, we compiled a list of priority topics regarding societal issues of synthetic biology for the years ahead. The points presented here are intended to encourage all stakeholders to engage in the prioritisation of these issues and to participate in a continuous dialogue, with the ultimate goal of providing a basis for a multi-stakeholder governance in synthetic biology. Here we show possible ways to solve the challenges to synthetic biology in the field of safety, security, ethics and the science–public interface
Long-term follow-up of patients with mantle cell lymphoma (MCL) treated with the selective Bruton’s tyrosine kinase inhibitor tirabrutinib (GS/ONO-4059)
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