12,090 research outputs found
Incentivising Privacy in Cryptocurrencies
Privacy was one of the key points mentioned in Nakamoto's Bitcoin whitepaper,
and one of the selling points of Bitcoin in its early stages. In hindsight,
however, de-anonymising Bitcoin users turned out to be more feasible than
expected. Since then, privacy focused cryptocurrencies such as Zcash and Monero
have surfaced. Both of these examples cannot be described as fully successful
in their aims, as recent research has shown. Incentives are integral to the
security of cryptocurrencies, so it is interesting to investigate whether they
could also be aligned with privacy goals. A lack of privacy often results from
low user counts, resulting in low anonymity sets. Could users be incentivised
to use the privacy preserving implementations of the systems they use? Not only
is Zcash much less used than Bitcoin (which it forked from), but most Zcash
transactions are simply transparent transactions, rather than the (at least
intended to be) privacy-preserving shielded transactions. This paper and poster
briefly discusses how incentives could be incorporated into systems like
cryptocurrencies with the aim of achieving privacy goals. We take Zcash as
example, but the ideas discussed could apply to other privacy-focused
cryptocurrencies. This work was presented as a poster at OPERANDI 2018, the
poster can be found within this short document
Relating cell shape and mechanical stress in a spatially disordered epithelium using a vertex-based model
Using a popular vertex-based model to describe a spatially disordered planar
epithelial monolayer, we examine the relationship between cell shape and
mechanical stress at the cell and tissue level. Deriving expressions for stress
tensors starting from an energetic formulation of the model, we show that the
principal axes of stress for an individual cell align with the principal axes
of shape, and we determine the bulk effective tissue pressure when the
monolayer is isotropic at the tissue level. Using simulations for a monolayer
that is not under peripheral stress, we fit parameters of the model to
experimental data for Xenopus embryonic tissue. The model predicts that
mechanical interactions can generate mesoscopic patterns within the monolayer
that exhibit long-range correlations in cell shape. The model also suggests
that the orientation of mechanical and geometric cues for processes such as
cell division are likely to be strongly correlated in real epithelia. Some
limitations of the model in capturing geometric features of Xenopus epithelial
cells are highlighted.Comment: 29 pages, 10 figures, revisio
Aspects of the pharmacokinetics of itraconazole and voriconazole in the tuatara (Sphenodon punctatus) and application in the treatment of an emerging fungal disease
Tuatara (Sphenodon punctatus) are unique, cold-adapted reptiles endemic to New Zealand. Recently, captive tuatara have been found to be affected by an emerging fungal pathogen, Paranannizziopsis australasiensis. P. australasiensis causes dermatitis in tuatara, and has caused fatal systemic mycosis in a bearded dragon (Pogona vitticeps), and in aquatic file snakes (Acrochordus spp). The discovery of P. australasiensis infections has prevented the release of tuatara from several captive institutions to offshore islands, and has negative implications for the long-term health and welfare of the animals.
A review of the literature revealed that infections caused by organisms related to P. australasiensis are being recognised worldwide as emerging pathogens of reptiles. Little is known about the epidemiology of these often-fatal infections, and treatment with a range of antifungals has met with varying success. There has been little research on antifungal use in reptiles, and none on how environmental temperature affects the pharmacokinetics of antifungals.
This study investigated the microbiological characteristics of P. australasiensis, primarily the growth rate of the fungus at different temperatures, and the Minimum Inhibitory Concentration (MIC) of various antifungal agents for P. australasiensis. It was determined that the optimal growth temperature for P. australasiensis encompasses the range from 20oC-30oC, with scant growth at 12oC, moderate growth at 15oC, and no growth at 37oC. The MICs of antifungals were tested at room temperature and at 37oC, and were not found to be significantly different. MICs of itraconazole and voriconazole for three isolates of P. australasiensis were found to be low, at 0.12mg/L for itraconazole and <0.008mg/L for voriconazole.
The single and multiple dose pharmacokinetics of itraconazole and voriconazole in tuatara were investigated at 12 and 20oC; these are the high and low ends of the tuatara’s preferred optimal temperature zone (POTZ). Results showed statistically significant differences in antifungal elimination half-life between temperatures. With the aid of population pharmacokinetic modelling, optimal dosing regimes for both antifungals were developed for tuatara of different weights. It was established that tuatara should be treated at 20oC, at the high end of POTZ, to facilitate rapid attainment of therapeutic antifungal concentrations, improve clinical outcomes and reduce the risk of adverse effects.
While itraconazole demonstrated more predictable pharmacokinetics than voriconazole in tuatara, itraconazole treatment was associated with significant adverse effects. These included elevated bile acids and uric acid concentrations, and weight loss. While voriconazole appears to be safer, its pharmacokinetics are less predictable, with high inter-individual variability in tuatara administered the same dose rate (a phenomenon also observed in humans). While voriconazole may be a useful antifungal in clinically affected tuatara where dosage can be adjusted based on the response to treatment, its use in an asymptomatic quarantine setting may be limited. The use of higher voriconazole doses may increase the likelihood of maintaining therapeutic concentrations in all treated animals, however the risk of adverse effects increases concomitantly. Furthermore, there are currently no published reports of successful treatment of P. australasiensis in tuatara with voriconazole.
This study also established haematologic and biochemical reference ranges in a group of tuatara. These demonstrated variability in several parameters based on sex and season, and will be a useful tool for assessing health and disease in these and other tuatara
Mechanical characterization of disordered and anisotropic cellular monolayers
We consider a cellular monolayer, described using a vertex-based model, for
which cells form a spatially disordered array of convex polygons that tile the
plane. Equilibrium cell configurations are assumed to minimize a global energy
defined in terms of cell areas and perimeters; energy is dissipated via dynamic
area and length changes, as well as cell neighbour exchanges. The model
captures our observations of an epithelium from a Xenopus embryo showing that
uniaxial stretching induces spatial ordering, with cells under net tension
(compression) tending to align with (against) the direction of stretch, but
with the stress remaining heterogeneous at the single-cell level. We use the
vertex model to derive the linearized relation between tissue-level stress,
strain and strain-rate about a deformed base state, which can be used to
characterize the tissue's anisotropic mechanical properties; expressions for
viscoelastic tissue moduli are given as direct sums over cells. When the base
state is isotropic, the model predicts that tissue properties can be tuned to a
regime with high elastic shear resistance but low resistance to area changes,
or vice versa.Comment: 9 figure
Polymer-stabilized sialylated nanoparticles : synthesis, optimization, and differential binding to influenza hemagglutinins
During influenza infection, hemagglutinins (HAs) on the viral surface bind to sialic acids on the host cell's surface. While all HAs bind sialic acids, human influenza targets terminal α2,6 sialic acids and avian influenza targets α2,3 sialic acids. For interspecies transmission (zoonosis), HA must mutate to adapt to these differences. Here, multivalent gold nanoparticles bearing either α2,6- or α2,3-sialyllactosamine have been developed to interrogate a panel of HAs from pathogenic human, low pathogenic avian, and other species' influenza. This method exploits the benefits of multivalent glycan presentation compared to monovalent presentation to increase affinity and investigate how multivalency affects selectivity. Using a library-orientated approach, parameters including polymer coating and core diameter were optimized for maximal binding and specificity were probed using galactosylated particles and a panel of biophysical techniques [ultraviolet-visible spectroscopy, dynamic light scattering, and biolayer interferometry]. The optimized particles were then functionalized with sialyllactosamine and their binding analyzed against a panel of HAs derived from pathogenic influenza strains including low pathogenic avian strains. This showed significant specificity crossover, which is not observed in monovalent formats, with binding of avian HAs to human sialic acids and in agreement with alternate assay formats. These results demonstrate that precise multivalent presentation is essential to dissect the interactions of HAs and may aid the discovery of tools for disease and zoonosis transmission
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