150 research outputs found
The spectra of the spherical and euclidean triangle groups
We derive the spectrum of the Laplace-Beltrami operator on the quotient
orbifold of the non hyperbolic triangle groups.Comment: accepted in the Journal of the Australian Mathematical Societ
Boundary condition at the junction
The quantum graph plays the role of a solvable model for a two-dimensional
network. Here fitting parameters of the quantum graph for modelling the
junction is discussed, using previous results of the second author.Comment: Replaces unpublished draft on related researc
Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species
Burkholderia pseudomallei is a soil-dwelling organism present throughout the tropics. It is the causative agent of melioidosis, a disease that is believed to kill 89,000 people per year. It is naturally resistant to many antibiotics, requiring at least two weeks of intravenous treatment with ceftazidime, imipenem or meropenem followed by 6 months of orally delivered co-trimoxazole. This places a large treatment burden on the predominantly middle-income nations where the majority of disease occurs. We have established a high-throughput assay for compounds that could be used as a co-therapy to potentiate the effect of ceftazidime, using the related non-pathogenic bacterium Burkholderia thailandensis as a surrogate. Optimization of the assay gave a Z' factor of 0.68. We screened a library of 61,250 compounds and identified 29 compounds with a pIC50 (-log10(IC50)) greater than five. Detailed investigation allowed us to down select to six "best in class" compounds, which included the licensed drug chloroxine. Co-treatment of B. thailandensis with ceftazidime and chloroxine reduced culturable cell numbers by two orders of magnitude over 48 hours, compared to treatment with ceftazidime alone. Hit expansion around chloroxine was performed using commercially available compounds. Minor modifications to the structure abolished activity, suggesting that chloroxine likely acts against a specific target. Finally, an initial study demonstrates the utility of chloroxine to act as a co-therapy to potentiate the effect of ceftazidime against B. pseudomallei. This approach successfully identified potential co-therapies for a recalcitrant Gram-negative bacterial species. Our assay could be used more widely to aid in chemotherapy to treat infections caused by these bacteria
Inducing Ito,f and phase 1 repolarization of the cardiac action potential with a Kv4.3/KChIP2.1 bicistronic transgene
The fast transient outward potassium current (I(to,f)) plays a key role in phase 1 repolarization of the human cardiac action potential (AP) and its reduction in heart failure (HF) contributes to the loss of contractility. Therefore, restoring I(to,f) might be beneficial for treating HF. The coding sequence of a P2A peptide was cloned, in frame, between Kv4.3 and KChIP2.1 genes and ribosomal skipping was confirmed by Western blotting. Typical I(to,f) properties with slowed inactivation and accelerated recovery from inactivation due to the association of KChIP2.1 with Kv4.3 was seen in transfected HEK293 cells. Both bicistronic components trafficked to the plasmamembrane and in adenovirus transduced rabbit cardiomyocytes both t-tubular and sarcolemmal construct labelling appeared. The resulting current was similar to I(to,f) seen in human ventricular cardiomyocytes and was 50% blocked at ~0.8 mmol/l 4-aminopyridine and increased ~30% by 5 μmol/l NS5806 (an I(to,f) agonist). Variation in the density of the expressed I(to,f), in rabbit cardiomyocytes recapitulated typical species-dependent variations in AP morphology. Simultaneous voltage recording and intracellular Ca(2+) imaging showed that modification of phase 1 to a non-failing human phenotype improved the rate of rise and magnitude of the Ca(2+) transient. I(to,f) expression also reduced AP triangulation but did not affect I(Ca,L) and I(Na) magnitudes. This raises the possibility for a new gene-based therapeutic approach to HF based on selective phase 1 modification
Оптимизация режимов работы автономной фотоэлектрической станции
Цель работы: оптимизация режимов работы автономной фотоэлектрической станции. В результате исследования построены графики выработки и потребления электрической энергии, выбрано основное энергетическое оборудование миниФЭС, разработана схема, в соответствии со схемой, произведено сравнение тарифов миниФЭС с накопителями энергии и без них.Objective: operating mode optimization of stand- alone PV- station. The study graphs of production and consumption of electric energy, select the main power equipment mini PV-station, a scheme, in accordance with the scheme, a comparison of tariffs and mini PV-station with the storage system and without it
Insights into the Electronic Structure of CuII Bound to an Imidazole Analogue of Westiellamide.
Three synthetic analogues of westiallamide, HL, have previously been synthesized (HL) that have a common backbone (derived from l-valine) with HL but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and oxazoline). Herein we explore in detail through high-resolution pulsed electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy in conjunction with density functional theory (DFT) the geometric and electronic structures of the mono- and dinuclear Cu complexes of these cyclic pseudo hexapeptides. Orientation-selective hyperfine sublevel correlation, electron nuclear double resonance, and three-pulse electron spin echo envelope modulation spectroscopy of [Cu(HL)(MeOH)] reveal delocalization of the unpaired electron spin onto the ligating and distal nitrogens of the coordinated heterocyclic rings and that they are magnetically inequivalent. DFT calculations confirm this and show similar spin densities on the distal heteroatoms in the heterocyclic rings coordinated to the Cu ion in the other cyclic pseudo hexapeptide [Cu(HL)(MeOH)] complexes. The magnetic inequivalencies in [Cu(HL)(MeOH)] arise from different orientations of the heterocyclic rings coordinated to the Cu ion, and the delocalization of the unpaired electron onto the distal heteroatoms within these N-methylimidazole rings depends upon their location with respect to the Cu dx-y orbital. A systematic study of DFT functionals and basis sets was undertaken to examine the ability to reproduce the experimentally determined spin Hamiltonian parameters. Inclusion of spin-orbit coupling (SOC) using MAG-ReSpect or ORCA with a BHLYP/IGLO-II Wachters setup with SOC corrections and ∼38% Hartree-Fock exchange gave the best predictions of the g and A(Cu) matrices. DFT calculations of the N hyperfine and quadrupole parameters for the distal nitrogens of the coordinated heterocyclic rings in [Cu(HL)(MeOH)] with the B1LYP functional and the SVP basis set were in excellent agreement with the experimental data, though other choices of functional and basis set also provided reasonable values. MCD, EPR, mass spectrometry, and DFT showed that preparation of the dinuclear Cu complex in a 1:1 MeOH/glycerol mixture (necessary for MCD) resulted in the exchange of the bridging methoxide ligand for glycerol with a corresponding decrease in the magnitude of the exchange coupling
Point singularities and suprathreshold stochastic resonance in optimal coding
Motivated by recent studies of population coding in theoretical neuroscience,
we examine the optimality of a recently described form of stochastic resonance
known as suprathreshold stochastic resonance, which occurs in populations of
noisy threshold devices such as models of sensory neurons. Using the mutual
information measure, it is shown numerically that for a random input signal,
the optimal threshold distribution contains singularities. For large enough
noise, this distribution consists of a single point and hence the optimal
encoding is realized by the suprathreshold stochastic resonance effect.
Furthermore, it is shown that a bifurcational pattern appears in the optimal
threshold settings as the noise intensity increases. Fisher information is used
to examine the behavior of the optimal threshold distribution as the population
size approaches infinity.Comment: 11 pages, 3 figures, RevTe
Re-entrant percolation in active Brownian hard disks
Non-equilibrium clustering and percolation are investigated in an archetypal model of two-dimensional active matter using dynamic simulations of self-propelled Brownian repulsive particles. We concentrate on the single-phase region up to moderate levels of activity, before motility-induced phase separation (MIPS) sets in. Weak activity promotes cluster formation and lowers the percolation threshold. However, driving the system further out of equilibrium partly reverses this effect, resulting in a minimum in the critical density for the formation of system-spanning clusters and introducing re-entrant percolation as a function of activity in the pre-MIPS regime. This non-monotonic behaviour arises from competition between activity-induced effective attraction (which eventually leads to MIPS) and activity-driven cluster breakup. Using an adapted iterative Boltzmann inversion method, we derive effective potentials to map weakly active cases onto a passive (equilibrium) model with conservative attraction, which can be characterised by Monte Carlo simulations. While the active and passive systems have practically identical radial distribution functions, we find decisive differences in higher-order structural correlations, to which the percolation threshold is highly sensitive. For sufficiently strong activity, no passive pairwise potential can reproduce the radial distribution function of the active system
A sense of embodiment is reflected in people's signature size
BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size
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