1,101 research outputs found
Ensemble Transport Adaptive Importance Sampling
Markov chain Monte Carlo methods are a powerful and commonly used family of
numerical methods for sampling from complex probability distributions. As
applications of these methods increase in size and complexity, the need for
efficient methods increases. In this paper, we present a particle ensemble
algorithm. At each iteration, an importance sampling proposal distribution is
formed using an ensemble of particles. A stratified sample is taken from this
distribution and weighted under the posterior, a state-of-the-art ensemble
transport resampling method is then used to create an evenly weighted sample
ready for the next iteration. We demonstrate that this ensemble transport
adaptive importance sampling (ETAIS) method outperforms MCMC methods with
equivalent proposal distributions for low dimensional problems, and in fact
shows better than linear improvements in convergence rates with respect to the
number of ensemble members. We also introduce a new resampling strategy,
multinomial transformation (MT), which while not as accurate as the ensemble
transport resampler, is substantially less costly for large ensemble sizes, and
can then be used in conjunction with ETAIS for complex problems. We also focus
on how algorithmic parameters regarding the mixture proposal can be quickly
tuned to optimise performance. In particular, we demonstrate this methodology's
superior sampling for multimodal problems, such as those arising from inference
for mixture models, and for problems with expensive likelihoods requiring the
solution of a differential equation, for which speed-ups of orders of magnitude
are demonstrated. Likelihood evaluations of the ensemble could be computed in a
distributed manner, suggesting that this methodology is a good candidate for
parallel Bayesian computations
Bioengineering Lantibiotics for Therapeutic Success
peer-reviewedSeveral examples of highly modified antimicrobial peptides have been described.
While many such peptides are non-ribosomally synthesized, ribosomally synthesized
equivalents are being discovered with increased frequency. Of the latter group, the
lantibiotics continue to attract most attention. In the present review, we discuss the
implementation of in vivo and in vitro engineering systems to alter, and even enhance,
the antimicrobial activity, antibacterial spectrum and physico-chemical properties,
including heat stability, solubility, diffusion and protease resistance, of these compounds.
Additionally, we discuss the potential applications of these lantibiotics for use as
therapeutics.DF,CH,PC,RR are supported by the Irish Government under the National Development Plan, through a Science Foundation Ireland (SFI) Technology and Innovation Development Award
(TIDA14/TIDA/2286) to DF, a SFI Investigator awards to CH and RR (10/IN.1/B3027),SFI-PIfunding(11/PI/1137) to PDC and the Alimentary Pharmabiotic Centre under Grant Number SFI/12/RC/2273
Fermented beverages with health-promoting potential: Past and future perspectives
peer-reviewedFermentation is an ancient form of food preservation, which also improves the nutritional content of foods. In many regions of the world, fermented beverages have become known for their health-promoting attributes. In addition to harnessing traditional beverages for commercial use, there have recently been innovative efforts to develop non-dairy probiotic fermented beverages from a variety of substrates, including soy milk, whey, cereals and vegetable and fruit juices. On the basis of recent developments, it is anticipated that fermented beverages will continue to be a significant component within the functional food market
Antimicrobial antagonists against food pathogens; a bacteriocin perspective
peer-reviewedEfforts are continuing to find novel bacteriocins with enhanced specificity and potency. Traditional plating techniques are still being used for bacteriocin screening studies, however, the availability of ever more bacterial genome sequences and the use of in silico gene mining tools have revealed novel bacteriocin gene clusters that would otherwise have been overlooked. Furthermore, synthetic biology and bioengineering-based approaches are allowing scientists to harness existing and novel bacteriocin gene clusters through expression in different hosts and by enhancing functionalities. The same principles apply to bacteriocin producing probiotic cultures and their application to control pathogens in the gut. We can expect that the recent developments on bacteriocins from Lactic Acid Bacteria (LAB) described here will contribute greatly to increased commercialisation of bacteriocins in food systems.This work was funded by the Alimentary Pharmabiotic Centre, a research centre funded by Science Foundation Ireland (SFI), through the Irish Governmentâs National Development Plan. The authors and their work were supported by SFI (grant no. 12/RC/2273
The Feasibility of Magnetic Reconnection Powered Blazar Flares from Synchrotron Self-Compton Emission
Order of magnitude variability has been observed in the blazar sub-class of
Active Galactic Nuclei on minute timescales. These high-energy flares are often
difficult to explain with shock acceleration models due to the small size of
the inferred emitting region, with recent particle-in-cell (PIC) simulations
showing that magnetic reconnection is a promising alternative mechanism. Here,
we present a macroscopic emission model physically motivated by PIC
simulations, where the energy for particle acceleration originates from the
reconnecting magnetic field. We track the radial growth and relative velocity
of a reconnecting plasmoid, modelling particle acceleration and radiative
losses from synchrotron and synchrotron self-Compton (SSC) emission. To test
the viability of magnetic reconnection as the mechanism behind rapid blazar
flares we simultaneously fit our model to the observed light-curve and SED from
the 2016 TeV flare of BL Lacertae. We find generally that, without considering
external photons, reconnecting plasmoids are unable to produce Compton-dominant
TeV flares and so cannot reproduce the observations due to overproduction of
synchrotron emission. Additionally, problematically large plasmoids, comparable
in size to the entire jet radius, are required to emit sufficient SSC
gamma-rays to be observable. However, our plasmoid model can reproduce the
rapid TeV lightcurve of the flare, demonstrating that reconnection is able to
produce rapid, powerful TeV flares on observed timescales. We conclude that
while reconnection can produce SSC flares on the correct timescales, the
primary source of TeV emission cannot be SSC and the size of plasmoids required
may be implausibly large.Comment: Replaced with accepted version. Contains additional figures and
considers the effect of a magnetic guide fiel
Use of the FĂschlĂĄr video library system
FĂschlĂĄr is a shared video retrieval system that lets users record, browse and watch television programmes using their web browser. In FĂschlĂĄr, the programmes users can watch and record are organised by channel, by theme and by personal recommendation as provided by the ChangingWorldsâ ClixSmart personalisation engine. Our initial results from user trials illustrate the usage of each of these features
Beneficial modulation of the gut microbiota
peer-reviewedThe human gut microbiota comprises approximately 100 trillion microbial cells and has a significant effect on many aspects of human physiology including metabolism, nutrient absorption and immune function. Disruption of this population has been implicated in many conditions and diseases, including examples such as obesity, inflammatory bowel disease and colorectal cancer that are highlighted in this review. A logical extension of these observations suggests that the manipulation of the gut microbiota can be employed to prevent or treat these conditions. Thus, here we highlight a variety of options, including the use of changes in diet (including the use of prebiotics), antimicrobial-based intervention, probiotics and faecal microbiota transplantation, and discuss their relative merits with respect to modulating the intestinal community in a beneficial way.C.J.W, C.M.G. and P.D.C are supported by a SFI PI award âObesibioticsâ (11/PI/1137
In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms
peer-reviewedThe development and spread of pathogenic bacteria that are resistant to the existing
catalog of antibiotics is a major public health threat. Biofilms are complex, sessile
communities of bacteria embedded in an organic polymer matrix which serve to further
enhance antimicrobial resistance. Consequently, novel compounds and innovative
methods are urgently required to arrest the proliferation of drug-resistant infections in
both nosocomial and community environments. Accordingly, it has been suggested
that antimicrobial peptides could be used as novel natural inhibitors that can be used
in formulations with synergistically acting antibiotics. Nisin is a member of the lantibiotic
family of antimicrobial peptides that exhibit potent antibacterial activity against many
Gram-positive bacteria. Recently we have used bioengineering strategies to enhance
the activity of nisin against several high profile targets, including multi-drug resistant
clinical pathogens such as methicillin-resistant Staphylococcus aureus, vancomycinresistant
enterococci, staphylococci, and streptococci associated with bovine mastitis.
We have also identified nisin derivatives with an enhanced ability to impair biofilm
formation and to reduce the density of established biofilms of methicillin resistant
S. pseudintermedius. The present study was aimed at evaluating the potential of
nisin and nisin derivatives to increase the efficacy of conventional antibiotics and
to assess the possibility of killing and/or eradicating biofilm-associated cells of a
variety of staphylococcal targets. Growth curve-based comparisons established that
combinations of derivatives nisin V C penicillin or nisin I4V C chloramphenicol had
an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius
DSM21284, respectively, compared to the equivalent nisin A C antibiotic combinations
or when each antimicrobial was administered alone. Furthermore, the metabolic activity
of established biofilms treated with nisin V C chloramphenicol and nisin I4V C
chloramphenicol combinations revealed a significant decrease in S. aureus SA113 and
S. pseudintermedius DSM21284 biofilm viability, respectively, compared to the nisin A C
antibiotic combinations as determined by the rapid colorimetric XTT assay. The results
indicate that the activities of the nisin derivative and antibiotic combinations represent a
significant improvement over that of the wild-type nisin and antibiotic combination and
merit further investigation with a view to their use as anti-biofilm agents.DF,CH,PC,RR are supported by the Irish Government under the National Development Plan, through a Science Foundation Ireland (SFI)Technology and Innovation Development Award
(TIDA14/TIDA/2286)to DF,a SFI Investigator awards to CH
and RR(10/IN.1/B3027),SFI-PI funding(11/PI/1137)to PC and the Alimentary Pharmabiotic Centre under Grant Number SFI/12/RC/2273
A degenerate PCR-based strategy as a means of identifying homologues of aminoglycoside and Ă-lactam resistance genes in the gut microbiota
peer-reviewedBackground: The potential for the human gut microbiota to serve as a reservoir for antibiotic resistance genes has been the subject of recent discussion. However, this has yet to be investigated using a rapid PCR-based approach. In light of this, here we aim to determine if degenerate PCR primers can detect aminoglycoside and β-lactam resistance genes in the gut microbiota of healthy adults, without the need for an initial culture-based screen for resistant isolates. In doing so, we would determine if the gut microbiota of healthy adults, lacking recent antibiotic exposure, is a reservoir for resistance genes.
Results: The strategy employed resulted in the identification of numerous aminoglycoside (acetylation, adenylation and phosphorylation) and β-lactam (including bla
OXA, bla TEM, bla SHV and bla CTX-M) resistance gene homologues. On the basis of homology, it would appear that these genes originated from different bacterial taxa, with members of the Enterobacteriaceae being a particularly rich source. The results demonstrate that, even in the absence of recent antibiotic exposure, the human gut microbiota is a considerable reservoir for antibiotic resistance genes.
Conclusions: This study has demonstrated that the gut can be a significant source of aminoglycoside and β-lactam resistance genes, even in the absence of recent antibiotic exposure. The results also demonstrate that PCR-based approaches can be successfully applied to detect antibiotic resistance genes in the human gut microbiota, without the need to isolate resistant strains. This approach could also be used to rapidly screen other complex environments for target genes.Fiona Fouhy is in receipt of an Irish Research Council EMBARK scholarship
and is a Teagasc Walsh fellow. Research in the PDC laboratory is also
supported by the Irish Government under the National Development Plan through the Science Foundation Ireland Investigator award 11/PI/113
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