4,667 research outputs found
Accelerating Asymptotically Exact MCMC for Computationally Intensive Models via Local Approximations
We construct a new framework for accelerating Markov chain Monte Carlo in
posterior sampling problems where standard methods are limited by the
computational cost of the likelihood, or of numerical models embedded therein.
Our approach introduces local approximations of these models into the
Metropolis-Hastings kernel, borrowing ideas from deterministic approximation
theory, optimization, and experimental design. Previous efforts at integrating
approximate models into inference typically sacrifice either the sampler's
exactness or efficiency; our work seeks to address these limitations by
exploiting useful convergence characteristics of local approximations. We prove
the ergodicity of our approximate Markov chain, showing that it samples
asymptotically from the \emph{exact} posterior distribution of interest. We
describe variations of the algorithm that employ either local polynomial
approximations or local Gaussian process regressors. Our theoretical results
reinforce the key observation underlying this paper: when the likelihood has
some \emph{local} regularity, the number of model evaluations per MCMC step can
be greatly reduced without biasing the Monte Carlo average. Numerical
experiments demonstrate multiple order-of-magnitude reductions in the number of
forward model evaluations used in representative ODE and PDE inference
problems, with both synthetic and real data.Comment: A major update of the theory and example
Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections.
BACKGROUND: Monitoring resistance phenotypes for Plasmodium falciparum, using in vitro growth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.
METHODS: Plasmodium falciparum isolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations in pfatp6 and pfmdr1.
RESULTS: Resistance to artemether in vitro was significantly associated with a pfatp6 haplotype encoding two amino acid substitutions (pfatp6 A623E and S769N; (mean IC50 (95% CI) values of 8.2 (5.7 - 10.7) for A623/S769 versus 623E/769 N 13.5 (9.8 - 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number of pfmdr1 was not itself associated with increased IC50 values for artemether, but when interactions between the pfatp6 haplotype and increased copy number of pfmdr1 were examined together, a highly significant association was noted with IC50 values for artemether (mean IC50 (95% CI) values of 8.7 (5.9 - 11.6) versus 16.3 (10.7 - 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs in pfmdr1 are also associated with differences in sensitivity to some artemisinins.
CONCLUSIONS: These findings were further explored in molecular modelling experiments that suggest mutations in pfatp6 are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations in pfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed
Absorption enhancement due to scattering by dipoles into silicon waveguides
We develop an optical model for absorption enhancement and diffuse reflectance by metal nanoparticles on a siliconwaveguide. A point dipole treatment is used, including the effects of the waveguide on both the angular emission spectrum and scattering cross section of the dipoles. The model agrees very well with our experimental results of greatly enhanced electroluminescence and photocurrent from silicon-on-insulator light-emitting diodes and also gives very good agreement with previously reported diffuse reflectance measurements. The results suggest that the main mechanism in the enhancement of diffuse reflectance in this system is a dramatic enhancement in the scattering cross section of waveguided light, rather than a waveguide-mediated dipole-dipole interaction. We also put lower bounds on the radiative efficiency of scattering by the nanoparticles.One of the authors K.R.C. acknowledges the support of
an Australian Research Council fellowship. The authors acknowledge
the support of the Centre of Excellence for Advanced
Silicon Photovoltaics and Photonics, supported by
the Australian Research Council
Can we still call Australia home? The right to return and the legality of Australia’s COVID-19 travel restrictions
In the two years since Australia logged its first COVID-19 case and sealed its borders, thousands of citizens and permanent residents were locked out. Despite having a formal right to return, their ability to come home was hampered by a ‘one size fits all’ approach to hotel quarantine, travel caps linked to state/territory capacity, and a lack of federal facilities. This article examines the legality of Australia’s entry controls in light of international and domestic law. It documents the evolution of Australia’s response from the initial outbreak in China to the 2021 Delta outbreak in India, analysing the (limited) publicly available information as to the rationale for the restrictions. It examines the right to return in Australian domestic law, including whether citizens have a constitutionally protected right of entry. It also analyses the right to enter under international law, evaluating whether Australia’s settings constitute an arbitrary restriction of that right—especially since the drafters of the International Covenant on Civil and Political Rights thought it ‘inconceivable’ that a government would prevent citizens from returning for public health reasons
Prospects of development of marine fisheries resources in Lakshadweep
A good data base has already been developed by CMFRI on various marine resources of Lakshadweep islands and related conservation problems. In the present paper, the potentialities and the areas where future research and developmental activities need to be directed are briefly discussed
Description of the male of Caligus hilase Shaw (Copepoda, Caligidae)
Caligus hil.rae Shen, 1957, is unique in the possession of a comparatively very long four-segmented abdomen, long anal laminae which are nearly three times as long as broad and in the absence of the sternal fork
Fishable concentrations of fishes and crustaceans in the offshore and deep sea areas of the Indian Exclusive Economic Zone based on observations made onboard FORV Sagar Sampada
Bottom trawling data of FORV Sagar Sampada pertaining to a total of 350 fishing hauls with a duration of 330 effective
trawling hours for depths beyond 40 m was utilized in the present study. Abundance of selected fishery resources such
as threadfin bream, bull's eye, drift fish, lizard fish, ribbon fish, cat fish, barracudas, mackerel, deep sea prawns and deep
sea lobster in the offshore and deep sea waters of the Indian EEZ in space and time is indicated
Tuna fisheries and fishery in the Indian EEZ- An update
The scenario of tuna fishery in the Indian EEZ in recent years show that
it is still limited to the small scale fishery sector with little inputs from the
industrial sector. The results obtained till date from the surveys carried out by
the Government of India vessels (FSl and CIFNET) in the EEZ beyond the traditional
fishing grounds, the industrial longline operations of foreign fleets in the
Indian EEZ and contiguous high seas, the rapid increasing rate of skipjack and
yellowfin tuna production in the traditional sectors of the neighbouring insular
states such as Maldives and Sri Lanka and the fast pace of growth, expansion
and production in the tuna purse seine fishery of foreign fleets of France, Spain,
Panama and Ivory Coast in the tropical Western Indian Ocean area - all these
have indicated tuna resource availability and rich tuna fishing grounds in our
EEZ and contiguous high seas
In vitro micropropogation Of Sphaeranthus amaranthoides Burm.F
Sphaeranthus amaranthoides commonly known as garden Lavender / Kesavardini is used to cure eczema, skin diseases, worm infestation, pile, aphrodisiac etc, from Ancient Era. In present investigation the auxillary buds and shoot tips were used as explants for invitro micropropogation. The initiation and best multiple shoots was developed at 4mg/L of BAP with a highest frequency of 70% and good root proliferation was observed at 2.0mg/L of IBA
An instance of total drying up of Pillaimadam lagoon during 1986-'87 in South-East coast of India
Pillaimadam Lagoon is located in Ramanathapuram District, has been playing a role in the economy of the fishermen living in its neighbourhood, any marked change in its ecology and fisheries is bound to influence the fishermen there, in one way or the other. In view of this, an instance of total drying up of the lagoon observed during 1987 is documented and recorded. The ecology of the lagoon is influenced by two principal climatic condition.. When the rains cease, summer prevails and the barmouth closes, thus cutting off freshwater, salinity reaches as high as 73 to 93 %0. Run off water from the land accumulates in the lagoon, the bar gets opened, the lagoon water becomes brackish and salinity values became low (25-33 %0). Due to the existing single bar mouth and under the climatic conditions prevailing, capture fisheries as well as culture projects can be undertaken in the lagoon only from about October till the following March
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